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

Manfred Almeida¹  Frances Davies²  Ilona Brzeska-Trafny²  Rosemary Maxfield³  Hugo Donaldson⁴  Timothy Miles Rawson⁴  Mark Gilchrist⁵  Luke SP Moore⁵  Ximena Gonzalo⁵ 

[1] Corresponding author. Mailing address: Centre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.;Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK;Imperial College Healthcare NHS Trust, Paddington, London, UK;Centre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, London, UK;North West London Pathology, London, UK;

关键词: Ceftazidime-avibactam;    Aztreonam;    Synergy;    New Delhi metallo-beta-lactamase;    Combination treatment;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 <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%. Conclusion: 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.

【 授权许可】

Unknown