The incidence of isolates resistant to ceftazidime/avibactam (CAZ/AVI) is low but carries a major impact on therapeutic options. This study aimed to evaluate the frequency of resistance to CAZ/AVI in Klebsiella pneumoniae producing KPC (KP-KPC). Cross-sectional study conducted in a high-complexity private hospital in Brazil (500 beds), between 2019 and 2024. Clinical cultures from all sites with KP-KPC growth were analyzed. Meropenem susceptibility was assessed by disk diffusion according to BrCAST, and CAZ/AVI by disk diffusion or gradient strip. Carbapenemase production was evaluated using phenotypic methods (disk diffusion with inhibitors or Blue Carba Plus). Detection of serine carbapenemase was interpreted as KPC. Since 2020, CAZ/AVI has been recommended as first-line therapy for infections caused by KPC producing Enterobacterales in the institution, with consumption measured in Defined Daily Doses (DDD) per 1000 patient-days. A total of 6,751 cultures from 3,462 patients were analyzed. Among these, 2,240 cultures from 1,000 patients showed meropenem resistance. After excluding 479 isolates producing metallo-β-lactamases and 100 with no detected carbapenemase, 1,661 KP-KPC isolates from 749 patients remained. None were sensitive or intermediate to meropenem. Among KP-KPC isolates, 696 (41.9%) were from urine, 296 (17.8%) from respiratory secretions, 252 (15.2%) from blood, and 417 (25.1%) from other clinical materials. Thirteen isolates positive for Klebsiella pneumoniae carbapenemase-producing strains (KP-KPC) were identified among 1,661 cultures analyzed, and eight cases among 749 patients evaluated, corresponding to a prevalence of 0.78% (95% CI: 0.36–1.20) per isolate and 1.07% (95% CI: 0.35–1.78) per patient. Cases occurred in 2019 (4 isolates from 2 patients), 2021 (5 isolates from 4 patients), and 2022 (4 isolates from 2 patients). Median DDD/1000 patient-days were 2.23 (0.72–12.74) in 2020, 21.48 (11.38–39.09) in 2021, 19.35 (13.43–26.97) in 2022, 19.39 (10.8–22.07) in 2023, and 19.63 (14.91–26.55) in 2024. A low frequency of resistance was observed despite sustained high use of CAZ/AVI. Moreover, the prevalence of KP-KPC isolates was lower than generally reported in the literature. As a limitation, previous CAZ/AVI exposure among resistant isolates could not be assessed.
Pizzi et al. (Sun,) studied this question.
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