Outpatient Antibiotic Therapy for Acute Osteomyelitis in Children: Balancing Safety and Efficacy

The ability to provide long-term antibiotic therapy for acute osteomyelitiswas revolutionizedby theuseofperipherally 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 lengthof stay and improved their quality of life.However, PICCs canbe complicatedby infectious andnoninfectious sequelae.1 Cliniciansmustweigh the risks of intravenous (IV) therapy against the risk for treatment failurewhen considering a change from IV to oral therapy in childrenwith 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 treatmentcoursewithoutcompromisingclinicaloutcomes, thereby avoiding the long-term use of PICCs. The investigators included2060childrenwithacuteosteomyelitis across 36 institutions from 2009 to 2012.2 These children were otherwise healthy without underlyingmedical conditionsorrecenthospitalizations,whichexcludedmanychildrenwithadischargediagnosisofacuteosteomyelitis.Thestudy included 1005 children undergoing the transition to oral antibiotictherapyatthetimeofhospitaldischargeand1055whocontinuedIVtherapywith the insertionofaPICCbefore leaving the hospital.Althoughthey foundthat theprevalenceof treatment failure and antibiotic-related adverse events was equivalent between the groups in a propensity score–matched analysis, 15.0% of childrenwith PICCs had catheter-associated complications, includingsubsequentbloodstreaminfections, exit-site or tunnel infections, venous thrombosis, or linebreakage, that warranted additional visits to the emergency department. Inthisstudy,theinvestigatorscapitalizedonaccesstoalarge number of patient encounters through amulticenter administrativedatabase.Theuseofadministrativedataoffersmanyadvantages,butthemethodisvulnerabletocertain important limitations, includingmisclassification of pertinent variables. The investigatorsattemptedtoameliorate this limitationbyreviewing medical records to evaluate microbiological data, postdischarge treatment data, and clinical course data for all included patients. This “big data” approachprevented the investigators fromdeterminingtheappropriatenessof theantibioticsselected ineachof the treatmentgroups.Forexample, theauthorswere not able to identify imbalances between antibiotic agentswith adequate invitroactivityagainst thecausativepathogens.Similarly,althoughtheproportionsofchildrenwhounderwentbone debridement or abscess drainage between the treatment arms were similar, thepercentageof children ineachgroupwhohad inadequate source control ismore important and unknown. It isunknownwhether childrenwhounderwentPICCplacement andprolongedIVantibioticadministrationhadmorecomplicated clinicalcourses,suchasprolongedbacteremia, thromboembolic clots, undrained fluid collections, or metastatic disease, comparedwith patientswho underwent transition to oral therapy. Despite these limitations, thepresent studyadds toagrowing body of published evidence—including more than 2000 children—that early conversion to oral antibiotics is equally as effective as the continueduseof IV agents for the treatment of acute osteomyelitis.3-10 Several oral antibiotics exist that are highlybioavailable andprovide excellent coverage against the most common pathogens implicated in acute osteomyelitis.11 Conducting a multicenter randomized clinical trial to further evaluate this questionwouldbehighly resource intensive. Becausethepresentstudyisinagreementwithallstudiespublished todate indemonstratingequipoisebetweenboth treatmentapproachesforacuteosteomyelitis inchildren,moreclinicianswill likely adopt earlyoral therapy, and recruitment intoa randomizedclinical trialmayprovedifficultbecausethecliniciansmight hesitate torandomizepatients toreceivemore invasive therapy. Some institutions included in this studyhad 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. Thework by Keren and colleagues2 reminds us that when considerable variability exists acrosshospitals inuseof resources for the samecondition, opportunities oftenemerge for standardizationof care, which likely results in improvedoutcomes 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 withobvious implications forchildrenandtheircaregivershoping to avoid PICC-associated complications. In the absence of datademonstrating that long-termIVantibioticsenhanceclinical outcomes compared with oral therapy, clinicians should stronglyconsider transitiontooralantibiotic therapyat thetime of discharge for the treatment of acute osteomyelitis in otherwise healthy children. Related article page 120 Opinion