In Vitro Activities of Ceftazidime–Avibactam and Aztreonam–Avibactam at Different Inoculum Sizes of Extended-Spectrum β-Lactam-Resistant Enterobacterales Blood Isolates
Moonsuk Bae,
Taeeun Kim,
Joung Ha Park,
Seongman Bae,
Heungsup Sung,
Mi-Na Kim,
Jiwon Jung,
Min Jae Kim,
Sung-Han Kim,
Sang-Oh Lee,
Sang-Ho Choi,
Yang Soo Kim,
Yong Pil Chong
Affiliations
Moonsuk Bae
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Taeeun Kim
Division of Infectious Diseases, Department of Medicine, Nowon Eulji University Hospital, Seoul 01830, Korea
Joung Ha Park
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Seongman Bae
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Heungsup Sung
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Mi-Na Kim
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Jiwon Jung
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Min Jae Kim
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Sung-Han Kim
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Sang-Oh Lee
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Sang-Ho Choi
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Yang Soo Kim
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Yong Pil Chong
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
β-lactam–avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime–avibactam and aztreonam–avibactam against extended-spectrum β-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum β-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime–avibactam, and aztreonam–avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime–avibactam and 99% had low aztreonam–avibactam MICs (≤8 mg/L). Ceftazidime–avibactam and aztreonam–avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam–avibactam was more active than ceftazidime–avibactam. The frequencies of the inoculum effect with ceftazidime–avibactam and aztreonam–avibactam were lower than with meropenem (14% vs. 38%, p p = 0.03, respectively). The β-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam–avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime–avibactam.