Neurotoxicity in patients treated with intravenous polymyxin B: Two case reports

Weinstein, Lenny; Doan, Thien-Ly; Smith, Miriam A.

doi:10.2146/ajhp080065

Cited by 34 publications

(28 citation statements)

References 13 publications

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“…The emergence of drug-resistant P. aeruginosa strains, which exhibit increased MICs even for polymyxin B (PMB) (10), requires the development of effective dual-and triple-drug combinations for medical treatment of these infections (7,11). Despite the high effectiveness of polymyxins, the neuro-and nephrotoxicity associated with this treatment, especially during intravenous administration, increase the risk of using this drug (12,13). However, daily subcutaneous administration of polymyxins resulted in decreased nephrotoxicity (14,15), and inhaled polymyxin E, better known as colistin, showed no adverse effects (16).…”

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confidence: 99%

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

Berditsch

Jäger

Strempel

et al. 2015

Antimicrob Agents Chemother

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Multidrug-resistant Pseudomonas aeruginosa is a major cause of severe hospital-acquired infections. Currently, polymyxin B (PMB) is a last-resort antibiotic for the treatment of infections caused by Gram-negative bacteria, despite its undesirable side effects. The delivery of drug combinations has been shown to reduce the required therapeutic doses of antibacterial agents and thereby their toxicity if a synergistic effect is present. In this study, we investigated the synergy between two cyclic antimicrobial peptides, PMB and gramicidin S (GS), against different P. aeruginosa isolates, using a quantitative checkerboard assay with resazurin as a growth indicator. Among the 28 strains that we studied, 20 strains showed a distinct synergistic effect, represented by a fractional inhibitory concentration index (FICI) of <0.5. Remarkably, several clinical P. aeruginosa isolates that grew as smallcolony variants revealed a nonsynergistic effect, as indicated by FICIs between >0.5 and <0.70. In addition to inhibiting the growth of planktonic bacteria, the peptide combinations significantly decreased static biofilm growth compared with treatment with the individual peptides. There was also a faster and more prolonged effect when the combination of PMB and GS was used compared with single-peptide treatments on the metabolic activity of pregrown biofilms. The results of the present study define a synergistic interaction between two cyclic membrane-active peptides toward 17 multidrug-resistant P. aeruginosa and biofilms of P. aeruginosa strain PAO1. Thus, the application of PMB and GS in combination is a promising option for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant or biofilm-forming P. aeruginosa. Pathogenic Gram-negative Pseudomonas aeruginosa possesses both intrinsic and adaptive resistance toward many currently available antibiotics and causes infections that are effectively untreatable (1-3). P. aeruginosa "superbugs" are resistant to fluoroquinolones, expanded-spectrum cephalosporins, carbapenems, aminoglycosides, and in a few cases, even polymyxins, a last-resort class of antibiotics used to treat P. aeruginosa infections (4-7). One important mechanism for the intrinsic antibiotic resistance of Gram-negative pathogens, especially multidrug-resistant (MDR) P. aeruginosa clinical isolates, is their ability to efflux antibacterial agents via tripartite efflux pumps located in the inner and outer membranes, a mechanism that limits the access of the drug to intracellular targets (8). However, the overexpression of the P. aeruginosa efflux pump protein MexAB was unable to confer resistance to the host defense peptides (HDPs) cathelicidin LL-37 and defensins (9). One way in which pathogens acquire adaptive resistance to positively charged antimicrobial peptides is to modify lipid A by substitution with aminoarabinose (6). The emergence of drug-resistant P. aeruginosa strains, which exhibit increased MICs even for polymyxin B (PMB) (10), requires the development...

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confidence: 99%

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

Berditsch

Jäger

Strempel

et al. 2015

Antimicrob Agents Chemother

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“…Several antibiotic classes, including polymyxins and aminoglycosides, are known to be associated with neuromuscular blockade [4,7]. Polymyxin B causes a non-competitive neuromuscular blockade that is not responsive to cholinesterase inhibitors [2,5], leading to respiratory arrest as in our case. No known treatments exist beyond supportive care such as mechanical ventilation.…”

Section: Discussionmentioning

confidence: 86%

“…They are used to treat severe multidrug-resistant (MDR) gram-negative infections [2,3,5,6]. As the rates of MDR infections continue to rise worldwide, there is a concomitant resurgence in the use of antimicrobial agents typically seen as last-line therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

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Polymyxin B infusion leading to cardiac arrest: a case report and literature review

2014

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“…Sobieszczyk et al [58] reported neuropathy manifesting as seizures and neuromuscular weakness which were possibly related to polymyxin B in two (7%) cases. Weinstein et al [59] recently reported two cases of polymyxin B induced neuropathy. First case was 60-year-old obese diabetic female with other multiple ailments and was on treatment with multiple medication including varenicline and quetiapine.…”

Section: Efficacy Of Polymyxin B: Combination Therapymentioning

confidence: 99%

Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence

Garg

Singh

Juneja

et al. 2017

Critical Care Research and Practice

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Neurotoxicity in patients treated with intravenous polymyxin B: Two case reports

Abstract: Two patients developed symptoms of neurotoxicity after receiving intravenous polymyxin B for the treatment of MDR gram-negative infections.

Cited by 34 publications

References 13 publications

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

Polymyxin B infusion leading to cardiac arrest: a case report and literature review

Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence

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