Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study.

INTRODUCTION

This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection.

METHODS

We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings.

RESULTS

A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329-2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221-4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191-2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia.

CONCLUSION

Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings.