TY - JOUR
T1 - A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia
AU - Chaftari, Anne Marie
AU - Dagher, Hiba
AU - Hachem, Ray
AU - Jiang, Ying
AU - Lamie, Peter
AU - Dib, Rita Wilson
AU - John, Teny
AU - Haddad, Andrea
AU - Philip, Ann
AU - Alii, Shahnoor
AU - Mulanovich, Patricia
AU - Yuan, Ying
AU - Chaftari, Patrick
AU - Raad, Issam
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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 followup (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.
AB - 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 followup (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.
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U2 - 10.1093/jac/dkae254
DO - 10.1093/jac/dkae254
M3 - Article
C2 - 39092963
AN - SCOPUS:85205525075
SN - 0305-7453
VL - 79
SP - 2543
EP - 2553
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 10
ER -