A multicenter, randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer.
OBJECTIVE
To evaluate the effectiveness of oral amoxicillin/clavulanate (25 mg/kg every 12 h) for prevention of fever and/or infection in neutropenic children with cancer.


METHODS
Multicenter, prospective, randomized, double blind placebo-controlled trial.


RESULTS
In the intention-to-treat analysis, amoxicillin/clavulanate had a 12% benefit increase in terms of reduction in the incidence of febrile or infectious episodes, compared with placebo [44 of 83 (53%) vs.55 of 84 (65%); 95% confidence interval, -28% to +3%; P = 0.101]. This benefit was also associated with a 30% increase in the probability of failure-free survival at Day 15 (P = 0.138). A logistic regression analysis showed the effect of prophylaxis to be relevant, especially in patients with leukemia or lymphoma and in those not receiving hematopoietic growth factors, with 17 and 15% absolute benefit increases (logistic P = 0.014 and 0.034, respectively). Compliance with oral drugs was good, with very few and nonsevere drug-related adverse events.


CONCLUSIONS
In this study amoxicillin/clavulanate was associated with a detectable clinical effect in the reduction of fever and infection in neutropenic children with cancer, especially those with acute leukemia and not receiving growth factors; the study was not powered to demonstrate a statistically significant effect in the overall patient population.
Castagnola
Elio
E
Infectious Disease Unit, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
Boni
Luca
L
Giacchino
Mareva
M
Cesaro
Simone
S
De Sio
Luigi
L
Garaventa
Alberto
A
Zanazzo
Giulio
G
Biddau
Pierfrancesco
P
Rossi
Mario R
MR
Schettini
Francesco
F
Bruzzi
Paolo
P
Viscoli
Claudio
C
D000293:Adolescent; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000009:adverse effects; D019072:Antibiotic Prophylaxis; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000517:prevention & control*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy; D009503:Neutropenia / Q000188:drug therapy / Q000517:prevention & control*; D010349:Patient Compliance; D011446:Prospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
D019980:Amoxicillin-Potassium Clavulanate Combination