Prolonged Intravenous Therapy Versus Early Transition to Oral Antimicrobial Therapy for Acute Osteomyelitis in Children
Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R
The study authors note that osteomyelitis, bacterial infection of bone, causes approximately 1% of all pediatric hospitalizations. Current recommendations are that pediatric patients with osteomyelitis receive 4-6 weeks of parenteral (intravenous or IV) antibiotic therapy, but this recommendation is based more on expert opinion than experimental evidence.
In an effort to add to our knowledge about the need to treat intravenously for prolonged periods, Zaoutis and colleagues conducted a retrospective comparison of outcomes of patients who received a prolonged IV course vs those of patients who had “early transition” to oral antibiotics. Subjects’ data were drawn from 29 hospitals participating in the Pediatric Health Information System, a multihospital pediatric administrative database that contains patient, treatment, diagnosis, and outcome variables, including antibiotics and their route.
Subjects were 2-17 years of age, and the data were drawn from 2000-2005 discharges. The authors first identified subjects with osteomyelitis and related codes in discharge diagnoses, and then excluded children with conditions likely to confound outcome, such as immunodeficiencies, sickle cell disease, and other chronic conditions. Osteomyelitis of the head or skull was also excluded.
The authors sought to identify subjects who were otherwise healthy children with acute osteomyelitis. They classified a subject as having “prolonged” parenteral therapy if there was evidence of central venous line placement during the index hospitalization. Otherwise, the subjects were considered to have been transitioned to oral antibiotic therapy at or around discharge.
The outcome of interest was the rate of treatment failure, defined as rehospitalization within 6 months of discharge with a new diagnosis of osteomyelitis, chronic osteomyelitis, or other complication of osteomyelitis. The authors also looked at all-cause rehospitalization, adverse drug reactions, and catheter complications.
They identified 6348 children with osteomyelitis in the dataset and excluded all but 1969 for incomplete data, follow-up time of less than 6 months, or exclusionary conditions. Of the 1969 in the analyses set, 1021 (52%) had an central venous catheter placed. For all children, the treatment failure rate was 4.7%. The rates were essentially the same for the 2 groups, with a failure rate of 5% in the children with prolonged IV therapy compared with 4% in those with early transition to oral therapy. After full adjustment for hospital clustering and variation among hospitals, the difference in failure rate was not significant. The time to failure was not significantly different between the 2 groups at approximately 15 days overall.
Three percent of the prolonged-therapy group experienced a catheter complication and 1.5% experienced an adverse event related to antibiotics (compared with 0.4% of the oral-therapy group). The all-cause rehospitalization was higher (10%) in the group that received prolonged IV therapy group vs 5.9% in the group that had early transition to oral therapy.
The authors concluded that early transition to oral antibiotics in otherwise healthy children with uncomplicated osteomyelitis is as effective as prolonged IV therapy.
Zaoutis and colleagues point out that the relatively low failure rate would require a very large trial to demonstrate a difference between oral and prolonged IV therapy for osteomyelitis, so that evidence may never actually be compiled. Large observational studies such as this one may offer the best available evidence, but they still can’t overcome biases that may influence who gets placed on different therapies or other biases that might be difficult to detect by retrospective data review. It is revealing that almost half of the otherwise healthy children treated for osteomyelitis in these free-standing children’s hospitals do not receive prolonged IV treatment, making it more difficult to argue that prolonged IV therapy is the “standard of care.” In any case, the strength of this study lies in the number of patients observed. The results suggest that moving toward quicker transition to oral antibiotics is reasonable for otherwise healthy children with uncomplicated osteomyelitis.