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

ABSTRACT: Objectives: 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. Methods: 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. Results: 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