Antimicrobial activity of cephamycins and β-lactam/β-lactamase inhibitors against ESBL-producing Escherichia coli and Klebsiella pneumoniae under standard and high bacterial inocula
Yu Mi Wi, Ji Young Choi, Da Eun Lee, So Hyun Jun, Ki Tae Kwon, Kwan Soo Ko
Abstract
This study investigated the in vitro antimicrobial activity of cephamycins and novel β-lactam/β-lactamase inhibitor combinations, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates. ESBL-producing blood isolates were obtained between January and May 2023. The antibiotic susceptibility of the isolates was determined by broth microdilution method using standard (10 5 CFU/mL) and high (10 7 CFU/mL) inoculum sizes. Two randomly selected ESBL-producing isolates were subjected to time-kill assays for cephamycin. More than 80% of the isolates exhibited susceptibility to cefoxitin, cefmetazole, flomoxef, ceftazidime/avibactam, cefepime/enmetazobactam and imipenem/relebactam. Ceftolozane/tazobactam demonstrated in vitro efficacy against 62.1% of the ESBL-producing isolates. At the higher inoculum size, cefoxitin, cefmetazole, flomoxef, ceftolozane/tazobactam, ceftazidime/avibactam, cefepime/enmetazobactam, and imipenem/relebactam demonstrated in vitro efficacy against 48.3%, 75.9%, 70.0%, 0%, 82.8%, 100%, 89.7% of the ESBL-producing isolates. The frequencies of the inoculum effect with cefoxitin (3.7%), cefmetazole (14.8%), flomoxef (88.9%), ceftolozane/tazobactam (96.0%), ceftazidime/avibactam (34.5%), cefepime/enmetazobactam (10.3%), and imipenem/relebactam (10.3%) were identified. With standard inoculum, cephamycins reduced bacterial growth within 2–24 h. However, high inoculum resulted in regrowth after 12 h of cephamycin exposure. Cephamycins demonstrated high in vitro activity against ESBL-producing isolates at standard inoculum sizes. However, the in vitro time-kill experiments revealed that the efficacy of cephamycins is not fully maintained at high inoculum sizes.