What are the main side effects of vancomycin. How does vancomycin affect kidney function. What is red man syndrome caused by vancomycin. How can vancomycin-induced ototoxicity be prevented. What drug interactions occur with vancomycin. How is vancomycin dosing determined for patients. When is vancomycin used as a first-line antibiotic treatment.

Overview of Vancomycin and Its Clinical Importance

Vancomycin is a powerful antibiotic that has played a crucial role in treating severe bacterial infections for decades. First approved by the FDA in the 1950s, vancomycin’s initial formulations were less pure, leading to a higher incidence of side effects. Despite its effectiveness against drug-resistant bacteria, these side effects initially limited its widespread use.

Over time, improved purification methods and the growing threat of antibiotic-resistant bacteria led to vancomycin’s resurgence in clinical practice by the 1980s. Today, it remains a vital tool in the fight against serious infections, often recommended as a first-line treatment before the specific infecting bacteria is identified.

Historical Context of Vancomycin Use

The history of vancomycin illustrates the delicate balance between therapeutic efficacy and potential side effects in antibiotic development. Why did vancomycin’s use decline initially? The early, less pure formulations caused more frequent and severe side effects, making clinicians hesitant to prescribe it when other options were available. However, as purification techniques improved and the threat of antibiotic-resistant bacteria grew, vancomycin’s benefits began to outweigh its risks in many clinical scenarios.

Major Side Effects of Vancomycin

While modern vancomycin formulations are much safer than their predecessors, the drug still carries risks of significant side effects. Understanding these potential adverse reactions is crucial for healthcare providers and patients alike. What are the primary side effects associated with vancomycin use?

• Nephrotoxicity (kidney damage)
• Ototoxicity (hearing loss)
• “Red man” or “red person” syndrome
• Allergic reactions
• Hematological effects (e.g., neutropenia, eosinophilia)
• Vasculitis or phlebitis
• Gastrointestinal discomfort

It’s important to note that many of these side effects are dose-dependent rather than true allergic reactions, emphasizing the critical need for proper dosing and monitoring during vancomycin therapy.

Nephrotoxicity: Vancomycin’s Impact on Kidney Function

One of the most significant concerns with vancomycin use is its potential to cause kidney damage, particularly in high doses. How does vancomycin affect kidney function? The drug is primarily cleared by the kidneys, and in excessive amounts, it can lead to acute kidney injury (AKI). This risk necessitates careful monitoring of kidney function throughout treatment.

Monitoring Kidney Function During Vancomycin Therapy

Clinicians use serum creatinine levels as a key indicator of kidney function. Creatinine, a byproduct of muscle metabolism, is normally filtered by the kidneys at a consistent rate. How is kidney function assessed during vancomycin treatment? By measuring serum creatinine levels and calculating the glomerular filtration rate (GFR), healthcare providers can track changes in kidney function and adjust vancomycin dosing accordingly.

Red Man Syndrome: A Unique Vancomycin Side Effect

Red man syndrome is a distinctive adverse reaction associated with vancomycin infusion. What causes red man syndrome? This reaction typically occurs when vancomycin is administered too rapidly, leading to histamine release. The syndrome manifests as a rash or flushing, often accompanied by itching and, in severe cases, hypotension and chest pain.

Managing and Preventing Red Man Syndrome

How can red man syndrome be prevented or managed? The primary prevention strategy involves slowing the rate of vancomycin infusion. For patients who have experienced this reaction, premedication with antihistamines may be considered for future doses. In most cases, red man syndrome is not a true allergy and does not preclude future vancomycin use with proper precautions.

Ototoxicity: Vancomycin’s Impact on Hearing

Ototoxicity, or damage to the inner ear structures leading to hearing loss, is another serious potential side effect of vancomycin. How does vancomycin cause ototoxicity? The exact mechanism is not fully understood, but it’s believed to be related to damage to the hair cells in the cochlea. This side effect is particularly concerning because it can be permanent.

Preventing and Monitoring for Ototoxicity

What strategies can be employed to prevent vancomycin-induced ototoxicity? Regular monitoring of vancomycin levels in the blood is crucial, as ototoxicity is more likely to occur with sustained high concentrations. Audiometric testing may be recommended for patients on long-term vancomycin therapy or those with pre-existing hearing issues. Prompt recognition and adjustment of dosing can help mitigate the risk of permanent hearing damage.

Drug Interactions and Vancomycin

Understanding potential drug interactions is crucial for safe and effective vancomycin use. What significant drug interactions occur with vancomycin? Some notable interactions include:

1. Aminoglycosides: Combining vancomycin with aminoglycoside antibiotics can increase the risk of nephrotoxicity and ototoxicity.
2. Loop diuretics: Drugs like furosemide may enhance vancomycin’s ototoxic effects.
3. Anesthetics: Some anesthetics may potentiate the neuromuscular blocking effects when used with vancomycin.
4. Piperacillin-tazobactam: This combination may increase the risk of acute kidney injury.

How are these interactions managed in clinical practice? Careful monitoring, dose adjustments, and in some cases, avoiding concurrent use are strategies employed to minimize risks associated with these interactions.

Optimizing Vancomycin Dosing and Administration

Given the potential for serious side effects, proper dosing of vancomycin is critical. How is vancomycin dosing determined for patients? Several factors influence dosing decisions:

• Patient’s weight
• Kidney function
• Site and severity of infection
• Minimum inhibitory concentration (MIC) of the infecting organism

Modern approaches to vancomycin dosing often involve therapeutic drug monitoring, where blood levels of the drug are measured to ensure they remain within a therapeutic and safe range.

Continuous vs. Intermittent Infusion

What are the different methods of administering vancomycin? Traditionally, vancomycin has been given as intermittent infusions, typically every 8-12 hours. However, continuous infusion has gained attention as a potential alternative. How does continuous infusion compare to intermittent dosing? Some studies suggest that continuous infusion may lead to more stable drug levels and potentially reduce the risk of nephrotoxicity, though more research is needed to definitively establish its benefits.

Clinical Indications for Vancomycin Use

Despite its potential side effects, vancomycin remains a crucial antibiotic in modern medicine. When is vancomycin used as a first-line antibiotic treatment? Common indications include:

• Methicillin-resistant Staphylococcus aureus (MRSA) infections
• Severe skin and soft tissue infections
• Complicated bloodstream infections
• Endocarditis
• Meningitis caused by resistant organisms
• Clostridioides difficile infections (oral vancomycin)

In many cases, vancomycin is initiated empirically when MRSA or other resistant gram-positive bacteria are suspected, pending culture results.

Vancomycin in the Era of Antibiotic Resistance

How has the role of vancomycin evolved in the face of growing antibiotic resistance? As resistance to other antibiotics has increased, vancomycin has become an increasingly important tool in treating serious infections. However, the emergence of vancomycin-resistant enterococci (VRE) and vancomycin-intermediate Staphylococcus aureus (VISA) has highlighted the need for judicious use and ongoing development of new antibiotics.

In conclusion, vancomycin remains a vital antibiotic in the treatment of severe bacterial infections, particularly those caused by resistant organisms. While its side effect profile requires careful consideration and monitoring, proper dosing and administration can mitigate many of these risks. As antibiotic resistance continues to pose challenges in healthcare, understanding the benefits and risks of drugs like vancomycin is crucial for optimal patient care.

Gender differences in antibiotic prescribing in the community: a systematic review and meta-analysis

Objectives:

Determinants of inappropriate antibiotic prescription in the community are not clearly defined. The objective of this study was to perform a systematic review and meta-analysis evaluating gender differences in antibiotic prescribing in primary care.

Methods:

All studies analysing antibiotic prescription in primary care were eligible. PubMed and MEDLINE entries with publication dates from 1976 until December 2013 were searched. The primary outcomes were the incidence rate ratio (IRR) (measured as DDD/1000 inhabitants/day) and the prevalence rate ratio (PRR) (measured as prevalence rate/1000 inhabitants) of antimicrobial prescription, stratified by gender, age and antibiotic class. Random-effects estimates of the IRR and PRR and standard deviations were calculated.

Results:

Overall, 576 articles were reviewed. Eleven studies, comprising a total of 44 333 839 individuals, were included. The studies used data from prospective national (five studies) or regional (six studies) surveillance of community pharmacy, insurance or national healthcare systems. Women were 27% (PRR 1.27 ± 0.12) more likely than men to receive an antibiotic prescription in their lifetimes. The amount of antibiotics prescribed to women was 36% (IRR 1.36 ± 0.11) higher than that prescribed for men in the 16 to 34 years age group and 40% (IRR 1.40 ± 0.03) greater in the 35 to 54 years age group. In particular, the amounts of cephalosporins and macrolides prescribed to women were 44% (IRR 1.44 ± 0.30) and 32% (IRR 1.32 ± 0.15) higher, respectively, than those prescribed for men.

Conclusions:

This meta-analysis shows that women in the 16 to 54 years age group receive a significantly higher number of prescriptions of cephalosporins and macrolides in primary care than men do. Prospective studies are needed to address reasons for gender inequality in prescription and to determine whether a difference in adverse events, including resistance development, also occurs.

Vancomycin Side Effects – Adverse Effects, Drug Interactions, Dosages, Treatment and More

Vancomycin (brand name: Vancocin®) is an antibiotic that can be used for multiple severe bacterial infections. When first approved by the FDA in the 1950’s, vancomycin was less pure than it is today¹, resulting in a higher risk of side effects.

Even though the medication was effective against drug resistant bacteria, the side effects of vancomycin and the availability of other FDA approved drugs made its use much less common.

Over time, the methods used to purify vancomycin improved and the risk of drug-resistant bacteria grew substantially

By the 1980s, vancomycin became a mainstay in clinical practice.¹

To this day, multiple treatment guidelines recommend vancomycin as one of the first antibiotics that should be started in patients with severe infections before the infecting bacteria has been identified.²

Even with a decreased risk of side effects due to improved manufacturing, clinicians must make sure that the patient is receiving just the right amount of vancomycin.

The balance of treating the patient’s serious infection while making sure they do not receive too much medication is delicate, as side effects of too much vancomycin can be dangerous.

Vancomycin side effects include the following³:

• Kidney damage (nephrotoxicity)
• Hearing loss (ototoxicity)
• “Red man” or “red person” syndrome
• Other less common side effects such as:
  • allergic reactions: hives, difficulty breathing or wheezing
  • Low white blood cells (neutropenia) or high eosinophil counts (eosinophilia)
  • Blood vessel inflammation (vasculitis or phlebitis) 
  • Stomach pain, muscle pain, abdominal pain, or back pain 

An important caveat when reviewing these side effects is that they are not all allergic reactions, but instead a normal occurrence in patients receiving too much vancomycin, or an infusion given too rapidly.         

Kidney Damage

Vancomycin is cleared primarily in the kidneys.

In large amounts, vancomycin can cause kidney problems such as acute kidney injury (AKI).

To calculate kidney function, clinicians collect a serum creatinine value. Creatinine is produced when muscles are broken down.

When this muscle byproduct reaches the kidney, it flows freely into the urine at a specific rate called the creatinine clearance.⁴

The creatinine clearance is then used to estimate how frequently vancomycin and other medications that are cleared by the kidney should be given to the patient.

Since this calculation relies on muscle breakdown, patients with a very high muscle mass can give the illusion that they have poor kidney function, as they have more circulating creatinine.

Likewise, patients with a low muscle mass can appear to have much more efficient kidneys.

This difference in clearance from patient to patient highlights the need for an accurate representation of the patient’s vancomycin level to prevent acute kidney injury.

There are multiple definitions of AKI that exist.

In the 2020 vancomycin consensus guidelines,⁵ AKI is defined as the following:

• An increase in serum creatinine of > 0.5 mg/dL or
• A 50% increase from baseline in two consecutive daily readings, or
• A decrease in calculated creatinine clearance of 50% from baseline on two consecutive days in the absence of an alternative explanation.

Another definition of AKI used in the literature comes from the international acute kidney injury guidelines published by the Kidney Disease Improving Global Outcomes (KDIGO) organization.⁶

The KDIGO guidelines define AKI as a 0.3 mg/dL or greater increase in the patient’s serum creatinine within 48 hours of a previous serum creatinine lab draw.

Some researchers will use the same definition as the 2020 vancomycin consensus guidelines to detect AKI, and others will use the KDIGO definitions.

There are also some studies that will include patients who have other reasons for having kidney damage, such as other medications or chronic medical conditions.

The different ways acute kidney injury from vancomycin is studied is the most likely reason for such a range in AKI reports.

Prescription drugs, medical conditions, and patient characteristics that increase the risk of AKI when combined with vancomycin include but are not limited to the following^7-11:

Medications 

• Acyclovir
• Amikacin
• Amphotericin B
• Gentamicin
• Loop diuretics (i.e., furosemide, torsemide)
• Piperacillin-tazobactam
• Tobramycin

Medical conditions

• AIDS
• Cancer
• Chronic kidney disease
• Diabetes
• Heart diseases
• Muscle wasting diseases such as cerebral palsy or amyotrophic lateral sclerosis (ALS)
• Severely high or low blood pressure

Patient characteristics

• Advanced age  
• Amputation of one or more limbs
• Very high or low body weight

The way that vancomycin causes acute kidney injury is not well understood.

In animal studies, vancomycin has been associated with an increase in free radicals causing inflammation in the kidneys.

In most patients, kidney damage caused by vancomycin is reversible and the kidneys recover on their own after the medication is stopped.

In severe cases of kidney injury where vancomycin therapy is not adjusted, patients may need dialysis.

Human studies evaluating how the kidneys are damaged from vancomycin use are limited as most cases resolve without requiring kidney biopsy.

Without a strong understanding of how vancomycin causes kidney injury, predicting which patients may experience this side effect can be challenging.

Rates of acute kidney injury in patients who receive vancomycin range from 5-7% all the way up to over 40%.⁷

Without the addition of medications that cause drug interactions or medical conditions that increase the risk of kidney damage, AKI from vancomycin is much less likely.

It is also easier to predict who might experience AKI by testing the amount of vancomycin in the patient’s blood.

Testing vancomycin levels was recommended in the 2009 vancomycin consensus guidelines.¹²

In 2009, the most accurate way to predict if the patient had safe and effective levels of vancomycin in their blood was by using collected levels to calculate the vancomycin area-under-the-curve (AUC).

The AUC measures the exposure of the drug in the body to the infecting bacteria. Calculating the AUC was considered to be time-consuming in 2009 when the guidelines were written.

Instead, the 2009 vancomycin consensus guidelines recommended that the trough level could be used in place of the AUC.

Trough levels are collected when the drug concentration is at its lowest in the blood, which is right before the next scheduled dose.

By assuring that the trough stayed above a minimum level, it was assumed that the AUC was also within range.

Unfortunately, this practice led to AUC levels that were often above or below the range needed to treat the patient’s infection safely and effectively.

Between 2009 and 2020, software programs that could easily estimate the AUC became commercially available.

Through direct AUC estimation, it was found that the rate of AKI could be decreased by roughly 50% compared to using trough levels.¹³

In 2020, the vancomycin consensus guidelines recommended AUC monitoring instead of trough-only monitoring and specifically highlighted the capabilities of software programs to perform these calculations.

Hearing Loss

When vancomycin was first brought to market, impurities in the drug were believed to increase the patient’s risk of hearing problems.

This occurrence was more common if vancomycin drug levels in the patient were maintained over twice as high than is currently recommended for therapeutic use.¹⁰

Most of the evidence that vancomycin may cause hearing loss is from studies conducted decades prior.

To this extent, vancomycin induced hearing loss remains very rare and controversial.

Animal models have not identified this side effect with today’s version of vancomycin, supporting that the impurities previously present in the drug may have been to blame.

When combined with other medications that are known to cause hearing loss in high doses, there is a theoretical risk that vancomycin may contribute to this side effect.

Interestingly, some of the same medications that increase the risk of kidney damage have also been found to contribute to hearing loss.

Specifically, the aminoglycosides such as tobramycin, gentamicin, and amikacin were highlighted in the 2009 vancomycin consensus guidelines as medications that may potentially increase this risk.

Without the combination of one or more added drugs that can cause hearing loss, the 2009 vancomycin guidelines did not recommend monitoring for this side effect.

Thus, monitoring for hearing loss is not common practice.

In the 2020 vancomycin consensus guidelines, routine evaluation of the patient’s hearing before, during, and after vancomycin therapy is not recommended.

Red Man Syndrome

Red man syndrome is a hypersensitivity reaction.

It is also known as red person syndrome, and it is the most common hypersensitivity reaction associated with vancomycin. 

Red man syndrome should not be confused with a drug allergy. In some patients, administration of vancomycin too quickly can cause itching and a rash.

The rash seen in red man syndrome is commonly on the face, neck, chest, and upper arms.

Patients may also experience flu-like symptoms.

In most cases, this adverse reaction is mild in nature and resolves when the infusion is stopped or slowed.

The appearance and symptoms of red man syndrome can be summarized as follows:

• Itchy, red skin rash on the face, neck, chest, and upper arms
• Dizziness
• Agitation
• Chills
• Fever
• In severe cases, chest pain, swelling of the lips and face, and shortness of breath

Red man syndrome is caused by a histamine response to the active ingredient.

This means that antihistamines such as diphenhydramine can be used to decrease the effects of red man syndrome.

This reaction is more common when vancomycin is administered more quickly.

Knowing this risk, vancomycin is commonly given at a rate of 60 minutes per gram of drug or longer.

In patients with known or suspected red man syndrome, infusion rates are cut in half (i.e., 120 minutes per gram of vancomycin) and patients are sometimes pre-treated with antihistamines.

Some patients seem to be more likely than others to experience this side effect.

Currently, there is no reliable method of identifying which patients may experience red man syndrome prior to receiving vancomycin.

The odds of having this infusion reaction also ranges considerably from as low as 3.7% to as high as 47% of patients who receive the drug.

On occasion, red man syndrome can be delayed and present near the end of a vancomycin infusion in patients who have received the drug for at least 7 days.

Summary

As with any medication, vancomycin has side effects that require consideration of the risks and benefits of using the drug. Some of these side effects include:

• Kidney damage, which requires very close monitoring of drug levels and changes in risk based on the patient’s characteristics, disease states, and other medications
• Hearing loss, which is very rare with today’s version of the drug, but may still be possible when combined with other medications that can cause hearing damage
• “Red man” or “red person” syndrome, which is related to the rate of the infusion of the drug and is easily reversible by decreasing the rate and pre-treatment with antihistamines

In practice, close monitoring of vancomycin can prevent or decrease the severity of these side effects.

With the help of precision dosing software such as provided by DoseMeRx, clinicians can make sure that their patients have just the right amount of vancomycin to treat their infection while decreasing their risk of some of these adverse effects.

About the author:

Brandon Reynolds, Pharm.D., BCPS
Clinical Pharmacist
Learn More

Related Articles

Intravenous Vancomycin

References

1. Levine, DP. Vancomycin: A History. Clin Infect Dis. 2006;42:S5-S12.
2. Liu C, Bayer A, Cosgrove S et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011; 52(3):e18-e55
3. Patel S, Preuss CV, Bernice F. Vancomycin. StatPearls [Internet]. Last update Feb 2020.
4. Shahbaz H, Gupta M. Creatinine clearance. StatPearls [Internet]. Last update July 2019.
5. Rybak MJ, Le J, Lodise T, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.  Am J Health-Syst Pharm. 2020; 77(11):835-864.
6. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2:1–138.
7. Bamgbola O. Review of vancomycin-induced renal toxicity: an update. Ther Adv Endocrinol Metab. 2016; 7(3):136-147
8. Sivagnanam S, Deleu D. Red man syndrome. Crit Care. 2003; 7(2):119-120
9. Cappelletty D, Jablonski A, Jung R. Risk factors for acute kidney injury in adult patients receiving vancomycin. Clin Drug Investig. 2014; 34(3):189-193
10. Brummett RE, Fox KE. Vancomycin- and erythromycin-induced hearing loss in humans. Antimicrob Agents Chemother. 1989; 33(6):791-796
11. Farooqi S, Dickhout J. Major comorbid disease processes associated with the incidence of acute kidney injury. World J Nephrol. 2016; 5(2):139-146
12. Rybak MJ, Lomaestro BM, Rotscahfer JC, et al.  Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists.Clin Infect Dis. 2009; 49(3):325-327
13. Finch N, Zasowski E, Murray K, et al. A quasi-experiment to study the impact of vancomycin area-under-the-concentration-time curve-guided dosing on vancomycin-associated nephrotoxicity. Antimicrob Agents Chemother. 2017; 61(12):e01293-17

The Pros and Cons of Antibiotics

When it comes to antibiotics, can too much of a good thing be harmful?

Antibiotics are powerful drugs that help our bodies ward off diseases caused by bacteria. When used appropriately, they quickly and effectively eliminate infections, causing us to feel better in a matter of days. However, when used to treat other health conditions, antibiotics are not only ineffective but can be harmful to our overall health.

According to a growing body of research, the more we take antibiotics to cure bacterial infections, the more our bodies build resistance, which wipes out their effectiveness in making us well.

How do you know when they will work?

Antibiotics fight bacteria that cause strep throat and ear, sinus and urinary infections. They do not work for the flu, colds, coughs and sore throats. Consult with your doctor about your symptoms, which can help determine the origin of your illness. Ask your doctor about the benefits and drawbacks of taking antibiotics for your diagnosis.

Following are a few pros and cons of taking antibiotics:

Pros of taking antibiotics

• Antibiotics can slow the growth of and kill many types of infection.
• In some cases, such as before surgery, antibiotics can prevent infection from occurring.
• Antibiotics are fast-acting; some will begin working within a few hours.
• They are easy to take: Most antibiotics are oral medications. Your doctor may decide to give you an injection, if it is imperative that the medicine gets into your system quickly.

Cons of taking antibiotics

• If you take antibiotics often, your body can build a resistance to antibiotic drugs, which could cause antibiotics to become less effective.
• The longer the course of treatment for an antibiotic, the more damage that can be done to the body’s immune system.
• Some antibiotics can have side effects, from digestive issues to bone damage to sensitivity to sunlight. Make sure to read the fine print that comes with your medicine, so that you know the risks.

“Inappropriate use of antibiotics is creating a huge threat to the health of our communities,” says Jennifer R. Boozer, DO, clinical assistant professor of family medicine (clinician educator) at the Keck School of Medicine of USC. By taking antibiotics when we do not need them, we increase the chances of bacteria becoming resistant to the medication and then, when we really need it, those antibiotics will not be effective. This can lead to an increase in hospitalizations, due to the need for IV antibiotics, or even increased chances of death.

“It is important that you protect yourself and your family, by only taking antibiotics that are prescribed to you, when your doctor advises you to do so,” expresses Boozer, who is also a family medicine physician at Keck Medicine of USC. “Sharing antibiotics or taking leftover medications from a previous illness is never advised.”

Rules to follow to avoid misuse

• Do not take somebody else’s antibiotics.
• Any prescribed antibiotic should be finished without any being left over.

Also, be aware that colds are viral, and antibiotics are not going to help.

by Heidi Tyline King

Unsure about the right course of action for your condition? Reach out to a Keck Medicine professional for help. To consult with one of our specialists, call (800) USC-CARE (800-872-2273) or visit www.keckmedicine.org/request-an-appointment to make an appointment.

Cutaneous adverse reactions to antibiotics

Author: Dr Aarthy Uthayakumar, Core Medical Trainee, University College Hospital London, London, United Kingdom. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell/Maria McGivern. March 2018.

What are antibiotics?      

Antibiotics are drugs used to treat bacterial infections.

• They are mainly derived from soil bacteria and fungi, but there are also semi-synthetic and synthetic varieties of antibiotics that are made purely in a laboratory.
• They have several different mechanisms of action, allowing them to be bacteriostatic (inhibit or stop bacterial growth) or bactericidal (kill bacteria).

What is an adverse drug reaction?

An adverse drug reaction (ADR) is an unintended response to a drug at doses normally used for disease therapy. Cutaneous ADRs are ADRs affecting the skin.

Cutaneous adverse reactions to antibiotics

Who gets adverse drug reactions?

Adverse drug reactions are common, particularly in hospital inpatients, with estimates of 2–3% of hospitalised patients experiencing an ADR, and one in 20 of them being potentially fatal. [1,2].  

Cutaneous ADRs account for 10–30% of ADRs, and are most commonly due to antibiotics [1]. The reactions can vary in severity; most are mild-to-moderate, but severe reactions are estimated to occur in 0.1–2% of cases [2]. 

How are adverse drug reactions classified?

Adverse drug reactions can be classified as either non-immunological or immunological.

• The majority of ADRs are non-immunologically mediated.
• The reactions are often predictable pharmacological side effects.
• Dose-related ADRs may be due to underlying renal or hepatic disease.
• The ADRs can also be unpredictable and idiosyncratic.
• They can occur on a single occasion or on every occasion the drug is prescribed.

Non-immunological adverse drug reactions

Non-immunological ADRs caused by antibiotics include:

Antibiotic-induced cutaneous infections

Immunological adverse drug reactions

There are four main types of immunologically mediated hypersensitivity or allergic responses to drugs. These immunological ADRs make up approximately 20% of ADRs [3].

• Type I hypersensitivity reaction is an immediate hypersensitivity reaction to a drug and occurs within minutes to hours, due to pre-formed antigen-specific immunoglobulin (Ig) E antibodies and mast-cell degranulation. This type of reaction results in anaphylaxis, angioedema, and drug-induced urticaria due to rapid vasodilation and increased vascular permeability.
• Type II sensitivity reaction is less common and is due to the development of specific antibodies to the drug, resulting in stimulation or inhibition of immune pathways.  
• Type III hypersensitivity reaction results from drug and antibody immune complexities deposited in tissues (eg, cutaneous vasculitis, deposition and subsequent complement activation in the blood vessels of the skin leads to palpable purpura). Type III reactions can occur 1–3 weeks after exposure.
• Type IV hypersensitivity reactions or cell-mediated delayed responses to drugs develop over several hours. They are caused by immune T-cell responses and release of cytokines. Most severe cutaneous adverse reactions are Type IV reactions.

Severe ADRs to some antibiotics, such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) due to sulphonamides, are caused by complex immunological mechanisms [3].

How are cutaneous drug reactions classified?

Rashes due to antibiotics are most often morbilliform (exanthematous) or urticarial [1].

It usually takes 7–10 days to become allergic to a drug, so if a reaction is rapid, it is either non-immunological, or it is due to a previous encounter with the same drug or a chemically similar substance [4].

Morbilliform eruption

• Morbilliform eruption is the most common type of antibiotic rash. It is also called an exanthem.
• The exact pathogenesis is unclear. Some morbilliform eruptions do not recur when the patient is re-exposed to the causative drug.
• Many antibiotics cause morbilliform eruptions.
• A morbilliform rash usually starts within 7–14 days of starting a new antibiotic, and lasts for 5–10 days [4,5]. It may occur more quickly on re-exposure to the same drug.
• It can look similar to a viral exanthem but is usually pruritic, whereas similar viral rashes are not particularly itchy.
• The morphology consists of fine pink macules or papules; hence, it is sometimes called a maculopapular eruption.
• The rash starts as a relatively symmetrical, but often widespread, eruption on the trunk and progresses to involve the proximal limbs and then the distal limbs.
• There is no mucosal involvement.
• The rash may be more prominent on pressure-bearing points.
• Systemic features may include fever and leukocytosis or lymphopenia (reduced lymphocytes) on blood testing [5].
  

Acute urticaria

• Acute urticaria is the second most common form of cutaneous drug reaction (see Drug-induced urticaria).
• Many antibiotics can cause urticaria.
• Urticaria presents as pruritic, pale, or erythematous weals.
• Individual weals last less than 24 hours.
• The most common antibiotics causing urticaria are beta-lactams, sulfonamides, and tetracyclines [1].

Adverse cutaneous reactions to antibiotics

Several other ADRs affecting the skin can be due to antibiotics and are listed below alphabetically.

Acneform rash

Acute generalised exanthematous pustulosis

• Acute generalised exanthematous pustulosis (AGEP) is a rare reaction where sterile, superficial, small pustules, 1–2 mm in diameter, develop in areas of extensive erythema.
• AGEP is most often caused by beta-lactams, sulfonamides and tetracyclines.
• It usually develops within 1–2 days of starting a new drug.  
• Pustules are followed by desquamation, with healing after approximately two weeks.
• Internal organ involvement is rare [6].

Angioedema and anaphylaxis 

• Angioedema, anaphylaxis and urticaria in combination are due to an immediate Type-I hypersensitivity reaction.
• Antibiotics are the most frequent drug cause.
• These reactions are characterised by widespread vasodilation and increased vascular permeability, and subsequent deep soft tissue swelling, hypotension, and airway obstruction.
• Anaphylaxis is a life-threatening medical emergency. Angioedema can also be life-threatening due to airway involvement and can be persistent [1,4,6].

Drug hypersensitivity syndrome

• Drug hypersensitivity syndrome (DHS) is also known as ‘drug reaction with eosinophilia and systemic symptoms (DRESS)’.
• Antibiotic causes include sulfonamides and, less often, fluoroquinolones and minocycline.

DHS is a rare, life-threatening syndrome typically defined by the triad of fever, skin eruption, and internal organ involvement [7].

• It usually begins 2–6 weeks after drug exposure.
• There is usually a widespread morbilliform rash, high fever, lymphadenopathy, haematological abnormalities, and internal organ involvement, such as hepatitis [6].

Severe cutaneous reactions to antibiotics

Drug-induced pemphigus

• Drug-induced pemphigus is caused due to autoantibodies reacting with desmogleins.
• Antibiotic causes of pemphigus include penicillin, cephalosporin and vancomycin.
• Blistering may resolve after drug withdrawal, but more often persists with the same natural history as non-drug-associated pemphigus [4].
  

Erythema multiforme

• Erythema multiforme (EM) is characterised by target lesions: these are darker in the centre, paler peripherally, with concentric rings of erythema [4].
  
• It is classified into EM minor and EM major (in which there is mucosal involvement).
• EM is most commonly caused by infection, especially by herpes simplex virus.
• Some cases of EM due to antibiotics have been reported. Causative antibiotics include sulfonamides and penicillins.
• Note that EM is a different reaction to SJS/TEN (see below), but these diseases were originally thought to be due to the same immunological process.

Fixed drug eruption

• Fixed drug eruption presents as one or more localised skin lesions that recur with repeated drug exposure in the same location.
• It may be caused by tetracycline antibiotics, trimethoprim + sulphamethoxazole, amoxicillin, ciprofloxacin, clarithromycin, and others; antibiotics in meat have also been incriminated.
• Lesions usually appear 1–2 weeks after the first exposure, and within hours or a few days on subsequent exposure [1].
• Lesions have a predilection for the face, lips, genitalia, and buttocks, although they can appear anywhere.
• The fixed drug eruption starts an erythematous macule and progresses over a few days to form a blistered plaque.
• The rash may itch or cause a burning sensation.

Hypersensitivity vasculitis

• The hallmark of hypersensitivity vasculitis is palpable purpura (ie, through papules, plaques, bullae, and erosions/ulcers).
• Beta-lactam and sulfonamide antibiotics are the most common group of drugs to cause vasculitis.
• Palpable purpura most commonly affects the lower legs but may become widespread.
• The interval from exposure to the causative drug to the onset of rash ranges from days to weeks.
• Serum sickness-like reaction is a form of hypersensitivity vasculitis with specific skin features: erythema on the sides of fingers, hands, and toes, followed by a more widespread morbilliform or urticarial eruption [1]. The rash usually occurs two weeks after exposure to the causative drug, accompanied by a low-grade fever and arthralgia.
• Complement levels are low in drug-induced hypersensitivity vasculitis [6].

Blistering adverse reactions to antibiotics

Photosensitive reactions 

Stevens–Johnson syndrome / toxic epidermal necrolysis

• SJS/TEN is a serious, potentially fatal, systemic mucocutaneous reaction that is nearly always caused by a drug.
• The most common antibiotics known to cause SJS/TEN are sulfonamides and penicillins, but this reaction has also been reported with many other antibiotics.
• SJS/TEN occurs 4–28 days after the start of drug treatment [8].
  
• Management is supportive, and the patient’s SCORTEN score can be used to predict morbidity and mortality [6].
  

Symmetrical drug-related intertriginous and flexural exanthem (SDRIFE) 

What is the differential diagnosis for antibiotic reactions?

It is sometimes difficult to determine whether an antibiotic has caused a rash. Drugs are rarely deliberately given to the affected patient again, as re-challenge has the potential to cause a life-threatening response in some cases. This means the true incidence of ADRs is difficult to calculate.

There are important differential diagnoses to consider when examining a suspected cutaneous drug reaction; these include [9]:

Classification of antibiotics causing cutaneous adverse drug reactions

A large number of antibiotics have the potential to cause cutaneous drug reactions.  

Beta-lactams

The four classes of beta-lactam antibiotics are penicillins, cephalosporins, carbapenems, and monolactams. Allergic reactions to beta-lactam antibiotics are the most common cause of immunological ADRs. This is thought to be due to the structure of beta-lactams. IgG antibodies to penicillin can be detected in allergic patients and non-allergic patients taking penicillin [10,11].

There is some cross-reactivity between penicillins and cephalosporins. If a patient has an anaphylactic response to penicillins, cephalosporins should be avoided.  

Cutaneous ADRs caused by beta-lactams include:

Though structurally similar, carbapenems can usually be safely used in patients with anaphylactoid reactions to penicillin. The major non-cutaneous side effects of beta-lactam use are diarrhoea, increased Clostridium (Clostridioides) difficile, and drug-induced liver injury, particularly due to clavulanic acid/amoxicillin.

Macrolides

In comparison to most other antibiotics, macrolides are considered relatively safe drugs.

• Their side effects tend to be due to interactions with other drugs, due to their inhibition of the cytochrome p450 system.
• Reports of morbilliform and urticarial rashes, and rarely SJS/TEN, have been reported with macrolides [6,14].
  
• Other non-cutaneous reactions with macrolides include QT prolongation (delayed heart ventricular response) and liver injury.

Tetracyclines

Tetracycline antibiotics are frequently used in dermatology. Possible cutaneous reactions include:

Fluoroquinolones

Several older generation fluoroquinolones have been withdrawn from the market due to severe adverse reactions including photosensitivity [17].

Side effects of current-generation quinolones include tendinopathy and QT prolongation. Common cutaneous reactions include:

• Hypersensitivity vasculitis 
• Serum sickness-like reaction
• Morbilliform or urticarial rashes occurs in < 0.5–2% of cases [1]; they happen most commonly with ciprofloxacin (1%) and levofloxacin (0. 3%) [1,15]
  
• Fluoroquinolone photosensitivity can vary in severity, due to how they are altered by light (photodegradability) of the different fluoroquinolones; the most severe reactions are reported with lomefloxacin, with ciprofloxacin causing a mild reaction, and levofloxacin and gemifloxacin are unlikely to cause photosensitivity [1].
  
• AGEP [8]
  
• SJS/TEN [13].
  

Sulfonamides

Co-trimoxazole is a sulfonamide antibiotic commonly used in immunocompromised individuals, who are already more at risk of ADRs. The most frequent ADRs are morbilliform or urticarial rash; however, serious ADRs can result, most commonly SJS/TEN [16]. Observed cutaneous drug reactions with sulfonamides include:

Non-cutaneous reactions with sulfonamides include thrombocytopenia, anaemia, and electrolyte abnormalities [4].

Glycopeptides

• ‘Red man’ syndrome is a histamine-mediated reaction to the rapid infusion of vancomycin and is not an allergic reaction. This reaction can be minimised by administering the drug slowly when given intravenously [12].
  
• Drug hypersensitivity syndrome is also seen with glycopeptides [5,13].
  
• Non-cutaneous adverse reactions include thrombocytopenia [5].
  

Other antibiotics

How are antibiotic reactions diagnosed?

It is essential to take a careful history in the diagnosis of cutaneous drug reactions. Many affected patients have been taking several drugs. In these cases, it helps to form a timeline, including the initiation of any new drugs and the rash onset.

Sometimes, a skin biopsy will be taken to clarify the inflammatory pattern. The presence of eosinophils can be a helpful clue of an underlying drug cause but is non-specific.

Skin testing is sometimes undertaken, especially for penicillin [18].

What is the treatment for antibiotic reactions?

The first principle of management is the withdrawal of the causative drug.

Other measures include:

Conclusion

Antibiotics are one of the most significant discoveries in medicine, but they are not without complications.

Cutaneous side effects are commonly experienced and have the potential to be life-threatening, especially in at-risk groups. Among the classes, penicillins, cephalosporins, sulfonamides, and fluoroquinolones are the most common causes of cutaneous reactions, particularly severe ones.

Antibiotics could dramatically reduce sexually transmitted infections

The spread of some sexually transmitted infections could potentially be dramatically reduced by instructing people who have had unprotected sex to take antibiotics within 24 hours after the intercourse, a new study suggests.

But such a strategy, which was tested in a population of men who had frequent unprotected sex with a number of male sex partners, could spark a controversy over the use of antibiotics and the general threat of growing antibiotic resistance.

“My message with that study would be that we need to do more research to prevent STIs — because that’s a concern. And this strategy … could potentially be used,” said Dr. Jean-Michel Molina, head of infectious diseases at Saint-Louis Hospital in Paris and the lead author of the study.

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Molina insisted he would never support long-term use of antibiotics to prevent STIs, but said that the approach might be an effective short-term strategy when paired with other control approaches, like more frequent STI testing among high-risk populations.

“I don’t want this strategy to be used widely in any person, clearly,” Molina said. “But if you can select a group with a high incidence rate of syphilis or chlamydia, and you want to try to reduce the rate of syphilis quite quickly in this group of people, you may think that this strategy could be used for a couple of months.”

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Rates of syphilis in particular have risen steadily in recent years; the rate in 2015-2016 — 8. 7 cases per 100,000 people — was the highest since 1993, the Centers for Disease Control and Prevention reported. The rate of infection increased in every age group over the age of 15, in both men and women, and in all ethnic groups.

Molina’s study was recently published by the journal Lancet Infectious Diseases. The Bill and Melinda Gates Foundation was one of its funders.

The researchers randomly assigned 232 men to one of two groups. One of the groups was given antibiotics — the drug doxycycline — to take if they had unprotected sex. They were told to take two pills per encounter, and no more than six in a week, ideally within 24 hours and no later than 72 hours after the intercourse. In reality, the median use among the men was about 6.8 pills per month.

The men were tested regularly for STIs, and in the nine or so months they were followed, the rates of some sexually transmitted infections fell dramatically in the treatment group. The overall reduction of all STIs was 47 percent, but that average was dragged down by the fact that doxycycline doesn’t cure gonorrhea.

There was, however, a 70 percent reduction in chlamydia infections and cases of syphilis decreased by 73 percent. The authors noted, however, that the study length was short and they can’t tell if the strategy would work as well over the long term.

The results can’t be taken in isolation, others experts warned. Using doxycycline this way could drive the bacteria that cause the infections to develop resistance to the drug, warned Dr. Brad Spellberg, an infectious diseases specialist and chief medical officer at the Los Angeles County-University of Southern California Medical Center in Los Angeles.

Spellberg also said people who used the drug this way would be exposing the bacteria they have in their gastro-intestinal tracts — their own gut flora — to regular doses of doxycycline. And those bacteria too could develop resistance to the drug, leading to a host of other health problems.

“You’re causing friendly fire injury,” he said.

The full picture of the knock-on effects of exposing your gut flora to antibiotics is still coming into focus, said Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics, and Policy and a leading voice on the dangers of mounting antibiotic resistance. He noted a recent report in the journal Science revealed that some cancer immunotherapy drugs worked less well in people who had recently taken antibiotics.

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Molina noted that antibiotic resistance to doxycycline has not been seen in chlamydia or syphilis, despite the fact that the drug has been used to treat these infections for decades. Still, he said the possibility it could arise cannot be discounted.

A commentary published with the study argued that reducing infection rates in men who have sex with men and who are highly sexually active might lower STI infection rates more generally in a community.

Authors Christopher Fairley and Eric Chow, of Australia’s Melbourne Sexual Health Center at Monash University, said pressure from patients to be given doxycycline on a preventative basis might be substantial, given that the drug is also prescribed in six-month courses to treat acne. Like Molina and his co-authors, they said STI preventive use at this point is premature.

Laxminarayan did not dismiss the notion of this type of use out of hand, however. “I certainly think that for a small subset of the population, if this helps prevent syphilis, then it certainly is worth exploring further,” he said.

But he said additional studies should be conducted first to try to get a better picture of the potential consequences of using doxycycline this way, including the risk of resistance developing, the potential that it might further erode condom use, and any other unintended consequences.

When antibiotics turn toxic

Illustration by Oliver Munday

In 2014, Miriam van Staveren went on holiday to the Canary Islands and caught an infection. Her ear and sinuses throbbed, so she went to see the resort doctor, who prescribed a six-day course of the popular antibiotic levofloxacin. Three weeks later, after she had returned home to Amsterdam, her Achilles tendons started to hurt, then her knees and shoulders. She developed shooting pains in her legs and feet, as well as fatigue and depression. “I got sicker and sicker,” she says. “I was in pain all day.” Previously an active tennis player and hiker, the 61-year-old physician could barely walk, and had to climb the stairs on all fours.

Since then, she has seen a variety of medical specialists. Some dismissed her symptoms as psychosomatic. Others suggested diagnoses of fibromyalgia or chronic fatigue syndrome. Van Staveren is in no doubt, however. She’s convinced that the antibiotic poisoned her.

She’s not alone. Levofloxacin is one of a class of drugs called fluoroquinolones, some of the world’s most commonly prescribed antibiotics. In the United States in 2015, doctors doled out 32 million prescriptions for the drugs, making them the country’s fourth-most popular class of antibiotic. But for a small percentage of people, fluoroquinolones have developed a bad reputation. On websites and Facebook groups with names such as Floxie Hope and My Quin Story, thousands of people who have fallen ill after fluoroquinolone treatment gather to share experiences. Many of them describe a devastating and progressive condition, encompassing symptoms ranging from psychiatric and sensory disturbances to problems with muscles, tendons and nerves that continue after people have stopped taking the drugs. They call it being ‘floxed’.

For decades, regulatory agencies and the medical profession were sceptical that a brief course of antibiotics could have such a devastating, long-term impact. But after persistent campaigning by patient groups, attitudes began to change in 2008, when the US Food and Drug Administration (FDA) announced the first of what would be a series of strong alerts about the side effects of fluoroquinolone drugs, including tendon rupture and irreversible nerve damage. In 2016, the agency accepted the existence of a potentially permanent syndrome that it calls fluoroquinolone-associated disability (FQAD), and recommended that the drugs be reserved for serious infections. That move has triggered other regulatory agencies to reassess the antibiotics: Health Canada warned doctors of rare cases of persistent or disabling side effects in January 2017, and the European Medicines Agency (EMA) is expected to publish the results of a safety review this year, after a public hearing planned for June.

Fluoroquinolones are valuable antibiotics, and safe for most people. Yet they are so widely prescribed that their side effects might have harmed hundreds of thousands of people in the United States alone, say scientists who are working with patients to unpick FQAD’s causes. Fluoroquinolone toxicity, they say, provides a compelling example of an emerging understanding that antibiotics don’t just harm microbes — they can severely damage human cells, too. Until recently, investigations into the side effects of antibiotics have focused on how the drugs disrupt the human microbiome, says James Collins, a medical engineer at the Massachusetts Institute of Technology in Cambridge. “Antibiotics are also disrupting our cells, and in pretty hefty ways,” he says.

The dark side of fluoroquinolones

Quinolone antibiotics, first developed in the 1960s, kill bacteria by blocking enzymes called class II topoisomerases, which normally untangle DNA during cell replication. These enzymes usually cut DNA’s double helix, pass another part of the strand through the gap, and then mend the cut. But quinolones bind to the enzymes, preventing them from mending their cuts. In the 1980s, researchers added fluorine atoms to the quinolones’ structures. This allowed the antibiotics to penetrate tissues throughout the body, including the central nervous system, and boosted their effectiveness against a broad range of bacterial infections.

Some FDA-approved fluoroquinolones were swiftly withdrawn from the market after severe adverse reactions and several deaths — trovafloxacin, withdrawn in 1999, damaged livers, for instance. But others became the drug of choice both for serious infections and for routine complaints, despite rare side effects. “These are heavily used drugs because they are very effective,” says Joe Deweese, a biochemist who studies topoisomerases at Lipscomb University College of Pharmacy in Nashville, Tennessee. In the 1990s, ciprofloxacin (cipro) was given to US troops serving in the Persian Gulf as prophylaxis in case of exposure to anthrax spores. And in 2001, sales of cipro surged after a series of terrorist attacks involving anthrax; the US Centers for Disease Control and Prevention (CDC) recommended a 60-day course for anyone at risk of being exposed.

But by that point, some people had already flagged potential problems. In 1998, US journalist Stephen Fried (now at Columbia Journalism School in New York) published a book called Bitter Pills about his wife’s severe and long-lasting neurological reaction to ofloxacin. It helped to trigger a wave of reports on websites such as the Quinolone Antibiotics Adverse Reaction Forum, which by 2001 hosted more than 5,000 posts. The late Jay Cohen, then a psychiatrist and medical researcher at the University of California, San Diego, contacted patients through the sites and published 45 case studies¹. Cohen warned that after taking fluoroquinolones, some people had developed serious problems in multiple organs. These effects came on rapidly and lasted for months or years.

Cohen’s work was largely dismissed at the time because of his reliance on online forums. But complaints and patient petitions continued. From the 1980s to the end of 2015, the FDA received reports from more than 60,000 patients detailing hundreds of thousands of ‘serious adverse events’ associated with the 5 fluoroquinolones still on the market (most commonly tendon rupture, as well as neurological and psychiatric symptoms), including 6,575 reports of deaths. The FDA says that the reports of adverse events it receives — sent in by drug manufacturers, by doctors and directly by consumers — cannot be used to reach conclusions about the severity of problems associated with drugs. Still, the fluoroquinolones have attracted more complaints than other more widely used antibiotics. And only 1–10% of adverse events are estimated to be reported to the FDA, suggesting that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, a haematologist at the University of South Carolina’s College of Pharmacy in Columbia. Bennett is also director of the Southern Network on Adverse Reactions, a state-funded pharmaceutical-safety watchdog, which has been working with people affected by fluoroquinolones since 2010.

In 2008, the FDA announced ‘black box’ warnings of tendon rupture among those given the antibiotics; in 2013, it added a risk of irreversible nerve damage. (Such warnings are placed inside a black box on drug labels, and call attention to serious or life-threatening risks.) As alerts mounted, patients launched lawsuits against manufacturers of the drugs, claiming they had not been adequately informed of risks. These cases have been variously won, lost or settled for undisclosed sums, and many are still in progress; manufacturers argue that they handled risks appropriately, and work with the FDA to update safety labels.

In November 2015, the FDA voted to recognize FQAD as a syndrome on the basis of 178 cases that the agency regarded as clear-cut: otherwise healthy people who took fluoroquinolones for minor ailments and then developed disabling and potentially irreversible conditions². The FDA also noted a disturbing pattern: fluoroquinolones had a much higher percentage of disabilities among their serious-adverse-event reports than did other antibiotics.

Mitochondrial damage

Beatrice Golomb at the University of California, San Diego, has been working for a decade with people affected by fluoroquinolones, beginning with David Melvin, a police officer and keen cyclist who had to use a wheelchair after he was given levofloxacin for suspected epididymitis in 2007. Accumulating evidence, Golomb says, suggests that fluoroquinolones are damaging mitochondria, the power packs inside human cells that evolved from symbiotic, bacteria-like cells billions of years ago. This kind of harm can affect every cell in the body, explaining why a wide range of symptoms can appear and get worse over time.

Mitochondrial toxicity is a problem with many classes of drug, says Mike Murphy, who studies the biology of mitochondria at the University of Cambridge, UK. But because mitochondria retain some similarities to their bacterial ancestors, antibiotics can pose a particular threat to them. Researchers have shown, for example, that aminoglycoside antibiotics can cause deafness by damaging mitochondria in the hair cells of the ear³.

Isolated studies from the 1980s onwards have suggested that fluoroquinolones impair mitochondrial function, but a 2013 study⁴ by Collins and his colleagues is the most convincing, researchers say. They reported that antibiotics in several classes triggered oxidative stress — a build-up of reactive, oxygen-containing molecules — in mitochondria, inhibiting their function across a range of mammalian cells, as well as in mice. “We were surprised at how strong the effect was and how common the effect was across the different classes,” Collins says. But “the largest effects were seen in the quinolones”.

Pharmaceutical researchers had spotted the issue, too: in 2010, toxicologist Yvonne Will and her colleagues at Pfizer in Groton, Connecticut, reported an assay to detect mitochondrial damage early in drug development⁵. They found that some antibiotics affected mitochondria and others didn’t. Every fluoroquinolone they tested damaged mitochondria in human liver cells — having what the researchers described as “a strong effect” at therapeutic concentrations, although Will cautions that it isn’t possible to extrapolate from that result to clinical outcomes.

But the potential for mitochondrial damage still isn’t widely appreciated among antibiotics researchers and the medical community, Collins says. “I think people generally assume that antibiotics do not impact mammalian cells,” he says. One problem is that there is still no reliable biomarker that researchers can use to test for mitochondrial damage in people, tying cell-line research to clinical experience. Nor is it known precisely how the fluoroquinolones are damaging human cells. A 2013 FDA review of the antibiotics’ safety, for example, cited a 1996 study⁶ reporting that cipro caused DNA breaks in mitochondria in a variety of mammalian cell lines. But Neil Osheroff, a biochemist at Vanderbilt University in Nashville, Tennessee, who studies fluoroquinolones, is doubtful about that result. He has done his own lab tests, and found that, at therapeutic concentrations, the fluoroquinolones prescribed by doctors have very little effect on human DNA⁷. Meanwhile, mitochondrial damage isn’t the only theory in play: a 2015 study, done on human kidney cells⁸, reported that fluoroquinolones can bind to iron atoms from the active sites of several enzymes that modify DNA, leading to epigenetic changes that might be related to some of the drugs’ side effects.

At a conference last September, Bennett reported preliminary data that might hint at why only some people develop serious side effects from fluoroquinolones. He took saliva samples from 24 people who reported neuropsychiatric side effects — such as memory loss, panic attacks and depression — and found that 13 of them (57%) shared a gene variant usually seen in only 9% of the population. Bennett is not revealing the gene’s identity because he has a patent application in process, but he says that it seems to be a site related to poor metabolism of the quinolones. Such a mutation might cause dangerously high levels of the drug to accumulate in cells, including in the brain. Bennett is now conducting a trial with 100 more participants to see if he can replicate the result. If so, that might lead to a genetic test to identify people who should not be given the drugs.

Lack of support

Most scientists asked by Nature about fluoroquinolones said that more research is needed to understand their side effects. Collins hopes to explore mitochondrial damage by antibiotics in other animal models. He and Murphy have also found, in lab studies^4,9, that giving antioxidants alongside fluoroquinolones seems to mitigate the effects on mitochondria. Murphy is interested in trials to avoid mitochondrial toxicity in drugs; he owns shares in a company that aims to set some up. But such trials are difficult and expensive, particularly for drugs that are given in sometimes life-threatening situations, he says. Golomb is currently conducting an unfunded online survey to gather information on the experiences of thousands of patients. She hopes that it will lead to hypotheses about what might mitigate harms that could then be tested in clinical trials. But little support is available. That’s typical for research on drug safety. Investigating medications that have been on the market for years isn’t a priority for research agencies such as the US National Institutes of Health, says Bennett. Manufacturers don’t have an incentive to fund post-market safety studies, particularly for off-patent drugs such as cipro and levofloxacin, where the vast majority of sales are from generics firms. “So there is really nobody to champion this work,” says Bennett.

Another factor is scientists’ reluctance to publish results that drug companies might find unfavourable. “There’s a long history of adverse action against people who expose drug and chemical harms,” says Golomb. She cites a list made by the pharmaceutical firm Merck of doctors who criticized the anti-inflammatory drug Vioxx (rofecoxib), which was withdrawn from the market over an increased risk of heart attack and stroke. According to internal e-mails read out in court in 2009 as part of a Vioxx class-action case in Australia, a list e-mailed among Merck employees contained doctors’ names with the labels “neutralize”, “neutralized” or “discredit” next to them. (Merck did not respond to Nature’s request for comment.) Aggressive tactics are “a very big problem”, says Bennett, who says he has been threatened by drug companies in the past.

For Osheroff, there are more-pressing concerns about fluoroquinolones, such as how to combat the emergence of antibiotic-resistant infections and develop new antibiotics. But he and other scientists agree that doctors should not prescribe fluoroquinolones for relatively minor infections when they could use other drugs. The FDA’s warnings on drug labels, however, have been slow to produce results. Prescriptions for the drugs did not fall between 2011 and 2015, according to the CDC (see ‘Overprescribed antibiotics’). This suggests, says Bennett, that official alerts haven’t been enough to get physicians to change their habits. The labels for fluoroquinolones alone have changed around 20 times in the past 4 or 5 years, he says. “It is almost impossible for doctors to keep up.” Still, US prescriptions of fluoroquinolone antibiotics did drop by around 10% in 2016, and totals for the first half of 2017 suggest that prescriptions fell again last year, according to unpublished figures given to Nature by IQVIA, a health-data firm in Durham, North Carolina.

Meanwhile, van Staveren, in Amsterdam, complains that despite her medical training, she still can’t find a doctor who believes her. She is waiting for the EMA to make its recommendations, and hopes that it will follow the FDA in acknowledging FQAD, and warning about it. (The EMA declined to comment while the review is ongoing.) “I want doctors to be informed about the risks, no matter how rare or not they are,” van Staveren says. “I want warnings all over and I want the warnings to be taken seriously.”

Urinary Tract Infection (UTI) in Males Medication: Antibiotics, Analgesics, Urinary

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant S aureus (MRSA), S epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. This agent inhibits bacterial deoxyribonucleic acid (DNA) synthesis and growth. Ciprofloxacin is indicated for urinary tract infections (UTIs) and chronic bacterial prostatitis.

Levofloxacin (Levaquin)

Levofloxacin is a fluoroquinolone with better gram-positive activity but less activity against Pseudomonas aeruginosa than ciprofloxacin. This agent is an active L-isomer of ofloxacin. Ciprofloxacin is indicated for complicated and uncomplicated urinary tract infections. It is also used for the treatment of chronic bacterial prostatitis.

Ofloxacin (Floxin)

Ofloxacin is a pyridine carboxylic acid derivative with broad-spectrum bactericidal effect. In adults aged 18 years or older, the dosing regimen is by the oral or intravenous (PO/IV) route 200-400mg twice daily (bid). Ofloxacin is FDA approved for the treatment of prostatitis due to E coli.

Trimethoprim (Proloprim, Trimpex)

Trimethoprim is a dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. This agent is active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens such as Enterobacteriaceae and Staphylococcus saprophyticus. Resistance is usually mediated by decreased cell permeability or alterations in the amount or structure of dihydrofolate reductase.

Trimethoprim also demonstrates synergy with sulfonamides, potentiating the inhibition of bacterial tetrahydrofolate production.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a combination antimicrobial agent designed to take advantage of synergy between TMP and sulfonamides. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

SMZ inhibits dihydropteroate synthetase, preventing incorporation of para-aminobenzoic acid (PABA) into dihydrofolate and subsequent synthesis of tetrahydrofolate. This agent has broad bacteriostatic activity against aerobic gram-positive and gram-negative organisms, with little activity against anaerobes; unfortunately, SMZ does not penetrate well into the kidney.

Ampicillin (Omnipen, Polycillin, Principen)

Ampicillin is an aminopenicillin beta lactam that impairs cell wall synthesis in actively dividing bacteria by binding to and inhibiting penicillin-binding proteins in the cell wall. This agent has enhanced activity against anaerobes and gram-negative aerobes and is generally used in combination with an aminoglycoside for empiric or directed activity against E faecalis urinary tract infections (UTIs).

Amoxicillin (Moxatag, Trimox)

Amoxicillin is a penicillin antibiotic that interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Gentamicin (Garamycin, Gentacidin)

Gentamicin is a bactericidal aminoglycoside antibiotic that inhibits bacterial protein synthesis by binding to the ribosome. This agent has activity against a variety of aerobic gram-negative bacteria, as well as E faecalis and staphylococcal species, and it is used with or without ampicillin to treat acute prostatitis in the hospitalized patient when Enterococcus is a concern. Gentamicin is the only aminoglycoside with appreciable activity against gram-positive organisms.

The dosing regimens for gentamicin are numerous. Adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. Ideal body weight (IBW) should be used for calculations (the drug is not fat soluble).

Trough serum levels should be monitored to ensure adequate clearance and reduce toxicity (< 2 mcg/mL). Peak levels should also be monitored after 4-5 half-lives when it is dosed more often than once daily (qd).

Once-daily dosing should only be used when treating gram-negative infections, as this takes advantage of its concentration-dependent killing and its postantibiotic effect. However, gentamicin exhibits neither of these properties against gram-positive infections. (For synergy against gram-positive organisms, use 1 mg/kg q8h).

Tobramycin (TOBI)

Tobramycin is an aminoglycoside used for gram-negative bacterial coverage, with better pseudomonal coverage than gentamicin. This agent is commonly used in combination with agents against gram-positive organisms and those that cover anaerobes.

Consider using tobramycin when penicillins or other less-toxic drugs are contraindicated, when bacterial susceptibility tests and clinical judgment indicate its use, and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms. Its dosing regimens are numerous and are adjusted based on the CrCl and changes in the volume of distribution.

Plazomicin (Zemdri)

Semisynthetic aminoglycoside antibacterial derived from sisomicin. Plazomicin has been engineered to overcome aminoglycoside-modifying enzymes (AMEs), the most common aminoglycoside-resistance mechanism in Enterobacteriaceae, and has in vitro activity against extended-spectrum beta-lactamase–producing, aminoglycoside-resistant, and carbapenem-resistant isolates. It is indicated for complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible microorganism(s): E coli, K pneumoniae, P mirabilis, and E cloacae. Limited clinical safety and efficacy data are available; therefore, the prescribing information recommends to reserve treatment for use in patients with cUTI who have limited or no alternative treatment options.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin that has a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more penicillin-binding proteins, this agent arrests bacterial cell wall synthesis and inhibits bacterial growth.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third generation cephalosporin and a bactericidal agent that exerts its effect by inhibiting the enzymes responsible for cell wall synthesis. Caution should be used with this agent, as nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide.

In addition, chloramphenicol has been demonstrated to be antagonistic to beta-lactam antibiotics, including ceftazidime, based on in vitro studies and time kill curves with enteric gram-negative bacilli. Because of the possibility of antagonism in vivo, particularly when bactericidal activity is desired, avoid this drug combination.

Cefiderocol (Fetroja)

Cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of gram-negative pathogens by acting as a siderophore by binding to extracellular free ferric iron. Elicits bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins. It is indicated for complicated UTIs, including pyelonephritis, caused by susceptible gram-negative microorganisms in adults who have limited or no alternative treatment options.

Erythromycin (Erythrocin, Ery-Tab)

Erythromycin is a macrolide antibiotic that inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.

Vancomycin (Firvanq, Vancocin)

Vancomycin is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. It is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. It is used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Doxycycline (Vibramycin, Vibra-Tabs)

Doxycycline is a broad-spectrum, bacteriostatic antibiotic in the tetracycline class. It inhibits protein synthesis and, thus, bacterial growth by binding to the 30S and, possibly, the 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Ertapenem (Invanz)

Ertapenem has bactericidal activity from inhibition of cell wall synthesis, which is mediated through ertapenem binding to penicillin-binding proteins. This agent is stable against hydrolysis by a variety of beta lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta lactamases. Ertapenem is hydrolyzed by metallo–beta lactamases.

Aztreonam (Azactam, Cayston)

Aztreonam is a monobactam that inhibits cell wall synthesis during bacterial growth. It is active against gram-negative bacilli but has very limited gram-positive activity and is not useful against anaerobes. It lacks cross sensitivity with beta-lactam antibiotics, and it may be used in patients allergic to penicillins or cephalosporins.

Nitrofurantoin (Macrodantin, Furadantin)

Nitrofurantoin is a bactericidal antibiotic indicated for acute cystitis and UTIs caused by E coli, enterococci, S aureus, and strains of Klebsiella and Enterobacter species.

Rifampin (Rifadin)

Rifampin is an antituberculosis agent that inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.

Imipenem/cilastatin/relebactam (Recarbrio)

Three-drug combination containing previously approved imipenem/cilastatin and relebactam, a beta-lactamase inhibitor. It is indicated for complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections in adults with limited or no other treatment options. Dosage modifications are necessary for patients who have renal impairment.

90,000 8 side effects of antibiotics that are rarely reported even by doctors

The most common side effects of antibiotics are nausea and diarrhea. Almost everyone knows about them – either from doctors or from their own experience. But American scientists have found that at least 20% of people who have taken antibiotics at least once in their lives have experienced other side effects from the drugs. It is about them that we will talk about in this article.

We are in AdMe.Common crawl en We want to emphasize that different people may experience different side effects from taking medications. You can always find a complete list of them in the instructions for the drug.

1. Sun sensitivity

Certain antibiotics (tetracyclines, fluoroquinolones and sulfones) can affect how your skin reacts to UV radiation. Too much sunlight while taking medication can increase the chance of burns or severe flaking of the skin.

These same antibiotics can cause a rash, even if a person has been in the sun for only 15 minutes.

It is better not to be in the sun between 10:00 and 14:00, use sunscreen and hide your skin under your clothes.

2. Headache or dizziness

Headache and dizziness are two more common complaints from people taking antibiotics. But they usually go away after completion of the course of treatment.

If your head does not hurt much, then you can take pain relievers.If the pain is unbearable, then it is better to see a doctor. Most likely, he will change the antibiotic.

3. Fever

Fever can be a side effect of more than just antibiotics. If it manifested itself against their background, then, , you may have an allergic reaction to the medicine, which is accompanied by fever . If not, it’s a separate and frustrating side effect.

Fever can occur due to almost any antibiotic, but most often it accompanies the intake of beta-lactams, cephalexin, minocycline and sulfonamide.

If you get a fever while taking an antibiotic, it will most likely go away on its own pretty soon. But if the fever is strong and lasts too long, you need to try to bring it down and contact your doctor to change the antibiotic.

4. Fungal infection

Antibiotics change the bacterial environment of our bodies, so a person becomes vulnerable to fungi. They can occur in the mouth (stomatitis), on the skin or under the nails.

If your doctor has prescribed a long course of treatment for you, it is better to start taking anti-fungal drugs immediately along with antibiotics.

5. Heart problems

This is uncommon, but antibiotics can cause heart problems. They usually lead to arrhythmias or low blood pressure.

The most common side effects are erythromycin and some fluoroquinolones such as ciprofloxacin.

Consult a doctor to change the antibiotic.

6. Staining of teeth

Antibiotics of the tetracyclines group can cause staining or discoloration of teeth in children under 8 years old .And if you take them during pregnancy, then there is a great chance that the born baby will have problems with the enamel of the teeth.

Not so long ago, scientists found that the more modern antibiotic doxycycline (from the tetracyclines group) does not bind so strongly to calcium that it does not cause staining of the teeth. Therefore, it can be taken without fear of such consequences. But, of course, only as prescribed by a doctor.

7. Allergy

One of the most dangerous reactions of the body to antibiotics is allergy.In this case, the person may develop an itchy rash, swelling of the eyelids, lips, tongue and even throat, leading to anaphylaxis . Sometimes, in such situations, a dose of adrenaline received in an ambulance can save the patient.

But an allergic reaction to any one antibiotic does not mean that their intake is completely contraindicated for you.

Be sure to inform your doctor about your existing allergies and take another group of antibiotics. Also, be careful when starting a new medication that you have never tried before.At the first symptoms of allergy, you should consult a doctor or an ambulance.

8. Unwanted pregnancy

If you take the antibiotic rifamycin and oral contraceptives at the same time, the effectiveness of the latter is reduced. As a result, the chance of unwanted pregnancy increases. Other antibiotics reduce the effect of oral contraceptives to a lesser extent.

While taking antibiotics and for another week after completing the course, use an additional barrier method of contraception.For more information on the timing of additional protection, see the instructions for oral contraceptives.

If you have any of the side effects while taking antibiotics, do not self-medicate, do not ignore the unwell. Be sure to go to the doctor and consult.

Did you know about any of these side effects of medication?

90,000 What do you need to know before taking antibiotics?

Antibiotics are drugs that kill bacteria.The bacteria can cause infections such as sore throat, ear infections, urinary tract infections, and sinus infections (sinusitis). There are many types of antibiotics. Each works in its own way and acts on different types of bacteria. Your doctor will decide which antibiotic is best for your infection.

Antibiotics work most effectively when you take them exactly as prescribed by your doctor. You should keep taking them even if you feel better. Prescriptions are not written out for a certain period in vain.Healthcare professionals know that certain doses of antibiotics are required over a period of time to kill certain types of bacteria.

What you need to know if you are prescribed antibiotics

• Follow your doctor’s prescription, that is, take the correct dose for the correct period of time. The individually prescribed dose ensures that your antibiotics are at their best. Continue taking the prescribed course of antibiotics even if you feel better after a few days.
• Do not skip doses. Forgetting to take antibiotics can prolong the infection and negatively affect your recovery. If you experience side effects, ask your doctor or pharmacist.
• Do not share your prescribed antibiotics with others. Certain antibiotics have been prescribed for your treatment based on your specific needs.
• Do not dispose of partially used packaging with household waste, as antibiotics can enter the environment (eg contaminate waste water).Do not store antibiotics for other illnesses.

What you need to know if you have not been prescribed antibiotics

• The use of antibiotics is effective only in the treatment of bacterial infections. Some bacterial infections clear up on their own without antibiotics. Your doctor will not prescribe antibiotics until you really need them. Antibiotics do not work for viral infections (such as the flu or colds).
• In many cases, your body’s immune system is strong enough.A healthy body usually fights off simple infections with great efficiency. For example, fever is a sign of an active immune response.
• Improper consumption may cause antibiotic resistance. Some of the existing antibiotics have lost their effectiveness in fighting resistant bacteria. Therefore, the treatment of infectious diseases has become much more difficult or may even end in failure.
• Antibiotics can sometimes cause harmful side effects.If used improperly, the side effects of antibiotics can outweigh the benefits, as antibiotics, for example, can harm and weaken underlying bacteria and even contribute to the development of antibiotic resistance.

What questions should you ask your doctor at the reception

Questions to ask your doctor include:

1. Why do I need antibiotics?
2. What are the side effects of this antibiotic?
3. Is there anything I can do to prevent side effects?
4. How do I take an antibiotic? Do I take it at specific times of the day? Do I take it with food?
5. Will the antibiotic interact with other medications?
6. Does anything happen if I take this along with other medicines, certain foods or alcohol?
7. Do I need to keep antibiotics in the refrigerator? Are there any special storage instructions?

Antibiotics are generally safe.But it’s important to watch out for side effects. Common side effects include nausea, diarrhea, and abdominal pain. In women, antibiotics can cause vaginal yeast infections. In rare cases, antibiotics can cause a dangerous allergic reaction that requires emergency treatment.

If an antibiotic is causing side effects that really bother you, ask your doctor if treatment can help you manage the side effects. Some minor side effects are difficult to prevent, but if they are more serious, discuss them with your doctor.Or ask your doctor if there is another antibiotic that does not cause these effects, but the level of effectiveness in your case will be just as high.

3 rules for taking antibiotics

Three rules for taking antibiotics

Antibiotics

According to scientists, soon antibiotics will not be able to defeat diseases. People abuse them so much that bacteria develop resistance to the drugs used to fight them.How to properly treat with antibacterial agents so as not to harm your body?

Rule # 1: Go to the end

If you started taking antibiotics, you must drink their entire course. Even if after 2-3 days the state of health improves, you cannot stop taking the drug or adjust its dose. Otherwise, bacteria that have not died will adapt to the antibiotic and stop responding to it.

Moreover, they will transmit information to other pathogenic bacteria on how to deal with the antibacterial drug.The result will be multi-resistant bacteria that are not afraid of any antibiotic.

Rule number 2: your friend is water

During the period of taking antibiotics (plus 3 days after the end of the course), you should stop drinking alcohol, because it increases the side effects of the drug: it can cause nausea, dizziness, increased blood pressure and liver damage.

In addition, do not drink tablets with orange, grapefruit and pineapple juices, as well as milk: these drinks change the absorption of the antibiotic and can affect the effectiveness of treatment.

Rule # 3: Take prebiotics

Antibacterial drugs destroy not only bad, but also beneficial bacteria of the intestinal microflora, as well as the microflora of the genital organs. Therefore, it is so important to take prebiotics during and after the course of antibiotics. These are dietary supplements with live microorganisms: they colonize the intestines and return its microflora to its normal state. But it should be remembered that at least 2-3 hours should elapse between taking an antibiotic and a prebiotic.And at the first symptoms of a violation of the flora of the genital organs, start treatment under the supervision of a doctor.

Important: do not prescribe antibiotics yourself, only a doctor can assess the need for them. Uncontrolled use of antibacterial agents can seriously harm your health.

Antibiotics

How to minimize side effects from taking antibiotics

Antibiotics are natural or artificially synthesized substances that can affect the growth and development of bacteria.

Taking antibiotics is a necessary measure in the presence of some serious diseases that threaten human health.

Unfortunately, under the influence of antibiotics, not only pathogenic bacteria die, but also the beneficial microflora of the body. Therefore, the restoration of microflora after a course of antibiotic therapy is mandatory.
Most often antibiotics are prescribed for: pneumonia, tuberculosis, blood infections, acute gastrointestinal infections, postoperative complications, sexually transmitted infections.

Negative consequences of taking antibiotics:
o violation of intestinal microflora: synthetic antibiotics of a broad spectrum of action are aimed at the massive destruction of bacteria, including those necessary for normal human life. Because useful microflora can be restored rather slowly, new pathogenic bacteria and fungi can take its place in the intestine, which leads to a decrease in immunity and increases the risk of developing various chronic diseases;
o malfunctioning of the digestive system: taking antibiotics negatively affects the state of the digestive system due to the lack of enzymes produced by beneficial bacteria.This leads to irritation of the gastric mucosa, and also disrupts the work of the glands of external secretion;
o allergic reactions: individual intolerance to the drug can lead to acute allergic reactions: itching, redness, rash and edema;
o disturbances in the functioning of the nervous system: the use of antibiotics in rare cases can lead to malfunctions in the peripheral part of the vestibular analyzer, as well as the possible appearance of auditory or visual hallucinations;
o violation of cellular respiration: it has been proven that the intake of antibacterial drugs has a strong negative effect on the process of oxygen delivery to human organs and tissues, disrupting their normal functioning.

Preventive measures after a course of antibiotics
In order to minimize the negative consequences of taking antibiotics, a number of rules should be observed that are effective prevention of damage to health.
1. Only take antibiotics as directed by your healthcare professional. The decision on the advisability of taking antibiotics should be made only by a doctor. It is the specialist who will select the necessary drug, release form, dosage and establish the duration of treatment.The use of antibiotics is justified only in the case of diseases caused by bacterial infections. The use of antibacterial drugs for viral diseases is impractical.
2. Strictly follow the rules for taking the drug. To maintain the optimal amount of antibiotic in the blood, it is necessary to observe equal intervals of time between its doses. Some drugs are taken before meals and others after. Therefore, before starting to use an antibacterial drug, it is necessary to carefully study the instructions for use and strictly follow the rules of admission.Otherwise, the drug will not be effective.
3. Take the full course of antibiotics. It is strictly forbidden to interrupt the drug intake after the first signs of improvement. The course of treatment must always be completed completely.
4. Keep a record of your antibiotic intake. Record which drug was taken, for how long and for what disease it was prescribed. It is worth making notes when side effects or allergic reactions occur. This information must be provided to the attending physician for a more accurate prescription of subsequent treatment.
5. Do not try to adjust the dosage yourself. Taking antibiotics in insufficient quantities will only increase the resistance of pathogens to the drug, and uncontrolled use and an increase in the amount of antibiotics can lead to a number of negative health consequences.
6. Make dietary adjustments. When using antibiotics, stick to a sparing diet and avoid fatty, fried, spicy, sour foods, and alcohol.

Foods that minimize side effects
from the use of antibiotics
In order to minimize the negative effects on human health from taking antibiotics, you need to seriously revise your diet and introduce foods that help improve the functioning of the digestive system and strengthen the immune system. These food products include:
 Fermented milk products containing probiotics. The introduction of foods rich in “live cultures” into the diet will allow the body to gently get rid of stool disorder (one of the most common companions of antibiotic use).Probiotics also help generate lactic acid, which helps eliminate bacterial toxins from the body.
 Fermented food. These are products obtained using the fermentation process. These include sauerkraut and various pickles. They are already partially processed by bacterial enzymes and are easily absorbed by the body. In addition, such food improves appetite, speeds up metabolism and boosts immunity.
 Garlic. This is a product with pronounced antimicrobial properties that help fight bacterial infection.In addition, it contains substances that protect the kidneys and liver from possible damage by antibacterial drugs.
 Ginger. Possesses antimicrobial properties and the ability to prevent many health problems associated with various infections. Fresh ginger has antibiotic properties against foodborne pathogens and respiratory infections. It also effectively eliminates nausea, vomiting, and diarrhea associated with antibiotic use.

Do not self-medicate and promptly seek qualified medical help!

Anna Pigulevskaya,
paramedic-valeologist
of the public health department
of the Gomel regional CGE and OZ

90,000 Adverse reactions and consequences of taking antibiotics

12.01.2018

Antibiotics are effective medicines that in a matter of days can kill an infection that has arisen in the body and improve the patient’s condition from the first days. But the medal, as always, has two sides. Unfortunately, during and after taking antibiotics, side effects can occur.
What are the side effects of antibiotics, what to do in situations when they start to appear, and how to avoid them? Consider this issue below.

The most common side effects of antibiotics

The first thing to say: side effects after taking antibiotics do not always appear, because everything depends entirely on the body.But often taking antibiotics can make itself felt with some unpleasant reactions.

1. Disorder of the gastrointestinal tract.

Most often this problem is manifested by diarrhea or constipation, bloating, nausea and even vomiting, as well as exacerbation of chronic diseases. Almost always, symptoms (especially nausea and upset stools) can go away with antibiotics.

2. Dysbacteriosis when taking antibiotics.

Antibacterial drugs partially kill the good bacteria that live in our intestines.This disease is manifested by stool disorder and indigestion. Sometimes the body can recover on its own, but often special preparations may be needed to correct the microflora.

3. Allergy.

Usually, this unpleasant symptom is manifested by itching or a rash on the skin.

4. Women may experience candidiasis (thrush) or vaginal dysbiosis.

In this situation, everything is also logical: antibiotics worsen the microflora of the vagina, and, as a result, the yeast-like Candida fungi and bad bacteria begin to actively develop.

If at least one of the symptoms manifests itself, you should immediately inform the doctor who prescribed antibiotics, especially if unpleasant side effects appeared at the beginning of taking the drug.

If the consequences began to manifest themselves after taking, you should consult a specialized doctor, for example, a gastroenterologist or a gynecologist. Any minor disturbance can worsen health over time, especially if chronic conditions are present.

After antibiotics: what to drink to get rid of unpleasant consequences?

After taking antibiotics, doctors recommend that the intestinal microflora be restored immediately.Even if, at first glance, there are no unpleasant symptoms, in most cases the good microflora still suffers. Therefore, after antibiotic therapy, probiotics should be taken, which will restore the microflora and (in most cases) also normalize the stool if it is disturbed.

Which probiotics are better after antibiotics?

Of the popular and effective ones: Linex, Probiologist, Laktiale. Biogay drops are well suited for children.
When and for how long to drink them? Usually, doctors recommend drinking probiotics about 10-14 days after you stop taking antibiotics.Sometimes you can start taking probiotics from the first day of antibiotic therapy, especially if chronic diseases of the gastrointestinal tract or pelvic organs are present. In this case, you should drink good bacteria no earlier than 3 hours after taking antibiotics, before or during a meal.

Allergy while taking antibiotics

If an allergy occurs while taking antibiotics and the manifestations are minor, such as itching or slight redness, then in this case it is only necessary to eliminate the symptoms, since such troubles usually disappear at the end of the course.Aleron, Cetrin, Erius will help to cope with allergic symptoms. For children – Edem syrup.

As for vaginal dysbiosis, probiotics are also used in this case. If the situation worsens, the discomfort does not go away and suspicious discharge appears, it is better to immediately consult a gynecologist.

The most important thing when taking antibiotics is to listen to your body, do not start and do not tolerate adverse reactions! And, of course, do not stop drinking the prescribed antibacterial drug and do not adjust its dosage yourself.

Pay attention!

This article is for informational purposes only. Treatment for each specific case should be selected individually after the examination. Pharmacy 36 and 6 is not responsible for your decision to treat yourself with one or another drug. Remember that self-medication is dangerous for your health!

90,000 Drug warfare: antibiotics are 1.5 times more likely to cause severe COVID | Articles

COVID-19 is one and a half times more likely to become severe in people who drank antibiotics in the first days after diagnosis.This conclusion was made by foreign scientists after analyzing the case histories of 1.5 thousand patients. In addition, those who used antibiotics stay in the hospital longer. The drugs negatively affect the gastrointestinal tract, and this worsens the general condition of the patient and inhibits recovery, experts interviewed by Izvestia explained. Do not give up antibiotics at all, but they can be used only if a bacterial infection is confirmed, doctors say.

In a hurry, you will harm people

The effect of antibiotics on the course of COVID-19 was studied by scientists from Huazhong University of Science and Technology (China) under the leadership of Changjun Li.The authors of the work analyzed the data of more than one and a half thousand patients admitted to the hospital. All of them were at first in a state of moderate severity. Of these, 996 patients received antibiotics within two days after admission to the hospital, the rest were not given them at all or were given more than two days later in the hospital.

COVID-19 passed into a severe stage in 36% of people from the first group and only 22% from the second.

“In 30 days, the proportion of patients who developed severe COVID-19 was 1.5 times higher in the early antibiotic use group than in the comparison group.Antibiotic use has been associated with a higher likelihood of developing a severe type, ”the authors concluded.

Photo: Global Look Press / Britta Pedersen / dpa

In addition, the groups differed in the length of stay in the hospital. Those who took antibiotics right after being admitted to the hospital stayed there for an average of 18 days. In the second group – 13.

Moreover, the incidence of secondary bacterial infection (unbalanced response of the innate antiviral immunity system and uncontrolled inflammation) in the first group was almost two times higher than in patients who did not receive antibiotics.

The authors of the work especially noted patients who received antibiotic therapy not immediately after admission to the hospital – most likely, they were given drugs on purpose, to fight a certain infection. Their results were intermediate between the main groups – they were slightly more likely to progress to the severe stage and stayed in the hospital a little longer than patients who did not receive antibiotics at all.

Interestingly, the use of antimicrobial drugs had no effect on mortality.The authors of the work associate the disturbances of the intestinal microbiome, arising as a consequence of taking antibiotics, with a violation of the ability to remove infectious agents from the lungs.

To be more specific, in the first group the average age of patients was 54 years, in the second – 57 years. These are similar indicators, so they could not have a significant impact on the results of the study. The ratio of men and women in the groups was equal.

Side effect

Antibiotics negatively affect the GI microbiome and therefore disrupt the functioning of many organs.Therefore, it is logical that the general deterioration of the patient’s condition negatively affected the recovery time, according to Russian experts interviewed by Izvestia.

– All antibiotics have side effects that affect the functions of either the liver or the kidneys and, as a result, affect the excretion of decay products of the destroyed infected cells of the patient’s body, – explained Sergey Netesov.- Antibiotics strongly inhibit the intestinal and oral microflora, which can also affect the patient’s condition not for the better.

The expert also noted that the authors of the article did not disclose which antibiotics were used in the hospital. In any case, such drugs are antibacterial agents. And they do not affect viruses in any way, the expert summed up.

Photo: Izvestia / Zurab Javakhadze

“For any viral infections, be it flu or coronavirus, antibiotics are more harmful than good,” said Yulia Gainullina, professor at the Department of Social Sciences at the FEFU School of Arts and Humanities (the university is a member of the 5-100 Education Competitiveness Project).- The virus multiplies and lives in the cell, from which it leaves, and the cell dies. Antibiotics don’t work at this level, they act on larger microorganisms. But antibiotics can kill the beneficial flora with which a person with COVID-19 lives. In place of beneficial flora, unfavorable flora will surely come, for example, Pseudomonas aeruginosa, which is resistant even to large doses of these drugs. For a person with a strong immune system, it does not bring significant harm, but for a weakened patient, in intensive care, taking many other drugs, it becomes deadly.

Both place and time

However, there are times when antibiotics are really needed even with COVID-19. Their use is justified in cases where there are signs of a bacterial infection that has joined the disease, explained the immunologist-allergist Andrei Prodeus.

– This, for example, cough with phlegm, green mucus from the nose, fever with intoxication, – explained the scientist. – In addition, such signs include an increase in the proportion of neutrophils in peripheral blood leukocytes (circulates in blood vessels, and not in organs and tissues.- “Izvestia”). At the same time, statistics indicate that a very small proportion of patients with COVID-19 develop bacterial complications – within 5%.

Researcher of the Laboratory for Analysis of Population Health Indicators and Digitalization of Healthcare at the Moscow Institute of Physics and Technology David Naimzada cited an appeal from several professional communities on behalf of the Russian Medical Journal. It states that the appointment of antibiotic therapy in patients with COVID-19 is justified only if there are convincing signs of a bacterial infection.

Photo: Depositphotos

– Yes, the disease can be complicated by bacterial pneumonia, – said Yulia Gainullina. – It is often difficult to distinguish whether a patient has a viral or bacterial pneumonia. The latter may not be pneumococcal, as usual, but staphylococcal, when a separate group of antibiotics is needed.

Only a doctor can determine which drug is needed.

In Russia, patients with coronavirus are prescribed antibiotics in 90% of cases, although in reality only 10% of patients who develop bacterial complications need these drugs.This was previously reported in an interview with Izvestia by Sergei Yakovlev, Professor of the Department of Hospital Therapy at Sechenov University, President of the Alliance of Clinical Chemotherapists and Microbiologists of Russia. Uncontrolled use of drugs will lead to an increase in the number of drug-resistant bacteria strains three to four times, the specialist explained. He said that there are already model studies that show that if antibiotics are used as actively, then by 2050 10 million people in the world will die from infections caused by resistant microbes every year.

can I drink during and after treatment, side effects, how long can

A month ago I caught a cold – or rather, I thought so. The disease developed into something similar to bronchitis, and yesterday the doctor diagnosed pneumonia and prescribed antibiotics. But there is a problem: on the weekend my father’s birthday is 60 years. There will be a festive table and alcohol.

I have a question: how dangerous is it to combine alcohol and antibiotics and what will happen if you do drink so as not to offend your father and guests?

Alcohol does not affect the effectiveness of most antibiotics – drugs will fight disease-causing bacteria as effectively as if you were not drinking.However, some antibiotics interact with alcohol. This can lead to adverse reactions that would otherwise have been avoided.

What are antibiotics

Antibiotics are medicines that fight bacterial infections in humans and animals. These are bacterial poisons that act on the vulnerable points of microbes. As a result, the latter either die or lose the ability to grow and reproduce. Viruses do not have vulnerabilities characteristic of bacteria, so antibiotics do not work on them.

Like all medicines, antibiotics can cause side effects. The problem is that when taken together with some antibiotics, alcohol not only enhances unwanted reactions to the drug, but can also provoke new ones.

Why it is not recommended to mix antibiotics and alcohol – American Addiction Center

How alcohol affects the work of antibiotics

In addition to antibiotics, antidepressants, antihistamines, barbiturates, benzodiazepines, painkillers, anti-inflammatory drugs are not combined with alcohol.Even some herbal medicines can be harmful when taken with alcohol.

Alcohol and Drug Interactions – Alcohol and Health Research Journal PDF, 99 KB

Alcohol interacts with drugs in two ways.

Special proteins are responsible for neutralizing poisons – enzymes produced by the liver. If the liver receives not only an antibiotic, but also excess alcohol, the load on enzymes increases.As a result, they either do not have time to complete their work, or, conversely, do it too quickly. In the first case, the level of the antibiotic in the body increases, and this can lead to greater toxicity of the drug and side effects that could be avoided with an accurate dosage. And in the second case, the antibiotic is destroyed too quickly – before it has time to act.

Alcohol suppresses enzymes and increases antibiotic toxicity – International Drugs Database Drugs

Alcohol increases the side effects of the drug and provokes new ones. For example, metronidazole itself causes drowsiness and suppresses attention, and alcohol further enhances these effects. As a result, a person runs the risk of simply falling asleep at the festive table.

Alcohol and metronidazole – NHS

In addition, metronidazole in combination with alcohol gives additional side effects: it causes headache, nausea, abdominal pain and arrhythmia. No one knows why this happens: the interaction of this antibiotic with alcohol has not yet been sufficiently studied.

Apart from alcohol, antibiotics cannot be combined with other medications. These are anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbital, and pill antidiabetic drugs such as tolbutamide. Therefore, before you start taking antibiotics, you need to tell your doctor about all your diseases and medications that you are taking.

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Can I drink alcohol at the same time as antibiotics

It depends on what kind of antibiotic to take with alcohol and in what relationship a person is with alcohol.

Interaction of alcohol and antibiotics – journal “Antimicrobial drugs and chemotherapy” PDF, 536 KB

Erythromycin. Even small doses of alcohol accelerate the work of liver enzymes, which are responsible for the processing of the drug. As a result, the medication may not work – additional doses will be required.

Ketoconazole and griseofulvin. If a person drinks alcohol on the same day as one of these drugs, the risk of developing a disulfiram-like reaction will increase – this is the name for a condition similar to a very severe hangover.The person is nauseous and vomiting, his head is splitting, and some even have chest and abdominal pains.

Doxycycline. In people suffering from chronic alcoholism, doxycycline accelerates the work of liver enzymes, which are responsible for the processing of the drug. This is why alcohol addicts require higher dosages of this medication.

At the same time, not all antibiotics are equally poorly combined with alcohol. There are drugs that are relatively safe to take with alcohol.Moderate doses of alcohol, i.e. no more than one standard drink per day for women and two for men, compatible:

• with oral penicillins, fluoroquinolones and tetracyclines;
• some cephalosporins – cefdinir and cefpodoxime;
• azithromycin;
• with nitrofurantoin.

Standard Alcohol 14g Pure Ethanol – US National Institute of Alcohol Dependence and Alcoholism

How long after taking antibiotics can you drink alcohol

It is difficult to say which advice is more accurate.But perhaps it makes sense to wait at least two days.

Drink it or not

Although some antibiotics are combined with moderate doses of alcohol, alcohol is not recommended for patients being treated for bacterial infections. Alcoholic drinks not only affect the functioning of liver enzymes, but also disrupt normal sleep – all this interferes with a full recovery.