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

LCA revealed three distinct phenotypes: Severe Renal Failure (Class 1, 15.2%), Low-risk/Stable (Class 2, 62.0%), and High-Comorbidity/Non-RRT Severe Injury (Class 3, 22.8%). Baseline characteristics and 28-day mortality varied significantly across these phenotypes (9.6% vs. 4.4% vs. 8.6%; p = 0.033). The prognostic value of NPR was exclusively significant in Class 2, where a critical threshold effect was identified at 0.0167 (breakpoint test p < 0.001). Below this threshold, mortality risk rose sharply—a non-linear relationship that was obscured in high-severity phenotypes (Class 1 and 3).

CONCLUSION

Patients with CRAB infections receiving polymyxins exhibit three distinct nephrotoxicity phenotypes. The prognostic utility of NPR is phenotype-specific, with a critical threshold at 0.0167 identifying relative immune insufficiency exclusively within the Low-risk/Stable subgroup. Clinical phenotyping is therefore a prerequisite for accurate biomarker interpretation and personalized risk stratification in this population. CLINICAL TRIAL NUMBER: Not applicable.