Treatment of Febrile Neutropenia with Cefepime Monotherapy

Abstract

Background and Objective: The empirical administration of a broad-spectrum β-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. Methods: One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Results: Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Interpretation and Conclusions: Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be at higher risk for failure. However, with appropriate therapeutic changes the risk of dying from a bacterial infection is very low.

Cefepime versus ceftazidime as empirical therapy for fever in neutropenic patients with haematological malignancies

“…Severe studies have compared the effi cacy of cefepiem vs. ceftazidime in management of febrile episodes in neutropenia patients. The results of other previous studies [3][4][5][6][7][8] were comparable with our study that cefepime appears to be effi cacious as ceftazidime in the management of febrile episodes in neutropenic patients.…”

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].…”

“…The population studied in our trial was similar to that of other studies with respect to the main disease (acute leukemia in approximately half of the cases) [4,18,20,22,27,30] and the rates of granulocytopenia (>90% of episodes had <500 cells/mm 3 ). The time to defervescence was very short (a median of 3 days in both groups) and the need for changing or adding other antimicrobials was surprisingly low (39 and 33% of episodes, respectively) compared to other trials, with approximately two-thirds of the episodes (49-70%) in which the antibiotic therapy had to be modified [4,18,22].…”

“…Most published trials have evaluated the standard doses of piperacillin/tazobactam or cefepime [6,[17][18][19][20][27][28][29][30] side, although some studies with lower doses [21,31] have been conducted with good response rates. A synergistic effect against gram-negative bacteria and a lower incidence of bacterial resistance has been argued, favoring the classical combination therapy [26].…”

A meta-analysis of piperacillin/tazobactam versus cefepime treatment in cancer patients with febrile neutropenia

“…Cefepime is another fourth-generation cephalosporin antibiotic with a broader spectrum of activity against Gram-positive and Gram-negative bacteria. (JANDULA et al, 2001) It is widely applied in clinical trials against infection worldwide due to its superior pharmacological characteristics. Several reports have indicated the effectiveness of cefepime, both with monotherapy or combination therapy, on FN treatment.…”