Optimizing Polymyxin B Exposure in Carbapenem-Resistant Organism-Associated Hospital-Acquired Pneumonia: A Retrospective Observational Study

The area under the 24-hour concentration-time curve (AUC_0-24h) is a key pharmacokinetic parameter for polymyxin B (PMB), but the optimal exposure target in critically ill patients remains uncertain.

This study aimed to investigate the relationship between PMB AUC_0-24h and clinical efficacy in patients with carbapenem-resistant hospital-acquired pneumonia (HAP), and to identify the optimal therapeutic AUC_0-24h range for PMB.

This retrospective observational study included patients with carbapenem-resistant HAP who received intravenous PMB and therapeutic drug monitoring. Plasma PMB concentrations were measured by validated ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The primary outcome was 14-day clinical treatment success, and the secondary outcome included acute kidney injury (AKI). Logistic regression and restricted cubic spline analyses were used to assess exposure-outcome relationships.

A total of 138 patients were included, the median age was 68 years, and 110 (79.7%) were male. Clinical success was achieved in 63 (45.7%) patients. Carbapenem-resistant Acinetobacter baumannii accounted for 77.5% of infections. The median AUC_0-24h of PMB was 77.5 (55.6, 105.6) mg·h/L. An AUC_0-24h > 77 mg·h/L enabled to predict the clinical treatment success, while AUC_0-24h > 110 mg·h/L enabled to predict the AKI incidence. In multivariable analysis, AUC_0-24h < 77 mg·h/L was an independent risk factor for reduced clinical treatment success (OR: 0.33, 95% CI: 0.13-0.78; p = 0.013), while AUC_0-24h > 110 mg·h/L significantly increased AKI risk (OR: 3.24, 95% CI: 1.06-10.47; p = 0.043).

The AUC_0-24h of PMB is closely associated with both 14-day clinical treatment success rates and the incidence of AKI in patients with carbapenem-resistant HAP, with an optimal range from 77 to 110 mg·h/L.