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Comparative Study Between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae

Hatem Amer, Wesam, MD*; Abdel Rahman Elshweikh, Samah, MD; Mohammad Hablas, Nahed, MD

Infectious Diseases in Clinical Practice: May 2019 - Volume 27 - Issue 3 - p 138–142
doi: 10.1097/IPC.0000000000000716
Original Articles

Background In the era of the increase in carbapenem resistance, searching for alternative drugs becomes mandatory. In this study, an in vitro activity of β-lactam/β-lactamase inhibitors against extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) isolated from bloodstream infections was investigated.

Methods Blood samples were collected from patients with bloodstream infections in both pediatric and internal medicine intensive care units of Tanta University Hospitals, Egypt. BacT/ALERT was used, and positive blood cultures were subcultured on MacConkey, blood, chocolate agar and then incubated at 5% to 10% CO2, 37°C for 24 hours. Identification of the bacterial isolates was performed by VITEK 2TM Compact 15. Susceptibility testing was performed for isolated Escherichia coli and Klebsiella species using Kirby-Bauer disk diffusion and minimum inhibitory concentration. E test strips were used for cefoperazone/sulbactam, ceftazidime/avibactam, and ceftolozane/tazobactam. All isolates that were resistant to third-generation cephalosporins as per Clinical and Laboratory Standards Institute recommendations were confirmed for ESBL detection by modified double-disk synergy test, VITEK2 system, and multiplex polymerase chain reaction.

Results One hundred twenty-five Enterobacteriaceae were isolated; 100 of them (80%) were ESBL positive. The best used β-lactam/β-lactamase inhibitors were ceftazidime/avibactam and ceftolozane/tazobactam with lower minimum inhibitory concentration at which 50% of isolates are inhibited (≤0.016, 0.094 μg/mL, respectively) than that of meropenem (0.125 μg/mL), so they can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance.

Conclusions Ceftazidime/avibactam and ceftolozane/tazobactam can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance.

From the *Medical Microbiology and Immunology,

Internal Medicine and Hematology, and

Pediatric and Neonatology, Faculty of Medicine, Tanta University Hospitals, Tanta, Egypt.

Correspondence to: Wesam Hatem Amer, MD, Medical Microbiology and Immunology Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt. E-mail:

ORCID ID: 000-0002-5848-8972.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

The authors have no funding or conflicts of interest to disclose.

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