A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection

Rawson, Timothy Miles ORCID: 0000-0002-2630-9722, Brzeska-Trafny, Ilona, Maxfield, Rosemary, Almeida, Manfred, Gilchrist, Mark, Gonzalo, Ximena, Moore, Luke SP, Donaldson, Hugo and Davies, Frances (2022) A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection. JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE, 29. pp. 558-562.

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Official URL: http://dx.doi.org/10.1016/j.jgar.2022.01.025

Abstract

<h4>Objectives</h4>In response to infection with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM-producing Enterobacterales.<h4>Methods</h4>Minimum inhibitory concentrations (MICs) of clinical NDM-producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of the ATM breakpoint after the addition of CAZ/AVI was explored. A CAZ/AVI Etest/ATM disc method was compared with broth dilution.<h4>Results</h4>Of 43 isolates, 33 (77%) were ATM resistant (median [range] MIC = 56 [16-512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4 mg/L) in 29 of 33 resistant isolates (89%). Overall, the Etest/disc method correlated with the findings from broth dilution in 35 of 43 cases (81%). Etest/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%.<h4>Conclusion</h4>CAZ/AVI+ATM demonstrated significant synergy in most ATM-resistant NDM-producing Enterobacterales. The Etest/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory.

Item Type:	Article
Uncontrolled Keywords:	Ceftazidime-avibactam, Aztreonam, Synergy, New Delhi metallo-beta-lactamase, Combination treatment
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	28 Mar 2023 08:13
Last Modified:	28 Mar 2023 08:14
DOI:	10.1016/j.jgar.2022.01.025
Open Access URL:	https://doi.org/10.1016/j.jgar.2022.01.025
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169274