Antibiotic Synergy in A. baumannii Infections
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Questions and Answers

What is the primary concern regarding the use of colistin-based combination therapy for A. baumannii disease?

  • Higher cost compared to other antibiotic regimens
  • Higher toxicity compared to monotherapy
  • Increased risk of resistance development
  • No significant difference in clinical response or mortality (correct)

    • What was the range of Fosfomycin's MIC values against 191 A. baumannii isolates?

  • 128-8192 g/mL
  • 1-16 g/mL
  • 64-4096 g/mL
  • 32-2048 g/mL (correct)

    • What is the primary reason why Fosfomycin and aminoglycosides are more effective than other antibiotics against A. baumannii?

  • The exact mechanism is not fully understood (correct)
  • They have a lower MIC value
  • They have a higher bactericidal efficacy
  • They have a synergistic effect

    • What was the outcome of the time-kill kinetics experiments for the combination of Fosfomycin and conventional antibiotics against A. baumannii?

    <p>The combination failed to show bactericidal efficacy</p> Signup and view all the answers

    What was the cumulative incidence of resistance development during Fosfomycin monotherapy in a 2017 analysis of 128 studies?

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

    What was the primary finding of a 2017 analysis of 128 studies regarding the clinical effectiveness of Fosfomycin compared to other antibiotics?

    <p>Fosfomycin had similar clinical effectiveness to other antibiotics</p> Signup and view all the answers

    What is the primary focus of the study conducted from January 2017 to June 2020?

    <p>Assessing the risk variables related to survival or mortality in severe pneumonia</p> Signup and view all the answers

    What percentage of interactions were synergistic in the 2020 review?

    <p>33.7%</p> Signup and view all the answers

    Which bacteria had the highest susceptibility to Fosfomycin in the 2010-2015 study?

    <p>Escherichia coli</p> Signup and view all the answers

    What was the most common combination of antibiotics used in the study conducted from January 2017 to June 2020?

    <p>Fosfomycin and Colistin</p> Signup and view all the answers

    What was the minimum inhibitory concentration of Fosfomycin in the 2021 study?

    <p>128 µg/mL</p> Signup and view all the answers

    What percentage of isolates showed resistance to Fosfomycin in the 2021 study?

    <p>90.6%</p> Signup and view all the answers

    What is the primary advantage of combining Fosfomycin with other antibiotics?

    <p>Enhanced bactericidal efficacy and reduced antibiotic resistance</p> Signup and view all the answers

    In which bacteria was the most significant interaction observed with Daptomycin?

    <p>Enterococcus spp.</p> Signup and view all the answers

    What is the primary benefit of using Fosfomycin-based antibiotic combinations?

    <p>Enhancing the bactericidal efficacy and reducing antibiotic resistance</p> Signup and view all the answers

    What was the primary finding of the 2020 review regarding the interactions between Fosfomycin and other antibiotics?

    <p>The majority of interactions were additive or neutral</p> Signup and view all the answers

    What is the estimated number of cases of Acinetobacter baumannii reported annually globally?

    <p>1 million</p> Signup and view all the answers

    What is the primary goal of the SENTRY Antimicrobial Surveillance Program?

    <p>To track patterns of antimicrobial resistance and the efficacy of antimicrobials against the most significant pathogen isolates</p> Signup and view all the answers

    What is the preferred treatment for Stenotrophomonas maltophilia infections?

    <p>Trimethoprim-sulfamethoxazole (TMP-SMX)</p> Signup and view all the answers

    What type of Acinetobacter is the most prevalent and resistant to penicillins by nature?

    <p>A.baumannii</p> Signup and view all the answers

    What is the correlation found in the SENTRY Program investigation?

    <p>Between the decline in susceptibility rates to antimicrobials and the increase in the extensively drug-resistant (XDR) Acb complex phenotype</p> Signup and view all the answers

    What is the main reason for the decline in susceptibility rates to antimicrobials?

    <p>The global proliferation of foreign clones resistant to carbapenems due to the production of carbapenem-hydrolyzing class D-lactamases (CHDLs)</p> Signup and view all the answers

    What is the efficacy of Minocycline against extensively drug-resistant (XDR) Acb complex isolates?

    <p>72.7%</p> Signup and view all the answers

    What is the resistance rate of Sulbactam against Acinetobacter baumannii?

    <p>16.4%–58.9%</p> Signup and view all the answers

    What is the most common infection caused by Acinetobacter baumannii?

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

    What is the mortality rate linked to inappropriate empirical treatment for S.maltophilia infections?

    <p>37.5%</p> Signup and view all the answers

    What percentage of isolates showed multidrug resistance in a study in Dohuk province-Iraq?

    <p>94.4%</p> Signup and view all the answers

    What was the highest sensitivity rate found in a study in Dohuk province-Iraq?

    <p>31.5%</p> Signup and view all the answers

    What is the suggested effective therapy for severe CRAB infections?

    <p>Trimethoprim-sulfamethoxazole combined with colistin</p> Signup and view all the answers

    What was the trend observed in susceptibility rates for all antimicrobial agents across regions?

    <p>Significant decrease</p> Signup and view all the answers

    What is the primary mechanism by which Smx and Tmp inhibit Csu assembly?

    <p>Through folate stress</p> Signup and view all the answers

    What was the primary outcome in comparing TMP/SMX treatment to colistin or ampicillin–sulbactam treatment?

    <p>TMP/SMX had lower all-cause 30-day mortality</p> Signup and view all the answers

    What was the highest rate of extensively drug-resistant Acb complex isolates found in?

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

    What was the primary finding of the in vitro study comparing trimethoprim-sulfamethoxazole alone and combined with colistin?

    <p>Trimethoprim-sulfamethoxazole plus colistin was effective against all strains after 6 h</p> Signup and view all the answers

    What was the finding regarding the use of nebulized antibiotics in clinical trials for gram-negative ventilator-associated pneumonia?

    <p>No clinical benefit</p> Signup and view all the answers

    What was the prevalence of A.baumannii in clinical samples in a study in Dohuk province-Iraq?

    <p>7.2%</p> Signup and view all the answers

    What is a limitation of nebulized antibiotics in treating CRAB pneumonia?

    <p>Inadequate lung dispersion</p> Signup and view all the answers

    What was the outcome of the three RCTs comparing nebulized antibiotics to placebo in gram-negative ventilator-associated pneumonia?

    <p>No clinical benefit</p> Signup and view all the answers

    What was the primary reason for the effectiveness of minocycline against S.maltophilia isolates?

    <p>Susceptibility rates exceeding 99.0%</p> Signup and view all the answers

    What is the reason for the panel's advice against using nebulized antibiotics as supplementary therapy for CRAB pneumonia?

    <p>Lack of clinical benefit</p> Signup and view all the answers

    What was the primary outcome of the study on fluoroquinolones as a substitute for TMP-SMX in the treatment of S.maltophilia infections?

    <p>Fluoroquinolones were as effective as TMP-SMX</p> Signup and view all the answers

    What was the finding regarding the distribution of nebulized medicines in lung tissue?

    <p>Uneven distribution in infected lungs</p> Signup and view all the answers

    What was the primary association found in patients treated with TMP/SMX?

    <p>Admission for infection and septic shock</p> Signup and view all the answers

    What was the primary outcome of the study evaluating the effectiveness of TMP/SMX as a monotherapy for carbapenem-resistant Acinobacter baumannii infections?

    <p>TMP/SMX was effective in treating carbapenem-resistant Acinobacter baumannii infections</p> Signup and view all the answers

    What is the primary concern regarding the use of aerosolized colistin?

    <p>Inadequate lung dispersion</p> Signup and view all the answers

    What is the significance of the study on Acb complex and S.maltophilia isolates?

    <p>Highlighted the rise of extensively drug-resistant isolates</p> Signup and view all the answers

    What is the primary concern regarding antimicrobial resistance in Acinetobacter spp.?

    <p>Increasing carbapenem resistance</p> Signup and view all the answers

    What percentage of patients with pneumonia were caused by A. baumannii in the first trial?

    <p>65%</p> Signup and view all the answers

    What was the outcome of the three clinical studies comparing nebulized antibiotics to a placebo for the treatment of ventilator-associated pneumonia?

    <p>No improvement in clinical outcomes or survival advantage</p> Signup and view all the answers

    What was the result of the systematic review and statistical analysis of 13 trials involving 1,733 adults with ventilator-associated pneumonia?

    <p>Nebulized antibiotics resulted in partial resolution of infection-related clinical symptoms</p> Signup and view all the answers

    What is the likely reason why nebulized antibiotics do not effectively penetrate and distribute throughout lung tissue?

    <p>They are administered via parenteral formulations that were not designed for inhalation</p> Signup and view all the answers

    What is the recommendation of the panel regarding the use of nebulized antibiotics as an additional treatment for CRAB pneumonia?

    <p>Do not use nebulized antibiotics as an additional treatment for CRAB pneumonia</p> Signup and view all the answers

    What is the primary concern regarding the use of nebulized antibiotics?

    <p>Asymmetrical distribution in infected airways</p> Signup and view all the answers

    What is the recommended treatment approach for moderate to severe CRAB infections according to the International Society for Antimicrobials?

    <p>Combination therapy with at least two In-Vitro active antibiotics</p> Signup and view all the answers

    What is the primary reason why nebulized antibiotics are not effective in treating ventilator-associated pneumonia?

    <p>They do not effectively penetrate and distribute throughout lung tissue</p> Signup and view all the answers

    What is the result of the PK/PD modeling research on administering the prodrug of colistin via aerosolization?

    <p>It resulted in considerable concentrations of the active drug in the epithelial lining fluid</p> Signup and view all the answers

    What is the focus of recent years regarding Acinetobacter spp.?

    <p>Their susceptibility to resistance mechanisms</p> Signup and view all the answers

    What is the primary reason for the disparity in the effectiveness of Carbapenem and Sulbactam combination against CRAB infections?

    <p>Sulbactam susceptibility</p> Signup and view all the answers

    What is the limitation of using Tigecycline in treating MDR Acinetobacter spp. infections?

    <p>Insufficient levels at the infection site</p> Signup and view all the answers

    What is the primary benefit of using combination therapy over monotherapy in treating MDR Acinetobacter spp. infections?

    <p>Enhanced bactericidal activity</p> Signup and view all the answers

    Which of the following antibiotics is often used in combination with other antibiotics to treat MDR Acinetobacter spp. infections?

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

    What is the primary focus of further research into Sulbactam's effectiveness in treating MDR Acinetobacter spp. infections?

    <p>Investigating the minimum inhibitory concentration (MIC) breakpoints</p> Signup and view all the answers

    What is the primary advantage of using combination therapy in treating MDR Acinetobacter spp. infections, especially in cases where the primary therapy is Polymyxins or Ampicillin/Sulbactam?

    <p>Enhanced bactericidal activity</p> Signup and view all the answers

    What is the primary concern with nebulized antibiotics for CRAB pneumonia?

    <p>Risk of bronchioconstriction</p> Signup and view all the answers

    What is the recommended approach for moderate to severe CRAB infections?

    <p>Combination therapy with at least two active antibiotics</p> Signup and view all the answers

    What is the significance of High-dose Ampicillin/Sulbactam?

    <p>Most effective against MDR Acinetobacter spp.</p> Signup and view all the answers

    What is the concern with Carbapenem-Polymyxin without Ampicillin/Sulbactam?

    <p>Rejected by infectious guidelines</p> Signup and view all the answers

    What is the goal of Sulbactam MIC breakpoint studies?

    <p>To improve the efficacy of Ampicillin/Sulbactam combination therapy</p> Signup and view all the answers

    What is the significance of Polymyxins in combination therapy?

    <p>Shows synergistic action with Tigecycline</p> Signup and view all the answers

    What is the primary reason for the increased prevalence of CR-GNB?

    <p>Increased misuse of antibiotics</p> Signup and view all the answers

    What is the significance of Ampicillin/Sulbactam in combination therapy?

    <p>Acts against Acinetobacter spp. by directly saturating Penicillin-binding Proteins 1 &amp; 3</p> Signup and view all the answers

    What is the significance of Colistin in CR-GNB treatment?

    <p>Is one of the few CR-GNB treatments, with its action potentially increased by loading dosage, higher maintenance dose, adjunct local administration, and combination treatment</p> Signup and view all the answers

    What is the concern with Carbapenem-resistant Acinetobacter baumannii?

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

    What is the primary mechanism by which Colistin kills Gram-negative bacteria?

    <p>By damaging their outer membranes</p> Signup and view all the answers

    What was the outcome of the study aimed to test the In-Vivo efficacy of Colistin combined with Meropenem, Tigecycline, Fosfomycin, Fusidic acid, Rifampin, or Sulbactam against XDR-AB infections?

    <p>Colistin, Tigecycline, Rifampin, Fosfomycin, or Sulbactam combination dramatically reduced bacterial counts</p> Signup and view all the answers

    What was the finding regarding the effectiveness of Colistin monotherapy in the study?

    <p>It was effective against 91.7% of strains</p> Signup and view all the answers

    What was the result of the combination of Colistin and Rifampin in the study?

    <p>It was more effective than Colistin monotherapy</p> Signup and view all the answers

    What was the outcome of the multicenter, open-label, randomized study of life-threatening XDR-AB infections?

    <p>Rifampin plus Colistin largely increased microbial-eradication rate in the first days of combination</p> Signup and view all the answers

    What is the primary concern regarding the use of Colistin-based combination therapy for A. baumannii disease?

    <p>The potential for antibiotic resistance</p> Signup and view all the answers

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

    <p>Combination therapy with multiple antibiotics</p> Signup and view all the answers

    What was the finding regarding the correlation between Colistin and nephrotoxicity?

    <p>Colistin does not strongly correlate with nephrotoxicity</p> Signup and view all the answers

    What is the primary benefit of using combination therapy for CRAB infections?

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

    What was the finding regarding the effectiveness of Tigecycline in combination therapy for CRAB infections?

    <p>It was effective against non-bacteremia associated CRAB infections</p> Signup and view all the answers

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