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Published on: April 18, 2019
Polymyxin antibiotics for gram-negative infections
Tamra M Arnold1, Graeme N Forrest, Karen J Messmer
1Richard L. Roudebush Veterans Affairs Medical Center (VAMC), Indianapolis, IN 46202, and School of Medicine, University of Maryland, Baltimore, USA. tamra.arnold@va.gov
Purpose:
The role of polymyxin antibiotics in the treatment of multidrug-resistant gram-negative infections is reviewed.
Summary:
Antimicrobial resistance is an increasing problem across hospitals worldwide, especially in intensive care settings, where nosocomial infections are 5-10 times more likely to occur than on the general wards. The polymyxins, a group of basic polypeptide antibiotics, were first isolated from Bacillus species in the late 1940s and appear to have a surface detergent effect, making them active against most gram-negative organisms. Early clinical reports suggested a high rate of toxicity associated with the polymyxins, specifically nephrotoxicity (20%) and neurotoxicity (7%); thus the polymyxins had largely fallen out of favor. However, recent studies have suggested that the toxicities associated with the polymyxins may be less severe and less frequent than earlier reports. The emergence of multidrug-resistant gram-negative organisms has led to a reemergence in the use of this antibiotic class. Various clinical trials that evaluated the polymyxins for the treatment of multidrug-resistant gram-negative organisms found that these antibiotics have acceptable effectiveness and may be used if necessary.
Conclusion:
The polymyxins have become a last resort for the treatment of infections caused by multidrug-resistant gram-negative organisms. Recent studies have suggested that the frequency of polymyxin-associated nephrotoxicity and neurotoxicity may not be as high as was once thought. The polymyxins seem to be effective in treating various infections caused by multidrug-resistant gram-negative organisms but should not be used as first-line therapy until more is known about this class of antibiotics.
Insights
Polymyxin antibiotics are effective against multidrug-resistant gram-negative infections, offering a last resort option. Recent data suggest lower toxicity than previously reported, making them a viable treatment choice when necessary.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antimicrobial resistance is a growing global health crisis, particularly in hospital settings.
- Polymyxins, derived from Bacillus species, are effective against Gram-negative bacteria due to their detergent-like action.
- Historically, polymyxins were associated with significant nephrotoxicity and neurotoxicity, limiting their use.
Purpose of the Study:
- To review the role of polymyxin antibiotics in treating multidrug-resistant Gram-negative infections.
- To assess the current understanding of polymyxin efficacy and toxicity.
Main Methods:
- Literature review of clinical trials and studies on polymyxin antibiotics.
- Analysis of historical and recent data on polymyxin usage, effectiveness, and adverse events.
Main Results:
- Emergence of multidrug-resistant Gram-negative organisms has led to increased polymyxin use.
- Recent studies indicate that polymyxin-associated nephrotoxicity and neurotoxicity may be less frequent and severe than previously believed.
- Clinical trials demonstrate acceptable effectiveness of polymyxins for treating multidrug-resistant Gram-negative infections.
Conclusions:
- Polymyxins are a crucial last-resort treatment for infections caused by multidrug-resistant Gram-negative bacteria.
- While effective, polymyxins should not be considered first-line therapy until further research clarifies their safety profile.
- The reevaluation of polymyxin toxicity suggests a more favorable risk-benefit ratio in specific clinical scenarios.
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