In-vitro susceptibility testing to determine synergistic effect of ceftazidime-avibactam with aztreonam in metallo-β-lactamase producing Enterobacterales.

OBJECTIVE

The objective of study was to assess the synergistic effect of ceftazidime-avibactam (CZA) with aztreonam (ATM) against MBL-producing Enterobacterales by performing three distinct synergy testing methods and their antimicrobial susceptibility pattern.

MATERIALS AND

METHODS

A retrospective observational study was conducted at a tertiary care hospital. In this study, 176 Carbapenem resistant Enterobacterales (CRE) isolates from various clinical specimens were analyzed. Isolates were tested using CLSI-recommended assays-the Modified Carbapenem Inactivation Method (mCIM) and the EDTA-supplemented Carbapenem Inactivation Method (eCIM) to detect metallo-β-lactamase activity. Synergy testing for CZA + ATM combination was conducted using disk stacking (DS), double disk synergy testing (DDST), and disk elution (DE) methods in all MBL-producing Enterobacterales. The results of each method was analyzed.

STATISTICAL ANALYSIS: Data were entered and analyzed using Microsoft Excel 2021. Descriptive statistics including frequencies and percentages were used to summarize the data and the observed positivity rates of all three phenotypic synergy testing methods.

RESULTS

Out of the 176 CRE isolates, 166 (94.3%) were mCIM positive as well as eCIM positive confirming the MBL production. Among these isolates, DE method detected synergy in 165 (99.4%) isolates and DS and DDST methods detected synergy in 164 (98.8%) isolates. Two Klebsiella pneumoniae isolates failed to show synergy by DS and DDST methods, and one isolate failed by the DE method.

CONCLUSION

All three methods demonstrated comparable performance with DE offering practical advantages (ease of use and reduced labor) in low-resource settings, it can be practical option for preliminary testing synergy for CZA with ATM in clinical microbiology laboratories in low resource setting. The combination of CZA with ATM demonstrated synergy against MBL-Producing Enterobacterales. However, the absence of a standardized reference method and molecular validation limits definitive assessment of accuracy of these methods.