Rodrigo C da Fonseca, Beatriz Arns, Adriana Schmidt, Emerson Dos S Hoffmann, Nadiana Inocente, Amanda de F Balbinot, Erik M Martins, Jaysa Pizzi, Guilherme G L Sório, Renata D F Klafke, Luiza M Perez, Letícia C Marinho, Cristiane T da S Kawski, Alexandre P Zavascki
Aztreonam/nacubactam and cefepime/nacubactam demonstrated potent in vitro activity against Enterobacterales that carried serine-carbapenemases and MBLs, including those with chromosomal resistance mechanisms that compromise the current best-in-class β-lactam antibiotics for treating infections caused by MBL-positive organisms. The percentage of NDM-positive E. coli with insertions in PBP3 is alarming and warrants continued surveillance.
INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs) are associated with high mortality and limited treatment options. Evidence supporting ceftazidime-avibactam, with or without aztreonam, from studies exclusively with BSIs caused by CRKP remains scarce, particularly from Latin America, where there is a high burden of disease. In this study, we compared ceftazidime-avibactam-based regimens with other active antimicrobials (OAA) regimens for healthcare-associated CRKP BSIs in a Brazilian tertiary-care hospital.
METHODS: We conducted a retrospective cohort study including consecutive adult patients with healthcare-associated BSIs caused by CRKP between 2014 and 2024. Patients receiving ceftazidime-avibactam with or without aztreonam were compared with those receiving OAAs. The primary outcome was 30-day all-cause mortality. Secondary outcomes included acute kidney injury (AKI), the composite of death or AKI, and post-BSI length of hospital stay. Multivariable Cox regression was performed.
RESULTS: A total of 129 patients were included, of whom 73 received ceftazidime-avibactam-based therapy and 56 received OAAs. Carbapenemase types included class A (82.2%), class B (9.3%), and class A+B co-producing isolates (8.5%). Thirty-day mortality was significantly lower in the ceftazidime-avibactam group than in the OAA group (23.3% vs. 41.1%; P = 0.049). After adjustment, ceftazidime-avibactam-based therapy remained independently associated with lower 30-day mortality (hazard ratio, 0.51; 95% confidence interval, 0.27-0.96; P = 0.04). The composite of death or AKI was also significantly lower with ceftazidime-avibactam-based therapy (P = 0.047), whereas median post-BSI hospital stay among survivors was 8 days shorter (P = 0.06).
CONCLUSIONS: In this cohort, ceftazidime-avibactam with or without aztreonam was independently associated with lower 30-day mortality than OAAs in the treatment of CRKP BSIs. These findings extend the available evidence to BSIs caused by carbapenemase-producing isolates and support the need for broader access to ceftazidime-avibactam-based regimens in low- and middle-income countries, where therapeutic options remain limited.