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

• DOI: 10.1016/j.jgar.2022.01.025
• Publication Date: 2022-02-04T17:03:58Z
• Authors: Timothy Miles Rawson; Ilona Brzeska-Trafny; Rosemary Maxfield; Manfred Almeida; Mark Gilchrist; Ximena Gonzalo; Luke SP Moore; Hugo Donaldson; Frances Davies
• Keywords: 0301 basic medicine; Ceftazidime-avibactam; Microbiology; Ceftazidime; New Dehli Metallo-beta-lactamase; QR1-502; beta-Lactamases; 3. Good health; Synergy; Aztreonam; Drug Combinations; 03 medical and health sciences; Combination treatment; 616; Humans; New Delhi metallo-beta-lactamase; Azabicyclo Compounds

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.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.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%.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.