Parenteral polymyxin B use in patients with multidrug-resistant gram-negative bacteremia and urinary tract infections: A retrospective case series

BACKGROUND: Parenteral polymyxin use declined after the 1960s, due to safety concerns. An increase in multidrug-resistant (MDR) gram-negative infections and a shortage of new agents have prompted increased use of parenteral polymyxin. OBJECTIVE: To describe our clinical experience with parenteral polymyxin B for MDR gram-negative bacteremia and urinary tract infection (UTI). METHODS: Paper pharmacy records were used to identify patients aged 18 years or older, presence of MDR gram-negative bacteremia or UTI, and use of parenteral polymyxin 8 for at least 48 hours. Electronic and paper patient records were then retrospectively reviewed. Polymyxin B susceptibility was evaluated using the Kirby-Bauer method. MDR isolates were defined as resistant to at least 3 antimicrobial classes, excluding polymyxin B. Microbiologic clearance was defined by 1 repeat urine or 2 repeat blood cultures that were sterile or growing different organisms. Secondary outcomes included hospital mortality and nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dL or more, or a 50% reduction in creatinine clearance. RESULTS: Seventeen infections in 16 patients were treated with polymyxin B (1 pt. had 2 infections that were analyzed separately). Microbiologic clearance occurred in 14 of 16 (88%) cases of MDR gram-negative bacteremia or UTI in which repeat cultures were done. Ten of 16 patients died (all-cause mortality 63%). Five patients required hemodialysis prior to polymyxin B use. Six (55%) of the remaining 11 patients with baseline renal insufficiency developed nephrotoxicity, and none of them required hemodialysis. The mean +/- SD number of days from the initiation of therapy to the onset of nephrotoxicity was 7.5 +/- 2.3 (range 4-10) days. Three (50%) of 6 patients with nephrotoxicity died. CONCLUSIONS: Our data suggest that polymyxin B may be effective for MDR gram-negative infections in patients with limited therapeutic options, but precautions should be taken to avoid toxicity.