Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy

Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%. Method: This single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE). Results: A total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ± OXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ± OXA-48). Conclusions: This was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.