Outpatient, sequential, parenteral‐oral antibiotic therapy for lower risk febrile neutropenia in children with malignant disease

Abstract

BACKGROUNDRecent reports and previous randomized trials conducted at the authors' institution suggested that children with lower risk febrile neutropenic (LRFN) may benefit from substitution of oral antibiotic therapy for parenteral therapy. The objective of this study was to determine the efficacy of parenteral‐oral outpatient therapy in the management of children with LRFN who were receiving treatment for malignant disease.METHODSFrom August 2000 to April 2002, 135 children with a median age of 7.5 years (range, 1.6–15.8 years) who had a total of 177 episodes of LRFN were included in a prospective, randomized, single‐institution trial. Children with LRFN received a single dose of ceftriaxone and amikacin and completed a risk‐assessment work‐up. All patients were discharged immediately and, at 24 hours, were allocated randomly to two groups: Group A (89 episodes) received oral ciprofloxacin, and Group B (88 episodes) received intravenous ceftriaxone.RESULTSMost patients (61% in Group A and 51% in Group B) were receiving treatment for leukemia (P value not significant [NS]). Twenty‐eight children (31%) in Group A and 22 children (25%) in Group B displayed unexplained fever (P value NS). No significant differences in sites of initial infection were found between the two groups. The median duration of neutropenia was 4.2 days and 4.7 days for Group A and Group B, respectively (P value NS); the median duration of fever was 2.3 days and 2.6 days, respectively (P value NS); and the median duration of antibiotic treatment was 4.5 days and 4.8 days, respectively (P value NS). The overall results of the study were excellent. Only four treatment failures in Group A (5%) and 6 treatment failures in Group B (7%) were observed. These patients were readmitted to the hospital and did well with appropriate treatment.CONCLUSIONSIn children with LRFN who are receiving treatment for malignant disease, outpatient oral ciprofloxacin after 24 hours of a single dose of intravenous ceftriaxone and amikacin was as safe and efficacious as parenteral ceftriaxone. Outpatient management and early antibiotic withdrawal were safe for both groups. Cancer 2003;97:1775–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11251

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

“…The finding that the experimental treatment was non-inferior to continued standard treatment regarding efficacy is in line with results of published RCT on first-day step-down to oral antimicrobial therapy in pediatric low-risk FN, though with different definitions of efficacy [12][13][14][15]. These studies had found no significant difference of efficacy between oral and intravenous antimicrobial therapy, always applied in outpatient settings.…”

“…The non-inferiority [20,26,27] tests used here led to more stringent results than the difference tests used in the comparable RCT published [12][13][14][15] and in a recent meta-analysis [16]. This led to positive evidence here that the experimental treatment was non-inferior to the standard treatment regarding efficacy.…”

“…These studies had found no significant difference of efficacy between oral and intravenous antimicrobial therapy, always applied in outpatient settings. Oral therapy was used twice from the very beginning [13,15], and twice after step-down from intravenous therapy [12,14]. None of these studies had used a non-inferiority design of analysis, or included a power-analysis.…”

“…Intravenous antimicrobial therapy was replaced by a combination of oral ciprofloxacin (25-30 mg/kg/day, top dose 1,500 mg/day, given in 2 daily doses) [13,14,21,22] plus oral amoxicillin (65-80 mg/kg/day, top dose 2,250 mg/day, given in 2 daily doses) [22]. Modification of this therapy was suggested in case of bacteremia known after reassessment, signs and symptoms of a local infection, toxic appearance, or AE/intolerance requiring its discontinuation.…”

“…In many institutions, stepping-down late, that is, after 2-4 days from presentation with FN, but before resolution of neutropenia, is established for patients with a favorable course of FN [11]. For early or first-day stepping-down from intravenous to oral antimicrobial therapy, four single-center randomized controlled trials (RCT) did not find differences regarding efficacy or safety in low-risk FN [12][13][14][15]. None of these studies nor the corresponding meta-analysis have used a non-inferiority approach, however [16].…”