Toxicity of polymyxins: a systematic review of the evidence from old and recent studies

By Matthew E. Falagas, S. Kasiakou. Critical Care, 2006

796 citations recorded by the source corpus.

BackgroundThe increasing problem of multidrug-resistant Gram-negative bacteria causing severe infections and the shortage of new antibiotics to combat them has led to the re-evaluation of polymyxins. These antibiotics were discovered from different species of Bacillus polymyxa in 1947; only two of them, polymyxin B and E (colistin), have been used in clinical practice. Their effectiveness in the treatment of infections due to susceptible Gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii, has not been generally questioned. However, their use was abandoned, except in patients with cystic fibrosis, because of concerns related to toxicity.MethodsWe reviewed old and recent evidence regarding polymyxin-induced toxicity by searching Pubmed (from 1950 until May 2005).ResultsIt was reported in the old literature that the use of polymyxins was associated with considerable toxicity, mainly nephrotoxicity and neurotoxicity, including neuromuscular blockade. However, recent studies showed that the incidence of nephrotoxicity is less common and severe compared to the old studies. In addition, neurotoxic effects of polymyxins are usually mild and resolve after prompt discontinuation of the antibiotics. Furthermore, cases of neuromuscular blockade and apnea have not been reported in the recent literature.ConclusionNew evidence shows that polymyxins have less toxicity than previously reported. The avoidance of concurrent administration of nephrotoxic and/or neurotoxic drugs, careful dosing, as well as more meticulous management of fluid and electrolyte abnormalities and use of critical care services may be some of the reasons for the discrepancy between data reported in the old and recent literature.

Subfields: Epidemiology, Molecular Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/440d0e5fc592050021b327170787ac8bd8583ad6

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In Epidemiology

1. Robert E. W. Hancock
2. Jian Li
3. M. Kuehn
4. Roger L. Nation
5. P. Nordmann

In Molecular Medicine

1. L. Poirel
2. P. Nordmann
3. Robert E. W. Hancock
4. Jian Li
5. M. Kuehn
6. Marin Kollef
7. Roger L. Nation
8. S. Gellatly

In Pharmacology

1. P. Nordmann
2. L. Poirel
3. Robert E. W. Hancock
4. Jian Li
5. Roger L. Nation

Citations in the corpus

• Contribution of bacterial outer membrane vesicles to innate bacterial defense (2011, background): “Currently, AMPs are used as a last line of defense against some multi-drug resistant pathogens [22-24].”
• Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. (2007, background): “The drug displays a concentration-dependent bactericidal activity [122] and has recently been re-introduced for the management of pulmonary infections in cystic fibrosis patients, either by the intravenous route or in the form of an aerosol [124], with lower rates of toxicity than reported previousl”
• The Epidemiology, Pathogenesis and Treatment of Pseudomonas aeruginosa Infections (2012, background): “[121] Doripenem has a serum elimination halfin the setting of colistin overdose.[117] Despite the life, post-antibiotic effect against Gram-negative superior safety profile recently reported, certain pre- bacteria, and a seizure risk similar to that seen with cautions should be taken when administer”
• Antimicrobial Peptides: An Emerging Category of Therapeutic Agents (2016, background): “Moreover, given the low number of AMPs in clinical practice, the characterization of adverse effects in connection to administration in humans is limited with the exception of polymyxins, where systematicmetaanalysis of safety is available and high incidence of nephrotoxicity and neurotoxicity assoc”
• Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. (2007, background): “Nephrotoxicity and neurotoxicity are the most common potential toxicities with parenteral administration of polymyxins.(12,69) However, the toxicity observed in early clinical studies with colistimethate sodium was almost certainly due to a lack of understanding of its pharmacokinetics, pharmacodyna”
• Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. (2013, background): “…suffering recurrent infections of multidrug-resistant bacteria, colistin (a polymyxin drug) has for the past 15 years been routinely administered via inhalation (Falagas & Kasiakou, 2006), demonstrating that the antibiotic resistance problem has been influencing therapeutic choices for many years.”
• Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes (2017, background): “The most common neurotoxicological effect is paresthesia (occurring in 27% of patients), and there is no report of neuromuscular blockade or apnea in the recent literature (56).”