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

Abstract

Background: There is no clinical study investigating if using CAZ-AVI combination schemes with an in vitro non-susceptible antimicrobial could be superior to CAZ-AVI monotherapy against CRKP clinically. Methods: We performed a retrospective, cohort study at two tertiary hospitals in China for patients with CRKP infection who treated by CAZ-AVI at least 72 hours. A Cox-proportional hazards regression model was set up to evaluate covariates which potentially affected 30-day mortality. Results: Sixty-two patients were eligible in our study, 41 (66.1%) received CZA-AVI combination therapy and 21 (33.9%) received CZA-AVI 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 (HR 0.167, 95%CI 0.060-0.465, P=0.001), while higher APACHE II score, use of vasoactive drug and comorbidity of organ transplantation were considered as factors on increasing mortality. The propensity score showed no significant alteration with other variables after adding it into the final model. In the subgroup analysis, the protective effect revealed when combination with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with CrCl > 50 mL/min, stayed in ICU ≤30 days or underwent mechanical ventilation. Conclusions: CAZ-AVI combination with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease 30-day mortality rate for critically ill patients with CRKP infection. Further investigation should be carried out to confirm this conclusion and find out the autofit antimicrobials in CAZ-AVI combination schemes.