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The ability to provide long-term antibiotic therapy for acute osteomyelitis was revolutionized by the use of peripherally inserted central catheters (PICCs). Peripherally inserted central catheters provided an alternative for children to receive antibiotic therapy outside the health care setting, which reduced their hospital length of stay and improved their quality of life. However, PICCs can be complicated by infectious and noninfectious sequelae.1 Clinicians must weigh the risks of intravenous (IV) therapy against the risk for treatment failure when considering a change from IV to oral therapy in children with acute osteomyelitis. In this issue of JAMA Pediatrics, Keren and colleagues2 suggest that in otherwise healthy children, we may be able to convert therapy from IV antibiotics to oral agents early in the treatment course without compromising clinical outcomes, thereby avoiding the long-term use of PICCs.
The investigators included 2060 children with acute osteomyelitis across 36 institutions from 2009 to 2012.2 These children were otherwise healthy without underlying medical conditions or recent hospitalizations, which excluded many children with a discharge diagnosis of acute osteomyelitis. The study included 1005 children undergoing the transition to oral antibiotic therapy at the time of hospital discharge and 1055 who continued IV therapy with the insertion of a PICC before leaving the hospital. Although they found that the prevalence of treatment failure and antibiotic-related adverse events was equivalent between the groups in a propensity score–matched analysis, 15.0% of children with PICCs had catheter-associated complications, including subsequent bloodstream infections, exit-site or tunnel infections, venous thrombosis, or line breakage, that warranted additional visits to the emergency department.
In this study, the investigators capitalized on access to a large number of patient encounters through a multicenter administrative database. The use of administrative data offers many advantages, but the method is vulnerable to certain important limitations, including misclassification of pertinent variables. The investigators attempted to ameliorate this limitation by reviewing medical records to evaluate microbiological data, postdischarge treatment data, and clinical course data for all included patients. This “big data” approach prevented the investigators from determining the appropriateness of the antibiotics selected in each of the treatment groups. For example, the authors were not able to identify imbalances between antibiotic agents with adequate in vitro activity against the causative pathogens. Similarly, although the proportions of children who underwent bone debridement or abscess drainage between the treatment arms were similar, the percentage of children in each group who had inadequate source control is more important and unknown. It is unknown whether children who underwent PICC placement and prolonged IV antibiotic administration had more complicated clinical courses, such as prolonged bacteremia, thromboembolic clots, undrained fluid collections, or metastatic disease, compared with patients who underwent transition to oral therapy.
Despite these limitations, the present study adds to a growing body of published evidence—including more than 2000 children—that early conversion to oral antibiotics is equally as effective as the continued use of IV agents for the treatment of acute osteomyelitis.3-10 Several oral antibiotics exist that are highly bioavailable and provide excellent coverage against the most common pathogens implicated in acute osteomyelitis.11 Conducting a multicenter randomized clinical trial to further evaluate this question would be highly resource intensive. Because the present study is in agreement with all studies published to date in demonstrating equipoise between both treatment approaches for acute osteomyelitis in children, more clinicians will likely adopt early oral therapy, and recruitment into a randomized clinical trial may prove difficult because the clinicians might hesitate to randomize patients to receive more invasive therapy.
Some institutions included in this study had almost 100% of patients receiving delivery of antibiotics through PICCs for acute osteomyelitis, whereas other institutions had virtually no patients with PICCs for this indication. The work by Keren and colleagues2 reminds us that when considerable variability exists across hospitals in use of resources for the same condition, opportunities often emerge for standardization of care, which likely results in improved outcomes and reduced costs. The investigators have provided very necessary information about how we can best organize and deliver care to children with a relatively common pediatric diagnosis while improving outcomes, reducing costs and untoward effects, and improving patient satisfaction.
In summary, this study addresses an important question with obvious implications for children and their caregivers hoping to avoid PICC-associated complications. In the absence of data demonstrating that long-term IV antibiotics enhance clinical outcomes compared with oral therapy, clinicians should strongly consider transition to oral antibiotic therapy at the time of discharge for the treatment of acute osteomyelitis in otherwise healthy children.
Corresponding Author: Aaron M. Milstone, MD, MHS, Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N Wolfe St, Ste 3141, Baltimore, MD 21287 (firstname.lastname@example.org).
Published Online: December 15, 2014. doi:10.1001/jamapediatrics.2014.2850.
Conflict of Interest Disclosures: Dr Tamma receives research support from Pfizer and Merck, unrelated to the present study. No other disclosures were reported.
Tamma PD, Milstone AM. Outpatient Antibiotic Therapy for Acute Osteomyelitis in Children: Balancing Safety and Efficacy. JAMA Pediatr. 2015;169(2):108–109. doi:10.1001/jamapediatrics.2014.2850
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