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Ceftaroline allergies. Ceftaroline: Uses, Side Effects, and Warnings for This Antibiotic

by alexxlab

What are the main uses of ceftaroline. How does ceftaroline work in the body. What are the most common side effects of ceftaroline. Are there any serious warnings associated with ceftaroline use. How does ceftaroline compare to other antibiotics in its class.

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Understanding Ceftaroline: A Powerful Antibiotic in Modern Medicine

Ceftaroline, marketed under the brand name TEFLARO®, is a cutting-edge antibiotic that has garnered significant attention in the medical community. This cephalosporin antibiotic plays a crucial role in combating various bacterial infections, particularly those resistant to other treatments. To fully grasp its importance, we must delve into its mechanisms, applications, and potential side effects.

The Mechanism of Action: How Ceftaroline Fights Infections

Ceftaroline operates by interfering with bacterial cell wall synthesis, a process essential for bacterial survival and reproduction. By binding to penicillin-binding proteins (PBPs), including the modified PBP2a in methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline effectively weakens the bacterial cell wall, leading to cell death.

Does ceftaroline work against all types of bacteria. While highly effective against many gram-positive and some gram-negative bacteria, ceftaroline is not a universal antibiotic. Its spectrum of activity includes:

  • Streptococcus pneumoniae (including multidrug-resistant strains)
  • Staphylococcus aureus (including methicillin-resistant strains)
  • Haemophilus influenzae
  • Klebsiella pneumoniae
  • Escherichia coli

This targeted approach helps reduce the risk of antibiotic resistance while effectively treating specific infections.

Primary Uses of Ceftaroline in Clinical Practice

Ceftaroline has been approved for use in several critical infectious conditions. Its primary applications include:

  1. Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
  2. Community-Acquired Bacterial Pneumonia (CABP)

These indications highlight ceftaroline’s versatility in treating both skin-related infections and respiratory tract infections, two common areas where antibiotic resistance poses significant challenges.

Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

ABSSSIs encompass a range of skin infections, including cellulitis, wound infections, and major cutaneous abscesses. Ceftaroline’s efficacy against MRSA makes it particularly valuable in treating these conditions, especially when traditional antibiotics fail.

Community-Acquired Bacterial Pneumonia (CABP)

CABP remains a significant cause of morbidity and mortality worldwide. Ceftaroline’s ability to target key respiratory pathogens, including drug-resistant strains of Streptococcus pneumoniae, positions it as a crucial tool in managing severe cases of CABP.

Adverse Reactions and Side Effects: What Patients Need to Know

Understanding the potential side effects of ceftaroline is crucial for both healthcare providers and patients. According to clinical trials, no adverse reactions occurred in more than 5% of patients receiving TEFLARO. However, several side effects were observed at lower frequencies:

Gastrointestinal Disorders

  • Diarrhea (5% in TEFLARO group vs. 3% in pooled comparators)
  • Nausea (4% in both groups)
  • Constipation (2% in both groups)
  • Vomiting (2% in both groups)

Other Observed Side Effects

  • Increased transaminases (2% in TEFLARO group vs. 3% in pooled comparators)
  • Hypokalemia (2% in TEFLARO group vs. 3% in pooled comparators)
  • Rash (3% in TEFLARO group vs. 2% in pooled comparators)
  • Phlebitis (2% in TEFLARO group vs. 1% in pooled comparators)

Are these side effects cause for concern. While the observed side effects are generally mild and occur in a small percentage of patients, it’s essential to monitor for any adverse reactions during treatment. Patients should report any unusual symptoms to their healthcare provider promptly.

Comparing Ceftaroline to Other Antibiotics: Advantages and Considerations

Ceftaroline’s unique properties set it apart from many other antibiotics in its class. Its ability to target MRSA and other resistant strains gives it a significant advantage in treating infections that may not respond to traditional cephalosporins or penicillins.

How does ceftaroline compare to vancomycin in treating MRSA infections. While both antibiotics are effective against MRSA, ceftaroline has shown comparable or superior efficacy in certain studies, with potentially fewer side effects. However, the choice between these antibiotics often depends on specific patient factors and local resistance patterns.

Dosage and Administration: Ensuring Optimal Efficacy

Proper dosing of ceftaroline is crucial for maximizing its therapeutic benefits while minimizing the risk of side effects. The typical dosage for adults with normal renal function is:

  • 600 mg administered every 12 hours by intravenous (IV) infusion over 5 to 60 minutes
  • The duration of treatment usually ranges from 5 to 14 days, depending on the type and severity of infection

Is dose adjustment necessary for patients with renal impairment. Yes, patients with impaired kidney function may require dose adjustments to prevent drug accumulation and potential toxicity. Healthcare providers should calculate creatinine clearance and adjust the dose accordingly.

Special Populations: Considerations for Diverse Patient Groups

Ceftaroline’s use in special populations requires careful consideration and, in some cases, additional monitoring:

Pediatric Patients

Ceftaroline has been approved for use in pediatric patients aged 2 months and older. Dosing is based on weight and age, with adjustments made for severity of infection and renal function.

Geriatric Patients

Elderly patients may be at increased risk of adverse effects due to age-related changes in renal function. Dose adjustments may be necessary based on creatinine clearance.

Pregnant and Breastfeeding Women

Limited data exist on ceftaroline use during pregnancy and lactation. The potential benefits must be weighed against the risks, and decisions should be made on a case-by-case basis.

Antibiotic Stewardship: Responsible Use of Ceftaroline

As with all antibiotics, the responsible use of ceftaroline is crucial to prevent the development of resistance. Healthcare providers should adhere to antibiotic stewardship principles, including:

  • Prescribing ceftaroline only when clinically indicated
  • Using the correct dose and duration of therapy
  • Considering local resistance patterns when selecting antibiotics
  • Educating patients on the importance of completing the full course of treatment

Can proper antibiotic stewardship help preserve ceftaroline’s effectiveness. Absolutely. By using ceftaroline judiciously and only when necessary, we can help maintain its efficacy against resistant pathogens and extend its useful lifespan in clinical practice.

Future Perspectives: The Role of Ceftaroline in Combating Antibiotic Resistance

As antibiotic resistance continues to pose a global health threat, ceftaroline’s unique properties make it a valuable asset in our antimicrobial arsenal. Ongoing research is exploring its potential in treating other resistant infections and its role in combination therapies.

Will ceftaroline remain effective against evolving bacterial strains. While it’s difficult to predict long-term efficacy, ceftaroline’s novel mechanism of action against resistant pathogens provides hope for its continued usefulness. However, ongoing surveillance and responsible use are essential to preserve its effectiveness.

Monitoring and Managing Potential Allergic Reactions

Although rare, allergic reactions to ceftaroline can occur and require prompt attention. Healthcare providers should be aware of the signs and symptoms of allergic reactions, which may include:

  • Skin rash or hives
  • Itching
  • Swelling of the face, lips, tongue, or throat
  • Difficulty breathing or swallowing
  • Severe dizziness

Patients with a history of severe allergic reactions to other beta-lactam antibiotics should be closely monitored when receiving ceftaroline. In some cases, alternative antibiotics may be considered.

Is cross-reactivity with other beta-lactam antibiotics a concern. While cross-reactivity is possible, studies have shown that ceftaroline may be better tolerated in patients with penicillin allergies compared to other cephalosporins. However, caution is still advised, and a thorough allergy history should be obtained before prescribing.

Drug Interactions: Maximizing Safety and Efficacy

Understanding potential drug interactions is crucial for safe and effective use of ceftaroline. While ceftaroline has fewer drug interactions compared to some other antibiotics, healthcare providers should still consider the following:

Probenecid

Concurrent use of probenecid with ceftaroline may increase ceftaroline exposure. This interaction is due to probenecid’s inhibition of renal tubular secretion of ceftaroline.

Live Vaccines

As with other antibiotics, ceftaroline may reduce the efficacy of live bacterial vaccines. It’s recommended to complete vaccinations before starting ceftaroline therapy or to delay vaccination until after treatment completion.

Laboratory Test Interactions

Ceftaroline may interfere with certain laboratory tests, particularly those measuring serum creatinine levels. Healthcare providers should be aware of this potential interaction when interpreting test results.

Are there any foods that interact with ceftaroline. Unlike some antibiotics, ceftaroline doesn’t have significant food interactions. However, maintaining adequate hydration during treatment is generally recommended to support kidney function and help prevent potential side effects.

Economic Considerations: Cost-Effectiveness of Ceftaroline

As a relatively new antibiotic, the cost of ceftaroline treatment can be higher compared to older, generic antibiotics. However, its effectiveness against resistant pathogens may lead to overall cost savings in certain clinical scenarios:

  • Reduced length of hospital stay
  • Fewer treatment failures requiring additional interventions
  • Decreased need for more expensive second-line therapies

Is ceftaroline a cost-effective option for all infections it’s approved to treat. The cost-effectiveness of ceftaroline can vary depending on the specific infection, local resistance patterns, and individual patient factors. In cases of suspected or confirmed MRSA infections or other resistant pathogens, the benefits of ceftaroline may outweigh its higher upfront cost.

Patient Education: Empowering Informed Decision-Making

Educating patients about ceftaroline is crucial for ensuring treatment adherence and early recognition of potential side effects. Key points to communicate include:

  • The importance of completing the full course of treatment, even if symptoms improve
  • Potential side effects and when to seek medical attention
  • The need for regular monitoring during treatment, including blood tests
  • Proper storage and handling of the medication if self-administering at home

How can patients actively participate in their treatment with ceftaroline. Patients can play an active role by:

  1. Keeping a symptom diary to track their progress and any side effects
  2. Adhering strictly to the prescribed dosing schedule
  3. Communicating openly with their healthcare provider about any concerns or questions
  4. Informing all healthcare providers about their ceftaroline treatment to avoid potential drug interactions

Emerging Research: Expanding the Horizons of Ceftaroline Use

Ongoing research continues to explore new potential applications for ceftaroline and its role in combating antibiotic resistance. Some areas of current investigation include:

Combination Therapies

Researchers are studying the efficacy of ceftaroline in combination with other antibiotics to treat highly resistant infections or to prevent the development of resistance.

Extended Indications

Clinical trials are underway to evaluate ceftaroline’s effectiveness in treating other types of infections, such as endocarditis and osteomyelitis.

Pediatric Applications

Further studies are exploring the safety and efficacy of ceftaroline in various pediatric populations, including neonates and infants.

Will these research efforts lead to new approved uses for ceftaroline. While it’s too early to predict specific outcomes, the ongoing research underscores the potential of ceftaroline to address unmet needs in infectious disease treatment. As results become available, they may inform future clinical guidelines and expand the role of ceftaroline in medical practice.

TEFLARO® (ceftaroline fosamil) Adverse Reactions

In clinical trials, no adverse reactions occurred in >5% of patients receiving TEFLARO

1

















ABSSSI and CABP Pooled Adverse Reactions From Phase 3 Clinical Trials1


Adverse Reaction

TEFLARO

(N=1300)
Pooled Comparators*
(N=1297)

Gastrointestinal disorders
 
 

Diarrhea
5%
3%

Nausea
4%
4%

Constipation
2%
2%

Vomiting
2%
2%

Investigations
 
 

Increased transaminases
2%
3%


Metabolism and
nutrition disorders

 
 

Hypokalemia
2%
3%


Skin and subcutaneous
tissue disorders

 
 

Rash
3%
2%


Vascular disorders

 
 

Phlebitis
2%
1%


























ABSSSI and CABP Pooled Adverse Reactions From Phase 3 Clinical Trials1

TEFLARO

(N=1300)
Pooled Comparators*
(N=1297)

Adverse Reaction

Gastrointestinal disorders

Diarrhea

5%
3%

Nausea

4%
4%

Constipation

2%
2%

Vomiting

2%
2%

Investigations

Increased transaminases

2%
3%

Metabolism and
nutrition disorders

Hypokalemia

2%
3%

Skin and subcutaneous
tissue disorders

Rash

3%
2%


Vascular disorders

Phlebitis

2%
1%


Comparators included vancomycin 1 g IV every 12h plus aztreonam 1 g IV every 12h in the Phase 3
ABSSSI trials, and ceftriaxone 1 g IV every 24h in the Phase 3 CABP trials.


  • In the four pooled Phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5%)
    of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs.1

Next: Incidence of Discontinuation

INDICATIONS AND USAGE


  • TEFLARO® (ceftaroline fosamil) is indicated in adult and pediatric patients (at least 34 weeks gestational age and 12 days postnatal age and older) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.


  • TEFLARO is also indicated in adult and pediatric patients 2 months of age and older for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.


  • To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEFLARO and other antibacterial drugs, TEFLARO should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

IMPORTANT SAFETY INFORMATION

Contraindications

  • TEFLARO is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis has been reported with ceftaroline.

Warnings and Precautions
Hypersensitivity Reactions

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibacterial drugs. Before therapy with TEFLARO is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been clearly established.


  • If an allergic reaction to TEFLARO occurs, discontinue TEFLARO and institute appropriate treatment and supportive measures.

Clostridioides difficile-Associated Diarrhea


  • Clostridioides difficile-Associated Diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including TEFLARO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.

Neurological Adverse Reactions

  • Neurological adverse reactions have been reported during postmarketing surveillance in patients treated with cephalosporins, including TEFLARO. These reactions include encephalopathy and seizures. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation of TEFLARO or after hemodialysis. If neurological adverse reactions associated with TEFLARO therapy occur, consider discontinuing TEFLARO or making appropriate dosage adjustments in patients with renal impairment.

Direct Coombs’ Test Seroconversion

  • In adults, seroconversion from a negative to a positive direct Coombs’ test result occurred in 120/1114 (10. 8%) of patients receiving TEFLARO and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled adult Phase 3 trials.


  • In children, seroconversion from a negative to a positive direct Coombs’ test result occurred in 42/234 (17.9%) of patients receiving TEFLARO and 3/93 (3.2%) of patients receiving comparator drugs in the three pooled pediatric trials.


  • No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with TEFLARO, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of TEFLARO should be considered and supportive care should be administered to the patient if clinically indicated.

Development of Drug-Resistant Bacteria

  • Prescribing TEFLARO in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions in Adults

  • In the four pooled adult Phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5%) of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7%) of patients receiving TEFLARO and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the TEFLARO group and 0.5% in the comparator group.


  • The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the adult pooled Phase 3 clinical trials were diarrhea (5%), nausea (4%), and rash (3%).

Adverse Reactions in Pediatrics

  • In the three pooled pediatric clinical trials, serious adverse reactions occurred in 10/257 (4%) of patients receiving TEFLARO and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving TEFLARO and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with TEFLARO.


  • The most common adverse reactions occurring in ≥ 3% of patients receiving TEFLARO in the pooled pediatric clinical trials were diarrhea (8%), rash (7%), vomiting (5%), pyrexia (3%), and nausea (3%).

Drug Interactions

  • No clinical drug-drug interaction studies have been conducted with TEFLARO. There is minimal potential for drug-drug interactions between TEFLARO and CYP450 substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow.

Use in Specific Populations

  • There have been no adequate and well-controlled studies with TEFLARO in pregnant or nursing women. TEFLARO should only be used if the potential benefit justifies the potential risk in these populations.


  • Safety and effectiveness of TEFLARO for the treatment of ABSSSI in pediatric patients less than 34 weeks gestational age and less than 12 days postnatal age have not been established. Safety and effectiveness for the treatment of CABP in pediatric patients below the age of 2 months have not been established as no data are available.


  • Because elderly patients, those ≥65 years of age, are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Dosage adjustment for elderly patients should therefore be based on renal function.


  • Dosage adjustment is required in adult patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30mL/min) renal impairment and in patients with end-stage renal disease (CrCl 2.


  • The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.



Please also see full Prescribing Information.


References:


  1. TEFLARO® (ceftaroline fosamil) [prescribing information]. Allergan USA, Inc.


  2. Elixhauser A, Owens P. Reasons for being admitted to the hospital through the emergency department, 2003. Healthcare
    Cost and Utilization Project Statistical Brief #2. February 2006. Agency for Healthcare Research and Quality,
    Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb2.pdf.
    Accessed February 7, 2020.


  3. FDA Guidance ABSSSI. Guidance for industry: acute bacterial skin
    and skin structure infections: developing drugs for treatment. October 2013. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071185.pdf. Accessed February 7, 2020.


  4. Data on file. Allergan, Inc.


  5. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized,
    double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in
    complicated skin and skin-structure infection. Clin Infect Dis. 2010;51(6):641-650.


  6. Friedland HD, O’Neal T, Biek D, et al. CANVAS 1 and 2: analysis of clinical response at day 3
    in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute
    bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015;56(5):2231-2236.


  7. Eckburg PB, Friedland HD, Llorens L, et al. Day 4 clinical response of ceftaroline fosamil versus ceftriaxone for
    community-acquired bacterial pneumonia. Infect Dis Clin Pract. 2012;20:254-260.


  8. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, double-blinded,
    multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with
    community-acquired pneumonia. Clin Infect Dis. 2010;51(12):1395-1405.



TEFLARO® and its design are registered trademarks of Allergan Sales, LLC, an AbbVie company.

© 2023 AbbVie. All rights reserved. US-TEF-230008 04/23


This site is intended for U.S. healthcare professionals only. If you are a patient, and have any questions,
please discuss them with your doctor or healthcare professional. For additional information about TEFLARO,
call AbbVie Medical Information at 1.800.678.1605.

Zinforo | European Medicines Agency


ceftaroline fosamil

Table of contents

  • Overview
  • Authorisation details
  • Product information
  • Assessment history

Overview

Zinforo is an antibiotic. It is used to treat adults and children (including newborn babies) who have:

  • complicated infections of the skin and soft tissue (tissue below the skin). ‘Complicated’ means that the infection is difficult to treat;
  • community-acquired pneumonia (an infection of the lungs that is caught outside of hospital).

Prescribers should consider official guidance on the appropriate use of antibiotics.

Zinforo contains the active substance ceftaroline fosamil.

This EPAR was last updated on 22/07/2022

Authorisation details

Product details
Name

Zinforo

Agency product number

EMEA/H/C/002252

Active substance

Ceftaroline fosamil

International non-proprietary name (INN) or common name

ceftaroline fosamil

Therapeutic area (MeSH)
  • Community-Acquired Infections
  • Skin Diseases, Infectious
  • Pneumonia
Anatomical therapeutic chemical (ATC) code

J01DI02

Publication details
Marketing-authorisation holder

Pfizer Ireland Pharmaceuticals

Revision
Date of issue of marketing authorisation valid throughout the European Union

22/08/2012

Contact address

Operations Services Group
Ringaskiddy
County Cork
Ireland

Product information

Assessment history

  • Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2019

    28/06/2019

  • Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 25-28 April 2016

    29/04/2016

Related content

  • Zinforo: Paediatric investigation plan

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    Description of CEFTAROLINE FOSAMIL indications, dosages, contraindications of the active substance CEFTAROLINE FOSAMIL

    Rec. INN
    WHO registered


    drug interaction

    Included in preparations:
    list

    Pharmacological action

    Antibiotic of the 5th generation cephalosporin group. After intravenous administration, the ceftaroline prodrug fosamil is rapidly converted to the active ceftaroline.

    It has a bactericidal effect, which is due to inhibition of the biosynthesis of the bacterial cell wall, due to binding to penicillin-binding proteins (PBPs). Ceftaroline exhibits bactericidal activity against Staphylococcus aureus due to its high affinity for PSB2a and against Streptococcus pneumoniae due to its high affinity for PSB2x.

    The antibacterial activity of ceftaroline, as well as other beta-lactam antibiotics, correlates well with the time period during which the concentration of ceftaroline remains above the MIC for the infecting microorganism (%T > MIC).

    Ceftaroline is not active against strains of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) of the TEM, SHV or CTX-M families, serine carbapenemases (such as bovine), class B or class C metallo-β-lactamases (AmpC cephalosporinases). ).

    Although cross-resistance may develop, some strains resistant to other cephalosporins may be sensitive to cefatrolin.

    Ceftaroline is generally active against Gram-positive microorganisms – Staphylococcus aureus (methicillin-sensitive and methicillin-resistant), Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius and S. constellatus), Streptococcus dysgalactiae , Streptococcus pneumoniae, Streptococcus pyogenes; Gram-negative microorganisms – Haemophilus influenzae, Haemophilus parainfluenzae; anaerobes – Fusobacterium spp., Peptostreptococcus spp., Prevotella spp., Propionibacterium acnes.

    Microorganisms for which acquired resistance is possible: gram-negative microorganisms – Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii.

    Naturally resistant microorganisms: Chlamydophila spp. , Legionella spp., Mycoplasma spp., Pseudomonas aeruginosa.

    Pharmacokinetics

    With a single administration of ceftaroline fosamil in the dose range from 50 to 1000 mg C max and AUC of ceftaroline increase almost proportionally to the dose No noticeable cumulation of ceftaroline was observed after repeated intravenous administration at a dose of 600 mg for 6 0 min every 12 h for 14 days to healthy volunteers with normal kidney function.

    Plasma protein binding of ceftaroline is low – about 20%; does not penetrate into erythrocytes. V d in the equilibrium state in healthy adult men after a single intravenous injection of 600 mg of isotope-labeled ceftaroline fosamil was 20.3 l, which almost corresponds to the volume of extracellular fluid.

    Ceftaroline fosamil is a prodrug and is rapidly converted to the active ceftaroline in plasma by the action of phosphatases; prodrug concentrations are measurable in plasma, preferably during intravenous infusion. Upon hydrolysis of the beta-lactam ring of ceftaroline, a microbiologically inactive metabolite, ceftaroline M-1, is formed. The ratio of the average AUC values ​​of ceftaroline M-1 to cefatrolin in plasma after a single intravenous administration of 600 mg of ceftaroline fosamil to healthy volunteers is approximately 20-30%.

    The metabolism of ceftaroline proceeds without the participation of enzymes of the cytochrome P450 system.

    Ceftaroline is excreted primarily by the kidneys. The renal clearance of ceftaroline is approximately equal to or slightly lower than the glomerular filtration rate in the kidneys, studies of transporters in vitro show that active secretion does not contribute to the renal elimination of ceftaroline. The average T 1/2 ceftaroline in healthy adults is approximately 2.5 hours. After a single intravenous administration of 600 mg of isotope-labeled ceftaroline fosamil to healthy adult men, approximately 88% of the radioactivity was found in the urine and 6% in the feces.

    Indications of the active substance
    CEFTAROLINE FOSAMIL

    Complicated skin and soft tissue infections caused by sensitive strains of the following gram-positive and gram-negative microorganisms: Staphylococcus aureus (including methicillin-sensitive and meticillin-resistant strains), Streptococcus pygenes, streptococ CUS AGALACTIAE, Escherichia Coli, Klebsiella Pneumoniae, Klebsiella oxyloca and Morganella Morganii.

    Community-acquired pneumonia caused by susceptible strains of the following gram-positive and gram-negative organisms: Streptococcus pneumoniae (including cases accompanied by bacteremia), Staphylococcus aureus (methicillin-susceptible strains only), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli.

    Open list of ICD-10 codes

    J13 Pneumonia due to Streptococcus pneumoniae
    J14 Pneumonia due to Haemophilus influenzae [Afanasiev-Pfeiffer wand]
    J15. 0 Pneumonia due to Klebsiella pneumoniae
    J15.2 Staphylococcus pneumoniae
    J15.5 Pneumonia due to Escherichia coli
    J16 Pneumonia due to other infectious agents not elsewhere classified
    L01 Impetigo
    L02 Skin abscess, furuncle and carbuncle
    L03 Phlegmon
    L08.0 Pyoderma
    L08.8 Other specified local skin and subcutaneous tissue infections
    T79. 3 Post-traumatic wound infection, not elsewhere classified

    Dosage regimen

    Administered as an infusion over 60 minutes.

    Single dose – 600 mg. The interval between injections is 12 hours.

    In renal failure for patients with 30

    Side effects

    From the digestive system: often – diarrhea, nausea, vomiting, abdominal pain, constipation, increased activity of liver transaminases; infrequently – hepatitis, colitis caused by Clostridium difficile.

    From the side of the nervous system: often – headache, dizziness; infrequently – convulsions.

    From the side of the cardiovascular system: often – phlebitis, bradycardia; infrequently – a feeling of palpitations.

    From the side of metabolism: often – hyperglycemia, hypokalemia; infrequently – hyperkalemia.

    From the skin and subcutaneous tissues: often – rash, itching; infrequently – urticaria.

    From the urinary system: infrequently – impaired renal function (increased blood creatinine concentration).

    Allergic reactions: infrequently – hypersensitivity / anaphylaxis. infrequently – lengthening of prothrombin time, increase in INR.

    General reactions: often – fever.

    Local reactions: infrequently – reactions at the site of infusion (erythema, phlebitis, pain).

    Contraindications for use

    Severe renal failure (CC <30 ml/min), end-stage renal disease; children and adolescents up to 18 years of age; hypersensitivity to ceftaroline fosamil or L-arginine; hypersensitivity to any antibacterial agent that has a beta-lactam structure (for example, cephalosporins, penicillins or carbapenems).

    Use in pregnancy and lactation

    There are no clinical data on the use of ceftaroline fosamil during pregnancy. Ceftaroline fosamil should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

    It is not known if ceftaroline is excreted in breast milk. However, due to the fact that many beta-lactam antibiotics are excreted in breast milk, if ceftaroline fosamil therapy is necessary, it is recommended to stop breastfeeding.

    In preclinical animal studies, no adverse effects of ceftaroline fosamil on fertility, pregnancy, childbirth or postpartum development have been identified.

    Precautions

    Use with caution in patients with a history of seizures.

    Before starting therapy, the patient should be carefully examined for hypersensitivity reactions to beta-lactam antibiotics.

    If a severe allergic reaction develops, ceftaroline fosamil should be discontinued and appropriate measures taken.

    Consideration should be given to the possibility of developing colitis if diarrhea occurs during the use of ceftaroline fosamil. In this case, it is necessary to stop therapy with ceftaroline fosamil and carry out supportive measures and prescribe specific treatment for Clostridium difficile.

    A positive direct antiglobulin test (DAT) can be obtained with cephalosporins.

    Influence on the ability to drive vehicles and mechanisms

    During therapy, dizziness may occur, so patients should be careful when driving vehicles and when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

    Community acquired pneumonia. Modern and promising approaches to antibiotic therapy | Beloborodov V.B.

    Improving the treatment of community-acquired pneumonia (CAP) remains relevant to this day. This is primarily due to the fact that CAP remains one of the most common causes of death, and treatment is associated with significant material costs [1]. After the introduction of antibiotics into clinical practice, the effectiveness of CAP treatment has dramatically increased. Nevertheless, at present, the overall mortality of patients with CAP is 8–15%, and the number of those hospitalized in intensive care units (ICUs) reaches 30% [2].

    Much attention is paid to the problem of CAP: recommendations for treatment have been developed, risk groups for patients with poor outcomes have been identified, and criteria for choosing empirical antimicrobial therapy have been determined [3–5]. It has been proven that strict adherence to such recommendations leads to improved treatment outcomes and reduced costs [6]. Nevertheless, the problem of treatment inefficiency remains, associated with the emergence of antibiotic resistance and new pathogens of this infection [7]. Therefore, the improvement of diagnostics and treatment, the development of new antibacterial drugs remain important tasks of modern healthcare.

    Current guidelines for antibiotic therapy of CAP

    Recommendations for the treatment of CAP were developed by various national organizations, including in our country [8]. The best known are the recommendations of the American Society of Infectious Diseases and the American Thoracic Society (IDSA/ATS) [3], the British Thoracic Society [5], and the European Society of Clinical Microbiologists and Infectious Diseases [4]. In our country, the credit for the development of such recommendations belongs to the Russian Respiratory Society, they are presented in guidelines and monographs [8, 9]. In general, domestic recommendations correspond to the essence of most of the above recommendations, however, they take into account the peculiarities of the etiological structure, the sensitivity of CAP pathogens, and include drugs on the market.

    Empirical therapy is an important part of the problem of CAP treatment, it has been shown that the choice of starting regimens and the timeliness of starting therapy are factors that have a major impact on the course and outcomes of the disease. The choice of drugs for empiric treatment of CAP should be based on an assessment of the relevance of the most common pathogens and the risk of an unfavorable infection outcome in certain groups of patients. Other important factors in the choice of antibacterial drugs are their pharmacokinetic and pharmacodynamic properties, the likelihood of allergy or intolerance, consideration of previous antibiotic use, the ability of patients to follow doctor’s prescriptions, the cost of drugs, the likelihood of adverse events, and an understanding of the general properties of the classes of drugs that are used. for the purpose of treatment. The goal of antibiotic therapy is to reduce the concentration or complete eradication of bacteria in the focus of inflammation, which determines the clinical success of treatment in general, and to reduce the likelihood of selection of resistant flora [10].

    The spectrum of CAP pathogens is potentially very wide, however, when choosing antibiotic therapy, the most probable ones are taken into account. The most common and dangerous pathogen is Streptococcus pneumoniae. Other pathogens may be Haemophilus influenzae, atypical CAP pathogens – Mycoplasma pneumoniae, Chlamydophila pneumoniae, which usually cause infections that are not so severe and do not require hospitalization of patients in the ICU. On the contrary, pathogens such as Staphylococcus aureus, gram-negative microbes and Legionella can cause severe infections that require treatment in the ICU [3–5]. Relatively recently, new pathogens have been described – community-acquired Staphylococcus aureus, resistant to methicillin (CA-MRSA), and influenza viruses A (h2N1) pdm09that can cause severe EP [11, 12].

    According to current recommendations, patients admitted to specialized departments are usually prescribed a combination of β-lactam with a macrolide or monotherapy with respiratory fluoroquinolones [8, 9]. When patients are admitted to the ICU, the choice of antibiotics depends on the presence of risk factors for infection caused by unusual flora, such as Pseudomonas. Usually, in severe pneumonia, combined antibiotic therapy is prescribed.

    Antibiotic resistance of causative agents of CAP

    Antibiotic resistance must be taken into account when choosing an empiric regimen. However, it is necessary to keep in mind the presence of a wide geographical variability in resistant microbes and take into account the peculiarities of the regional flora. Therefore, in case of confidence in the diagnosis and the detection of insufficient effectiveness of the starting regimen of empirical therapy, it is necessary, first of all, to assume a meeting with a resistant causative agent of CAP and use new drugs that can overcome this resistance.

    Streptococcus pneumoniae

    Thanks to the advances in antimicrobial therapy and the introduction of the pneumococcal conjugate vaccine, combined with new opportunities for radiological and microbiological diagnostics, our understanding of the significance and characteristics of antibiotic resistance of Streptococcus pneumoniae has expanded. In 1998–2009 The international SENTRY study was conducted, during which 14,934 strains of Streptococcus pneumoniae were analyzed [13]. Moreover, 71% of the strains were isolated from the upper and lower respiratory tract, the rest – mainly from the blood. The results obtained showed that in 2004–2009gg. there was a significant (p<0.05) decrease in sensitivity to β-lactams (amoxicillin / clavulanate) from 93.8 to 82.7%, penicillin - from 94.7 to 84.1%, ceftriaxone - from 97.4 to 87 .5%), macrolides (erythromycin) - from 82.2 to 60.8% and clindamycin - from 96.2 to 79.1%. In European countries, high resistance to macrolides (>20% of strains) has been identified in Belgium, Bulgaria, Hungary, Italy, Spain, Cyprus, Poland, Portugal, Romania, Finland and France; low levels of resistance (<5%) have been described in the UK, Denmark, Norway and Sweden [14]. A later study (AWARE Ceftaroline Surveillance Program, 2008–2010) found that out of 3329strains of Streptococcus pneumoniae isolated in the United States, resistance to penicillin was observed in 1.7% of strains isolated from cerebrospinal fluid and in 21.1% of strains isolated from the respiratory tract [15]. In addition, a slight increase in resistance to erythromycin (from 38.4 to 41.7%) and levofloxacin (from 0.6 to 1.09%) was found. In Spain, an increase in the resistance of Streptococcus pneumoniae to fluoroquinolones (3.3%) was found, and these strains remained sensitive to penicillin and were resistant to erythromycin and clindamycin [16]. Recently, the CAPNETZ study showed a low level of resistance to fluoroquinolones in Streptococcus pneumoniae in Germany [17].

    According to the results of the just completed study of topical respiratory pathogens in Russia (ZERBERUS), pneumococcal resistance to penicillin is 3.7%, to erythromycin – 15.5% [18]. These indicators, according to the authors, confirmed the previously obtained data on the resistance of Streptococcus pneumoniae to penicillin. However, they refer only to resistant strains and do not include strains with intermediate resistance, which make up about 10%. Clinical significance (in terms of reducing the effectiveness of antibiotics) is precisely the sum of these strains, i.e., the indicator is about 14%. Accounting for strains with intermediate resistance is also of great clinical importance, since this can lead to a decrease in the effectiveness of standard empiric therapy regimens. In addition, the interpretation of the sensitivity of strains according to the CLSI criteria (USA), which differ significantly from the more reasonable clinical criteria EUCAST (European Union), leads to an unreasonable underestimation of pneumococcal resistance rates. According to the resistance of pneumococci in some regions, for example, in St. Petersburg, the number of penicillin-resistant strains of pneumococci (EUCAST) isolated from patients with pneumonia can reach 50% [Sidorenko S.V., preliminary data].

    Macrolide resistance increased, with clindamycin active against 6. 5% of erythromycin-resistant strains, indicating the spread of resistance in Streptococcus pneumoniae associated with the presence of the mef gene.

    Haemophilus influenzae

    According to the AWARE study (2009–2010), out of 1545 strains of Haemophilus influenzae, 26.3% were resistant to ampicillin [15]. In addition, a low level of resistance to azithromycin (0.8–1.4%) and an increase in resistance to trimetaprim/sulfamethoxazole (from 19.4 to 24.4%). In the UK, more than 90% of Haemophilus influenzae strains were susceptible to all antibiotics studied, with the exception of ampicillin (susceptible – 84.6%), trimethoprim (susceptible – 84.0%), cefuroxime (susceptible – 82.9%), amoxicillin (susceptible – 82.9%). – 77.2%) and cefaclor (sensitive – 11.7%).

    In Russia, 11.8% of strains resistant to ampicillin were found, which indicates a significant increase in their number compared to those identified in previous studies [18]. No strains resistant to azithromycin were found.

    Mycoplasma pneumoniae

    Mycoplasma pneumoniae strains isolated from children and adults with CAP show resistance to macrolides in Denmark, China (80–90%), Japan (>40%), Europe, and the USA (3–10%) [19]. In a recent study in the Netherlands, no macrolide-resistant Mycoplasma pneumoniae was found among 114 strains isolated from patients with pneumonia from 4390 samples obtained from acute respiratory infections [20].

    Community CA-MRSA

    CA-MRSA strains are commonly isolated from skin and soft tissue infections. In recent years, the number of publications on invasive infections, including CAP, has increased. Moreover, in the United States, these microbes were the causative agents of pneumonia with a mortality rate of more than 50% [12, 21]. In Australia, 16 patients aged 11 months. up to 86 years of age with CAP caused by CA-MRSA, an x-ray picture of multilobar infiltration with necrosis and empyema was found [22]. Moreover, in all cases there was a delay in the start of adequate antibiotic therapy (from 18 hours to 11 days). In 7 patients, there was a need for hospitalization in the ICU, in 3 – complications within 72 hours from the onset of clinical manifestations. A prospective observational study examined the clinical manifestations and risk factors for CAP due to CA-MRSA in adults: prior exposure to MRSA, nursing home stay for 1 year, close contact in the previous month with sick skin infections, multiple infiltrates or cavities on x-ray chest organs, impaired consciousness to the level of coma, the need for intubation, the appointment of vasopressors, death in the emergency department [23]. Recently, 11 cases of MRSA infections were identified in Spain among 3523 patients with CAP [24].

    There is evidence of a low prevalence of SA-MRSA in the Russian Federation – less than 1%. At the same time, there is a tendency for the spread of hospital-acquired MRSA strains, which differ from CA-MRSA in a number of functional and genetic characteristics, in the environment. Their share among all isolated Staphylococcus aureus is currently 61. 2%, which was more than the figures obtained in a recent multicenter study (49.9%) [18]. Vancomycin sensitivity is maintained in 99.5% of MRSA strains, with strains with a minimum inhibitory concentration (MIC) of 1 µg/mL being 69.6%, and MIC 2 μg / ml – 18.3%. This may be clinically significant in reducing the effectiveness of vancomycin treatment of MRSA infections. In addition, 60.4% of the strains were resistant to ciprofloxacin.

    Other exciters

    Among 456 strains of Moraxella catarrhalis studied in the framework of the AWARE studies, 96.4% were resistant to penicillin [15, 16, 18]. Resistance to other antibiotics was significantly lower (<2.5%). In the UK, penicillin resistance in Moraxella catarrhalis has been associated with the production of β-lactamase (more than 91%) [16]. These strains were found to be susceptible to β-lactamase inhibitors, macrolides, and tetracyclines.

    Relatively recently, during an influenza epidemic, the possibility of pneumonia caused by the A(h2N1)pdm09 influenza virus was proven [10, 25]. At the same time, the influenza virus turned out to be resistant to amantadine, but sensitive to neuraminidase inhibitors. Resistance to oseltamivir remained low during the epidemic period.

    New antibiotics

    In recent years, several new antibiotics have emerged that have high potential in the treatment of CAP. One group of such antibiotics are cephalosporins, which are usually recommended as first-line drugs for the treatment of CAP. Some of these drugs have already been studied in clinical practice. Currently, in the Russian Federation, only ceftaroline is approved for the treatment of patients with CAP among the drugs listed below.

    Ceftaroline

    The drug is a representative of the fifth generation of cephalosporins, which are distinguished by their ability to block the activity of penicillin-binding proteins and prevent the synthesis of the bacterial wall. It is active against a wide range of Gram-positive and Gram-negative bacteria. In addition, it is the first drug approved for clinical use that is active in vitro against MRSA [26]. It was initially approved for clinical use in the USA (2010), then in Europe (2012) and the Russian Federation (2013). The efficacy and safety of intravenous ceftaroline (600 mg 2 times a day) for the treatment of CAP have been proven in several studies. The FOCUS 1 and 2 randomized, double-controlled, multicenter, phase III trial showed high clinical efficacy (>82%) and no less efficacy than ceftriaxone in hospitalized patients with CAP with PSI III–IV risk class [27, 28]. Clinical cure was defined as complete resolution or reduction of all symptoms of pneumonia and no need for further antibiotics. The exclusion criteria were very low or very high (PSI risk classes I–II or V) severity of the condition, severe kidney damage, immunosuppression, confirmed or suspected atypical flora, the presence of risk factors for MRSA, or another pathogen that is potentially resistant to generation III cephalosporins (ceftriaxone Comparative drug proposed by regulatory authorities), admission to the ICU. The study demonstrated a safe profile and good tolerability of ceftaroline, similar to that of ceftriaxone and other cephalosporins.

    In the Russian Federation, the high activity of ceftaroline in vitro against topical gram-positive and gram-negative pathogens, including MRSA, isolated in 2008–2012, has been proven. [18]. When observed during these years, no significant fluctuations in its activity against key pathogens were found, regardless of the geographical location of the centers participating in the study. Moreover, the unfavorable epidemic situation associated with the spread of MRSA clones in the territory of the Russian Federation indicates the high relevance of the new drug, which can be used to solve complex clinical problems.

    Ceftobiprol

    The new broad-spectrum parenteral cephalosporin is active in vitro against most common CAP bacteria, including MRSA. There are results from a multicenter, double controlled study of hospitalized patients with severe CAP who received ceftobiprole (500 mg as a 2-hour infusion every 8 hours) and ceftriaxone (as monotherapy or in combination with linezolid) [29]. Patients already treated for more than 24 hours in the previous 3 days with suspected or proven atypical pneumonia or aspiration pneumonia were excluded. There were no significant differences between the main indicators in the experimental and control groups. In terms of main control points, clinical cure and microbiological eradication, ceftobiprol was no worse than the comparator drug. However, the incidence of treatment-related adverse events was higher in the ceftobiprol group (36%) than in the control group (26%). The main manifestations were nausea and vomiting. There were no differences between the groups in the frequency of discontinuation of the drug associated with the occurrence of an adverse event. Ceftobiprol has been present on the Russian market for some time, but in 2013 its registration was terminated, and the further fate of the drug remains uncertain.

    Ketolides

    Ketolides are a subclass of macrolides that have been developed specifically against macrolide-resistant respiratory tract infections. Recently, ketolides have been developed for the treatment of CAP.

    Cethromycin. To evaluate the new ketolide in patients with mild to moderate CAP, 2 double-blind, controlled, randomized, multicenter phase III trials were conducted [30]. The activity of cethromycin in vitro has been proven against the main pathogens of CAP. The drug overcomes the resistance of Streptococcus pneumoniae associated with the mechanism of efflux and macrolide methylation. Randomized patients received oral cethromycin (300 mg/day for 7 days) or clarithromycin (250 mg 2 times/day for 7 days). Two studies showed equal efficacy and safety of cethromycin and clarithromycin in patients with CAP. However, the study was conducted only in adult outpatients with CAP. Clinical efficacy and microbiological eradication were similar in both studies. Cethromycin appeared to be more effective in the treatment of pneumonia caused by bacteremic Streptococcus pneumoniae, but the fact that the study included a small number of patients makes it necessary to refrain from drawing far-reaching conclusions on this matter. The most common adverse events were diarrhea, nausea, taste perversion and headache. However, metallic taste in the mouth was significantly more common in patients treated with cethromycin. There were no patients with risk factors for hepatotoxicity among those randomized.

    Solithromycin (Solithromycin). The drug demonstrates high activity in vitro against the main pathogens of CAP and infections of the skin and soft tissues on 10,670 strains isolated from patients in 52 medical centers in the USA and Europe [31]. Recently, the results of a phase I study (171 volunteers) and a phase II study (64 patients with CAP) were obtained: the use of the drug turned out to be safe [32].

    Quinolones

    Quinolones play an important role in the treatment of CAP, and their use in patients with CAP has been increasing over the past decade.

    Nemonoxacin (Nemonoxacin). Nemonoxacin is a novel non-fluorinated quinolone with high in vitro and in vivo activity against CAP pathogens, including multiresistant Streptococcus pneumoniae. A randomized, double-blind, multicentre study demonstrated the safety and efficacy of nonmonoxacin (versus levofloxacin) in 265 adult patients with moderate CAP [33]. Approximately 80–85% of infections were classified as PSI risk class I–II. Nemonoxacin (750 and 500 mg) was taken orally for 7 days, clinical and microbiological activity was higher than that of the reference drug (levofloxacin). There were no significant differences in the number of drug-related adverse events. However, side effects such as diarrhea, irritability, and headache were more common with nonmonoxacin. Information was received on the completion of registration of the drug in the United States.

    Zabofloxacin (Zabofloxacin). A phase II, double-blind clinical trial examined the safety and efficacy of two dosing regimens of zabofloxacin (a fluoroquinolone) compared with those of levofloxacin in CAP [34]. Preliminary results of a double-blind, randomized, multicenter study in South Korea showed that zabofloxacin has clinical and microbiological efficacy equal to moxifloxacin in adult patients with moderate CAP [35].

    JNJ-Q2. JNJ-Q2 is a new fluorinated quinolone with a fluorine atom at the 4-position, which was developed to suppress bacteria – the causative agents of infections of the skin, soft tissues and respiratory tract, including CAP. Recently, a study was completed in which JNJ-Q2 showed high activity against CAP pathogens [36].

    KPI-10. The new fluoroquinolone KPI-10 demonstrated high activity against CAP pathogens, including CA-MRSA, in the study of strains isolated from patients in America, Europe and the Asia-Pacific region [37].

    Antibiotics of other groups

    BC-3781 is a semi-synthetic antibiotic pleuromutilin. A phase II clinical trial of pleuromutilin in patients with skin and soft tissue infections has recently been completed. It showed high activity against pathogens of respiratory tract infections, and it did not decrease in the presence of resistance to antibiotics of other groups [38].

    Conclusion

    In recent years, there has been a clear trend towards increased resistance of CAP pathogens to commonly used antibiotics.