Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia

• Published in: Supportive care in cancer 2018-11, Vol.26 (11), p.3899-3908
• Main Authors: Ponraj, M., Dubashi, Biswajit, Harish, B. H., Kayal, S., Cyriac, S. L., Pattnaik, Jogamaya, Ranjith, K., Pillai, Unni S., Jadhav, Naresh, Matta, Kiran K., Singh, Jagdeep, Jaffa, Esha, Prakash, Bhanu
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Amikacin - administration & dosage; Amikacin - adverse effects; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Antibiotic Prophylaxis - adverse effects; Antibiotic Prophylaxis - methods; Antibiotics; Antifungal agents; Antineoplastic Agents - therapeutic use; Cancer; Cefepime; Cefoperazone - administration & dosage; Cefoperazone - adverse effects; Cephalosporins - administration & dosage; Cephalosporins - adverse effects; Chemotherapy-Induced Febrile Neutropenia - drug therapy; Chemotherapy-Induced Febrile Neutropenia - epidemiology; Child; Child, Preschool; Clinical trials; Comparative analysis; Drug therapy; Drug Therapy, Combination; Effectiveness; Female; Fever; Humans; Lactams; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasms - drug therapy; Neoplasms - mortality; Neutropenia; Nursing; Nursing Research; Oncology; Original Article; Pain Medicine; Rehabilitation Medicine; Sulbactam - administration & dosage; Sulbactam - adverse effects; Survival Analysis; Withholding Treatment; Young Adult
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/s00520-018-4260-8

Purpose 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. Methods 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. Results 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%). Conclusions 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.