Association of polymyxin B MIC with pharmacokinetic/pharmacodynamic target attainment and clinical outcomes in carbapenem-resistant enterobacterales infections.

BACKGROUND: Polymyxin B (PMB) remains a last-resort agent against carbapenem-resistant Enterobacterales (CRE). This study integrated pharmacokinetic/pharmacodynamic (PK/PD) analyses with real-world clinical outcomes to evaluate the clinical risk-stratification value of a PMB MIC threshold >1 mg/L. METHODS: This single-center cohort study included 98 non-overlapping PMB treatment episodes contributed by 94 patients. Episodes were stratified into a low-MIC group (≤1 mg/L, n = 61) and a high-MIC group (>1 mg/L, n = 37). Multivariable logistic regression and sensitivity analyses were used to evaluate the association between MIC group and clinical cure. PTA for AUC/MIC ≥50 was compared between groups. RESULTS: Clinical cure was less frequent in the high-MIC group than in the low-MIC group (27.0% vs. 55.7%, P = 0.007). MIC >1 mg/L was independently associated with lower odds of clinical cure (adjusted OR = 0.311; 95% CI, 0.119-0.809; P = 0.017). PTA was 90.2% in the low-MIC group and 13.5% in the high-MIC group (P < 0.001). Results remained consistent in generalized estimating equation and first-episode sensitivity analyses. CONCLUSION: A PMB MIC >1 mg/L was associated with reduced clinical cure and markedly lower PK/PD target attainment in CRE infections. This threshold may support clinical risk stratification and provides hypothesis-generating evidence for prospective breakpoint evaluation. TRIAL REGISTRATION: https://www.chictr.org.cn; identifier, ChiCTR2300067946.