Exclusive oral antibiotic therapy on acute uncomplicated osteomyelitis in children: a multicenter, non-inferiority, randomized, open- labelled, controlled clinical trial

Abstract

BACKGROUND: Acute hematogenous osteomyelitis is the most frequently diagnosed type of osteomyelitis (OM) in pediatric patients, being essential optimizing antibiotics to avoid complications as chronic osteomyelitis, sepsis, and impairments in bone development. Long intravenous medication (classical treatment), for 4-6 weeks, transitioning to oral medication when recovery was almost complete was the reference approach to treat the disease until it was demonstrated that an early switch to oral administration (current treatment) has similar cure rates and simplifies the entire treatment process (required hospital stay, bacterial resistance, risk of adverse events and costs). There is no evidence about that OM may be treated with exclusive oral therapy during the whole course of the disease, although it has been demonstrated that children with milder infections without risk factors may have a favorable outcome with only oral antibiotics. OBJECTIVE: The purpose of the present study is to demonstrate the same or higher proportion of resolution of the disease in children with uncomplicated OM who receive exclusively oral antibiotic therapy compared with patients that receive the standard intravenous plus oral therapy. DESIGN AND SETTING: A multicenter, non-inferiority, randomized, open-labelled, controlled clinical trial will be performed among four different hospitals of Catalonia. INTERVENTION AND METHOD: A stratified by age randomized sample will be performed in order to generate two therapy groups (A and B) with participants between >1 to ≤15 years of age. Patients from group A (n=49) will receive intravenous therapy (cefazolin for one week) followed by only oral (cefadroxil during two weeks), while group B patients (n=49) will receive exclusive oral therapy (cefadroxil for two weeks) as a treatment of their acute OM. The duration of the treatment will be three weeks for both groups, taking into account that the group A will require hospitalization during one week, while the other group will take the medication at home. The main outcome will be disease resolution, defined as absence of fever at 72h and decrease of the pre-admission maximum CRP value above 30% at 72h in case that the patient presents fever at the moment of the diagnosis, or as a reduction on the severity of the pain >50% at 72h in patients that do not present fever at the moment of diagnosis. Exhaustive controls will be done during the first 72 hours of the treatment, assessing body temperature, CRP, pain severity and possible side-effects due to the treatment. Follow-up visits up at 72h after the onset of the treatment and 1, 2 and 6 months after the end of the treatment will be scheduled for both groups, consisting mainly in clinical examination of body temperature, pain and function of the affected bone