Polymyxin B Dosing and Indications for Multidrug-Resistant Gram-Negative Bacteria

Indications

The Infectious Diseases Society of America recommends polymyxin B for serious infections caused by multidrug-resistant gram-negative bacteria, including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Enterobacterales (CRE), when less toxic drugs are ineffective or contraindicated 1

A loading dose of 2-2.5 mg/kg is recommended, followed by maintenance dosing of 1.5-3 mg/kg/day divided into two doses, with dosing based on total body weight rather than renal function 1, 2
Continuous infusion may be suitable in some cases 1
The loading dose should be administered in all patients, including those with renal dysfunction 1

Polymyxin B is administered intravenously and is not a prodrug (unlike colistin methanesulfonate) 1, 2
Therapeutic drug monitoring (TDM) is encouraged when available due to high interpatient variability 3, 4

The European Society of Clinical Microbiology and Infectious Diseases strongly recommends polymyxin B combination therapy over monotherapy for treating multidrug-resistant gram-negative infections 3
For CRAB infections, if meropenem MIC is ≤32 mg/L, consider polymyxin B-carbapenem combination with extended-infusion of meropenem for 3 hours 3
For CRE bloodstream infections, polymyxin B can be combined with tigecycline or meropenem 5, 6

Monitor renal function during treatment, as nephrotoxicity occurs in approximately 14% of patients with normal baseline renal function 3
Avoid concurrent use of other nephrotoxic or ototoxic drugs 3, 4

Polymyxin B sulfate: 1 mg = 10,000 units 3, 4
For comparison with colistin: 1 million international units (IU) of colistin = 80 mg colistin methanesulfonate (CMS) = 33 mg colistin base activity (CBA) 3, 4

The incidence of renal failure appears to be lower with polymyxin B than with colistin 1, 2
Combination therapy reduces treatment failure rates by approximately 119 cases per 1000 patients compared to monotherapy 3, 4

The combination of polymyxin B and fosfomycin shows synergistic activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) 7
Treatment efficacy of 54.2% is reported in ICU patients with CRKP and carbapenem-resistant Pseudomonas aeruginosa (CRPA) when combined with fosfomycin 7
Therapeutic drug monitoring (TDM) should be performed whenever available due to high interpatient variability in achieving therapeutic concentrations, with only 65-75% of critically ill patients with normal renal function achieving target concentrations (Css,avg ≥1 mg/L) 7
TDM optimizes dosing, improves clinical efficacy, and reduces adverse reactions 7