Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia
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Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN.
One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents.
Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%).
Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.
KeywordsFebrile neutropenia Cefepime Cefoperazone/sulbactam Amikacin
We thank Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) for providing logistics and other support for carrying out the study. We also thank all the research staffs of the participating departments. Part of this study was presented for poster discussion in ESMO-ASIA 2016 Congress 16 Dec–19 Dec 2016, Singapore, and published as abstract; Annals of Oncology (2016) 27 (suppl_9): ix170-ix176. https://doi.org/10.1093/annonc/mdw599
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all enrolled patients and study was approved by the Institute Ethics Committee. The study was conducted in accordance with the Declaration of Helsinki and Indian Council of Medical Research (ICMR) guidelines. Study is registered with Clinical Trial Registry, India (CTRI/2017/06/008829).
Study concept and design: Ponraj M, Dubashi B, Kayal S, Cyriac SL, Harish BN, Ranjith K, and Jogamaya P. Provision of patient and study material: Ponraj M, Dubashi B, Kayal S, Cyriac SL, Harish BN, Unni S, and Naresh J. Data collection and analysis: Ponraj M, Kayal S, Dubashi B, Cyriac SL, Jogamaya P, Ranjith K, Unni S, Naresh J, Kiran K, Jagdeep S, Esha J, and Bhanu Prakash. Manuscript writing: Ponraj M, Kayal S, Dubashi B, Cyriac SL, Kiran K, Jagdeep S, Esha J, and Bhanu Prakash. Final approval of the manuscript: all authors.
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