Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4^th‐generation cephalosporin + aminoglycosides: Comparative study

Abstract

In 1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/µL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/µL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/µL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN. Am. J. Hematol. 71:248-255, 2002.

European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

“…Most studies report that treatment in patients for fever of unknown origin (FUO) or clinically (CDI) and/or microbiologically (MDI) documented infections was continued for at least seven days, with at least 4-5 afebrile days. 62,[76][77][78][79][80][81][82][83] although, in one study, empirical therapy for FUO was continued for only 48 h after defervescence. 62 These studies excluded severely-ill patients, such as those with severe renal or hepatic impairment, septic shock, central nervous system infection, lung infiltrates, high probability of death in 48 h and blast crisis of chronic myeloid leukemia.…”

Animal Model Methodology: Immunocompetent or Leucopenic Rats, Which Is the Best? Results from a Model of Experimental Pneumonia due to Derepressed Cephalosporinase-Producing <b><i>Enterobacter cloacae</i></b>

“…Actually, it is well accepted that for the maximal clinical effect to be obtained, an aminoglycoside peak over the MIC higher than 8–12 is required [18,19,20], otherwise the combinations tested can easily turn into de facto monotherapies with an additional risk of inappropriate initial treatment [21,22]. The same constraints are observed with cefepime as well as all other β-lactams [23,24,25]; in a cohort of 36 patients with severe Gram-negative infections, microbiological success was significantly correlated with the proportion of the dosing interval that cefepime concentrations exceeded levels 4-fold the MIC [26]. In the present study, the administration of 1 mg/kg uranyl nitrate was optimal to impair the renal function of rats so as to simulate the pharmacokinetics of cefepime and amikacin in healthy humans [3,4]; indeed, amikacin concentrations obtained 6 h after dosing were 10- to 13-fold the MIC, and cefepime concentrations 12 h after dosing, corresponding to the trough drug concentration, were maintained above 4-fold the MIC.…”

Clinical efficacy and safety of cefepime in febrile neutropenic patients with lung cancer

“…In a study by Kwon et al [14] the success rate for the cefepime group reached 91.8% for 61 FN patients. In Japan, Tamura et al [15] reported a success rate of 66% at day 3 and 71% at day 7 for 38 patients with hematological malignancy. Ministry of Health, Labour and Welfare approved cefepime for FN in Japan based on this data.…”