# Antimicrobial Susceptibility of Ceftazidime-Avibactam in Clinical Isolates of Carbapenemase-Producing Enterobacterales

## TL;DR

This study shows that ceftazidime-avibactam is effective against some drug-resistant bacteria but not others, and combining it with aztreonam improves results.

## Contribution

The study evaluates ceftazidime-avibactam's efficacy and synergy with aztreonam against carbapenemase-producing bacteria in a clinical setting.

## Key findings

- Ceftazidime-avibactam was effective against 87.6% of class A carbapenemase producers.
- The drug was only effective against 15.8% of metallo-β-lactamase (MBL) producers.
- Combining ceftazidime-avibactam with aztreonam showed synergistic activity in 84.2% of MBL-producing isolates.

## Abstract

Background: Carbapenemase-producing Enterobacterales (CPE) are a major threat to public health around the world due to their extensive drug resistance mechanism. Ceftazidime-avibactam has emerged as a drug of choice for treating carbapenemase-producing organisms.

Objective: In this study, we aimed to evaluate the antimicrobial susceptibility of ceftazidime-avibactam against Klebsiella pneumoniae and Escherichia coli isolates that produce carbapenemases and to assess the synergistic effect of combining ceftazidime-avibactam with aztreonam against metallo-β-lactamase (MBL)-producing strains.

Methodology: It was a cross-sectional study, and data was collected over a period of six months in the Department of Microbiology, in a tertiary care teaching hospital of Southern Rajasthan. One hundred fifty clinical isolates, which were resistant to one of the carbapenems (imipenem, meropenem, or ertapenem) by the Kirby-Bauer disk diffusion method, were included in the study. All these isolates were subjected to carbapenemase detection by phenotypic methods, i.e., modified carbapenem inactivation method (mCIM) and ethylenediaminetetraacetic acid (EDTA)-carbapenem inactivation method (eCIM), and the results were analyzed to find out carbapenemase production as per Clinical and Laboratory Standards Institute (CLSI) 2023. Ceftazidime-avibactam susceptibility was determined using E-strips, and synergy with aztreonam was evaluated using disk approximation method.

Results: Among 150 isolates, 142 (94.7%) were confirmed as carbapenemase producers. Class A carbapenemases were detected in 89 (62.7%) isolates, class B MBLs in 38 (26.8%) isolates, and 15 (10.5%) showed mixed carbapenemase production. Ceftazidime-avibactam was effective against 87.6% of class A carbapenemase producers but only 15.8% against MBL producers. The combination of ceftazidime-avibactam and aztreonam showed synergistic activity in 84.2% of MBL-producing isolates.

Conclusion: Ceftazidime-avibactam shows excellent activity against class A carbapenemase-producing Enterobacterales but limited efficacy against MBL producers. The combination with aztreonam significantly enhances activity against MBL-producing strains which suggests a possible way to treat infections caused by these tough bacteria.