Guidelines for Treating Multidrug-Resistant Gram-Negative Bacterial Infections with Polymyxin B

Indications and Spectrum of Activity

Polymyxin B is effective against multidrug-resistant gram-negative bacteria, including carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales, when less toxic drugs are ineffective or contraindicated 1

For severe carbapenem-resistant Pseudomonas aeruginosa infections, combination therapy with polymyxin B plus another in vitro active agent is suggested, with a conditional recommendation and very low certainty of evidence 2, 1
For carbapenem-resistant Acinetobacter baumannii infections, polymyxin B is a treatment option when the organism is resistant to sulbactam 3
Strong recommendation against polymyxin-meropenem or polymyxin-rifampin combination therapy for carbapenem-resistant Acinetobacter baumannii infections 4, 3

A loading dose followed by maintenance dosing is recommended for critically ill patients 1

Combination therapy with polymyxin B may reduce mortality, treatment failure, and pathogen eradication failure compared to polymyxin monotherapy 1
For pan-resistant carbapenem-resistant gram-negative bacteria, treatment with the least resistant antibiotic(s) based on MICs relative to the breakpoints is considered good clinical practice 4, 3

For carbapenem-resistant Acinetobacter baumannii with meropenem MIC ≤8 mg/L, carbapenem combination therapy using high-dose extended-infusion carbapenem dosing may be considered 4, 3
Optimal source control should always be prioritized to improve outcomes 5
Therapeutic drug monitoring should be utilized when available 5

Newer agents like ceftolozane-tazobactam should be used over polymyxin B when available and active in vitro due to lower nephrotoxicity 1