IntroductionIt is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs). MethodsWe conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors. ResultsA total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001). ConclusionThe appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae/carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality.