Randomized Trial of Cefepime Monotherapy or Cefepime in Combination with Amikacin as Empirical Therapy for Febrile Neutropenia

Abstract

A multicenter open randomized trial was conducted to compare cefepime monotherapy with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had microbiologically and 10.6% had clinically documented infections. Excellent response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients, respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of <500/ mu L receiving dual therapy had a better response than did those receiving monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with leukemia. Adverse events were minimal, and early death was observed in 7 patients in the dual therapy group and 5 patients in the monotherapy group. Overall, cefepime monotherapy is as effective as dual therapy for the initial treatment of febrile neutropenic patients. Further study is warranted for patients with severe neutropenia and leukemia who may benefit from dual therapy.

Low-dose β-lactam plus amikacin in febrile neutropenia: cefepime vs. piperacillin/tazobactam, a randomized trial

“…In our trial, the overall resolution of the febrile episode was observed in 92% of cases in both groups, similar to other studies [18][19][20][21][22][23][24][25][26][27][28][29].…”

“…A synergistic effect against gram-negative bacteria and a lower incidence of bacterial resistance has been argued, favoring the classical combination therapy [26]. The addition of an aminoglycoside achieves a better response in the more profound neutropenic patients (<500 granulocytes/mm 3 ), as demonstrated in the study conducted by Tamura et al [22]. A pharmacokinetic study in an in vitro model against two strains of P. aeruginosa showed that, in the mucoidproducing strain, the dose of cefepime 2 g/12 h was less effective than cefepime 2 g/8 h or cefepime 2 g/12 h plus tobramycin [32]; these results could be explained by the synergy achieved with the addition of the aminoglycoside.…”

“…Thus, in the case of piperacillin/tazobactam, 4 g/500 mg q/6 h is an approved dosing regimen for fever and granulocytopenia [5,17,18], and in the case of cefepime, 2 g/8 h is the standard of care in this setting [6,[18][19][20]. However, lower doses of both antibiotics have been used in some studies [4,9,21,22]. When a combination of agents is used, it is plausible that lower dosing can be administered [23].…”

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

“…As in previous studies, 20-25% of patients included in the present study received concurrent administration of an aminoglycoside with one of the guideline-recommended drugs as initial treatment. One previous study reported a higher efficacy rate in patients receiving adjuvant aminoglycoside than in those receiving monotherapy [16]. In the present study, on the other hand, the efficacy rate in patients receiving concurrent aminoglycoside was slightly lower compared with that in patients on monotherapy in both treatment groups, although the difference was not statistically significant (P = 0.29 and 0.95 in the 4th Cephs and P/T groups, respectively).…”

“…The main limitations of this study were its non-prospective design and the efficacy evaluation being not solely based on fever reduction as in previous Japanese studies [16,17]. Here, treatment efficacy was evaluated based on the need for switching antimicrobial drugs, because this was determined by attending hematologists on the basis of comprehensive assessments of clinical symptoms, laboratory tests, and radiological findings in individual patients.…”