Oral administration of cefixime to lower risk febrile neutropenic children with cancer

Abstract

BACKGROUND Febrile neutropenia is a heterogeneous condition. Recently, several risk factors have been defined, permitting the definition of a lower risk group of patients who may benefit form less aggressive therapy. The use of an oral antibiotic approach was tested in the current trial. METHODS From May 1997 to March 1998, 154 episodes of lower risk febrile neutropenia in 128 children with a mean age of 62 (range, 8–200) months were enrolled in this randomized, single‐institution trial. Inclusion criteria were fever (> 38 °C), neutropenia (absolute neutrophil count < 500/mm3), lower risk features (i.e., absence of severe comorbidity factors, good clinical condition, negative blood cultures, control of local infection, no fever during the last 24 hours), and compliance of parents. After 3 days of ceftriaxone (100 mg/kg/day administered intravenously [i.v.]) every 12 hours plus amikacin (15 mg/kg/day i.v.) every 24 hours for 3 days, all patients were discharged and randomized to be allocated to 2 treatment arms. Group A (n = 74) received ceftriaxone cefixime (8 mg/kg/day administered orally) every 24 hours for 4 days, whereas Group B (n = 80) was treated with ceftriaxone plus amikacin for 7 days. Failure was defined as the need for second hospitalization during the same episode of neutropenia, or fever during the 7 days after discharge. RESULTS Most of the patients (49% in Group A and 55% in Group B) had acute leukemia. Fifty‐four (72%) children in Group A and 46 (56%) in Group B had fever of unknown origin (P = not significant [NS]). No significant differences were found in the sites of initial infection between the two groups. Overall results were outstanding, with a favorable outcome in 73 of 78 cases (98.6%) in Group A and 78 of 80 cases (97.5%) in Group B (P = NS). Three patients needed a second hospitalization due to failure of the initial therapy: one in Group A and two in Group B. All three did well with secondary treatment. CONCLUSIONS In lower risk febrile neutropenic children receiving anticancer therapy, the efficacy of oral cefixime, given for 4 days after 72 hours of intravenous ceftriaxone plus amikacin, was similar to that of 7 days of parenteral ceftriaxone plus amikacin. The oral outpatient therapy approach to the treatment of lower risk febrile neutropenia after chemotherapy is safe and may be cost‐saving. This strategy might be adopted as standard therapy in the future. Cancer 2000;88:2848–52. © 2000 American Cancer Society.

A prospective, multicentric scoring system to predict mortality in febrile neutropenic children with cancer

“…Other studies have analyzed variables related to FN in low-risk patients to test ambulatory and oral therapies. 8,9,[13][14][15][16][17] Several factors predict the onset of severe bacterial infections, bacteremia, or infection-related mortality, such as underlying disease characteristics (bone marrow involvement, recurrence, second tumor, highly myelotoxic chemotherapy, genetic diseases, delayed bone marrow recovery), severe neutropenia, predicted neutropenia for >7 days, absolute monocyte count <100/mm 3 , fever >398C, thrombocytopenia <50.000/mm 3 , fever onset <7 days after the last chemotherapy course, signs of sepsis, arterial hypotension, and associated comorbid factors. [3][4][5][6][7][8][9][10]22,25,26 A score to predict mortality is a useful tool to evaluate and manage patients with severe infections.…”

“…Likewise, the identification of low-risk patients could provide a basis for the development of less expensive and less aggressive therapies. In fact, it is becoming a frequent strategy to treat these kinds of patients on sequential parenteral-oral [14][15][16] or oral 17 schedules in an ambulatory setting. [18][19][20][21][22][23] The objective of the current prospective study was to test a scoring system to assess mortality in children with FN.…”

2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients With Cancer

“…Treatment of carefully selected febrile neutropenic patients with oral antibiotics alone appears to be feasible for adults at low risk for complications (A-I) [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. In general, the use of antibiotics by the oral route may be considered only for patients who have no focus of bacterial infection or symptoms and signs suggesting systemic infection (e.g., rigors, hypotension) other than fever.…”

“…Factors favoring low risk for serious infections among febrile neutropenic patients, which have been identified in controlled studies, are listed in table 3 [4,[42][43][44][45][46][47][48][49][50][51][52][53]. These characteristics may serve as guidelines for the selection of patients for outpatient therapy.…”

“…As an alternative to initial outpatient therapy, early discharge with continued outpatient therapy for selected patients may be considered after a brief inpatient admission during which intravenous therapy is initiated, fulminant infection is excluded, and the status of initial culture specimens is ascertained [52,53].…”