Carbapenems in Treating Carbapenem-Resistant Acinetobacter Baumannii Infections
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Questions and Answers

Which combination of antibiotics may be effective against Polymyxins-resistant CRAB?

  • High-dose Fosfomycin and High-dose Trimethoprim
  • High-dose Meropenem and High-dose Ampicillin/Sulbactam (correct)
  • High-dose Rifamycins and High-dose Aminoglycosides
  • High-dose Minocycline and High-dose Tigecycline

    • What is the purpose of adding β-Lactamases Inhibitors (BLIs) to β-Lactam Antibiotics?

  • To enhance the effect of β-Lactam Antibiotics against MDR/EDR GNB infections (correct)
  • To increase the resistance of Gram-negative Bacteria to β-Lactam Antibiotics
  • To reduce the effectiveness of β-Lactam Antibiotics
  • To replace β-Lactam Antibiotics with other types of antibiotics

    • What is the recommended daily dose of Meropenem to treat severe CRAB infections?

  • ≥8 grams per day
  • ≥2 grams per day
  • ≥6 grams per day (correct)
  • ≥4 grams per day

    • What is the alternative antibiotic combination to Carbapenems for treating CRAB infections?

    <p>Minocycline and Tigecycline</p> Signup and view all the answers

    Which of the following antibiotics may be effective against High-dose Extended, Prolonged, or Continuous Infusion Meropenem-resistant Acinetobacter baumannii isolates?

    <p>High-dose Imipenem/Cilastatin</p> Signup and view all the answers

    What is the goal of using High-dose Extended, Prolonged, or Continuous Infusion Carbapenems in combination with other antibiotics?

    <p>To treat severe MDR/EDR GNB infections, including CRAB</p> Signup and view all the answers

    What is the recommended dosage of Meropenem in combination therapy for CRAB infections?

    <p>≥6 g/day</p> Signup and view all the answers

    What is the mortality rate in the Colistin monotherapy group in the first study?

    <p>46%</p> Signup and view all the answers

    What is the clinical failure rate in the Colistin/Meropenem combination therapy group in the second study?

    <p>64%</p> Signup and view all the answers

    What is the overall mortality rate in the combination Antibiotics' regimens in the systematic review/meta-analysis study?

    <p>28.6%-70%</p> Signup and view all the answers

    What is the range of Microbiological eradication rates in the combination Antibiotics' regimens?

    <p>32.7%-67.3%</p> Signup and view all the answers

    What is the dosage of Sulbactam in High-dose Extended Infusion Ampicillin/Sulbactam combination therapy?

    <p>6-9 grams per day</p> Signup and view all the answers

    What is the recommended dosage of Meropenem in the Triple-Combination Regimen?

    <p>2 grams infused over 3 hours every 8 hours</p> Signup and view all the answers

    What is the alternative to High-dose Minocycline in the Triple-Combination Regimen?

    <p>High-dose Tigecycline</p> Signup and view all the answers

    What is the dosage of Ampicillin/Sulbactam in High-dose Extended Infusion combination therapy?

    <p>2-4 grams of Sulbactam infused over 4 hours every 8 hours</p> Signup and view all the answers

    What is the potential benefit of the Triple-Combination Regimen in treating CRAB infections?

    <p>Potentially eradicating Carbapenem-resistant Acinetobacter baumannii (CRAB) infections</p> Signup and view all the answers

    What did studies comparing the efficacy of Colistin monotherapy to that of Colistin in combination with Meropenem find?

    <p>The combination of Colistin and Meropenem was ineffective</p> Signup and view all the answers

    What is the minimum inhibitory concentration (MIC) of Meropenem and/or Imipenem that distinguishes CRAB isolates?

    <p>8 µg/ml</p> Signup and view all the answers

    Why does the IDSA discourage the use of Meropenem or Imipenem/Cilastatin in CRAB treatment?

    <p>Due to increased β-lactam toxicity without clinical advantage</p> Signup and view all the answers

    What is the recommended regimen for CRAB infections according to the ESCMID guidelines?

    <p>High-dose Extended Infusion Ampicillin/Sulbactam</p> Signup and view all the answers

    What is the recommended additional medication to add to the dual core regimen of High-dose Extended Infusion Ampicillin/Sulbactam for CRAB infections?

    <p>Meropenem or Imipenem/Cilastatin</p> Signup and view all the answers

    What is the primary mechanism of action of Cefiderocol?

    <p>Inhibition of OXA-type Class D β-lactamases</p> Signup and view all the answers

    What is the recommended use of Cefiderocol in CRAB infections?

    <p>Only for CRAB infections that are resistant to other antibiotics or refractory to standard combinations</p> Signup and view all the answers

    According to international surveillance studies, what percentage of CRAB isolates are responsive to Cefiderocol at 4 µg/ml or below?

    <p>95%</p> Signup and view all the answers

    What is the primary indication for Cefiderocol?

    <p>Severe urinary tract infections (UTI) caused by susceptible MDR-GNB</p> Signup and view all the answers

    What is the recommended duration of infusion for High-dose Extended Infusion Meropenem in CRAB infections?

    <p>3 hours every 8 hours</p> Signup and view all the answers

    What is the minimum inhibitory concentration (MIC) of Cefiderocol against baumannii-infected mice thigh and lung models?

    <p>4 µg/ml or less</p> Signup and view all the answers

    What percentage of CRAB isolates are susceptible to Cefiderocol, according to the CLSI susceptibility criteria?

    <p>95%</p> Signup and view all the answers

    What is the recommended approach for treating CRAB infections with Cefiderocol, according to the IDSA panel?

    <p>Using Cefiderocol in combination with other drugs</p> Signup and view all the answers

    What is the mortality rate at the conclusion of the clinical study involving 54 patients with CRAB infections in the Cefiderocol group?

    <p>49%</p> Signup and view all the answers

    What is the main challenge in determining the susceptibility of CRAB to Cefiderocol?

    <p>The inconsistent iron levels in the medium</p> Signup and view all the answers

    What is the probability of recurrent CRAB infection in the Cefiderocol group in the observational trial?

    <p>17%</p> Signup and view all the answers

    What is the recommended approach for treating CRAB infections, according to the ESCMID guidelines?

    <p>Restricting the use of Cefiderocol to instances in which all other treatment options have failed</p> Signup and view all the answers

    What is the minimum inhibitory concentration (MIC90) of Cefiderocol against Acinetobacter.baumannii bacteria?

    <p>1-8 µg/ml</p> Signup and view all the answers

    What is the main difference between the Cefiderocol and High-dose Extended-infusion Meropenem treatment regimens in the randomized trial?

    <p>No significant difference</p> Signup and view all the answers

    What is the purpose of using Cefiderocol in combination with other drugs, according to the IDSA panel?

    <p>To increase the likelihood of including at least one efficacious agent in the treatment regimen</p> Signup and view all the answers

    What is the primary outcome of the CREDIBLE randomized controlled trial for patients with CRAB infections?

    <p>No clinical or microbiological benefits of Cefiderocol over BAT</p> Signup and view all the answers

    In the APEKS-NP randomized controlled trial, what was the outcome for patients with pneumonia caused by Acinetobacter baumannii?

    <p>Comparable mortality, clinical improvement, and microbiological outcomes between Cefiderocol and High-dose Extended-infusion Meropenem</p> Signup and view all the answers

    What is the recommended use of Cefiderocol for CRAB infections?

    <p>As a component of combination therapy for CRAB infections</p> Signup and view all the answers

    What is the mechanism of action of Rifamycin antibiotics?

    <p>Inhibition of bacterial RNA Polymerase</p> Signup and view all the answers

    What is the potential therapeutic advantage of using Rifabutin instead of Rifampin?

    <p>Uncertain</p> Signup and view all the answers

    What is the proposed mechanism of synergy between Rifabutin and Polymyxins?

    <p>Polymyxins disrupt bacterial membrane permeability, allowing Rifabutin to penetrate cells</p> Signup and view all the answers

    What is the outcome of the three randomized trials examining CRAB patients with Colistin or Rifampin?

    <p>Comparable mortality rates between Colistin alone and Colistin plus Rifampin</p> Signup and view all the answers

    Why do infectious diseases guidelines’ panels not recommend Rifabutin or other Rifamycins for CRAB therapy?

    <p>Due to toxicity and drug interactions associated with Rifamycins</p> Signup and view all the answers

    What is the limitation of using Rifamycin antibiotics for CRAB infections?

    <p>Toxicity and drug interactions</p> Signup and view all the answers

    What is the outcome of the study comparing Colistin monotherapy and Colistin plus Rifampin for CRAB pneumonia?

    <p>Non-significant difference in mortality rates between Colistin alone and Colistin plus Rifampin</p> Signup and view all the answers

    What is the minimum creatinine clearance required for Colistin monotherapy to achieve 90% PTA for fAUC24h/MIC 25 against Acinetobacter baumannii isolates with MIC of 2 µg/ml?

    <p>&gt;50 mL/min</p> Signup and view all the answers

    What is significantly associated with acute kidney injury (AKI) in patients receiving Colistin treatment?

    <p>Plasma concentration &gt;3.3 µg/ml on the seventh day</p> Signup and view all the answers

    What is the effect of combining Colistin with Sulbactam or Fosfomycin on CRAB strains?

    <p>Synergistic effect</p> Signup and view all the answers

    What is the significance of Monte Carlo simulation principles in optimizing medication regimens?

    <p>Identifying appropriate antibiotic regimens for empirical or documented treatment</p> Signup and view all the answers

    What is the benefit of reducing the dose of Colistin in patients with high MICs?

    <p>Preventing nephrotoxicity</p> Signup and view all the answers

    What is the significance of the study on optimizing Colistin monotherapy regimens against CRAB infections?

    <p>Optimizing medication regimens using susceptibility data as MIC values</p> Signup and view all the answers

    What is the percentage of clinical CRAB isolates found to be Colistin-resistant in a European study?

    <p>45.5%</p> Signup and view all the answers

    What is the effect of combining Colistin with Fosfomycin on mortality rates?

    <p>Reduced mortality rates</p> Signup and view all the answers

    What is the significance of the review and meta-analysis of seven controlled trials on Colistin?

    <p>Colistin is as effective as Imipenem/Cilastatin, Tobramycin, and Tigecycline</p> Signup and view all the answers

    What is the type of infection caused by MDR-AB and XDR-AB strains?

    <p>Nosocomial infections</p> Signup and view all the answers

    What is the primary concern with using Fosfomycin to treat life-threatening conditions?

    <p>There is a lack of evidence for its use in such conditions.</p> Signup and view all the answers

    What is the significance of Fosfomycin in treating multidrug-resistant pathogens?

    <p>It is effective against a wide range of microorganisms, including Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Enterococcus spp.</p> Signup and view all the answers

    Why are synergistic regimens with Fosfomycin important?

    <p>To increase the bactericidal efficacy of Fosfomycin and prevent antimicrobial resistance.</p> Signup and view all the answers

    What is the significance of the AUCss,24h value of approximately 50 µg*h/ml?

    <p>It is the target value for unbound Colistin plasma concentration in patients with creatinine clearance 80 mL/min.</p> Signup and view all the answers

    What is the primary concern with using Polymyxins for treating CRAB infections?

    <p>They do not meet Pharmacokinetics/Pharmacodynamics objectives.</p> Signup and view all the answers

    What is the significance of Acinetobacter baumannii in hospitals?

    <p>It is a significant cause of nosocomial infections due to its resistance to multiple antimicrobials, including Carbapenems.</p> Signup and view all the answers

    What is the significance of Fosfomycin in the treatment of MDR pathogens?

    <p>It is a Phosphonic antibiotic discovered in 1969, employed to treat Multidrug-resistant Enterobacteriaceae.</p> Signup and view all the answers

    Why is it essential to develop novel treatments for MDR pathogens?

    <p>To enhance antimicrobial action and reduce resistance.</p> Signup and view all the answers

    What is the significance of the daily dose of at least 450 mg of Colistin base activity?

    <p>It is equivalent to approximately 15 MIU of Colistin Methane-Sulfonate.</p> Signup and view all the answers

    What is the significance of Carbapenem-resistant Acinetobacter baumannii (CRAB) infections?

    <p>They pose a significant public health threat due to Carbapenem resistance.</p> Signup and view all the answers

    What is the primary mechanism of action of Fosfomycin?

    <p>Affecting the synthesis of peptidoglycan</p> Signup and view all the answers

    Which of the following factors is NOT a risk factor for Acinetobacter MDR colonization?

    <p>Age less than 18 years</p> Signup and view all the answers

    What is the typical antibiotic resistance profile of ICU isolates of A.baumannii?

    <p>Resistant to β-Lactams, Aminoglycosides, and Fluoroquinolones</p> Signup and view all the answers

    What is the primary advantage of Fosfomycin in treating infections?

    <p>All of the above</p> Signup and view all the answers

    What is the recommended treatment approach for CRAB infections?

    <p>Combination antimicrobial therapy</p> Signup and view all the answers

    What is the mechanism by which Fosfomycin modifies immune responses?

    <p>Affecting TNF-, IL-1, and IL-6 levels in lymphocytes, monocytes, and neutrophils</p> Signup and view all the answers

    What is the significance of Fosfomycin in treating nosocomial infections?

    <p>It is crucial for treating nosocomial infections</p> Signup and view all the answers

    What is the typical resistance rate of IV Fosfomycin?

    <p>3.4%</p> Signup and view all the answers

    What is the significance of colistin in treating CRAB infections?

    <p>It is the most favored treatment for CRAB infections</p> Signup and view all the answers

    What is the primary goal of primary infection control measures for A.baumannii?

    <p>Screening for resistant bacteria and providing chlorhexidine baths for source management</p> Signup and view all the answers

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