Ceftazidime-Avibactam for blood stream infections caused by carbapenemase-producing Klebsiella pneumoniae: pharmacoepidemiology and retrospective cohort study at a single tertiary-care center in Italy

Background: Multi-drug resistant (MDR) Klebsiella pneumoniae is a common healthcareassociated pathogen causing a variety of severe systemic infections, including bloodstream infections (BSIs).In response to the medical need for new treatment options, several new antibiotics have been developed such as the β-lactamase inhibitor (BLI) combination ceftazidimeavibactam (CAZ-AVI). Methods:We conducted a retrospective study on KPC-Kp BSIs between 2010 and 2021.The primary objective was to describe trends and change in susceptibility rates in KPC-Kp BSI cases and in antimicrobial use (CAZ-AVI, carbapenems, and colistin), expressed in DDD/1000 patientdays during a prevalence period (August 2019-January 2021).Secondary objectives were to describe risk factors for KPC-BSI and outcomes with CAZ-AVI treatment on 30-day mortality.Results: We included 524 patients.Older age, higher Charlson score, congestive heart failure, invasive devices and seven-day nephrotoxicity in colistin and aminoglycoside treatments were significantly associated with 30-day mortality.The length of stay in the CAZ-AVI group was significantly lower than the standard of care (SOC) group.CAZ-AVI therapy was shown to be a protective factor for mortality.Mortality was significantly higher in the SOC group compared to the ceftazidime-avibactam group.Carbapenem use significantly decreased during the observed period for antibiotic use.Conclusions: Invasive procedures, prolonged hospital stays, and colonization increased the risk of KPC-Kp BSI calling for effective source control and appropriate empiric therapy.New drugs, such as CAZ-AVI, are now available for the treatment of such invasive infections, and have significantly contributed to improving patient outcome in this setting.Identifying changes in the resistance profile should be an alarm for healthcare institutions to further focus efforts in stewardship programs and infection control practices.