A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.

Autor:	Chaftari AM; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Dagher H; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Hachem R; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Jiang Y; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Lamie P; Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wilson Dib R; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., John T; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Haddad A; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Philip A; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Alii S; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Mulanovich P; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Yuan Y; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chaftari P; Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Raad I; Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2024 Oct 01; Vol. 79 (10), pp. 2543-2553.
DOI:	10.1093/jac/dkae254
Abstrakt:	Background: Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. Methods: We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42). Results: A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Conclusions: Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered. (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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