Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study

Abstract

Background: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections.

Methods: The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression.

Results: The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae. The mean duration of PMB therapy was 11 days (range 7-38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 10⁹/l vs 9.28 × 10⁹/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%).

Conclusions: Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.

Keywords: 28-day mortality; Adverse effects; Carbapenem-resistant Gram-negative bacilli; Infections; Polymyxin B.

Fig. 1

Survival analysis at 28 days: Kaplan–Meier curve. Survival rate from the receiving intravenous PMB to 28 days

Fig. 2

Kaplan–Meier 28-day survival curve comparing patients on mechanical ventilation or with septic shock. A 28-day mortality rate was 59% and 20% in patients with mechanical ventilation and not on mechanical ventilation, respectively (log-rank, P < 0.01). B 28-day mortality rate was 65% and 16% in patients with septic shock and without septic shock, respectively (log-rank, P < 0.01)