Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Abstract

Background: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae.

Methods: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality.

Results: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060-0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation.

Conclusions: Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.

Keywords: Carbapenem-resistant Klebsiella pneumoniae; Ceftazidime-avibactam; Combination therapy; Critically ill patients; Mortality.