The relationship between the alveolar epithelial lining fluid concentration of intravenous plus inhaled polymyxin B and clinical efficacy in patients with pneumonia caused by carbapenem-resistant gram-negative bacilli: a prospective cohort study.

Background: Nebulization combined with intravenous polymyxin B (PMB) for carbapenem-resistant gram-negative bacilli (CRGNB) pneumonia still has a number of failures that may be related to insufficient alveolar epithelial lining fluid (ELF) concentration of PMB. This study aimed at determining the relationship between the alveolar ELF concentration of PMB and clinical efficacy after intravenous (IV) plus inhaled (IH) PMB.

Methods: Seventy-five patients with pneumonia caused by CRGNB were treated with IH plus IV PMB. Alveolar lavage fluid was collected before and after nebulization, and ELF was calculated according to the urea dilution equation. Differences in clinical outcomes between patients with high and low peak and trough concentrations of ELF concentration of PMB were compared separately according to the ROC curve grouping strategy. The primary outcome was favorable clinical outcome. The secondary outcomes included microbiological outcome and time to bacterial eradication, time to renormalize body temperature, CRGNB-related and all-cause mortality, 28-day survival, length of hospitalization, inflammation marker levels and side effects related to PMB.

Results: Clinical efficacy and bacterial clearance were higher in the high ELF peak concentration group than in the low one (total efficacy: 94.44% vs. 48.72%, total bacterial clearance: 63.89% vs. 38.46%, both P < 0.05). The clinical effective rate was higher in the high ELF trough concentration group than in the low one (88.89% vs. 43.33%, P < 0.05). The 28-day survival rate was higher in the high ELF peak and trough concentration group than in the low one (peak: 86.11% vs. 38.46%, trough: 75.56% vs. 40.00%, both P < 0.05).

Conclusions: Patients with high PMB alveolar ELF concentrations demonstrated more favorable clinical outcomes than those with low concentrations.

Trial registration: This trial was registered. The Chinese trial registration number is ChiCTR2100044087. The date of registration is 9-3-2021. The registered name is that clinical study on intravenous drip and aerosol inhalation of polymyxin B for the treatment of pneumonia due to multidrug-resistant gram-negative bacteria.