Ceftazidime-avibactam in the treatment of infections from carbapenem-resistant Klebsiella pneumoniae: Ceftazidime-avibactam against CR-KP infections

Abstract

Objectives: Clinical experience with ceftazidime-avibactam (CAZ-AVI) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections is not well evaluated. The aim of this study was to assess its efficacy in a single-centre cohort of patients infected with CR-KP.

Methods: We conducted a retrospective observational study of consecutive patients treated for >72 h with CAZ-AVI or other active antibiotics (OAAs) for CR-KP infections. The primary outcome was 30-d mortality. The secondary outcomes were 14-d clinical failure and 14-d microbiological failure. Multivariate regression and propensity score matching were used to evaluate the relationship between CAZ-AVI treatment and outcomes.

Results: Ninety infections caused by CR-KP were documented in our study. Forty-two patients were treated with CAZ-AVI and 48 with OAAs. The crude 30-d mortality (8/42 vs. 22/48, P=0.007), 14-d clinical failure (14/42 vs. 24/48, P=0.046) and 14-d microbiological failure (11/42 vs. 15/48, P=0.034) were significantly lower in patients with CAZ-AVI treatment. The Kaplan-Meier survival curves of 30-d mortality confirmed the findings (logrank=0.004). In the multivariable models, the odds ratio (OR) of 30-d mortality (OR 0.23 95% CI 0.10-0.51, P<0.000), 14-d clinical failure (OR 0.37, 95% CI 0.14-0.95, P=0.039) and 14-d microbiological failure (OR 0.17, 95% CI 0.08-0.93, P=0.038) remain consistently significant. In the subgroup analysis, CAZ-AVI was associated with decreased 30-d mortality in the positive blood culture (OR 0.23, 95% CI 0.08-0.63, P=0.004), septic shock (OR 0.23, 95% CI 0.07-0.78, P=0.019), SOFA score (>5, OR 0.13, 95% CI 0.04-0.36, P<0.000), mechanical ventilation (OR 0.13, 95% CI 0.04-0.36, p<0.000) and Charlson comorbidity index (>3, OR 0.15, 95% CI 0.04-0.55, P=0.004). After propensity score matching, 29 cases from each group were well matched. The 30-d mortality remained significantly lower in the CAZ-AVI group (6/29 vs. 13/29, P=0.05).

Conclusion: CAZ-AVI may be a more valuable therapeutic option for severe CR-KP infections than for mild cases and further randomized controlled trials are needed to evaluate the efficacy.

Keywords: Carbapenem-resistant Enterobacteriaceae; Ceftazidime-avibactam; Klebsiella pneumoniae.