Clinical Phenotyping of Polymyxin-Associated Nephrotoxicity and Phenotype-Specific Prognostic Utility of Neutrophil-to-Platelet Ratio in Carbapenem-Resistant Acinetobacter baumannii Infections

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infections remain therapeutically challenging, often necessitating last-line polymyxin therapy despite substantial nephrotoxicity. Conventional risk assessments for polymyxin-associated acute kidney injury (AKI) frequently overlook patient heterogeneity. We sought to delineate clinical phenotypes of polymyxin-associated AKI and determine whether the prognostic value of the neutrophil-to-platelet ratio (NPR) for mortality varies by phenotype. Methods We conducted a retrospective cohort study (2020–2025) of 547 patients with CRAB infections treated with polymyxins. Latent class analysis (LCA) identified clinical phenotypes using baseline risk factors and renal outcomes. Multivariable logistic regression incorporating restricted cubic splines (RCS), followed by piecewise regression, evaluated non-linear associations between NPR and 28-day mortality and tested effect modification by phenotype. Results CA revealed three phenotypes: Severe Renal Failure (Class 1, 15.2%), Low-risk/Stable (Class 2, 62.0%), and High-risk/Non-dialysis-dependent Injury (Class 3, 22.8%). Baseline characteristics and 28-day mortality differed across phenotypes (13.3% vs 5.6% vs 10.4%; p = 0.033). The prognostic value of NPR was confined to Class 2: within this subgroup (n = 339), NPR showed a significant association with mortality (p < 0.05). Piecewise regression identified a breakpoint at NPR = 0.0167 (likelihood-ratio test p = 0.00061); NPR ≤ 0.0167 was associated with higher 28-day mortality (p = 0.00276), with no association above this threshold. Conclusion Patients with CRAB infections receiving polymyxins exhibit three distinct nephrotoxicity phenotypes, and the prognostic utility of NPR is phenotype-specific, with a pronounced non-linear threshold confined to the Low-risk/Stable subgroup; phenotype-based stratification is therefore essential for valid interpretation of commonly used prognostic biomarkers.