About all

What antibiotic treats sepsis: Sepsis (Septicemia) Definition, Treatment, Causes, Stages & Diagnosis

Содержание

Sepsis Treatment: Options Your Doctor May Recommend

Sepsis is a rare complication of an infection and occurs when an extreme immune system response triggers widespread inflammation throughout the body. (1) Sepsis can be mild or severe. But regardless of severity, it’s a potentially life-threatening illness that requires immediate medical attention.

Symptoms of sepsis include high fever, high heart rate, and fast breathing rate. As the infection progresses, some people experience difficulty breathing, stomach pain, confusion, and dizziness. Sepsis can also lead to dangerously low blood pressure and organ failure (septic shock). (1)

Due to the gravity of this illness, sepsis isn’t something you treat at home. It requires an emergency room visit, where you’ll likely receive around-the-clock treatment in the intensive care unit.

Symptoms of sepsis develop after an infection such as a urinary tract infection, a skin infection, or pneumonia. It can also occur after surgery or after hospitalization for another illness. If you experience any of the symptoms of sepsis, go to the hospital or call 911. (1)

There isn’t a single treatment for sepsis. Treatment varies and depends on the cause of the infection that led to sepsis, as well as the severity of symptoms. (2) Because mild sepsis can rapidly progress to severe sepsis and then septic shock, doctors must work quickly to reduce inflammation.

Common treatments for sepsis include:

1. Antibiotics

Although various organisms can cause an infection that turns into sepsis, such as bacteria, viruses, or fungi, the main treatment for sepsis is antibiotics due to the fact that most cases are caused by a bacterial infection, (3) says Rebecca Lee, a registered nurse based in New York City and the founder of the natural health resource RemediesForMe.com.

You’ll receive antibiotics immediately after your doctor diagnoses sepsis, even when tests results haven’t yet confirmed a bacterial infection. Ideally, you should receive antibiotics within an hour of diagnosis. (2)

Different antibiotics work better with certain types of bacteria. But because it takes time to identify the bacterium that causes an infection, you’ll receive an antibiotic that can kill different types of bacteria and then switch to a more targeted antibiotic later. (3)

“Antibiotic treatment for sepsis varies broadly with what is infected, how at risk you are for certain types of bacteria, resistance patterns, and even availability,” says Kimberly Brown, MD, MPH, an ER doctor at the University of Tennessee Health Science Center in Memphis.

“We know what bacteria typically cause certain infections, so we start with broad-spectrum antibiotics to cover all possible culprits,” she continues. “This includes ceftriaxone, azithromycin, ciprofloxacin, vancomycin, and piperacillin-tazobactam.”

If you have mild sepsis, you may receive a prescription for antibiotics to take at home. But if your condition progresses to severe sepsis, you will receive antibiotics intravenously in the hospital. This method helps the medicine get into your bloodstream quicker so it can fight the infection sooner. Once treatment begins, it can take a few hours to days for you to respond to treatment, explains Dr. Brown.

After a few days of intravenous antibiotics, your doctor may switch you to a tablet antibiotic, which you’ll continue to take for 7 to 10 days. (3)

Treatment – Sepsis Alliance

Sepsis is a medical emergency. It needs to be treated as such. In other words, sepsis should be treated as quickly and efficiently as possible as soon as it has been identified. Treatment includes rapid administration of antibiotics and fluids. The risk of death from sepsis increases by an average of up to 7.6% with every hour that passes before treatment begins. (Critical Care Medicine)

Patients with severe sepsis or septic shock who are treated in an intensive care unit (ICU) can experience issues related to the illness and medications, the lack of sleep, and the overstimulation of having people and noise around them 24 hours a day. This can result in agitation, confusion, even hallucinations.

Treatment

Antibiotics

Physicians prescribe antibiotics (usually more than one type) based on the type of infection. Broad-spectrum antibiotics are the first-line medications. These antibiotics work against several of the more common bacteria. These are intravenous antibiotics so they can get into the blood system quickly and efficiently.

IV Fluids

Antibiotics alone won’t treat sepsis; you also need fluids. The body needs extra fluids to help keep the blood pressure from dropping dangerously low, causing shock. Giving IV fluids allows the health care staff to track the amount of fluid and to control the type of fluid.

Ensuring the body has enough fluids helps the organs to function and may reduce damage from sepsis.

Several types of fluid

While there are several types of IV fluids, some are standard in treating sepsis. Normal saline is one commonly given fluid. It is a crystalloid fluid. These are fluids that contain minerals, such as sodium, and are water-soluble, or dissolve in water. These add fluid to the blood system.

Colloids, another type of fluid, are thicker fluids. For example, blood is a colloid. Colloids given by IV include albumin and dextran. Colloids do not dissolve as quickly as crystalloids. More crystalloid fluid is needed than colloid fluid to achieve the same goal of boosting body fluid volume, but crystalloids are less expensive.

Additional Possible Treatments and Equipment

Since all patients are different and there are many causes of sepsis, not every available treatment is right for each patient. To find out what treatment is being you or your loved one need and why, speak with your health care provider.

Here are treatments, medications, and types of equipment that may be used on a patient with sepsis or septic shock.

Extracorporeal Therapies

Extracorporeal therapies are treatments done using machines and techniques such as continuous renal replacement therapy (a type of dialysis) or extracorporeal membrane oxygenation, or ECMO (life support).

Special types of IVs

Arterial lines – Arterial lines look like IV lines but they go directly into an artery, usually the wrist or groin. Nurses can monitor blood pressure and take frequent blood samples without inserting a needle in a vein each time one is needed. A special cap protects the line. It allows blood draws directly from the line. The line and cap must be monitored closely because the pressure caused by the blood pumping from the heart can result serious bleeding if the line becomes undone. 

Central lines – Central lines are large IV catheters most often inserted into a large vein near the shoulder. They they can go in any large vein, such as the neck or groin. Central lines have larger catheters than IVs. They provide fluids more quickly and easily. They also don’t need to be changed as often as an IV, which may be more comfortable for the patient. 

Medications

Corticosteroids – Although doctors don’t know why corticosteroids work for some patients who have sepsis and not others, they can be helpful. Corticosteroids can help reduce inflammation in the body and depress the immune system, making it less active.

Vasopressors – Physicians prescribe vasopressors to patients who are in shock and whose blood pressures have dropped dangerously low. The vasopressors act constrict or tighten up the blood vessels, forcing the blood pressure to go up.

Oxygen – Patients usually get oxygen, by mechanical ventilator, mask or nasal cannula. This ensures the body has enough oxygen in its system. A pulse oximetry monitor, often called a pulse ox, is a small piece of equipment that fits over the tip of a finger or toe, or on the ear lobe. It measures the amount of oxygen in the blood.

Equipment

Endotracheal Tube – An endotracheal tube, or ET tube, goes through the mouth into the trachea (windpipe) and is attached to a ventilator. A patient who has an ET tube is intubated. When the tube comes out, they are extubated. Patients with ET tubes cannot speak as the tube passes through the vocal cords. If there is damage in the mouth but a patient needs intubation, the doctor can insert a nasotracheal tube through the nose. Patients who are intubated may be restrained, their hands fastened down, if there is a danger of them unknowingly pulling the tube out. The physicians may opt to perform a tracheostomy if a patient must be on a ventilator for an extended time or there is too much damage to the mouth or throat. The doctor makes an opening in the throat for direct access to the trachea. A tube is inserted through the opening, fastened down, and connected to the ventilator. 

Intracranial Pressure Monitor – An intracranial pressure (ICP) monitor measures the fluid pressure in the brain. A sensor placed directly below the skull is attached to the monitor. 

Kidney dialysis (renal replacement therapy) – Patients may need dialysis if their kidneys cannot filter the blood as they should. A portable dialysis machine allows patients to undergo dialysis in the ICU. A special catheter is inserted into a large vein and attached to the dialysis machine. Blood flows through the machine, which filters out toxins in the blood. This is what the kidneys normally do. Once the blood is filtered, it flows back into the body.

Mechanical ventilation – Ventilators, sometimes called respirators, help patients breathe. The machines can either do all the work for the patient by pushing the air into the lungs at a preprogrammed speed, or they may only help when needed. The machine records how often the patient breathes. If there are not enough breaths within a certain period, the machine will assist by taking over as needed.

Nasogastric Tube – A nasogastric (NG) tube goes through the nose and down into the stomach. When inserted through the mouth, it is called an oral-gastric tube, but through the nose is the most common approach. This tube may be connected to a suction bottle, which draws out stomach contents to help reduce nausea and vomiting.  

PreSep™ catheter –  This type of catheter monitors the oxygen levels in the blood that is returning to the heart.

Pulmonary artery catheter – This type of catheter goes into the pulmonary artery – the blood vessel that carries blood from the heart to the lungs, where the blood can be supplied with oxygen. “Pulmonary” means something is related to the lungs.

Urinary Catheter  –  A urinary catheter is a tube inserted through the urethra to the bladder. It helps drain urine into a bag attached to the side of the bed or strapped to a leg. Patients may need a urinary catheter for a few hours or indefinitely, depending on the situation. If the catheter remains in for an extended period, it needs to be changed according to the facility’s protocol. 

 

Updated March 25, 2021

What is the antibiotic choice in bacteremia due to carbapenem resistant Enterobacteriaceae?

World J Clin Cases. 2017 Aug 16; 5(8): 324–332.

Fatema Alhashem, Department of Pediatrics, King Hamad University Hospital, Busaiteen 24343, Muharraq, Bahrain

Fatema Alhashem, Nicolette Leonie Tiren-Verbeet, Bone marrow Transplantation Department, Erciyes University Hospital, 38039 Kayseri, Turkey

Emine Alp, Mehmet Doganay, Department of Infectious Diseases, Faculty of Medicine, Erciyes University, 38039 Kayseri, Turkey

Author contributions: All authors contributed equally in the preparation of the manuscript.

Correspondence to: Mehmet Doganay, MD, Professor of Infectious Diseases, Department of Infectious Diseases, Faculty of Medicine, Erciyes University, Melikgazi District, 38039 Kayseri, Turkey. [email protected]

Telephone: +90-352-2076666-22055 Fax: +90-352-4375273

Received 2017 Mar 28; Revised 2017 May 16; Accepted 2017 May 30.

Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

This article has been cited by other articles in PMC.

Abstract

Sepsis is one of the major challenges of today. Although gram-positive bacteria related infections are more prevalent in hospital setting, the highest mortality rate is associated with gram-negative microorganisms especially Enterobacteriaceae. Enterobacteriaceae, including Escherichia coli, Klebsiella spp., Proteus spp., Enterobacter spp. and Serratia spp. Resistance to β-lactams in Enterobacteriaceae is primarily attributed to the production of B-lactamase enzymes with subsequent antibiotic hydrolysis and to a lesser extent by alteration of efflux pump or porins expression. Carbapenem resistant Enterobacteriaceae (CRE) and Acinetobacter baumannii are the most notorious pathogens due to the high incidence of morbidity and mortality especially in the immunocompromised patients in the intensive care unit. The most appropriate antimicrobial therapy to treat CRE is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage of micro-organisms, due to its synergetic effect and to prevent development of further resistance. Current suggested therapies for CRE resistance as well as promising antibiotics that are currently under investigation for winning the war against the emerging CRE resistance are reviewed and discussed.

Keywords: Carbapenem resistant Enterobacteriaceae, Sepsis, Bacteraemia, Bacteremia, Treatment, Antibiotics

Core tip: Carbapenem resistant Enterobacteriaceae (CRE) is the most notorious pathogens contributing to a significant morbidity and mortality rate in septic patients especially in the intensive care unit. The most appropriate antimicrobial therapy to treat CRE is still controversial. This review is conducted to discuss the effectiveness of available therapies at this moment and to elaborate on different promising drugs that are still under investigation in order to win the combat on rising antimicrobial resistance.

INTRODUCTION

Sepsis is a global healthcare problem and one of the major challenges that health care practitioners face worldwide[1]. It has become one of the major causes of death and its incidence is continuing to rise making it a huge burden in terms of increased morbidity and mortality, prolonged hospital stay, increased risk of having antimicrobial resistance and increasing hospital cost. It was estimated that the incidence of septic cases increased 13.7% each year over a period of 22 years[2-4]. Sepsis is newly re-defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities substantially increase mortality[5].

Sepsis is a medical emergency; hence, antimicrobial treatment should be started as soon as sepsis is suspected. To prevent development of further complications and progression of the patient into septic shock and multi organ failure, profound knowledge of the causative pathogens is needed to select the proper antibiotic treatment. To reduce sepsis associated mortality, it has been widely advocated to start empirical antibiotic therapy from the first hour following sepsis identification. This strategy leads to a reduction in mortality of 13.7%[6-8]. The most common primary site involved in sepsis is the respiratory tract, mainly pneumonia, followed by genitourinary tract infections. Other sites involved are the abdomen, wound and soft tissue infections, the central nervous system (CNS) and the cardiovascular system. In some cases, the source origin is unknown (Table )[6,9,10]. However, the most commonly isolated pathogens depend on the infection site. In wound infections Staphylococcus aureus and coagulase negative staphylococci was found to be the most causative organism of both meningitis and pneumonia, while Escherichia coli is the most prevalent cause of urinary tract infections (UTI) related sepsis[11,12]. Regarding blood stream infection (BSI), coagulase negative staphylococci and E. coli are the notable organisms isolated[10].

Table 1

The most common sites of infection and mortality rates in sepsis

Site of infection Mortality (%)
Blood stream infection 34.2
Respiratory 22
Genitourinary 8.2
Wound and soft tissue infection 10.55
Abdomen 10.25
CNS 17. 4
Device related 9.5
Endocarditis 25.95
Others 7.05

In the intensive care unit (ICU) setting, the most common isolated pathogens causing severe sepsis are S. aureus followed by Pseudomonas infection, Enterobacteriaceae and fungal infection, respectively. Acinetobacter baumannii was involved in 9% of all infections[10]. But in general, gram negative pathogens are the most commonly found in sepsis patients[2,4,11,13].

Although gram-positive bacteria related infections (especially Staphylococcus) are more prevalent in the hospital setting (62.2%), the highest mortality rate is associated with gram-negative micro-organisms. Enterobacteriaceae are the most common microorganisms in gram-negative sepsis[14].

EPIDEMIOLOGY OF

ENTEROBACTERIACEAE

Enterobacteriaceae, a family of Gram negative pathogens, includes E. coli, Klebsiella spp., Proteus spp., Enterobacter spp. and Serratia spp. These organisms account for half of the bacteremia’s that are usually caused by overspill of bacteria from their primary sites[14]. E. coli and K. pneumoniae, in particular, are the major community and hospital acquired pathogens that usually cause intra-abdominal infections, urinary tract infections and primary bacteremia[15]. The emergence of multi-drug resistant microorganisms has become one of the most important hazards that health care is facing worldwide. Development of such resistance can be attributed to many risk factors including previous ICU admission, presence of a central venous catheter especially in hemato-oncology patients who are receiving chemotherapy, presence of an indwelling catheter insertion, prolonged use of antibiotics, prolonged hospital stay, hospitalization in an area endemic for multidrug resistance (MDR) and a history of previous colonization or infection with these microorganisms[16,17]. Resistance to β-lactams in Enterobacteriaceae is primarily attributed to the production of B-lactamase enzymes with subsequent antibiotic hydrolysis and to a lesser extent by alteration of efflux pump or porins expression[18]. One of the main causes of Enterobacteriaceae resistance is extended spectrum beta-lactamases (ESBL) production. ESBLs are plasmid encoded enzymes that are able to hydrolyze penicillins, broad-spectrum cephalosporins with an oxyiminoside chain, e.g., cefotaxime, ceftazidime and ceftriaxone as well as oxyimino-monobactams such as azetreonam. However, they are ineffective against cephamycins or carbapenems and their antimicrobial activity is inhibited by clavulanic acid[19,20]. The main problem concerning ESBL-producing bacteria is that they usually acquire multiple antimicrobial resistance mechanisms causing not only resistance to cephalosporins but also to aminoglycosides and fluoroquinolones, which further narrows the choices of finding an effective therapeutic agent[21].

Regrettably, these organisms belonging to the β-lactamases producing Enterobacteriaceae have acquired new genetic mutations and became resistant to carbapenem antimicrobial therapy.

These carbapenemase producing Enterobacteriaceae are classified into group A, B and D. β-lactamases micro-organisms based on the type of gene mutation (Table ). Class A and D have a serine based hydrolytic mechanism, but class B consists of metallo- β-lactamase[22-24].

Table 2

Resistance mechanisms of carbapenemase producing Enterobacteriaceae

Class Genetic mutation Clavulanic acid inhibition
Class A Chromosomal encoded (NmcA, Sme, IMI-1, SFC-1) Partially inhibited
Plasmid encoded (IMI-2, GES, KPC)
Class B Metallo-β-lactamase (IMP, VIM and NDM-1, SIM, GIM, SPM) Resistant to clavulanic acid
Class D Plasmid encoded oxa-48 Resistant to clavulanic aci

Carbapenem resistant Enterobacteriaceae (CRE) and A. baumannii are the most notorious pathogens due to the high incidence of morbidity and mortality especially in the immunocompromised patients in the ICU. The incidence of CRE was reported in various countries worldwide including East Asia, India, USA and many European countries. A multicenter study, conducted in Shanghai, China, revealed a high proportion of ESBL type E. coli as a cause of bloodstream infections. In addition, it was noted that the most common involved gene was CTX-M (CTX-M-15 CTX-M-14 and CTX-M-55, respectively). No carbapenemases producing Enterobacteriaceae were reported[25]. On the contrary, in Turkey a retrospective study evaluating ICU patients over ten years, showed that antibiotic resistance most dramatically increased due to carbapenem resistant A. baumannii followed by Pseudomonas spp, E. coli and K. pneumoniae, respectively. In addition, a reduction in methicillin resistant S. aureus (MRSA) prevalence from 96% to 54% was noticed[26]. In the United States, it was reported in CRE outbreaks that resistance, especially to K. pneumoniae and to a lesser extent other Enterobacteriaceae, were important in CRE resistance[27].

A case control study in New York showed that the majority of deaths due to bacteremia in neutropenic oncology patients were caused by CRE infections in 53%, of which gram negative Enterobacteriaceae was found in 13%-18% of the patients. Independent risk factors for increased CRE susceptibility were: Previous use of β -lactam antibiotics (e.g., 3rd or 4th generation cephalosporins or carbapenems) within the last 30 d; receiving trimethoprim-sulfamethoxazole or glucocorticoids at the time of onset of blood stream infection and having previous CRE infection isolate[27]. In order to avoid development of more resistance, it is crucial to be selective in the choice of antibiotics. Choosing the proper antibiotic regimen should be based on clinical findings supported by rapid diagnosis[22].

Goodman et al[16] tried to develop a clinical decision tree to predict whether a patient with bacteremia was infected with an ESBL-producing pathogen. They retrospectively studied a cohort of patients with bacteremia in Johns Hopkins hospital to identify clinical criteria to diagnose those patients with ESBL bacteremia, especially gram negative Enterobacteriaceae, to avoid misuse of antibiotics in the future. The clinical criteria were: A history of ESBL colonization or infection in the last 6 mo with chronic usage of indwelling venous catheter or dialysis, patient age ≥ 43 years, recent hospitalization in an ESBL high-burden area and a history antibiotic use for ≥ 6 d in the previous 6 mo. They made a clinical decision based on these five yes-or-no questions. When the patient had a history of ESBL colonization or infection in the last 6 mo with chronic usage of indwelling venous catheter or dialysis they had a 92% chance of being ESBL positive. With these criteria, positive predictive value was 90. 8% and negative predictive value was 91.9%. In addition, they found that 43% of patients with an ESBL positive culture had received chemotherapy in the recent history.

Another score has been developed to identify patients with high suspicion of CRE or ESBL-BSI so antibiotic therapy might be started on time to reduce mortality (Table ). Risk factors were chemotherapy in the last 3 mo, foreign invasive device, absence of peripheral vascular disease, reduced level of consciousness, hospitalization of > 3 d and age < 65 years old. With a total score ≥ 32 patients were considered as high risk for CRE BSI infections and required antimicrobial therapy targeted for CRE BSI infections. Although this test showed a lower sensitivity and specificity, its negative predictive value might prevent needless use of toxic antibiotics[28].

Table 3

Bed side risk score for carbapenem resistant Enterobacteriaceae

Risk factor Score (points)
History of chemotherapy in the last 3 mo 19
Invasive devices 10
Absence of peripheral vascular disease 10
Impairment of level of consciousness at the time of illness 9
Hospitalization for 3 or more days before development of BSI 7
Age < 65 years old 6

The Carba NP test is such a rapid diagnostic with a very high sensitivity and specificity that can differentiate between class A, B and C CRE. In addition, other promising tests such as PCR assay and matrix assisted laser desorption ionization might facilitate CRE diagnosis. In addition, fast gram-negative blood culture assays and film array blood culture can help in identifying carbapenemase genes within two hours[29,30]. However, deciding on the most appropriate antibiotic choice in bacteremia due to CRE can be very challenging.

TREATMENT OF CRE

The most appropriate antimicrobial therapy to treat CRE is still controversial. No consensus has been reached regarding the optimal choice of antibiotic therapy. As a consequence of the evolving broad spectrum antibiotic resistance, the old fashioned antibiotics, previously discarded because of their side effects, e.g., polymyxin E (colistin), polymyxin B, aminoglycosides and fosfomycin, have reappeared, because of effectiveness to some extent[31,32]. Despite the numerous publications on the subject, no consensus has been reached even on the preference of monotherapy or combination therapy[33].

Monotherapy vs combination therapy for treatment of sepsis

In a study conducted in a mice sepsis model, no significant difference was shown between colistin monotherapy and tigecycline monotherapy in treating carbapenem-resistant K. pneumoniae. In addition, combination of both colistin and tigecycline did not show superiority over monotherapy[34]. However, several studies suggested that combination therapy might be superior to monotherapy in terms of mortality rates. A review conducted by Falagas et al[35] described a cohort of 692 patients in which majority had confirmed Klebsiella pneumoniae carbapenemase producing K. Pneumoniae (KPC-KP) isolates and most of them related to bacteraemia. Mortality rate among those who received combination antimicrobial therapy ranged from 50% to 67% with the lowest rate associated with combination of tigecycline and gentamicin and highest rate with colistin and carbapenem (50% mortality rate in combination of tigecylcine with gentamicin, 64% in tigecycline-colistin and 67% for carbapenem-colistin combination). Patients who received colistin monotherapy had a mortality rate of 57% and patients who received tigecycline monotherapy 80%. The superiority of using combination therapy was shown in only three studies. No hard conclusions can be drawn from this review to decide on the use of single agent or combined therapy. Except in the critically ill patients, it is preferable to use combination therapy with superiority of tigecycline and gentamicin as a first choice, but randomized clinical trials need to confirm this statement.

But even with combination therapy, mortality rate remains high in patients with CRE related bacteremia. The underlying illness of the patient remains the most important risk factor for mortality. Tumbarello et al[36] showed the lowest mortality rate in patients with KPC-KP related sepsis using combined antimicrobial regimens especially those containing meropenem (when MIC ≤ 8 mg/L).

In a retrospective cohort study by Tumbarello et al[36] it was shown that combined therapy was superior to monotherapy in treating KPC-KP infection. Survival in patients with blood stream infection (mainly septic patients) with KPC-KP receiving monotherapy had a mortality rate of 54.3% while those receiving a combination therapy had a mortality rate of 34.1%. The same study demonstrated that a combination of tigecycline or colistin with meropenem had a better outcome compared to other combination therapies (12.5% mortality rate compared to 16.6% for tigecyclin, gentamicin with meropenem, 57% for colistin-gentamicin, 50% for tigecyclin-gentamicin and 30.4% tigecycline and colistin combination therapy).

Interestingly, in a prospective study by de Maio Carrilho et al[37] in patients with infections caused by KPC-KP (but also Enterobacteriaceae and E. coli) regimens of three or more antibiotics did not show any improved survival in comparison to regimens with two antibiotics. Moreover, monotherapy was just as effective as combination therapy in patients with UTI. Other independent risk factors such as dialysis, older age and septic shock seem to influence patient outcome more than monotherapy vs combination therapy.

Nevertheless, taken all current evidence into account, combination therapy can have a significant association with a lower mortality rate and increase the cure rate compared to monotherapy in the septic patient since each drug has its own mechanism of action, which can create a synergistic environment while combating resistant bacterial strains. The limited number of antimicrobial agents currently available to treat CRE will be further discussed in this review.

Colistin

Colistin is one of polymyxin antibiotics with bactericidal activity against Gram-negative bacterial infection[38]. Although the usage of this antibiotic was banned for many years due to its nephrotoxicity and neurotoxicity effect, it was reintroduced again due to emergence of MDR microorganisms. However, the use of colistin in treating CRE infection is still controversial[39].

Qureshi et al[40] retrospectively evaluated a cohort of 41 patients admitted to the ICU from two different hospitals in the United States with almost similar clinical and demographic variables. Of the 41 patients who developed bacteremia with a KPC-producing K. pneumoniae, seven patients died before initiating treatment. Among those who received combination therapy with carbapenem/tigecycline or carbapenem/colistin 28 d survival was significantly higher than in those on monotherapy (2 out of 15 patients receiving combination therapy died compared to 11 out of 19 patients receiving monotherapy).

Regarding the optimal dose for colistin, Gibson et al[41] showed that use of high dose colistin (> 4.4 mg/kg per day) in patients with CRE bacteremia was associated with a better clinical outcome, i.e., reduction of leucocyte < 12000 cells/mm3, no fever for 48 h and hemodynamically stable without any vasopressor. Also a better microbiological outcome was demonstrated, i.e., eradication of CRE on day 7 after starting colistin.

Unfortunately, although still rare, colistin resistant CRE species are emerging in China, United States and different European countries. It is most often observed in Enterobacteriaceae harboring the mcr-1 gene along with carbapenemase resistant gene[42-44].

Despite the fact that some investigators showed that development of colistin resistant CRE did not correlate with an increased mortality compared to patients without colistin resistant CRE[37], others have found that having colistin resistant KP is an independent risk factor of death especially in those with bacteremia[36,43].

Colistin seems to be a good alternative in vulnerable patients (without any evidence of renal impairment) especially when combined with other antibiotics such as carbapenems. However, it is very important to pay extra-attention for colistin resistant strains.

Carbapenems

Despite the fact of developing resistance to carbapenems anti-microbial therapy, they still can be of use especially in combination with other antimicrobial agents in colistin resistant Enterobacteriaceae. In a review by Bassetti et al[45], it was recommended that patients with KPC-KP and a MIC of isolate between 8 mg/L-16 mg/L or < 8 mg/L should receive a high dose of carbapenem containing therapy with a prolonged infusion together with colistin, tigecycline or an aminoglycoside. The underlying reason was prevention of developing new resistance to the rest of CRE antimicrobial therapy

In a case report on ertapenem and meropenem combination therapy, it was reported that an elderly patient with KPC-producing E. coli isolated from surgical site and nosocomial pneumonia with a contra-indication to colistin use due to a recent renal transplantation was started on combination therapy with ertapenem and meropenem showing good response. Unfortunately, the patient died later due to hemorrhagic shock[46].

In order to have a better outcome in colistin resistant Enterobacteriaceae, double carbapenem treatment was introduced. In two patients with carbapenemase-producing K. pneumoniae who were also colistin resistant, a combination of meropenem 2 g every 8 h and ertapenem 1 g every 24 h were given. In a third patient, dosages were adjusted for renal function. Both patients showed clinical improvement and also in vitro bactericidal activity was maintained up to 24 h. In conclusion, in such select cases like resistance to colistin, where options to treat CRE related sepsis are limited, a combination of two carbapenem antibiotics could be beneficial[47].

In a trial performed by Cprek et al[48] ertapenem/carbapenem double therapy (consisting of one gift of 1 g ertapenem given daily 1 h before administration of meropenem 2 g or doripenem 500 mg and the rest of the daily doses of meropenem or doripenem given normally) a favorable outcome was observed with maximum benefit in patients with CRKP bacteremia (43%) followed by pneumonia, intraabdominal, UTI and skin associated CRE infections.

Taking these observations into account, a combination of two carbapenems can be effective and even superior to other combination regimens in bacteremia patients due to its synergistic effect.

Tigecycline and other tetracyclines

Tetracyclines are a group of antibiotics that exhibit bacteriostatic activity by reversible binding to 30S ribosomes that interfere with protein synthesis. It is widely used due to its coverage of both gram-positive and gram-negative bacteria as well as some anaerobes and parasites[49]. Tigecycline is a glycylcycline, which is a tetracycline derivative and exhibits broad spectrum activity covering many organisms including MDR pathogens[50]. Many studies were conducted to evaluate the efficacy of tetracyclines mainly tigecycline in treating CRE related sepsis. A systematic review demonstrated that tigecycline did not significantly improve sepsis related mortality[51]. However, combination therapy containing tigecycline did significantly improve survival. In addition, it was found that administration of high dose regimen was associated with better outcome compared to standard dose tigecycline in combination therapy.

Administration of tigecycline monotherapy was associated with a high mortality rate[52]. Tigecycline might have a role in the treatment of CRE if it is used as a part of combination therapy particularly with aminoglycoside group or colistin[52]. Other tetracyclines, minocycline and eravacycline, are also studied in the treatment of CRE. Although high dose intravenous minocycline (200 mg twice daily) can be effective in carbapenem resistant A. baumannii up to 74%, its efficacy is less when dealing with CRE with only 12% of the CRE susceptible to minocycline[53]. Another promising agent is eravacycline, belonging to the fluorocyclines. In vitro it showed a potent effectiveness to MDR organisms[54]. An ongoing phase 3 clinical trial with eravacycline (GNITE4) might give us more data on its effectiveness[55]. The preliminary results suggest that there is no place for the use of tetracyclines in the treatment of CRE related sepsis; however the definitive results have not been published until now.

Aminoglycosides

The antibiotic group of aminoglycosides consists of gentamicin, amikacin, streptomycin, paromomycin, streptomycin and plazomicin, the last one still under clinical research. This group covers mainly gram negative and to some extent gram-positive pathogens and Mycobacteria[56]. It is usually used in combination with other antimicrobial agents in serious infections due to its synergistic effect[57]. The major side effects are ototoxicity and nephrotoxicity together with its narrow therapeutic window it can limit its use[58]. Aminoglycosides (especially gentamicin and amikacin) have shown their efficacy in treating carbapenem resistant KP UTI compared to other carbapenem resistant antimicrobial treatment (88% clearance compared to tigecycline and colistin), but its role in carbapenem resistant bacteremia as monotherapy is still uncertain[58]. A retrospective cohort study demonstrated that administration of gentamicin is an independent factor, which can improve 30 d mortality mainly in cases of KPC-KP related sepsis.

Especially in patients with both Carbapenem and colistin resistant KP, it decreased the mortality rate to 20.7% in comparison to 61.9% in patients treated with non-gentamicin containing therapy[59].

In conclusion, the role of aminoglycosides, mainly gentamicin, was studied previously particularly in combination with tigecycline with promising results. Now, it can be considered as a good option in the CRE patient with sepsis. Regarding the rest of aminoglycoside group antibiotics, further prospective studies are recommended.

Fosfomycin

The same might be applied for fosfomycin which has shown only its effectiveness in the treatment of patients with CRE UTI, but up until now no sufficient data exists supporting the use of fosfomycin either as a monotherapy or as part of a combination therapy in treating sepsis[58]. In a study by Bowers et al[60], 68 patients were treated with intravenous fosfomycin either in combination with colistin or with tigecycline. Effectiveness was demonstrated in 54.2% of patients at day 14. Mortality rate was 37.5% at day 28, with the highest mortality in having bacteremia; ventilator associated pneumonia and CRE KP isolates or P. aeruginosa isolates. Interestingly, three patients developed fosfomycin resistance shortly after treatment.

PROMISING NEW TREATMENTS

Alternative combination regimens can be considered in the future as curative agents in CRE related sepsis, but further clinical trials and prospective studies are required to assess its effectiveness. Fortunately, many new promising drugs might win the current battle against the current CRE resistance. One of them is plazomicin that belongs to the group of aminoglycosides. Recently, a phase 3 clinical trial was published showing efficacy of plazomicin. It was demonstrated that plazomicin significantly reduced mortality rate and reduced complications in patients with severe infection including CRE bacteremia, ventilation associated pneumonia and hospital acquired pneumonia related to CRE compared to colistin (28 d mortality rate was 11.4% in the plazmicin group compared to 40% in the colistin group). It also showed that plazomicin has the same efficacy of ertapenem in treating UTI[61], therefore it might play an important role in ceftazidime-avibactam combination therapy. In a recent study by Wu et al[62], three patients with CRE bacteremia (one patient with septic shock and one patient with suspected endocarditis) were successfully treated with ceftazidime-avibactam combination therapy. Combination of ceftazidime-avibactam is effective against oxa-48 and KP CRE[63].

Another option in the battle of CRE might be the addition of vabobactam to meropenem. Vabobactam is a boronic acid beta-lactamase inhibitor, which acts mainly on the serine carbapenamase and it has shown its efficacy in treating complicated UTI including those caused by CRE in phase 1 and 2 trials. A phase 3 trial is still ongoing now. In addition, its role in treating bacteremia needs further investigation[64].

In addition, combination of relebactam with imipenem and cilastatin is a promising option. Relebactam belongs to same group of vabobactam antibiotics. A phase 3 trial is designed to compare this combination with piperacillin/tazobactam in the treatment of complicated UTI. Its role in treatment of bacteraemia has not been investigated up until now[65].

One of the promising discoveries that can help in reducing the rate of CRE resistance is the peptide-conjugated phosphorodiamidate morpholino oligomer. It is a neutral DNA analogue which can inhibit gene expression of carbapenemases. It has been demonstrated that PRMO can target NDM1 (class B carbapenemases). It was shown that in combination with meropenem, it improved patient survival up to 92% because it re-established meropenem function[66].

CONCLUSION

The most appropriate antibiotics to treat CRE related sepsis is still debatable. Combination therapy is preferred over monotherapy in most of the studies due to its broad-spectrum coverage of organisms, its synergetic effect and to prevent development of further resistance.

In severely ill patients with co morbidities, a combination of two or more antibiotics is preferred. One of the best treatments up until now has been a combination of meropenem, tigecycline and colistin. A second option might be the combination therapy with tigecycline, gentamicin and meropenem. In moderately ill patients, it is recommended to administer the combination of tigecycline and gentamicin. If the MIC is less than 8 μg/mL, it is advisable to switch to a carbapenem containing therapy. In case of colistin resistance, a combination of two carbapenems can be used (e.g., ertapenem with meropenem or ertapenem with doripenem) besides the combinations shown in the algorithm (Figure ). Many promising antibiotics are currently under investigation. The most optimal treatment still needs to be determined to win the battle against the emerging CRE resistance.

Suggested algorithm for antibiotic choice in patient with bacteriaemia of carbapenem resistant Enterobacteriaceae1. 1The algorithm is based on the following references: [35,36,40,45,51,59]. CRE: Carbapenem resistant Enterobacteriaceae.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Medicine, research and experimental

Country of origin: Turkey

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C, C

Grade D (Fair): D

Grade E (Poor): 0

Conflict-of-interest statement: None.

Peer-review started: March 29, 2017

First decision: May 8, 2017

Article in press: May 31, 2017

P- Reviewer: Akbulut S, Desai DJ, Mehdi I, Vij M S- Editor: Ji FF L- Editor: A E- Editor: Wang S

References

1. Stehr SN, Reinhart K. Sepsis as a global health problem-why we need a global sepsis alliance. Shock. 2013;39 Suppl 1:3–4. [PubMed] [Google Scholar]2. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554. [PubMed] [Google Scholar]3. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief. 2011;62:1–8. [PubMed] [Google Scholar]4. Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2014;18:596. [PMC free article] [PubMed] [Google Scholar]5. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315:801–810. [PMC free article] [PubMed] [Google Scholar]6. Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42:1749–1755. [PubMed] [Google Scholar]7. Daniels R. Surviving the first hours in sepsis: getting the basics right (an intensivist’s perspective) J Antimicrob Chemother. 2011;66 Suppl 2:ii11–ii23. [PubMed] [Google Scholar]8. Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, Shofer FS, Goyal M. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38:1045–1053. [PubMed] [Google Scholar]10. Mayr FB, Yende S, Linde-Zwirble WT, Peck-Palmer OM, Barnato AE, Weissfeld LA, Angus DC. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis. JAMA. 2010;303:2495–2503. [PMC free article] [PubMed] [Google Scholar]11. Ayub M. Isolation of Pathogens Causing Sepsis, Pus and Infected Wounds from Critical Care Unit: A Retrospective Study. Ann Clin Lab Res. 2015;3:4. [Google Scholar]14. Wilson J, Elgohari S, Livermore DM, Cookson B, Johnson A, Lamagni T, Chronias A, Sheridan E. Trends among pathogens reported as causing bacteraemia in England, 2004-2008. Clin Microbiol Infect. 2011;17:451–458. [PubMed] [Google Scholar]15. Donnenberg MS. Enterobacteriaceae. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. United States: Elsevier; 2010. pp. 2815–2834. [Google Scholar]16. Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH, Milstone AM, Massey CJ, Tamma PD; Antibacterial Resistance Leadership Group. A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum β-Lactamase-Producing Organism. Clin Infect Dis. 2016;63:896–903. [PMC free article] [PubMed] [Google Scholar]17. Paño-Pardo JR, López Quintana B, Lázaro Perona F, Ruiz Carrascoso G, Romero-Gómez MP, Loeches Yagüe B, Díaz-Pollán B, Martínez-Virto A, Mingorance J, García Rodríguez J, et al. Community-Onset Bloodstream and Other Infections, Caused by Carbapenemase-Producing Enterobacteriaceae: Epidemiological, Microbiological, and Clinical Features. Open Forum Infect Dis. 2016;3:ofw136. [PMC free article] [PubMed] [Google Scholar]18. Gazin M, Paasch F, Goossens H, Malhotra-Kumar S; MOSAR WP2 and SATURN WP1 Study Teams. Current trends in culture-based and molecular detection of extended-spectrum-β-lactamase-harboring and carbapenem-resistant Enterobacteriaceae. J Clin Microbiol. 2012;50:1140–1146. [PMC free article] [PubMed] [Google Scholar]20. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14:933–951, table of contents. [PMC free article] [PubMed] [Google Scholar]21. Díaz PQ, Bello HT, Domínguez MY, Trabal NF, Mella SM, Zemelman RZ, González GR. [Resistance to gentamicin, amikacin and ciprofloxacin among nosocomial isolates of klebsiella pneumoniae subspecie pneumoniae producing extended spectrum beta-lactamases] Rev Med Chil. 2004;132:1173–1178. [PubMed] [Google Scholar]23. Davies TA, Marie Queenan A, Morrow BJ, Shang W, Amsler K, He W, Lynch AS, Pillar C, Flamm RK. Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007-09. J Antimicrob Chemother. 2011;66:2298–2307. [PubMed] [Google Scholar]24. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012;67:1597–1606. [PubMed] [Google Scholar]25. Wang S, Zhao SY, Xiao SZ, Gu FF, Liu QZ, Tang J, Guo XK, Ni YX, Han LZ. Antimicrobial Resistance and Molecular Epidemiology of Escherichia coli Causing Bloodstream Infections in Three Hospitals in Shanghai, China. PLoS One. 2016;11:e0147740. [PMC free article] [PubMed] [Google Scholar]26. Alp E, Orhan T, Kürkcü CA, Ersoy S, McLaws ML. The first six years of surveillance in pediatric and neonatal intensive care units in Turkey. Antimicrob Resist Infect Control. 2015;4:34. [PMC free article] [PubMed] [Google Scholar]27. Bratu S, Mooty M, Nichani S, Landman D, Gullans C, Pettinato B, Karumudi U, Tolaney P, Quale J. Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York: epidemiology and recommendations for detection. Antimicrob Agents Chemother. 2005;49:3018–3020. [PMC free article] [PubMed] [Google Scholar]28. Leibman V, Martin ET, Tal-Jasper R, Grin L, Hayakawa K, Shefler C, Azouri T, Kaplansky T, Maskit M, Lazarovitch T, et al. Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae. Ann Clin Microbiol Antimicrob. 2015;14:31. [PMC free article] [PubMed] [Google Scholar]29. Nordmann P, Poirel L, Dortet L. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis. 2012;18:1503–1507. [PMC free article] [PubMed] [Google Scholar]30. Dodémont M, De Mendonça R, Nonhoff C, Roisin S, Denis O. Performance of the Verigene Gram-negative blood culture assay for rapid detection of bacteria and resistance determinants. J Clin Microbiol. 2014;52:3085–3087. [PMC free article] [PubMed] [Google Scholar]32. Theuretzbacher U, Van Bambeke F, Cantón R, Giske CG, Mouton JW, Nation RL, Paul M, Turnidge JD, Kahlmeter G. Reviving old antibiotics. J Antimicrob Chemother. 2015;70:2177–2181. [PubMed] [Google Scholar]33. Morrill HJ, Pogue JM, Kaye KS, LaPlante KL. Treatment Options for Carbapenem-Resistant Enterobacteriaceae Infections. Open Forum Infect Dis. 2015;2:ofv050. [PMC free article] [PubMed] [Google Scholar]34. Demiraslan H, Dinc G, Ahmed SS, Elmali F, Metan G, Alp E, Doganay M. Carbapenem-resistant Klebsiella pneumoniae sepsis in corticosteroid receipt mice: tigecycline or colistin monotherapy versus tigecycline/colistin combination. J Chemother. 2014;26:276–281. [PubMed] [Google Scholar]35. Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother. 2014;58:654–663. [PMC free article] [PubMed] [Google Scholar]36. Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, Losito AR, Bartoletti M, Del Bono V, Corcione S, Maiuro G, Tedeschi S, Celani L, Cardellino CS, Spanu T, Marchese A, Ambretti S, Cauda R, Viscoli C, Viale P; ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva) Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother. 2015;70:2133–2143. [PubMed] [Google Scholar]37. de Maio Carrilho CM, de Oliveira LM, Gaudereto J, Perozin JS, Urbano MR, Camargo CH, Grion CM, Levin AS, Costa SF. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome. BMC Infect Dis. 2016;16:629. [PMC free article] [PubMed] [Google Scholar]39. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005;40:1333–1341. [PubMed] [Google Scholar]40. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56:2108–2113. [PMC free article] [PubMed] [Google Scholar]41. Gibson GA, Bauer SR, Neuner EA, Bass SN, Lam SW. Influence of Colistin Dose on Global Cure in Patients with Bacteremia Due to Carbapenem-Resistant Gram-Negative Bacilli. Antimicrob Agents Chemother. 2015;60:431–436. [PMC free article] [PubMed] [Google Scholar]42. Mediavilla JR, Patrawalla A, Chen L, Chavda KD, Mathema B, Vinnard C, Dever LL, Kreiswirth BN. Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States. MBio. 2016;7:pii: e01191–16. [PMC free article] [PubMed] [Google Scholar]43. Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M, Venditti M, Bordi E, Capozzi D, Balice MP, et al. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect. 2013;19:E23–E30. [PubMed] [Google Scholar]44. Yu H, Qu F, Shan B, Huang B, Jia W, Chen C, Li A, Miao M, Zhang X, Bao C, et al. Detection of the mcr-1 Colistin Resistance Gene in Carbapenem-Resistant Enterobacteriaceae from Different Hospitals in China. Antimicrob Agents Chemother. 2016;60:5033–5035. [PMC free article] [PubMed] [Google Scholar]45. Bassetti M, Peghin M, Pecori D. The management of multidrug-resistant Enterobacteriaceae. Curr Opin Infect Dis. 2016;29:583–594. [PubMed] [Google Scholar]46. Oliva A, Cipolla A, Gizzi F, D’Abramo A, Favaro M, De Angelis M, Ferretti G, Russo G, Iannetta M, Mastroianni CM, et al. Severe Bloodstream Infection due to KPC-Producer E coli in a Renal Transplant Recipient Treated With the Double-Carbapenem Regimen and Analysis of In Vitro Synergy Testing: A Case Report. Medicine (Baltimore) 2016;95:e2243. [PMC free article] [PubMed] [Google Scholar]47. Oliva A, D’Abramo A, D’Agostino C, Iannetta M, Mascellino MT, Gallinelli C, Mastroianni CM, Vullo V. Synergistic activity and effectiveness of a double-carbapenem regimen in pandrug-resistant Klebsiella pneumoniae bloodstream infections. J Antimicrob Chemother. 2014;69:1718–1720. [PubMed] [Google Scholar]48. Cprek JB, Gallagher JC. Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2015;60:669–673. [PMC free article] [PubMed] [Google Scholar]51. Ni W, Han Y, Liu J, Wei C, Zhao J, Cui J, Wang R, Liu Y. Tigecycline Treatment for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review and Meta-Analysis. Medicine (Baltimore) 2016;95:e3126. [PMC free article] [PubMed] [Google Scholar]52. Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943–950. [PubMed] [Google Scholar]53. Pogue JM, Neelakanta A, Mynatt RP, Sharma S, Lephart P, Kaye KS. Carbapenem-resistance in gram-negative bacilli and intravenous minocycline: an antimicrobial stewardship approach at the Detroit Medical Center. Clin Infect Dis. 2014;59 Suppl 6:S388–S393. [PubMed] [Google Scholar]54. Sutcliffe JA, O’Brien W, Fyfe C, Grossman TH. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother. 2013;57:5548–5558. [PMC free article] [PubMed] [Google Scholar]57. McGrath BJ, Lamp KC, Rybak MJ. Pharmacodynamic effects of extended dosing intervals of imipenem alone and in combination with amikacin against Pseudomonas aeruginosa in an in vitro model. Antimicrob Agents Chemother. 1993;37:1931–1937. [PMC free article] [PubMed] [Google Scholar]58. van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75:115–120. [PMC free article] [PubMed] [Google Scholar]59. Gonzalez-Padilla M, Torre-Cisneros J, Rivera-Espinar F, Pontes-Moreno A, López-Cerero L, Pascual A, Natera C, Rodríguez M, Salcedo I, Rodríguez-López F, et al. Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2015;70:905–913. [PubMed] [Google Scholar]60. Bowers DR, Huang V. Emerging Issues and Treatment Strategies in Carbapenem-Resistant Enterobacteriaceae (CRE) Curr Infect Dis Rep. 2016;18:48. [PubMed] [Google Scholar]62. Wu G, Abraham T, Lee S. Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2016;63:1147–1148. [PubMed] [Google Scholar]63. Metan G, Akova M. Reducing the impact of carbapenem-resistant Enterobacteriaceae on vulnerable patient groups: what can be done? Curr Opin Infect Dis. 2016;29:555–560. [PubMed] [Google Scholar]66. Sully EK, Geller BL, Li L, Moody CM, Bailey SM, Moore AL, Wong M, Nordmann P, Daly SM, Sturge CR, et al. Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo. J Antimicrob Chemother. 2017;72:782–790. [PMC free article] [PubMed] [Google Scholar]

Sepsis in Newborns: Symptoms, Causes, Treatments

Overview

What is sepsis in newborns?

Sepsis is a serious medical condition caused by the body’s response to an infection. A newborn who has an infection and develops sepsis can have inflammation (swelling) throughout the body, leading to organ failure.

Symptoms and Causes

What causes sepsis in newborns?

Bacterial infections are the most common cause of sepsis. However, sepsis can also be caused by fungi, parasites or viruses. The infection can be located in any of a number of places throughout the body.

How do newborns get sepsis?

Newborns can get sepsis in several different ways:

  • If the mother has an infection of the amniotic fluid (a condition known as chorioamnionitis)
  • Premature birth (premature babies are at a higher risk for sepsis)
  • Low birth weight of the infant (risk factor for sepsis)
  • If the mother’s water breaks early (more than 18 hours before the baby is born)
  • If the baby is being treated for another condition while still in the hospital
  • If the mother’s birth canal is colonized with bacteria

What are some symptoms of infections in newborns?

Symptoms of infections in newborns include:

  • Not feeding well
  • Being very sleepy
  • Being very irritable
  • Rapid breathing or breathing pauses (apnea)
  • Vomiting or diarrhea
  • Fever (temperature over 100.4 degrees F or over 38.1 degrees C)
  • Inability to stay warm — having a low body temperature despite being clothed and wrapped in blankets
  • Pale appearance

Diagnosis and Tests

How is sepsis in newborns diagnosed?

Tests for sepsis in newborns can include:

  • Blood tests (blood cell counts, blood cultures)
  • Urine tests (urinalysis and culture)
  • Skin swabs
  • Spinal tap (also known as lumbar puncture) to test for meningitis. A spinal tap is a procedure in which a very small needle is inserted into the space around your child’s spine to withdraw spinal fluid to test for infections.

Management and Treatment

How is sepsis in newborns treated?

Babies who have sepsis are admitted to an intensive care unit. Treatments may include the following:

  • Intravenous (IV, directly into a vein) fluids
  • IV antibiotics
  • Medications for fever (rarely used in newborns)
  • Extra oxygen and other forms of respiratory support, if needed

Occasionally, babies may need blood transfusions.

Prevention

Can sepsis be prevented in newborns?

To prevent infection in the baby, expectant women can be treated with IV antibiotics for several hours before delivery, if indicated by prenatal screens or clinical signs such as maternal fever or uterine tenderness. Your obstetrician will decide if you should be given antibiotics before delivery.

Living With

How should I follow up with my doctor after my newborn has been discharged from the hospital?

After discharge, follow up with your pediatrician in 2 to 3 days to check for continued signs of recovery.

When should I call my healthcare provider about my newborn?

Call your healthcare provider if your newborn:

  • Is not feeding well.
  • Becomes more irritable or lethargic (sleepy).
  • Is breathing too fast or with difficulty.
  • Is breathing too slow, with pauses.

Doctor Turns Up Possible Treatment For Deadly Sepsis : Shots

Of the million or so Americans a year who get sepsis, roughly 300,000 die. Unfortunately, many treatments for the condition have looked promising in small, preliminary studies, only to fail in follow-up research.

Reptile8488/Getty Images/iStockphoto


hide caption

toggle caption

Reptile8488/Getty Images/iStockphoto

Of the million or so Americans a year who get sepsis, roughly 300,000 die. Unfortunately, many treatments for the condition have looked promising in small, preliminary studies, only to fail in follow-up research.

Reptile8488/Getty Images/iStockphoto

It’s hard not to get excited about news of a potentially effective treatment for sepsis, a condition that leads to multiple organ failure and kills more people in the hospital than any other disease.

But there have been so many false promises about this condition over the years, it’s also wise to treat announcements — like one published online by the journal, Chest — with caution.

The study, from Eastern Virginia Medical School in Norfolk, Va., reported some remarkable success in treating patients who were at high risk of sudden death.

The story began in January, 2016, when Dr. Paul Marik was running the intensive care unit at Sentara Norfolk General Hospital. A 48-year-old woman came in with a severe case of sepsis — inflammation frequently triggered by an overwhelming infection.

“Her kidneys weren’t working. Her lungs weren’t working. She was going to die,” Marik said. “In a situation like this, you start thinking out of the box.”

Marik had recently read a study by researchers at Virginia Commonwealth University in Richmond. Dr. Berry Fowler and his colleagues had shown some moderate success in treating people who had sepsis with intravenous vitamin C.

Marik decided to give it a try. He added in a low dose of corticosteroids, which are sometimes used to treat sepsis, along with a bit of another vitamin, thiamine. His desperately ill patient got an infusion of this mixture.

“I was expecting the next morning when I came to work she would be dead,” Marik said.”But when I walked in the next morning, I got the shock of my life.”

The patient was well on the road to recovery.

Marik tried this treatment with the next two sepsis patients he encountered, and was similarly surprised. So he started treating his sepsis patients regularly with the vitamin and steroid infusion.

After he’d treated 50 patients, he decided to write up his results. As he described it in Chest, only four of those 47 patients died in the hospital — and all the deaths were from their underlying diseases, not from sepsis. For comparison, he looked back at 47 patients the hospital had treated before he tried the vitamin C infusion and found that 19 had died in the hospital.

This is not the standard way to evaluate a potential new treatment. Ordinarily, the potential treatment would be tested head to head with a placebo or standard treatment, and neither the doctors nor the patients would know who in the study was getting the new therapy.

But the results were so stunning, Marik decided that from that point on he would treat all his sepsis patients with the vitamin C infusion. So far, he’s treated about 150 patients, and only one has died of sepsis, he said.

That’s a phenomenal claim, considering that of the million Americans a year who get sepsis, about 300,000 die.

“So that’s the equivalent of three jumbo jets crashing every single day,” Marik said.

An effective treatment for sepsis would be a really big deal.

“If it turns out in further studies that this is true, and we can validate it, then this will be an unbelievably huge deal,” said Dr. Craig Coopersmith, a surgery professor at Emory University School of Medicine. “But right now we should treat it as a preliminary deal that needs to be validated.”

Coopersmith, a top sepsis researcher, is cautious for a reason. There have been hundreds of exciting results from sepsis studies that failed in follow-up research.

A result “can look really exciting when you do it on a group in one hospital with one set of clinicians, and then when you try to validate with a larger group in multiple centers — thus far we’ve been unsuccessful with anything,” Coopersmith said.

Marik may face extra skepticism because the main ingredient is vitamin C, which has attracted a great deal of skepticism over the years. Fowler at VCU was concerned about that when he wanted to launch a study about the role of vitamin C in sepsis.

“Honestly, when we submitted the grant to the NIH, I was fully expecting them to say ‘vitamin C? Really?’ ” Fowler tells Shots.

But he’d made the case that vitamin C wasn’t simply a once-trendy antioxidant. When the vitamin is injected, as opposed to taken orally, it can influence the immune system’s response to inflammation, he told Shots.

The NIH gave him a $3.2 million grant to run a carefully controlled study of vitamin C to treat sepsis, with all the usual conditions: It includes placebos; the scientists don’t know who’s getting the active drug; and it’s being conducted at several universities.

That study could wrap up later this year. Fowler says some patients in the trial will probably have been given corticosteroids, as Marik’s patients were, but that’s not a formal part of the study.

Coopersmith said the extraordinary results reported from Norfolk clearly need that kind of careful scrutiny. Marik said he agrees, though he’s obviously not waiting for those results to emerge.

Taxpayers and drug companies have spent billions of dollars searching for an effective treatment for sepsis. Drug companies could reap billions in profits if they can develop a successful treatment for this common and often fatal disease.

But profit is not the motive here, Marik says. The ingredients cost about as much as a single dose of antibiotics.

“I obviously have no vested interest,” he says. “Nobody’s going to make money from this — so this is a very anti-capitalistic thing!”

You can reach Richard Harris at [email protected]

Blood Poisoning | Symptoms, Causes, Treatments

It is estimated that there are 31,000 cases of severe sepsis in England and Wales every year, and the number of cases seems to be rising. Approximately 30% to 50% of people with severe sepsis will die because of the condition.
Brought to you by NHS Choices

Introduction

Sepsis refers to an infection that has spread through the blood, causing symptoms throughout the whole body. This is known as a systematic response.

Sepsis is often referred to as either blood poisoning or septicaemia, though it could be argued that both terms are not entirely accurate. Sepsis is not just limited to the blood but can affect the whole body, including the organs. Septicaemia refers to a bacterial infection of the blood; whereas sepsis can also be caused by viral or fungal infections.

Usually, an infection is limited to one part of the body. This is referred to as a localised infection. However, if somebody is particularly vulnerable to infection, for example they have a weakened immune system, the infection can carry on spreading. The infection will spread first into the blood and then into other organs.

Unfortunately, rather that helping to get rid of sepsis, the immune system actually makes it worse. This is because the immune system releases a high number of infecting-fighting proteins known as cytokines. These proteins, rather than fighting the infection, actually cause damage to the organs of the body and affect blood circulation.

Severe sepsis and septic shock

If sepsis is allowed to progress, it can move into a more serious phase of the condition known as severe sepsis. Severe sepsis happens when one or more organs have been damaged by the infection, or there is a significant loss of blood supply to tissues and organs (hypoperfusion).

Septic shock is another type of sepsis where the infection causes a massive drop in blood pressure. This results in symptoms of shock, such as cold skin and increased heart beat.

Sepsis can interfere with many of the vital processes of the body, including blood pressure, breathing and organ function; all of which can result in death.

Treatment will normally require admission to an intensive care unit (ICU) where the functions of the organs and body can be supported while the infection is treated.

Symptoms

Symptoms of blood poisoning

The symptoms of sepsis may develop as a response to a localised infection or injury.

In some cases, symptoms may develop when you are already in hospital. For example, if you have recently had surgery or intravenous lines or catheters have been connected to your body.

The symptoms of sepsis usually develop quickly and include:

  • a fever,
  • fast heart beat, and
  • fast breathing.

Symptoms of severe sepsis or septic shock include:

  • low blood pressure which will result in you feeling dizzy when you stand up,
  • a change in mental behaviour such as confusion or disorientation,
  • diarrhoea,
  • reduced urine flow,
  • cold, clammy skin,
  • pale skin, and
  • loss of consciousness.

Severe sepsis and septic shock are medical emergencies. If you suspect that you or someone in your care are experiencing these conditions, phone 999 and ask for an ambulance.

Causes

Causes of blood poisoning

Sepsis begins either as a result of a localised (confined to a particular location) infection, such as lung infection (pneumonia), or as a result of a severe injury, such as a burn or gunshot wound.

Usually, your immune system will keep the infection localised in once place. Your body will produce white blood cells which travel to the site of the infection. This process is called inflammation. The function of the white blood cells is to destroy the infection and repair damaged tissue.

However, if your immune system is weakened, or the infection or injury is particularly severe, the infection can spread through the blood into other parts of the body. This causes the immune system to go into ‘overdrive’ which then spreads the process of inflammation throughout the entire body.

This can cause more problems than the actual infection, as widespread inflammation causes damage to tissue and interferes with the flow of blood. In turn, this leads to a drop in blood pressure and stops oxygen reaching your organs and tissue.

Sources of infection

Types of infection associated with sepsis are:

  • lung infection (pneumonia),
  • flu (influenza),
  • appendicitis,
  • infection of the lining of the digestive system (peritonitis),
  • an infection of the bladder, urethra or kidneys (urinary tract infection),
  • skin infections – often caused when an intravenous drip or catheter has been inserted into the body through the skin,
  • post-surgical (after surgery) infections, and
  • infections of the nervous system such as meningitis or encephalitis.

People at risk

People particularly vulnerable to sepsis include:

  • people who have a medical condition that affects their immune system such as HIV or leukaemia,
  • people who are receiving medical treatment that weakens their immune system, such as chemotherapy or long-term steroid injections, and
  • the very young or the very old.

Sepsis is also a risk for people who are already in hospital due to another serious illness. Despite the best efforts of doctors and nurses, secondary infections acquired in hospital are always a possibility. Also, hospital-acquired bacterial infections, such as MRSA, tend to be more serious as they have often developed a resistance to antibiotics.

Diagnosis

Diagnosing blood poisoning

There are three important goals when diagnosing sepsis. These are:

  • determine the type of infection,
  • determine the source of infection, and
  • determine which and how badly other body functions have been affected.

To diagnose sepsis, several tests may be carried out, including:

  • blood tests,
  • urine tests,
  • stool sample tests,
  • blood pressure tests,
  • a wound culture test – where a small sample of tissue, skin or fluid is taken from the affected area for testing,
  • respiratory secretion testing – which involves testing a sample of your saliva, phlegm or mucus,
  • imaging studies such as an X-Ray or CT Scan,
  • kidney, liver and heart function tests, and
  • a spinal tap – where a sample of cerebrospinal fluid is extracted from your back for testing.

Treatment

Treating blood poisoning

If your sepsis is detected early enough and has not affected organ or tissue function (uncomplicated sepsis), it may be possible to treat the condition at home. You will be prescribed a course of antibiotic tablets to be taken by mouth (oral antibiotics).

If the sepsis is severe or symptoms of shock are present, hospital treatment will be required, usually in an Intensive Care Unit (ICU’s).

ICU’s are able to help support any affected body function, such as breathing or blood circulation, while the medical staff focus on treating the infection.

Antibiotics

Severe sepsis is treated with intravenous antibiotics. Often there will not be time to wait until a specific type of infection has been identified. Therefore, the initial treatment uses what is known as ‘broad-spectrum’ antibiotics. Broad spectrum antibiotics are designed to work against a wide range of known infectious bacteria. They can also treat some fungal infections.

Once a specific bacterium has been identified, a more ‘focused’ antibiotic can be used. This has the advantage of reducing the chances of bacteria becoming resistant to antibiotics.

If the sepsis is caused by a virus, antibiotics will not work. It is necessary to wait until the body develops a resistance to the effects of the virus. In some cases, anti-viral agents may be given. However, it is likely that antibiotic treatment will be started anyway. This is because it would be too dangerous to delay antibiotic treatment until an accurate diagnosis is made.

Intravenous antibiotics usually have to be administered for seven to 10 days.

Source control

Source control means to treat the source of the infection, such as an abscess or infected wound. This may require draining pus from infected tissue.

In more serious cases, surgery may be required to remove the infected tissue and repair any damage.

Vasopressors

Vasopressors are medicines that are used to treat low blood pressure. The two types of vasopressors used in the treatment of sepsis are dopamine and norepinephrine.

Both of these are actually neurotransmitters which are naturally occurring chemicals found in the brain. They can help to increase blood pressure by stimulating the muscles involved in pumping blood around the body and widening the blood vessels.

Vasopressors are normally administered intravenously.

Extra fluids may also be administered intravenously as this will also help increase blood pressure.

Recombinant Human Activated Protein C (rhAPC)

Recombinant Human Activated Protein C (rhAPC) is a new type of medicine that is now being used to treat some cases of severe sepsis. The type of rhAPC used in the UK is known as drotrecogin alfa. It contains a genetically modified type of protein molecule called Protein C. Protein C is known to reduce levels of inflammation and help prevent blood clots; both important goals in the treatment of sepsis.

Drotrecogin alfa is known to cause internal bleeding in some people. So this treatment may not be suitable for you if you have had a previous history of stroke, internal injury or have recently had surgery.

Prevention

Preventing blood poisoning

If you have a weakened immune system, or are particularly vulnerable to the effects of infection, you will need to take extra precautions.

These are outlined below.

  • Avoid smoking – this will weaken your immune system.
  • Do not use illegal drugs – these also weaken your immune system.
  • Make sure that your immunisations are up to date – your GP will be able to advise you. Vaccinations are available for some of the common infections associated with sepsis such as pneumonia and influenza.
  • Eat a healthy diet – this will boost your immune system.
  • Take regular exercise – this will boost your immune system.
  • Wash your hands regularly – particularly after going to the toilet, before and after preparing food, and after spending time in crowded places.

You should also be watchful for the initial signs of infection and report any symptoms promptly to your GP.

These include:

  • redness or swelling in the affected area,
  • pain or tenderness in the affected area,
  • discharge, pus or foul-smelling fluid, and
  • fever

Complications of arthritis

Some treatments for arthritis have side effects that may cause additional problems. NSAIDs may damage the stomach and digestive system and are also associated with kidney problems in some people. Corticosteroids can cause reduction in bone density (osteoporosis) leading to increased risk of fractures and may also lead to the development of shingles, cataracts, and diabetes.

In the long term, arthritis can produce worsening pain, loss of mobility, and sometimes make walking difficult, or impossible. As a result, depression may accompany this condition.

General effects of rheumatoid arthritis may include:

  • loss of appetite and weight,
  • tiredness,
  • muscle pain,
  • lumps (nodules) under the skin,
  • inflammation of tendons,
  • sight problems,
  • anaemia (blood disorder), and
  • vasculitis (inflammation of the blood vessels)

NHS Choices links

External links

This article was originally published by NHS Choices

Drawing the Antibiotics Line for Sepsis Treatment

Some doctors reject a provocative proposal to delay antibiotics for sepsis patients without shock. But proponents argue antibiotics pose significant risks, too.

Drawing the line on antibiotics for sepsis patients is drawing scrutiny, pitting an antibiotic stewardship perspective against the established reliance on antibiotics.

A recent editorial in Journal of the American Medical Association calls for a more conservative approach for treating sepsis—delaying antibiotics treatment in some cases of sepsis without shock.

With its deadly mortality rate, an aggressive approach to treating sepsis patients with antibiotics is common practice.

Treating patients with possible sepsis or septic shock requires a nuanced approach, the editorial co-authors wrote.

“The need to treat patients rapidly and aggressively ought to reflect on the severity of illness and certainty of diagnosis rather than applied uniformly to all patients. If a patient clearly has a bacterial infection, prompt treatment is indicated. If there is diagnostic uncertainty, however, clinicians should calibrate their response to severity of illness and probability of infection,” they wrote.

The proposed approach challenges the standard of care, which calls for rapid administration of antibiotics to all sepsis patients whether they are in shock or not.

Aggressive track

 

Administering antibiotics to all sepsis patients should remain the standard of care, James O’Brien, MD, director of quality and patient safety at OhioHealth in Columbus, told HealthLeaders this week.

“The data supports that the sicker a patient is—and septic shock is probably the best example—the more likely they are to benefit from antibiotics. But there is evidence of patients with sepsis without shock who also benefit,” he said.

O’Brien said a family medical case exemplifies the advisability of administering antibiotics to sepsis patients without shock.

His mother had melanoma removed from her back, then she got confused at home. She went to the hospital with no signs of shock but was treated for sepsis.

“As a result of the care that the hospital provided—getting rapid antibiotics and opening the wound to drain—she recovered. But if we had waited for tests to come back, it’s very possible she could have progressed to develop shock. Then you’re dealing with somebody whose mortality jumps up significantly,” O’Brien said.

“So, I have hard time from the patient’s standpoint waiting until they have shock, then all of a sudden we’ll jump onboard,” he said.

Adverse impacts

 

Patients face significant risks from antibiotics, Michael Klompas, MD, the lead author of the JAMA editorial, told HealthLeaders this week.

“The risks of antibiotics extend beyond Clostridium difficile alone. They can cause organ damage, interact with other medications, and promote colonization and infection with drug resistant pathogens that then pose downstream treatment problems,” said Klompas, an infectious disease physician at Brigham & Women’s Hospital in Boston. 

The JAMA editorial lists several other adverse impacts from antibiotics: kidney injury, hepatitis, cytopenias, sever rash, mitochondrial toxicity, and alteration of the microbiome.

There are adverse effects associated with antibiotics, Klompas said.

“Studies estimate that a remarkable 20%-25% of hospitalized patients exposed to antibiotics develop some sort of adverse effect. This flies in the face of the commonly held perception amongst both doctors and the general public that antibiotics are “free”—they are very safe and there’s little downside.”

Treatment for sepsis

 

Treatment of sepsis requires the exercise of good medical judgment, O’Brien said.

“It’s more art than science now. For me, it winds up at the intersection between patient risk, the severity of illness, and the likelihood of alternative diagnoses. I factor all of those to determine the relative risk of treatment for sepsis versus the relative risk for not treating for sepsis,” he said.

Sepsis patients stretch across a continuum, O’Brien said.

“If I have a patient who is elderly, is currently being treated for leukemia, and was recently in the hospital, these are all risk factors for sepsis. If they come in with shock, and I don’t have an alternative diagnosis or reason for them to be in shock, I’m going to need to have significant evidence that the patient does not have sepsis.”

“Alternatively, I could have a healthy 22-year-old who has no medical problems, has not been in contact with healthcare, and comes in with unclear complaints. There’s no signs of shock and the patient is talking. That’s someone I am going to be more delayed with.”

Physicians are needed most keenly to treat more complicated sepsis cases, O’Brien said.

“There are a whole bunch of patients who end up being in that spectrum—between the polar opposites. In between is where you need a physician to integrate the data and make a decision when there is uncertainty.”

Christopher Cheney is the senior clinical care​ editor at HealthLeaders.

90,000 Sepsis: Medicines Used in Treatment

Sepsis is a serious human infectious disease that develops as a systemic inflammatory reaction when infectious agents or their toxins enter the bloodstream. “People” call sepsis blood poisoning.

General

This is a serious human infectious disease that develops as a systemic inflammatory reaction when infectious agents (bacteria or unicellular fungi) or their toxins enter the bloodstream.Among non-medical people, sepsis is often called blood poisoning. It is characterized by a severe progressive course and no tendency to spontaneous recovery. Despite the increased possibilities of antibacterial and antifungal therapy, the mortality rate in sepsis remains quite high.

Causes of sepsis

The causative agents of sepsis can be any bacteria (staphylococci, streptococci, pneumococci, meningococci, salmonella, enterococci, Pseudomonas aeruginosa, Klebsiella) or fungi (genus Candida, Aspergillus).The emergence of sepsis is due not so much to the properties of the pathogen itself, but to the state of the human immune system, in particular, the inability to localize the pathogen in the primary focus of infection. One and the same staphylococcus can be found on the mucous membranes in some individuals without the development of any pathology, and in others it can cause sepsis with a fatal outcome. Most often, sepsis develops in people with weakened immunity due to severe illness, extensive surgery, profuse blood loss, malnutrition, or the use of immunosuppressive drugs.

The ingress of infectious agents into the bloodstream can occur either with the generalization of any local infection, or with the introduction of microorganisms from the outside during surgery, vein catheterization and other medical procedures. The primary septic focus can be any infection of soft tissues, bones, joints and internal organs: an extensive wound or burn surface, purulent skin diseases (carbuncle, boil, phlegmon), osteomyelitis, urinary tract infections, etc.Infectious complications after childbirth or abortion require special attention; in this case, the “entrance gate” of the infection is the uterine mucosa. At a time when medical abortion was illegal and surgeries were performed clandestinely in non-sterile conditions, sepsis was the leading cause of death in pregnant women.

Symptoms

The peculiarity of sepsis is that its symptoms are similar regardless of the pathogen, since they are a kind of response of the human body to a super-strong infectious lesion, which the immune system is unable to cope with in the focus of infection.
The clinical picture consists of symptoms of general intoxication and manifestations of the disease caused by infectious foci. Intoxication is manifested by severe weakness, loss of appetite, fever with chills, tachycardia, decreased blood pressure and shortness of breath. Characterized by multiple lesions of organs and systems with the development of cardiac, respiratory, renal, adrenal insufficiency, etc. The examination reveals high leukocytosis, less often leukopenia, sharply increased ESR, lymphopenia, hypoproteinemia.

Diagnosis of sepsis

Diagnosis of sepsis is based on the clinical picture of the disease, the identification of pathogenic microorganisms in the blood, the detection of septic foci in various organs and tissues.

What can you do

You can see your doctor if you have symptoms of sepsis.

What a doctor can do with sepsis

The doctor examines the patient and prescribes appropriate treatment.

Preventive measures

Prevention of sepsis is based on the correct and timely treatment of local purulent processes and compliance with aseptic conditions during operations and other medical procedures.

The prevention of sepsis can also include the competent use of antibacterial agents. It should be understood that any bacteria and fungi are capable of developing drug resistance. The more powerful antibiotics we use, the stronger and smarter our opponents become. The use of antibiotics of the latest generations without appropriate indications deprives us of the means to fight in really serious situations, when these drugs could save lives. Any antibiotics should be used strictly as prescribed by your doctor.

Attention! Symptom chart is for educational purposes only. Do not self-medicate; for all questions regarding the definition of the disease and methods of treatment, contact your doctor. Our site is not responsible for the consequences caused by the use of information posted on the portal.

How gangrene and sepsis killed Nachalova

Among the diseases that killed the singer Yulia Nachalova are extremely dangerous gangrene and sepsis.Gazeta.Ru tells how to recognize them and be saved in time.

On March 16, singer Yulia Nachalova died, her health problems began with a wound on her leg. The singer was in no hurry to go to doctors, believing that the healing was delayed due to diabetes and lupus, the media write. This led to the development of gangrene, and later – to blood poisoning.

Gangrene is the death of body tissues. At the same time, they darken due to iron sulfide formed from the iron of hemoglobin in the presence of hydrogen sulfide.It can occur due to problems with the blood supply to tissues, infections, physical or chemical effects.

The main symptoms of gangrene are blackening of the affected tissues, tissue swelling around the wound, acute pain, numbness of the limbs. Convulsions may occur, trophic ulcers may form.

According to the consistency of dead tissues, gangrene is divided into dry and wet.

Dry gangrene affects a specific area of ​​the body and does not spread further. There is almost no decay of dead tissue, and the absorption of toxic products is so insignificant that intoxication is not observed.

Wet is more dynamic than dry, the whole organism is infected.

Gas gangrene occurs during infections due to the growth and reproduction in tissues of bacteria of the genus Clostridia. The growth of this microflora is possible only in the absence of oxygen, however, the spores of pathogens can persist for a long time in an oxygen environment. It received this name due to the fact that when pressing on the edges of the wound, gas bubbles with an unpleasant sweetish putrid odor are released from the tissues.

Rarely, gangrene can result in self-amputation without further tissue damage.

With the onset of ischemic (arising from a violation of the blood supply to the tissues) gangrene, treatment consists in restoring blood circulation in the diseased limb. Reconstructive operations on the arteries can limit the area of ​​necrosis and preserve the support function of the limb. After blood flow is restored, only clearly dead tissue is removed.

Gangrene of the entire segment requires amputation, but its level depends on the state of blood circulation.

Surgeons should strive to reduce amputation rates to preserve limb function, but not to the detriment of stump healing.

Infectious gangrene requires urgent amputation. The stump is formed after cleansing the wound from infection. Note that, as the PR director of Yulia Nachalova, Anna Isaeva, said in the First Channel program “Let the Talk”, the singer, being conscious, refused to amputate her finger. “She did not allow to remove this finger, where the infection had developed, while she was still conscious.I was very afraid of this. It is difficult to judge what would have happened if he had been removed, ”Isaeva said.

The main treatment for tissues damaged by gangrene is intramuscular injections of penicillin into the necrotic areas of the affected organs. Blood transfusion is also used. Prevention of gangrene comes down to early treatment and disinfection of the wound, as well as taking antibiotics.

Infectious gangrene can provoke sepsis – blood poisoning.

Unlike gangrene, it immediately affects the entire body.

If sepsis is not recognized early and treated promptly, it can cause septic shock, multiple organ failure and death.

Sepsis develops when the body’s response to an infection damages its own tissues and organs, and can lead to death or serious deterioration. The clinical course of sepsis can be lightning fast (rapid development of manifestations within 1-2 days), acute (up to 5-7 days), subacute and chronic.

Alarming signs and symptoms include fever and chills, changes in mental state, shortness of breath / rapid breathing, heart palpitations, weak heart rate / low blood pressure, cyanosis or marbling of the skin, cold extremities, and severe pain or discomfort in the body.

Sepsis can develop in anyone with an infection, but vulnerable populations – the elderly, pregnant women, newborns, hospitalized patients and people with HIV and AIDS, cirrhosis of the liver, cancer, kidney disease, autoimmune diseases and a removed spleen – are at increased risk.

Treatment is aimed at fighting infection (high doses of antibiotics) and increasing the body’s resistance. Infusion therapy is also important at an early stage to normalize the volume of circulating fluid. In the presence of wounds, timely removal of dead tissue, destruction of purulent foci, treatment of wounds with antibiotics and antiseptics is necessary.

Spontaneous recovery from sepsis is almost impossible.

In the absence of treatment, all organs are affected – abscesses of the lungs and brain, purulent meningitis, cystitis, heart failure develop.It is possible to develop septic shock – an acute condition in which blood supply deteriorates, which impairs the delivery of oxygen and other substances to tissues. Mortality in septic shock reaches 50%.

For the prevention of sepsis, it is recommended to promptly treat local purulent processes, disinfect any wounds and injuries. Hand hygiene and food preparation rules must also be observed.

Clinical studies confirm the effectiveness of Efferon

The journal “General Reanimatology” published an article by researchers from the Moscow City Clinical Hospital No. 1 named after N.I. Pirogov and the Federal Scientific and Clinical Center of Reanimatology and Rehabilitation (FNCC RR), which describes the experience of using Efferon LPS devices from the Skolkovo Efferon company in a series of clinical observations of nine patients.

Patients were hospitalized with septic shock, initially they underwent surgical debridement of the site of infection. Against the background of the absence of positive dynamics in the immediate postoperative period, selective hemosorption of lipopolysaccharides was included in the complex therapy.

Photo: Nanolek

As a result, the researchers noted the rapid stabilization of hemodynamic parameters, withdrawal from vasopressor support and regression of multiple organ failure over the next three days after the completion of selective hemosorption of lipopolysaccharides. These observations are confirmed by the dynamics of laboratory parameters – a decrease in the level of activity of endotoxin, interleukin-1beta, procalcitonin, C-reactive protein.

“The device for extracorporeal blood purification” Efferon LPS “has high potential as a means of life support for sepsis”, – emphasizes one of the authors of the article, Dr.MD, professor V.M. Pisarev.

Researchers emphasize the importance and feasibility of further expanded clinical trials demonstrating a reduction in high mortality in patients with septic shock.

“The results of this pilot study are encouraging: out of nine critically ill patients, seven were rescued. The survival rate in patients with septic shock receiving standard therapy is estimated by the authors of the work at 35%, says Ivan Bessonov, co-founder of Efferon.“The evidence base confirming the effectiveness and safety of our solutions will continue to grow.”

Co-founder of Efferon Ivan Bessonov. Photo: Efferon

Efferon produces disposable sorption columns for extracorporeal blood purification Efferon LPS and Efferon CT. Both medical devices received approval from Roszdravnadzor for clinical use in 2019. Currently, the columns are used in more than a hundred clinics in the Russian Federation, and are also exported.

Last July, Efferon’s products were presented at a meeting between FMBA head Veronika Skvortsova and the Skolkovo Foundation residents.

Sorption column “Efferon LPS” is used in the complex therapy of such life-threatening conditions as sepsis and septic shock. Sepsis is caused by a powerful toxin, lipopolysaccharide (LPS). To date, there are no drugs that can effectively treat sepsis. The antibiotic solves the problem of the infection itself, but not the body’s response to toxic LPS molecules.

“Efferon CT” columns contain a sorbent capable of selectively absorbing a different type of therapeutic target than LPS molecules; these are cytokine proteins, the overproduction of which leads to a deregulation of the inflammatory response.

According to Ms. Skvortsova, the proposed technique “can be in great demand for a wide range of tasks; in particular, there is potential for use in the therapy of COVID-19, but this, of course, requires detailed study. ”

Efferon continues to work in the area of ​​anticytokine sorption for patients with multiple organ failure caused by coronavirus infection.“This technique is now in great demand all over the world,” notes Ivan Bessonov.

Both types of products, “Efferon CT” and “Efferon LPS”, are in demand by Russian doctors in approximately equal measure. At the end of last year, both devices were entered into the INVIMA (Instituto Nacional de Vigilancia de Medicamentos y Alimentos) Sanitary Registry of Colombia and are now available in the South American country for clinical use.

In parallel, other contracts are being concluded for the supply of Efferon CT and Efferon LPS, in particular, to the countries of the Middle East, said the co-founder of Efferon.

Modern approaches to the management of patients with sepsis

Authors:
IN AND. Cherniy, A.N. Nesterenko

PDF article

On May 23-25 ​​in Odessa the IV International Congress on hemostasiology, anesthesiology and intensive care “Black Sea Pearl” was held. The event was attended by leading scientists and experts from Ukraine, as well as their foreign colleagues from France, Germany, Italy, Moldova, Russia, Israel.The congress participants discussed modern approaches to the diagnosis and treatment of many diseases and pathological conditions that intensive care physicians often encounter in their practice. Particular attention was paid to the treatment of sepsis, which for many decades has remained one of the most pressing problems of modern healthcare. In this review, we invite readers to familiarize themselves with some of the reports that present modern views on the pathogenesis and intensive care of sepsis.

Corresponding Member of the National Academy of Medical Sciences of Ukraine, Doctor of Medical Sciences, Professor Volodymyr Ilyich Cherniy spoke about the fundamentally important points in the treatment of sepsis and septic shock.

The speaker recalled that according to modern concepts, the term “sepsis” means a pathological process, which is based on the body’s response to an infection of various nature (bacterial, viral, fungal) in the form of generalized (systemic) inflammation.Due to the progression of the inflammatory process caused by microorganisms, a massive production of inflammatory mediators occurs, which, in turn, have a damaging effect on the vascular endothelium. This leads to a violation of vascular permeability, the development of ischemia of organs and tissues, multiple organ failure.

The severity of organ dysfunction due to infection is assessed using the SOFA (Sepsis-related Organ Failure Assessment) scale. The presence of septic shock is stated when persistent arterial hypotension is detected in a patient, requiring the use of vasopressors despite adequate infusion therapy to maintain an average arterial pressure of ≥65 mm Hg.Art. in combination with a lactate level> 2 mmol / L.

In patients with suspected sepsis or septic shock, a microbiological study is recommended before starting antibiotic therapy, provided that it does not lead to a significant delay in starting therapy. For this purpose, modern diagnostic systems can be successfully applied. For example, the use of the FilmArray system for the identification of bacterial blood isolates makes it possible to correctly identify 98% of monomicrobial cultures by bacterial genes within an hour.For the VITEK mass spectrometry system, this figure is about 94%.

The use of antibiotic therapy in a general hospital and specific hospitals should be based on daily data from continuous regional microbiological monitoring.

Prior to identification of the pathogen, it is necessary to prescribe empiric antibiotic therapy, taking into account all possible pathogens. It is recommended to give preference to the de-escalation method of empiric antibiotic therapy, which is associated with lower mortality and reduces the risk of developing resistance in patients with severe sepsis and septic shock.Patients at high risk or high severity of the condition (severe physical status, old age, decreased immune status) should initially receive combination antibiotic therapy. This can be carbapenem (imipenem, meropenem, or doripenem) in combination with piperacillin / tazobactam; levofloxacin or cefepime in combination with metronidazole.

For sepsis caused by methicillin-resistant aureus (MRSA) and epidermal (MRSE) staphylococcus aureus, do not use all available β-lactam antibiotics (including penicillins, cephalosporins and carbapenems), clindamycin, aminoglycosides.In this case, glycopeptides, linezolid, ceftaroline, daptomycin are indicated.

An important point in the treatment of sepsis is the replenishment of the volume of the intravascular fluid. The Pharmacovigilance Risk Assessment Committe (PRAC), which is part of the European Medical Agency, does not recommend the use of hydroxyethyl starch solutions in patients with sepsis or in critically ill patients. It is advisable to use balanced crystalloid solutions with reserve alkalinity as first-line drugs in the treatment of septic shock.The only colloidal solution that is safe for patients with sepsis is albumin. Its use may be considered in individuals with sepsis and hypoalbuminemia.

Hemodynamic response to fluid therapy with large bolus loads (20-30 ml / kg) can lead to volume overload. Therefore, P. Marik and R. Belloma (2016) in their review on fluid therapy for sepsis recommend preliminary “testing” of the response to fluid therapy by bolus administration of 200-500 ml of fluid followed by a leg lift test and monitoring cardiac output.

The failure of the immune system in sepsis is manifested by immune distress, which requires appropriate correction. Immunoglobulin therapy for sepsis is based on the concept of antimicrobial, anti-inflammatory and immunomodulatory effects of antibodies. Currently, three types of immunoglobulin preparations are used: polyvalent immunoglobulin containing almost exclusively IgG; immunoglobulin enriched in IgM and IgA; monoclonal specific immunoglobulins, in particular antibodies to endotoxin.The largest evidence base has been accumulated in relation to polyvalent IgG-containing immunoglobulin. In Ukraine, highly purified polyvalent IgG is represented by Bioven.

The efficacy of intravenous immunoglobulins in severe bacterial infections and sepsis has been proven by a number of meta-analyzes performed by the Cochrane community. So, in the Japanese recommendations for the management of sepsis, it is indicated that the use of intravenous immunoglobulins reduces the duration of mechanical ventilation (ALV), increases the survival rate of patients with sepsis.The recommended dose of immunoglobulin for a course of treatment is from 0.2 to 1 g / kg and is administered for at least 3 days.

Today, immunoglobulins are positioned as a second-line agent for the treatment of sepsis with a high risk of death, along with antibiotic therapy. At the same time, some researchers consider it expedient to use immunoglobulins for bacterial sepsis as a first-line drug along with antibiotic therapy.

Doctor of Medical Sciences, Professor Alexei Nikolaevich Nesterenko introduced the main provisions of the International Guidelines for Management of Sepsis and Septic Shock (revision 2016) (Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016).

Initial intensive care

Sepsis and septic shock are emergencies, therefore the updated International Guidelines for the Management of Sepsis and Septic Shock recommend starting intensive care immediately. Already within the first 3 hours, it is necessary to begin treatment of sepsis-induced hypoperfusion using an infusion of crystalloid solutions at a dose of at least 30 ml / kg. After the initial infusion therapy, the amount of further infusion therapy should be revised depending on the patient’s hemodynamic status.In patients with septic shock who require vasopressor support, it is recommended that the target mean arterial pressure be kept at least 65 mm Hg. Art.

Screening of sepsis and improving the efficiency of its diagnosis

According to the International Guidelines, all hospitals should develop programs to improve the effectiveness of measures aimed at detecting sepsis in severe patients and patients at high risk of developing sepsis.

Diagnostics

Appropriate routine microbiological testing (including blood cultures) should be performed prior to initiation of antibiotic therapy in patients with suspected sepsis or septic shock, unless waiting for test results will significantly delay initiation of antibiotic therapy.

Antimicrobial therapy

It is recommended to use intravenous antimicrobials / antibiotics as soon as possible after diagnosis, within one hour for sepsis or septic shock. Delay in antibiotic therapy significantly worsens survival prognosis. It has been shown that every hour of delay in the initiation of adequate antibiotic therapy reduces patient survival by 7.6% (A. Kumar, 2006).

Empiric antimicrobial therapy should be initiated with broad-spectrum drugs using one or more antimicrobial agents in patients presenting with sepsis or septic shock to cover all possible pathogens (including bacterial and possibly fungal or viral).In patients with sepsis or septic shock, it is recommended to use an antibacterial dosing regimen based on their pharmacokinetics / pharmacodynamics. Experts believe that at the initial stage of treatment for septic shock, combined empiric antibiotic therapy (using at least two antibiotics of different classes) should be directed to the most likely bacterial pathogen (s). Combination antibiotic therapy should not be routinely used for most other dangerous infectious processes, including bacteremia or sepsis without septic shock.

If a pathogenic microorganism or its sensitivity to antibacterial drugs is identified and / or an improvement in the clinical picture is noted, it is recommended to narrow down empirical antibiotic therapy. If combination therapy is used to treat septic shock, de-escalation should be performed with the combination therapy discontinued within the first few days if the clinical picture improves and / or there is evidence of resolution of the infection.

Long-term systemic antimicrobial prophylaxis is not recommended in patients with severe inflammatory processes of non-infectious origin (eg, severe pancreatitis, burn injury).

Experts believe that the duration of antimicrobial therapy for 7-10 days is sufficient for most dangerous pathogens that cause the development of sepsis and septic shock.

Longer courses are indicated for patients with slow positive clinical dynamics, with an undrained focus of infection, with bacteremia caused by Staphylococcus aureus , with some fungal and viral infections or with immunodeficiency, including neutropenia.

A daily assessment is recommended for de-escalation of antimicrobial therapy in patients with sepsis or septic shock.Experts believe that the study of the level of procalcitonin in the blood may become the basis for making a decision to discontinue empiric antibiotic therapy in patients with initial manifestations of sepsis, who subsequently did not have sufficient evidence of the presence of a focus of infection.

In addition, procalcitonin levels can be used to “manage” antibiotic treatment – to help identify patients with bacterial infections who are eligible for antibiotic therapy, and determine its duration.If the level of this marker exceeds 0.5 ng / ml, antibiotic therapy should be continued, less than 0.1 ng / ml – antibiotic therapy can be canceled.

Infusion therapy

Infusion therapy is recommended for as long as there is a need to improve hemodynamics. For volume replacement of intravascular fluid in patients with sepsis and septic shock, balanced crystalloid solutions or saline should be used at the initial stage of infusion intensive therapy.

Experts suggest the use of albumin in addition to crystalloid solutions at the initial stage of infusion intensive care and for volume replacement of intravascular fluid in patients with sepsis and septic shock when patients require significant amounts of crystalloids. In patients with sepsis and septic shock, experts do not recommend the use of hydroxyethyl starch solutions for intravascular fluid volume replacement.

Vasoactive drugs

It is recommended to use norepinephrine as the first-line vasopressor drug of choice.To reduce the dose of norepinephrine, experts recommend adding vasopressin (up to 0.03 U / min) or epinephrine to raise the mean blood pressure to the target.

Dopamine is proposed as an alternative vasopressor to norepinephrine, but only in carefully selected patients (eg, patients with a low risk of tachyarrhythmia and absolute or relative bradycardia). The use of low doses of dopamine for nephroprotection is not recommended.

In patients with signs of persistent hypoperfusion, despite adequate infusion load and the use of vasopressor drugs, it is suggested to use dobutamine.

Experts believe that all patients receiving vasopressors should have an arterial line (catheter) inserted as soon as possible with the availability of resources.

Corticosteroids

Intravenous hydrocortisone is not recommended in the treatment of septic shock if hemodynamics can be stabilized with adequate fluid loading and vasopressor therapy.If stabilization is unattainable, hydrocortisone 200 mg / day should be prescribed.

Blood preparations

Experts recommend RBC transfusion only for hemoglobin levels <70 g / L in adults without aggravated conditions such as myocardial ischemia, severe hypoxemia, or acute blood loss (strong recommendation, high quality evidence).

The use of erythropoietin is not recommended for the treatment of sepsis-related anemia.Fresh frozen plasma should not be used to correct the coagulation system in the absence of bleeding or planned invasive interventions.

Immunoglobulins

According to the authors of numerous studies, the additional opportunities that open up for the use of immunoglobulins in the treatment of sepsis should not be neglected. Immunoglobulin preparations contain specific antibodies against various bacteria, toxins and viruses. When combined with an antigen, immunoglobulins exhibit an opsonizing effect and modulate the complement system, neutralize the action of toxins and viruses, suppress the production of pro-inflammatory cytokines, and have an antibody-dependent bactericidal activity that directly affects the cell wall of pathogenic microorganisms.

The failure of the immune system in sepsis is manifested by immune distress and requires targeted immunocorrection. For the purpose of adjuvant (replacement) immunotropic therapy of sepsis, the use of human donor immunoglobulin for intravenous administration is justified. The effectiveness of intravenous immunoglobulins in severe bacterial infections and sepsis has been proven by a number of meta-analyzes carried out by experts from the Cochrane Community (M.M. Alejandria et al., 2013; M.O. Soares et al., 2012). The use of donor human immunoglobulin for intravenous use is included in the current Japanese guidelines for the management of patients with sepsis.

There are not so many high-quality preparations of human immunoglobulin G on the domestic pharmaceutical market. Ukrainian intensive care physicians are well acquainted with human donor immunoglobulin for intravenous administration Bioven produced by Biopharma.

Anticoagulants

According to the recommendations of international experts, the use of antithrombin is not recommended, and there are no data on the effectiveness of the appointment of thrombomodulin and heparin for the treatment of sepsis and septic shock.

Artificial lung ventilation

The recommended tidal volume of 6 ml / kg versus 12 ml / kg for adult patients with sepsis-induced acute respiratory distress syndrome (ARDS), the upper plateau pressure limit should be no more than 30 cm H2O. Art. In patients with severe sepsis-induced ARDS with a PaO 2 / FiO 2 <150 ratio, recruitment and ventilation maneuvers in the prone position are recommended.

High-frequency mechanical ventilation should not be performed in adult patients with sepsis-induced ARDS, and muscle relaxants should not be used for a long time (more than 2 days).

Sedation

Experts recommend minimizing prolonged and intermittent sedation in mechanically ventilated patients with sepsis.

Glycemic control

Insulin administration should be started when the blood glucose level (after double determination) is> 10 mmol / L.It is recommended to monitor the blood glucose level every 1-2 hours until the given level and the rate of insulin infusion are constant. After that, glycemic control is carried out every 4 hours. If the patient has an arterial catheter, blood samples should be taken from it (that is, not capillary blood).

Sodium bicarbonate injection

Experts do not recommend the routine use of sodium bicarbonate solution in order to improve hemodynamic parameters and / or reduce the need for vasopressor support, provided that the pH is ≥ 7.15.

Prevention of thromboembolic complications

In patients with sepsis and septic shock, pharmacological thromboprophylaxis using unfractionated (UFH) or low molecular weight (LMWH) heparin is recommended. In the absence of contraindications for use, LMWH is preferred over UFH. In the presence of contraindications to the use of pharmacological prevention of venous thromboembolism, mechanical preventive measures are recommended. The optimal method for the prevention of venous thromboembolism should be considered a combination of pharmacological and mechanical means.

Prevention of stress ulcers of the gastrointestinal tract

In the presence of risk factors for the development of gastrointestinal bleeding (GCC), the authors of the International Guidelines recommend prevention of stress-induced ulcers in patients with sepsis and septic shock. For this purpose, drugs from the group of proton pump inhibitors and H2-receptor antagonists are prescribed. It is not recommended to carry out the prevention of stress ulcers in patients without risk factors for the development of GCC.

Prepared by Vyacheslav Kilimchuk

STATTS ON THE TOPIC Surgery, orthopedics and anesthesia

27.07.2021

Surgery, orthopedics and anesthesia

Firing and health of the support-arm apparatus: from theory to practice

For example, in the spring, an online conference was held “Filling and health of the support-arm apparatus:
from theory to practice ”, organized by the Ukrainian Academy of Biological Medicine.Zakhid bulo was assigned to the 85th juvenile drug Traumeel S. Within the framework of the conference, new scientific rosettes were added, the prospects for a completely effective and safe treatment

27.07.2021

Surgery, orthopedics and anesthesia

COVID ‑ 19 and thrombosis: the latest tribute to thromboembolism

On the ear of the COVID-19 pandemic, there has been a lot of news about the great expansion of thromboembolism among hospitalized patients with SARS-CoV-2 infection.As a result, thrombosis does not remember the outpatients and patients who have been reported for a long time and they can win the vaccination. On the webinars “COVID-19 and thrombosis: the latest data on the prevention of thromboembolism”, the specialties presented the most relevant data on the prevention and treatment of thromboembolism in the hospital.

Salmonellosis

Salmonellosis is an infection caused by Salmonella, a bacterium that is widespread throughout the world.Salmonella can also cause another infectious disease – typhoid fever.

Most often, salmonellosis occurs as an intestinal infection and is manifested by an increase in body temperature, diarrhea and vomiting. However, sometimes it can be much more severe and threaten the patient’s life.

Infection usually occurs through the consumption of foods contaminated with Salmonella, usually chicken and eggs.

Mild forms of salmonellosis disappear without treatment within 3-5 days.In severe cases, hospitalization and antibiotics are necessary.

Synonyms Russian

Salmonella infection, nontyphoid salmonellosis, nontyphoid salmonellosis.

Synonyms English

Salmonellosis, Nontyphoidal salmonellosis, Nontyphoidal Salmonella Infections.

Symptoms

Typically, 1-2 days after infection, the following symptoms occur:

  • nausea;
  • vomiting, which may be repeated;
  • cramping abdominal pain;
  • yellow, green diarrhea, often watery, rarely bloody; multiple stools, up to 10-20 times a day;
  • Soreness when palpating the abdomen around the navel, in the right lower abdomen;
  • increase in body temperature (with a disease of moderate severity – up to 39-40 degrees), general weakness.

In typical cases, salmonellosis lasts 3-5 days and goes away on its own without treatment.

When blood is infected and the infection spreads throughout the body, the symptoms will depend on the primary damage to one or another organ.

General information about the disease

Salmonellosis is an extremely common infection. Several tens of millions of cases of the disease are recorded around the world every year.

Salmonella are bacteria that cause a large number of diseases in humans, including typhoid fever.Salmonellosis is understood to mean any disease caused by bacteria from the genus Salmonella, other than those that cause typhoid fever.

Salmonella live in the organisms of various domestic animals: cattle, sheep, pigs, chickens, ducks, domestic turtles. In addition, birds also excrete Salmonella: sparrows, pigeons, seagulls. Up to 50% of chickens are also infected with salmonella. Eggs can easily get infected. In dairy and meat products, Salmonella can survive for up to four months, multiplying in them.This does not change the taste and appearance of the products. Salmonella are resistant to salting, smoking, they survive even in dry and frozen foods. In the external environment, bacteria can persist for several months.

Animal meat can become infected with salmonella during transportation, handling, improper cooking, cooking on contaminated tables.

Outbreaks of the disease are more frequent in the summer due to deteriorating food storage conditions.Causes of infection: eating contaminated food, mainly chicken, eggs, as well as improperly prepared fruits, vegetables, dairy products.

Much less often, the source of infection can be infected people.

The incubation period (the period from contact with contaminated food to the onset of symptoms) is usually quite short – 12-48 hours (sometimes 6 hours). Entering the body through the mouth, bacteria enter the intestines through the human stomach. In the stomach, some of them die under the influence of gastric juice.For this reason, a large number of bacteria must enter the body for the development of salmonellosis. However, if the stomach is damaged, the acidity of the gastric juice decreases, only 1000 bacteria may be sufficient.

When bacteria enter the intestines, they cross the mucosal barrier and multiply, causing damage to the intestinal wall. Inflammation occurs, which leads to the formation of active substances that contribute to increased fluid secretion in the intestinal wall and, as a result, diarrhea.The cells of the immune system begin to fight Salmonella, the bacteria die, forming a toxin that enters the bloodstream and causes an increase in body temperature and general weakness.

In some cases, Salmonella enter the bloodstream and cause its infection (bacteremia), followed by screenings in various organs and the formation of purulent foci there, which significantly worsens the prognosis of the disease. This occurs in 10-15% of patients, especially in young children and the elderly, as well as in patients with impaired immunity (for example, HIV-infected).

Most often children suffer from salmonellosis. In adults, the disease is sometimes asymptomatic, although they may excrete Salmonella in their feces. Fecal excretion of the bacteria is infrequent, but can play a role in the spread of the disease, especially if the infected person works in a food service.

Blood infections in salmonellosis are dangerous by the development of the following complications:

  • Endocarditis is an inflammation of the heart valves that requires the use of powerful antibiotics for treatment and sometimes surgery.
  • Meningitis is an inflammation of the meninges, which develops more often in children and is fatal in half of the cases. Fortunately, it rarely develops.
  • Urinary tract infection. The risk of urinary tract inflammation increases in the presence of urinary tract diseases (kidney stones, abnormalities in the development of the kidneys and ureters).
  • Pneumonia. Inflammation of the lungs is especially common in older diabetic patients or alcoholics.
  • Abscesses of the liver and spleen.In the liver and spleen, as a result of the multiplication of Salmonella, cavities filled with pus – abscesses can form. Their appearance requires a surgical operation.
  • Suppurative inflammation of the joints (septic arthritis).
  • Osteomyelitis is a purulent inflammation of the bones.
  • Sepsis is a systemic inflammation associated with the spread of the pathogen through the blood and various organs. In this case, Salmonella can be found in the blood. The prognosis is extremely unfavorable.

Who is at risk?

  • Children under 5 years old
  • Seniors
  • People who have had their stomach or spleen removed
  • Persons with reduced immunity (patients with oncological (cancer) diseases of the lymphatic system, HIV-infected)
  • Workers of poultry farms, livestock farms
  • Persons who consume raw chicken, goose, duck eggs
  • Travelers

Diagnostics

Diagnosis of salmonellosis is carried out taking into account data on the presence of an outbreak of infection, history of the development of the disease, the isolation of salmonella from feces.

The following tests are performed to assess kidney function and check for dehydration:

  • Complete blood count
    • Leukocytes. An increase in leukocyte counts reflects the activity of inflammation. The more severe the salmonellosis, the higher the level of leukocytes.
  • Potassium, sodium, chlorine in serum. It is necessary to control the level of electrolytes in the blood, since their pronounced decrease as a result of dehydration can lead to severe complications.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The level of these liver enzymes can be increased in a significant number of patients with salmonellosis, reflecting the involvement of the liver in the pathological process.
  • Amylase and lipase in the blood. Amylase and lipase, enzymes secreted by the pancreas, are elevated when the pancreas is inflamed.
  • Serum creatinine and urea. An increase in the content of creatinine and urea indicates the development of renal failure.

The amount of additional examination is determined by the attending physician and depends on the severity of the disease and the complications that have arisen.

Treatment

In mild cases, it is sufficient to replace the loss of fluid with the use of saline solutions. The disease goes away on its own in a few days. The use of antibiotics is undesirable, since this increases the period of excretion of Salmonella from the body with feces.

In severe cases or with a high risk of complications, the patient must be admitted to an infectious diseases hospital, and antibacterial drugs (co-trimoxazole or ciprofloxacin) are prescribed.Typically, treatment lasts 3-5 days. If blood poisoning occurs, antibiotics can be extended by 1-1.5 months.

If purulent complications occur, surgery may be required.

Ill food workers should be excluded from cooking. In order to make sure that the pathogen has completely disappeared from the body, repeated cultures of feces are carried out for several weeks.

Prevention

Infection with salmonellosis cannot be ruled out, since its pathogens are ubiquitous.Prevention consists of preventing Salmonella contamination of food and maintaining good personal hygiene.

In order to prevent salmonellosis and other intestinal infections, the following recommendations must be observed:

  • Wash hands thoroughly before preparing food
  • Teaching children to follow good hygiene rules
  • Observe the rules for the preparation and storage of food, maintain the required temperature regime for cooking meat and eggs
  • Eat only pasteurized milk
  • If the patient has diarrhea, the preparation of food should be entrusted to others
  • It is not recommended to eat raw and boiled soft-boiled chicken, ostrich, goose and duck eggs

Also, preventive measures are being taken to prevent food contamination, compliance with sanitary and hygienic standards in livestock farms, trade, public catering

Recommended analyzes

Literature

Dan L.Longo, Dennis L. Kasper, J. Larry Jameson, Anthony S. Fauci, Harrison’s principles of internal medicine (18th ed.). New York: McGraw-Hill Medical Publishing Division, 2011.

90,000 Pyelonephritis: symptoms and treatment. How is pyelonephritis treated?

Description of the disease

Pyelonephritis – inflammation of the renal pelvis. It is caused by various bacteria, very often E. coli. The problem of diagnosing the disease is that its symptoms are similar to the symptoms of various diseases associated with inflammation in the urinary tract.Therefore, it is always necessary to consult a qualified urologist. These are the ones who work for us.

In our St. Petersburg clinic, we will offer you to undergo the necessary diagnostic procedures using the most modern equipment, to perform the entire range of laboratory tests to make an accurate diagnosis. Our experienced specialists will treat your illness according to an individual program.

Why pyelonephritis occurs

Bacteria can enter the urinary tract from organs close to them (intestines, genitals), or through the circulatory and lymphatic systems.Further, bacteria begin to multiply in the urinary system. Pyelonephritis can also occur when urine flows out of the kidney.

Risk groups

Everyone can get pyelonephritis, but more often they get it:

  • children under seven years of age,
  • women 18-30 years old (the onset of pyelonephritis is associated for them with the onset of sexual life, pregnancy, childbirth),
  • elderly men with prostate adenoma, urethritis, prostatitis.

The disease can occur when:

When you need to go to the clinic: symptoms

Pyelonephritis is divided into acute and chronic.

Acute form differs:

  • fever (39 or 40 C),
  • profuse sweating,
  • nausea, vomiting,
  • chills, weakness, headache,
  • dull lumbar pain ,
  • In the case of urolithiasis, the attack of pyelonephritis is usually preceded by an attack of renal colic.

It is impossible to hesitate in contacting the clinic, since the acute form of the disease can turn into a chronic one, or suppurative processes of the kidney will develop.

The most dangerous complication is sepsis, which is fatal.

Chronic pyelonephritis often develops as a consequence of untreated acute. Its symptoms are as follows:

  • dull aching persistent lower back pain, especially in cold damp weather,
  • increased blood pressure.

With chronic pyelonephritis, there are repeated exacerbations, then all the symptoms of an acute process appear.

Diagnostics in the clinic

To detect pyelonephritis, you will be prescribed in our clinic:

  • blood and urine tests,
  • ultrasound of the kidneys,
  • X-rays using contrast agents,
  • bacteriological culture of urine (to determine the type of bacteria) ,
  • PCR analysis for infections,
  • computed tomography (to exclude tumor processes).

Treatment in the clinic

Do not hope that you will cure pyelonephritis at home.At best, it will go into the chronicle. Treatment of chronic pyelonephritis requires a professional approach. The sooner you go to the clinic, the better.

In acute pyelonephritis or exacerbation of chronic pyelonephritis complex treatment is carried out. It includes antibiotics, antiseptic mixtures, decoctions of diuretic herbs, physiotherapy methods.

In chronic pyelonephritis, it is necessary to eliminate foci of infection, as well as factors that prevent the flow of urine: strictures of the ureter, urethra, benign prostatic hyperplasia, stones of the urinary system.

You will also be prescribed antibiotics, herbal preparations characterized by a diuretic, antiseptic, regenerative effect.

With prolonged forms of pyelonphritis, purulent foci appear in the kidney, and then an emergency operation is needed.

Prevention

Prevention of pyelonephritis is the elimination of a disease that can provoke pyelonephritis (urolithiasis, prostate adenoma, any disease in which the outflow of urine from the kidney is disturbed).
Pregnant women need a bacteriological analysis of urine once a month.

It is important to see a specialist in time if there is discomfort when urinating; swelling of the face, limbs, back pain, increased fatigue.

It is possible to diagnose and successfully cure acute or chronic pyelonephritis only in a good clinic with modern equipment and qualified personnel. Our doctors will take into account all the accompanying factors, existing contraindications, which will minimize the possibility of complications of pyelonephritis, and also minimize the risk of developing a chronic form of the disease.

Sattar Eraliev, pulmonologist: Treating viral pneumonia with antibiotics is nonsense!

According to the WHO at the beginning of 2020, about 50% of antibiotics in the world were used for other purposes. The problem of increasing resistance of microorganisms to antibiotics today poses a threat to all mankind. About how to use antibiotics correctly and what the uncontrolled use of them leads to, we talked with pulmonologist, chairman of the Public Association “City Respiratory Society” Sattar Eraliev.

– Sattar Molybekovich, what do you think is the reason for the uncontrolled use of antibiotics? What antibiotics do Kazakhstanis most often take off-label?

– When WHO says that 50% of antibiotics are misused, it means developing countries. Because in the West, in the same Great Britain, for example, it is simply impossible to get antibiotics. Unfortunately, Kazakhstan is a vivid negative example, because our patient can go to the pharmacy and buy an antibiotic on his own, without a prescription.

But, on the other hand, doctors abuse the prescription of antibiotics. The pandemic of coronavirus pathology just showed the consequences of this practice for both patients and doctors: in the summer in Kazakhstan there was a shortage of antibiotics.

Apparently, these are the consequences of the template – pneumonia is treated only with antibiotics. After all, before that we dealt only with bacterial pneumonia, where there is no way without antibiotics. On such a scale, the doctors of my generation had nothing to do with viral pneumonia. And they forgot that antibiotics cannot cure viral pneumonia. Not only pneumonia, viral diseases in general.

Let’s take the usual ARVI, which is popularly called colds. So 84% of all these colds are acute bronchitis. According to Australian clinical guidelines , acute bronchitis is 100% considered a viral disease, and antibiotics are not recommended for its treatment at all. In the USA, in 10% of cases, the use of antibiotics is allowed, when in winter during viral infections a layer of secondary infection occurs – chlamydia, mycoplasma, bordatella (the causative agent of whooping cough), , but in 90% of cases acute bronchitis passes without treatment I (symptomatic treatment is allowed: antipyretic , expectorant) and will not prescribe antibiotics there.

And most of our patients with acute bronchitis take antibiotics on their own or as prescribed by a doctor. . Moreover, Kazakhstanis like to take all classes of antibiotics: cephalosporins, new macrolides, the same azithromycin and, unfortunately, ciprofloxacin, ofloxacin. And they belong to the group of antibiotics (fluoroquinolones), which have severe side effects. Even doctors are advised to prescribe them only as a last resort and for special indications.

In 2016, WHO adopted a program for the rational prescription of antibiotics, and there, just as an example, they called not to prescribe ciprofloxacin for acute bronchitis and even mild urinary infections (for example, cystitis), and use only for pyelonephritis (inflammation of the kidneys) .And our dentist pulled out a tooth – and for the prevention of a secondary infection, he prescribes this particular drug (ciprofloxacin).

There are other issues of concern regarding antibiotics. The international scientific community draws attention to the fact that we (in Kazakhstan. – Red .) We use injectable antibiotics a lot for mild infections. Even patients buy cephalosporins and give themselves injections, while abroad prescribe tableted antibiotics for the treatment of outpatient bacterial diseases.

– Now they are discussing the consequences of using azithromycin. Is it true that it has a bad effect on the heart?

– In the reports that were disseminated by the media, was not only about azithromycin , it was mentioned, for example, lopinavir / ritonavir (its direct purpose is AIDS therapy), antimalarial drugs were also mentioned, which were used to treat “covid” at the height of the pandemic, but for some reason the correspondents identified azithromycin.

For the first time, the report that azithromycin negatively affects the work of the heart and can cause a life-threatening heart rhythm disturbance appeared back in 2010 (W.A. Ray et al.). After that, the US Federal Food and Drug Administration (FDA) obliged all manufacturers of azithromycin to write in the instructions for the drug, that it can cause heart rhythm disturbances. So this is not fresh news. In the same yesterday’s “sensational” reports, it was also about the deafness caused by azithromycin. But this is also “not new” news.

The fact is that azithromycin is a unique drug.It is not only an antibiotic, but has a pronounced anti-inflammatory effect, and it is in this capacity (not as an antibiotic, but as an anti-inflammatory drug) entered into the treatment protocol for “covid”.

There is a rare disease – the so-called diffuse panbronchiolitis, which affects only the inhabitants of Southeast Asia, and until recently it was considered an incurable disease. For the first time, Japanese doctors used azithromycin to treat this disease and received excellent results in most patients.With this pathology, azithromycin treatment lasts six months.

Or is there such a pulmonological problem – chronic obstructive pulmonary disease (COPD). Occasionally, with a severe course of this disease, by decision of the expert council, some patients are prescribed azithromycin for a year.

With such a long-term use of azithromycin, side effects are revealed that do not occur with a six-day appointment (the standard period for the treatment of bacterial pneumonia with azithromycin), in particular deafness.

Therefore, it cannot be categorically said that azithromycin kills. Drugs that cause side effects leading to death are immediately discontinued, as, for example, happened with fenspiride – a good anti-inflammatory drug.

In the instructions for azithromycin it is written: for patients with severe coronary heart disease, arrhythmia, this drug should be prescribed with caution or canceled.

Therefore, I want to note that journalists help us, doctors, but sometimes such “hyped sensations” cause irreparable damage, causing fear in patients.But, on the other hand, it may be good: our people like to prescribe it for themselves, and it is indicated (in pulmonology) only for pneumonia, especially caused by intracellular pathogens (mycoplasma, chlamydia).

This again suggests that the state should regulate this area, as in the West . The patient should not take antibiotics without a doctor’s prescription. Yes, and there is the problem of prescribing antibiotics for other purposes, but not on such a scale, and this problem is being studied and resolved in a timely manner.Although we also have conferences and webinars dedicated to this problem.

– What are the risks of taking antibiotics off-label? What are the most dangerous antibiotics in this regard?

– An antibiotic, like any chemical, if taken not for its intended purpose (and for its intended purpose too), becomes a burden on the body, disrupts the intestinal microbiome and reduces immunity. Finally, one of the most important problems facing doctors is the problem of resistance. Bacteria try to survive in any way, and the more often you take antibiotics, the faster they adapt to them. Microorganisms appeared on the earth 1.5 billion years ago, they survived even in an oxygen-free environment, with strong radiation (when the atmosphere was still forming) and will continue to survive.

I want to note that resistance arises even faster when you start a course of antibiotics and stop drinking them after two or three days, without completely killing the bacteria. What does not kill us makes us stronger – this is most likely said about microorganisms.

– Give examples of antibiotics that have already greatly lost in their effectiveness due to the fact that bacteria are used to them.

– Since 1996, no new antibiotic has been developed.

Vivid examples of the loss of effectiveness due to the uncontrolled use of antibiotics in the post-Soviet space are tetracyclines or the antimicrobial drug Biseptol. Although the same tetracycline (doxycycline) abroad, where the use of antibiotics is strictly controlled by doctors, is still included in the protocols for treating pneumonia, but for us it is already a lost drug.

Unfortunately, in our post-Soviet space, there are practically no clinical studies devoted to antibiotic resistance. We do not even know whether a patient in a hospital dies from resistance or from the fact that the disease is severe, or because of concomitant diseases. Meanwhile, the concept of “super-resistance of microorganisms” has appeared – for example, strains of mycobacterium tuberculosis, which are not taken by any anti-tuberculosis drug. Many people around the world die each year from antibiotic resistance .

Seeing this medical problem, one of the most authoritative scientific organizations in the world – the Infectious Diseases Society of America (IDSA) – made a request to the US Congress, drawing the attention of American legislators to the problem of antibiotic resistance.

In this request, to show the urgency of the problem, they cited a heartbreaking case: a 7-year-old girl in Florida fell off a bicycle and injured her knee. It looks like a small wound, but it is very inflamed.On the seventh day, she was hospitalized in serious condition with signs of sepsis, and then transferred to intensive care, where she died. It turned out that microbe that got from the soil into the wound is insensitive to any kind of antibiotics .

After this appeal from scientists and doctors, the US Congress allocated funds (subsidies) to pharmaceutical companies for the development of new antibiotics. This, of course, is encouraging, and it is possible that the situation will change for the better. The same American Society of Infectious Diseases at one time drew attention to the problem of resistance in the treatment of tuberculosis, and a number of effective antibiotics were developed against this pathology, although with relatively frequent side effects, unfortunately.

Still, the best way to solve the problem of resistance – is the use of antibiotics only when indicated and the exclusion of their uncontrolled intake

– Are there any other ways to reduce antibiotic resistance, because we cannot completely abandon them?

– There is another way, indirect, – this is vaccination. The vaccinated person does not get sick, therefore, does not take antibiotics, which means that resistance to them will decrease .By the way, no effective drug has been developed against the smallpox virus, and we defeated the deadly infection by vaccination. Improving the principles of antiseptics, of course, played a role – we learned how to wash our hands, run sewers and so on, but vaccines played a huge role in the victory over many epidemics.

And all over the world now, unfortunately, some groups are growing, movements directed against vaccination . Even the discussion of our Health Code showed how active such groups are.

I am an ardent supporter of vaccination. Of course, there is always a range of some contraindications, but this is a small population. If this is not a vector vaccine, then vaccines are shown even to cancer patients.

Now at the parliamentary level we are discussing the vaccination of the population. And we are very glad that our deputies paid attention to this problem. Just the other day there was a discussion about pneumococcal vaccination. In Western countries, everyone over 65 is vaccinated with this vaccine.By 2025, for example, in the United States, about 90% of people aged 65 and over will be vaccinated against pneumococcal vaccinations.

Because pneumonia is a scourge of the elderly, and a greater percentage of pneumonia is caused by Streptococcus pneumoniae, it is also the causative agent of meningitis in 12% of cases, as well as severe invasive pneumonic infections (sepsis).

Influenza vaccination is also relevant, because an influenza epidemic is predicted. This year, the flu vaccination began early, because it turned out that those who have had the coronavirus, immunity decreases and its recovery will take a long time. We are afraid that those who have recovered from “covid” may soon get sick with severe flu.

It should also be noted that there is a risk that a cure will not be invented against the coronavirus and the only salvation (as in the case of smallpox) will be a vaccine. Therefore, vaccination is very important!

– From what diseases do antibiotics help, and from which ones do not?

– The only indication for antibiotics is bacterial infection .How did Fleming first isolate the antibiotic? The microbiologist grew colonies of bacteria and noticed that a colony of some bacteria inhibits the growth of another. Microorganisms are at war among themselves for space, they, too, “the whole world is not enough.” And an antibiotic is a weapon that one type of bacteria makes to kill other types of bacteria. And it does not help against viruses (it does not work on them), but only kills bacteria!

The well-known Russian microbiologist Roman Kozlov cited the data of a survey conducted by the journalists of the newspaper “Komsomolskaya Pravda” among the population (not doctors): are antibiotics effective against viruses? In 2010 (first survey) 45% of respondents answered yes , antibiotics kill viruses , and five years later (repeated survey) – answered positively one percent more – 46%.It can be assumed that these people are taking antibiotics for ARVI.

And the fact that we treated viral pneumonia with antibiotics in the summer is nonsense! We are probably the only country that has been treated for viral (covid) pneumonia with antibiotics. People rushed to pharmacies and bought (got) antibiotics for fabulous money. Yes, someone will say: I feel good. But, sorry, coronavirus in the vast majority of cases proceeds like any viral infection that we carry on our feet.

So if you recovered, it’s not because of antibiotics, but in spite of them. As we sometimes say, “I drank dog fat and it got better.” Viral bronchitis as a viral infection lasts only 7-10 days, and in most cases a person recovers on his own, and dog fat has nothing to do with it (although a placebo effect is possible).

– Let’s be clear – do antibiotics help against coronavirus?

– No! They don’t help.

Sometimes there is a stratification of a secondary infection, especially if the patient has some kind of chronic infections.But the indications for taking antibiotics for these patients are purulent sputum and the level of procalcitonin in the blood (there is such a biomarker of bacterial infection (pneumonia)) exceeds the permissible limits – only then antibiotics are prescribed.

And in our country, probably about 90% of patients with coronavirus received antibiotics. Let’s see how much antibiotic resistance will grow later because of this. But this, probably, was typical for the entire post-Soviet space when viral infections were treated with antibiotics.

– Tell us in more detail why antibiotics do not work on viruses? What Kills Viruses?

– We do not yet know how viruses interact with each other and whether the virus secretes any product that is fatal for it against another virus – a semblance of an antibiotic. Therefore, there is no cure for a serious viral disease – for example, there is still no effective treatment for AIDS. Although chemicals have been synthesized that suppress the multiplication (replication) of the virus, this is, of course, also a success.

There is a drug against influenza – oseltamivir, but it effectively suppresses the multiplication of the influenza virus only in the first two days of illness – if you are late, then it is already useless.

Therefore, there are no effective (like antibiotics against bacteria) drugs against viruses as such. Only vaccines are effective against viruses, although their development is also very difficult. There is still no vaccine against the same AIDS, although the genome of the virus was deciphered relatively quickly.

– During the period of strict quarantine, many could not go to the clinic, get medical help. How can you independently determine the stage when a viral disease turns into a bacterial one and at least “light” antibiotics are needed?

– On your own – no way. In just a few hours, a coronavirus patient who had mild catarrhal symptoms can be admitted to intensive care. This is the insidiousness of this infection. There is a risk group – these are people with severe pathologies of the cardiovascular system, with severe diabetes mellitus, obesity, the elderly.

We have not experienced such a pandemic before. And, unfortunately, she exposed all the weaknesses of our healthcare. People were forced to undergo treatment on their own according to some fake protocols that were surfing the Internet, or on the advice of a neighbor.

But I think it was a good lesson, and now, when we are waiting for the second wave of covid, doctors are being trained, effective treatment protocols are being drawn up, taking into account what mistakes we made.

Another problem is that the covid pandemic has delayed screening or treatment for health reasons for many chronic diseases. In the UK, about 3 million cancer patients did not receive timely treatment (elective surgery, radiation and chemotherapy courses) due to the pandemic. And when treating these patients, every day is dear to them.

Answering your question: the indications for taking antibiotics must be determined by the doctor, and in medicine antibiotics are not officially divided into light or severe . Pregnant women are shown aminopenicillins or other beta-lactam antibiotics (amoxicillins, cephalosporins). But they sometimes give severe allergic reactions.So the ease for antibiotics is a relative characteristic.

– Is it possible to choose and buy antibiotics at the pharmacy on the advice of a pharmacist, or do you still need a doctor’s prescription?

– Buying an antibiotic on the advice of a pharmacist from us can be equated with buying it yourself. After all, the pharmacist does not examine you, does not conduct a medical appointment. The pharmacist has a different task. Abroad, even if a doctor has prescribed an antibiotic for you, you will not receive it immediately. You leave the prescription, the pharmacist will look in the automated database what contraindications you have, what is your allergic history, whether you are taking another drug for another pathology in order to assess the interaction – whether they can be taken together.

So, when pharmacists “prescribe” treatment to patients, this is another post-Soviet phenomenon. I myself sometimes go to the pharmacy and see how people stand at the window and ask the pharmacist what to take, and not a single pharmacist says – “go to the doctor.”

I believe that pharmacists can, of course, prescribe some kind of symptomatic treatment – for the throat, drugs that reduce high temperatures, but antibiotics are a serious thing. And if there is a severe reaction, severe cross-allergy? Everyone must do their job.

– How to distinguish acceptable side effects of antibiotics from systemic problems in the body when it is worth stopping them?

– Stopping antibiotics due to side effects depends on how severe the side effect is . And there are small side effects, for example, mild nausea, which disappears on the second or third day, and then it is worth continuing to take. If they cause great inconvenience to the patient, then stop and inform the doctor.

Some antibiotics, for example, fluoroquinolones, cause photodermatitis, we advise the patient in advance not to walk in bright sunlight or dress appropriately while taking this group of antibiotics.

There is an interesting observation of German researchers, according to which, if the patient reads in advance about the side effects, they are three times more likely than . Therefore, patients are not advised to read about side effects in advance.

We are not wooden, we react, there is a placebo effect.Yes, I do not mind if the patient reads contraindications, doctors do not always carefully collect anamnesis. But not the side effects.

There is such a problem: the appointment of antifungal drugs while taking antibiotics. For example, pharmacists in a pharmacy often confuse patients: “Oh, why didn’t your doctor prescribe an antifungal drug after antibiotics?” There is no guideline in the world to prescribe antifungal drugs after antibiotics. No one has proven that mycosis develops after them.

A patient while taking an antibiotic may develop a severe side effect – the so-called pseudomembranous enterocolitis. Against the background of suppression of normal microflora in the intestine, pathogenic bacteria – clostridia begin to multiply, severe diarrhea develops. A person can die from it, and, oddly enough, he is treated with another antibiotic – vancomycin. But antifungal antibiotics won’t save you from it. Yes, the intestinal microflora is disturbed, but fungi have nothing to do with it.

Another thing is if a person has chronic fungal diseases of other organs: you can preventatively drink a course of antifungal drugs. And the rest of the patients do not need it.

Just do not confuse side effects with allergies – this is an indication for the immediate cessation of antibiotics and any other medication.

– Which patients should definitely not use antibiotics?

Those who do not have bacterial infections should not! They practically do not need an antibiotic, as I have already said.Sometimes there is multiple intolerance to antibiotics, and then anaphylactic shock or Quincke’s edema is possible. Such patients are also not allowed. Although the doctor, sometimes for health reasons (life-threatening invasive infections) takes risks and conducts biological tests to assess tolerance (by the way, subcutaneous tests are now recognized as inaccurate).

I would like to point out that the age of the patient is taken into account when prescribing antibiotics. For example, for infants, elderly patients, we reduce the dosage or frequency of taking antibiotics.Pregnant women and children should not be prescribed antibiotics from the fluoroquinolone group.

– How important is it to manufacture medicines in your country?

– The covid pandemic just answered that question. It turns out that 80% of the chemical substrates for antibiotics for the world’s leading drug manufacturers are made in China. Not only medicines, but also the production of disposable masks, medical equipment too. And when China began to make a stock for its population and stopped exporting, not only in our country, even in Western Europe, there was an acute shortage of vital medicines (including antibiotics) and means of prevention.

This once again showed how necessary it is to localize the pharmaceutical industry in your country.

Just the other day it was reported that factories have already been built in France that will fully provide this country with respiratory and surgical masks in the event of a second wave of a pandemic.

Therefore, it is very good that we have such domestic manufacturers of as the SANTO plant, which has an international GMP quality certificate for all its products and, most importantly, effective antibiotics of all groups.

Our Ministry of Health also made a conclusion and learned a lesson from this situation: it increases the order of domestic drugs .