Ceftazidime-avibactam use for the treatment of OXA-48- and/or New Delhi metallo-ß-lactamase-producing Enterobacterales in cancer patients: a retrospective observational study.

BACKGROUND: Infection is the second-leading cause of death among cancer patients, but there have been few studies on the effectiveness of novel antimicrobial agents to treat carbapenem-resistant Enterobacterales in cancer patients. OBJECTIVE: Evaluate the mortality and clinical outcomes of ceftazi-dime-avibactam for OXA-48- and/or New Delhi metallo-ß-lactamase (NDM)-producing Enterobacterales infection in cancer patients. DESIGN: Retrospective observational cohort study. SETTING: Tertiary academic medical center in Riyadh, Saudi Arabia. SUBJECTS AND METHODS: This study included patients who had cancer and received ceftazidime-avibactam for at least 72 hours for infections caused by OXA-48- and/or NDM-producing Enterobacterales. We excluded patients who died within 72 hours of treatment, patients with polymicrobial infections, and patients who did not receive appropriate antimicrobial therapy. MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day mortality and hospital mortality. Secondary outcomes included clinical cure, relapse, and reinfection. SAMPLE SIZE: 32 cancer patients. RESULTS: The 30-day mortality among all patients was 15/32 (47%), clinical cure was achieved in 19/32 (59%) of the patients, and the relapse and reinfection rates were 2/19 (10.5%) and 4/17 (23.5%), respectively. CONCLUSION: This is the largest study to evaluate clinical outcomes associated with infections caused by OXA-48- and/or NDM-producing Enterobacterales in cancer patients. The mortality rate remains high; however, ceftazidime-avibactam is an encouraging alternative for treating severe infections in cancer patients. LIMITATIONS: Small sample size and single center.

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

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 ±â€ŠOXA-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 ±â€ŠOXA-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.