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 cli...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716522000297 |
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| author | Timothy Miles Rawson Ilona Brzeska-Trafny Rosemary Maxfield Manfred Almeida Mark Gilchrist Ximena Gonzalo Luke SP Moore Hugo Donaldson Frances Davies |
| author_facet | Timothy Miles Rawson Ilona Brzeska-Trafny Rosemary Maxfield Manfred Almeida Mark Gilchrist Ximena Gonzalo Luke SP Moore Hugo Donaldson Frances Davies |
| author_sort | Timothy Miles Rawson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T10:40:49Z |
| format | Article |
| id | doaj.art-ae1434d55fee4453819be3322b8eb8ca |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-12-12T10:40:49Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-ae1434d55fee4453819be3322b8eb8ca2022-12-22T00:27:04ZengElsevierJournal of Global Antimicrobial Resistance2213-71652022-06-0129558562A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infectionTimothy Miles Rawson0Ilona Brzeska-Trafny1Rosemary Maxfield2Manfred Almeida3Mark Gilchrist4Ximena Gonzalo5Luke SP Moore6Hugo Donaldson7Frances Davies8Centre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, London, UK; Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK; Imperial College Healthcare NHS Trust, Paddington, London, UK; Corresponding author. Mailing address: Centre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.North West London Pathology, London, UKNorth West London Pathology, London, UKNorth West London Pathology, London, UKCentre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, London, UK; Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK; Imperial College Healthcare NHS Trust, Paddington, London, UKImperial College Healthcare NHS Trust, Paddington, London, UKHealth Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK; North West London Pathology, London, UK; Chelsea and Westminster NHS Foundation Trust, London, UKHealth Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK; North West London Pathology, London, UK; Chelsea and Westminster NHS Foundation Trust, London, UKHealth Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Hospital, London, UK; Imperial College Healthcare NHS Trust, Paddington, London, UK; North West London Pathology, London, UKABSTRACT: 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.http://www.sciencedirect.com/science/article/pii/S2213716522000297Ceftazidime-avibactamAztreonamSynergyNew Delhi metallo-beta-lactamaseCombination treatment |
| spellingShingle | Timothy Miles Rawson Ilona Brzeska-Trafny Rosemary Maxfield Manfred Almeida Mark Gilchrist Ximena Gonzalo Luke SP Moore Hugo Donaldson Frances Davies 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 Ceftazidime-avibactam Aztreonam Synergy New Delhi metallo-beta-lactamase Combination treatment |
| title | A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection |
| title_full | A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection |
| title_fullStr | A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection |
| title_full_unstemmed | A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection |
| title_short | A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales infection |
| title_sort | practical laboratory method to determine ceftazidime avibactam aztreonam synergy in patients with new delhi metallo beta lactamase ndm producing enterobacterales infection |
| topic | Ceftazidime-avibactam Aztreonam Synergy New Delhi metallo-beta-lactamase Combination treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2213716522000297 |
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