Outcome of Intravenous and Inhaled Polymyxin B treatment in Patients with Multidrug-Resistant Gram-Negative Bacterial Pneumonia.

ABSTRACT

PURPOSE: The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. METHODS: This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. RESULTS: Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78), and 33.82 (0.83-126.68) mg/L at 0, 2, 6, and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6, and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were > 2 mg/L in most patients. Of the patients, 57.14 % were cured and 71.43 % showed a favorable microbiological response. The incidence of side effects with PMB was low. CONCLUSIONS: Inhaled plus intravenous PMB can achieve high ELF concentrations and favorable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.