Recent

  • Show all results for ""

🎧 New: AI-Generated Podcasts Turn your study notes into engaging audio conversations. Learn more

Colistin Resistance and Antibiotic Usage
56 Questions
0 Views

Colistin Resistance and Antibiotic Usage

Created by
@QuickerDatePalm

Podcast Beta

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary mechanism of action of polymyxins against Gram-negative bacteria?

  • Disruption of the bacterial cell membrane (correct)
  • Inhibition of protein synthesis
  • Inhibition of DNA replication
  • Inhibition of cell wall synthesis

    • What is the main reason for the limited use of polymyxins in treating CRAB infections?

  • Development of resistance to polymyxins
  • Higher cost compared to other antibiotics
  • Lack of in vitro activity against CRAB
  • Unavailability for target attainment and toxicity constraint (correct)

    • What is the primary characteristic of polymyxin that allows it to penetrate the outer cell membrane of bacteria?

  • Tripeptide core
  • N-terminal fatty acid acyl side chain
  • Cationic charge
  • Fatty acid chain (correct)

    • What is the main concern associated with the prolonged use of polymyxins?

    <p>Outbreak of polymyxin-resistant bacteria</p> Signup and view all the answers

    What is the term used to describe the process by which polymyxins disrupt the bacterial cell membrane?

    <p>Dissolution of the outer and inner membranes</p> Signup and view all the answers

    What is the primary reason for the need to modify polymyxin dosing in patients with impaired kidney function?

    <p>To avoid nephrotoxicity</p> Signup and view all the answers

    What is the primary mechanism by which Acinetobacter baumannii acquires carbapenem resistance?

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

    What is the primary concern associated with using higher doses of polymyxins to achieve target attainment?

    <p>Increased risk of nephrotoxicity</p> Signup and view all the answers

    What is the term used to describe the process by which polymyxins bind to the lipopolysaccharide of Gram-negative bacteria?

    <p>Selective binding</p> Signup and view all the answers

    What is the primary limitation of using polymyxins in patients receiving ECMO?

    <p>Difficulty in optimizing polymyxin dosing</p> Signup and view all the answers

    What is the mechanism of action of injectable polymyxins?

    <p>Disrupting the cytoplasmic membrane integrity</p> Signup and view all the answers

    What is the primary indication for the use of I.V. fosfomycin?

    <p>Urinary and extra-urinary infections</p> Signup and view all the answers

    What type of bacteria is fosfomycin active against?

    <p>Both gram-positive and gram-negative bacteria</p> Signup and view all the answers

    What is the primary reason for the increased use of colistin in recent times?

    <p>The global spread of multi-drug resistant Acinetobacter baumannii and Pseudomonas aeruginosa</p> Signup and view all the answers

    What is the role of fosfomycin in the prevention and treatment of chronic obstructive pulmonary conditions?

    <p>It is used as an inhaled therapy</p> Signup and view all the answers

    What is a major concern associated with the use of colistin?

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

    What is the effect of fosfomycin on the production of N-acetylmuramic acid?

    <p>It obstructs the production of N-acetylmuramic acid</p> Signup and view all the answers

    What is the primary benefit of combining colistin with intravenous fosfomycin?

    <p>Enhanced immunomodulatory effects</p> Signup and view all the answers

    What is a major gap in the understanding of polymyxin use?

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

    What is the result of fosfomycin's inhibition of the enolpyruvate transferase enzyme?

    <p>It obstructs the first stage of bacterial cell wall synthesis</p> Signup and view all the answers

    What is the primary concern associated with the use of polymyxin B?

    <p>Its well-known serious adverse effects</p> Signup and view all the answers

    What is the significance of fosfomycin's broad-spectrum activity?

    <p>It includes multidrug resistant pathogens, including MRSA, VRE, ESBL and carbapenemase producing Enterobacteriaceae</p> Signup and view all the answers

    What is the usual dosage of I.V. fosfomycin?

    <p>4 g every 6 h</p> Signup and view all the answers

    What is a major consequence of the global spread of multi-drug resistant Acinetobacter baumannii and Pseudomonas aeruginosa?

    <p>Escalating colistin consumption</p> Signup and view all the answers

    What is the primary goal of interventions involving polymyxin use?

    <p>To minimize the risk of nephrotoxicity and overdose</p> Signup and view all the answers

    What is the significance of polymyxins being amphipathic compounds?

    <p>They have cationic and hydrophobic chemical properties</p> Signup and view all the answers

    What is the primary association of multidrug-resistant Acinetobacter baumannii (MDRAB)?

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

    What is the result of the emergence of drug resistance to polymyxins?

    <p>The restricted use of polymyxins</p> Signup and view all the answers

    What is the primary reason for the adjustment of the dosage scheme of polymyxin B?

    <p>According to the pharmacokinetic and pharmacodynamic index data</p> Signup and view all the answers

    What is the therapeutic range of colistin in animal models of infection?

    <p>2-5 mg/kg body weight</p> Signup and view all the answers

    What is the key parameter for polymyxins to effectively exert their anti-infection effects?

    <p>AUC_0–24/MIC</p> Signup and view all the answers

    How is colistin primarily administered in clinical cases of gastrointestinal infections?

    <p>Intramuscularly, intravenously, or through other vascular access routes</p> Signup and view all the answers

    What is the primary mechanism of fosfomycin resistance in Escherichia coli?

    <p>The expression of murA in low levels</p> Signup and view all the answers

    What is the function of FosA family proteins in mediating resistance to fosfomycin?

    <p>Act as glutathione S-transferases</p> Signup and view all the answers

    What is the primary reason for the increase in clinical bacterial strains resistant to polymyxin?

    <p>The increased and inappropriate use of colistin and polymyxin</p> Signup and view all the answers

    How is the plasma colistin concentration typically measured?

    <p>By the high-performance liquid chromatography-fluorescence detector method</p> Signup and view all the answers

    What is the primary route of excretion of polymyxin?

    <p>Through the kidneys and urine</p> Signup and view all the answers

    What is the effective concentration of colistin in blood plasma to cure an infected patient?

    <p>Between 1 and 3 μg/mL</p> Signup and view all the answers

    What is the primary function of the Fos family proteins in relation to antimicrobial resistance?

    <p>Opening the ring of fosfomycin and forming stable glutathione adducts</p> Signup and view all the answers

    What is the most common mechanism of resistance to polymyxin in Gram-negative bacteria?

    <p>Addition of phosphoethanolamine to the secondary acyl groups of lipid A</p> Signup and view all the answers

    What is the primary advantage of using combination therapy with polymyxin and fosfomycin?

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

    What is the effect of the combination of polymyxin and fosfomycin on the expression of biomarkers associated with drug resistance?

    <p>Repressed expression of biomarkers</p> Signup and view all the answers

    What is the primary concern associated with the use of polymyxin in combination with other nephrotoxic agents?

    <p>Increased risk of nephrotoxicity</p> Signup and view all the answers

    What is the primary mechanism of synergy between polymyxin and fosfomycin in treating carbapenem-resistant Acinetobacter baumannii?

    <p>Polymyxin and fosfomycin have a synergistic effect on the inhibition of bacterial growth</p> Signup and view all the answers

    What is the primary advantage of using polymyxin in combination with fosfomycin in treating carbapenem-resistant Acinetobacter baumannii?

    <p>Enhanced bactericidal activity against carbapenem-resistant Acinetobacter baumannii</p> Signup and view all the answers

    What is the primary concern associated with the use of polymyxin in treating carbapenem-resistant Acinetobacter baumannii?

    <p>Increased risk of nephrotoxicity</p> Signup and view all the answers

    What is the primary mechanism of resistance to fosfomycin in Gram-negative bacteria?

    <p>Formation of stable glutathione adducts</p> Signup and view all the answers

    What is the primary advantage of using combination therapy with polymyxin and fosfomycin in treating MDR-GNB infections?

    <p>Enhanced bactericidal activity and prevention of the selection of multi-drug resistant strains</p> Signup and view all the answers

    What is the primary advantage of polymyxin analogs over traditional polymyxins?

    <p>Reduced nephrotoxicity and inherent LPS-sequestration</p> Signup and view all the answers

    What is the primary benefit of using CSP conglomerates in treating pathogenic bacteria?

    <p>Reduced lung edema and promotion of macrophage differentiation</p> Signup and view all the answers

    What is the primary goal of optimizing PK-PD-based dosing regimens for CSP therapy?

    <p>To minimize adverse effects and maximize bacterial killing</p> Signup and view all the answers

    What is the primary concern associated with using polymyxin combination therapy in critically ill patients?

    <p>Higher resistance evolution of bacterial antimicrobial compounds</p> Signup and view all the answers

    What is the primary characteristic of polymyxin-fosfomycin combination therapy?

    <p>Synergistic targeting of multidrug-resistant bacteria</p> Signup and view all the answers

    What is the primary benefit of combining polymyxin with rifampicin?

    <p>Synergistic targeting of multidrug-resistant bacteria</p> Signup and view all the answers

    What is the primary concern associated with the emergence of mcr genes in Acinetobacter baumannii?

    <p>Higher resistance evolution of bacterial antimicrobial compounds</p> Signup and view all the answers

    What is the primary benefit of using polymyxin-rifampicin combination therapy in critically ill patients?

    <p>Synergistic targeting of multidrug-resistant bacteria and preventing antimicrobial resistance evolution</p> Signup and view all the answers

    Study Notes

    Polymyxins and Fosfomycin in Treating Multidrug-Resistant Infections

    • Rise of Multidrug-Resistant Infections: The global spread of multidrug-resistant (MDR) pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa, has increased the use of colistin and polymyxin B.
    • Limitations of Polymyxins: Despite their effectiveness, polymyxins have limitations, including systemic toxicity, which remains a significant concern, and the potential for resistance.

    Mechanism of Action and Clinical Use of Polymyxins

    • Mechanism of Action: Polymyxins are cationic detergents that disrupt the outer and inner membranes of bacterial cells, leading to cell death.
    • Selective Binding: Polymyxins exhibit preferential binding to lipopolysaccharide on the cell membrane of Gram-negative bacteria, disrupting the cell membrane and ultimately leading to cell death.
    • Clinical Use: Polymyxins are used to treat nosocomial infections caused by MDR pathogens, such as A. baumannii, due to their potent in vitro antibacterial activity.

    Structure and Classification of Polymyxins

    • Cyclic Cationic Peptide Antibiotics: Polymyxins consist of a tripeptide core with an N-terminal fatty acid acyl side chain, which anchors the molecule to the lipid A motif of endotoxins.
    • Amphipathic Compounds: Polymyxins are categorized into ten different structural types (A-J) and possess cationic and hydrophobic chemical properties.

    Antibacterial Activity and Spectrum of Polymyxins

    • Broad-Spectrum Activity: Polymyxins exhibit antibacterial activity against a broad range of Gram-negative bacteria, including MDR and extensively drug-resistant pathogens.
    • Limited Use: The antibacterial spectrum of polymyxins is restricted to Gram-negative bacteria, and their use is limited due to the emergence of drug resistance.

    Fosfomycin: Mechanism of Action and Clinical Use

    • Mechanism of Action: Fosfomycin obstructs the production of N-acetylmuramic acid, a compound required for bacterial cell wall synthesis, by covalently bonding to the enolpyruvate transferase enzyme (MurA).
    • Clinical Use: Fosfomycin is used to treat urinary tract infections, prosthetic joint infections, and chronic obstructive pulmonary disease exacerbations.

    Pharmacokinetics and Pharmacodynamics of Polymyxins and Fosfomycin

    • Pharmacokinetics: The pharmacokinetics of polymyxins and fosfomycin are critical in determining their antibacterial efficacy and minimizing toxicity.
    • Pharmacodynamics: The pharmacodynamic indices of polymyxins and fosfomycin, such as peak concentration/minimum inhibitory concentration (Peak/MIC) and AUC_0–24/MIC, are essential in understanding their antibacterial effects.

    Combination Therapy: Rationale and Evidence

    • Rationale: Combination therapy with polymyxins and fosfomycin can prevent the emergence of resistance, enhance bactericidal activity, and improve clinical outcomes.
    • Evidence: Combination therapy with polymyxins and fosfomycin has shown synergistic effects, repressed the expression of biomarkers associated with drug resistance, and demonstrated therapeutic effects in treating carbapenem-resistant A. baumannii-infected pneumonia.

    Future Perspectives and Conclusion

    • Future Directions: Alternative CSP drugs, such as polymyxin analogs, and emerging CSP conglomerates may provide potential therapeutic options for treating MDR pathogens.
    • Optimized Dosing Regimens: PK-PD-based dosing regimens should be optimized for polymyxins and fosfomycin to maximize their antibacterial effects and minimize adverse effects.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Description

    This quiz assesses knowledge on the resurgence of colistin, its relation to multi-drug resistant bacteria, and its effectiveness in modern medicine. It covers the limitations and benefits of colistin usage, including adverse events and clinical effectiveness.

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser