A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.
J Antimicrob Chemother
; 79(10): 2543-2553, 2024 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-39092963
ABSTRACT
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 ß-lactam/ß-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%; Pâ=â0.042); 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gram-Negative Bacterial Infections
/
Azabicyclo Compounds
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Febrile Neutropenia
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Cilastatin, Imipenem Drug Combination
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Anti-Bacterial Agents
/
Neoplasms
Limits:
Adult
/
Aged
/
Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Antimicrob Chemother
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United kingdom