JAMA Pediatrics Journal Club Slides:
Postdischarge Treatment of
Acute Osteomyelitis
Keren R, Shah SS, Srivastava R, et al; Pediatric Research in
Inpatient Settings Network. Comparative effectiveness of intravenous
vs oral antibiotics for postdischarge treatment of acute osteomyelitis
in children. JAMA Pediatr. Published online December 15, 2014.
doi:10.1001/jamapediatrics.2014.2822.
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Introduction
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Background
– Postdischarge treatment of acute osteomyelitis in children requires
weeks of antibiotic therapy.
– Therapy can be administered orally or intravenously via a peripherally
inserted central catheter (PICC).
– PICCs carry a risk for serious complications.
– There is limited evidence about the effectiveness of oral therapy.
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Study Objective
– To compare the effectiveness and adverse outcomes of postdischarge
antibiotic therapy administered via the PICC or the oral route.
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Methods
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Study Design
– Retrospective cohort study.
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Setting
– 36 US children’s hospitals.
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Patients
– Children hospitalized from January 1, 2009, through
December 31, 2012.
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Intervention
– Postdischarge administration of antibiotics via the PICC or
the oral route.
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Methods
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Primary Outcome
– Treatment failure, defined as revisit to the emergency
department (ED) or a rehospitalization for the following:
• Change in the antibiotic prescribed or its dosage.
• Prolongation of antibiotic therapy.
• Conversion from the oral route to the PICC route.
• Bone abscess drainage.
• Debridement of necrotic bone.
• Bone biopsy.
• Drainage of an abscess of the skin or muscle.
• Arthrocentesis.
• Diagnosis of a pathologic fracture.
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Methods
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Secondary Outcomes
– Return to the ED or a rehospitalization for adverse drug reaction
(vomiting and/or diarrhea, dehydration, Clostridium difficile infection,
allergic reaction, urticaria, anaphylaxis, drug-induced neutropenia,
acute kidney injury, Stevens-Johnson syndrome, erythema multiforme,
or other).
– Return to the ED or a rehospitalization for PICC complication (fever
evaluation, infection at the site of the PICC insertion, bloodstream
infection, sepsis, thrombosis, or breakage, repair, adjustment,
manipulation, or removal of the PICC line with or without insertion of a
new line).
– Composite of treatment failure, adverse drug reaction, and PICC line
complication.
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Methods
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Propensity Score–Based Full Matching
– Method for dealing with confounding by indication.
– Propensity score calculated from logistic regression that includes age,
race, insurance, length of stay, infection location, surgical procedures
(arthrocentesis, osteotomy, soft-tissue incision and drainage, and
arthrotomy), and causative pathogen.
– Full matching links each child who received antibiotics via the PICC route
to the most similar child who received antibiotics via the oral route or vice
versa (based on propensity score).
– Matching within hospitals controls for hospital-level confounders,
analogous to cluster randomized trial.
– Matching across hospitals controls better for patient-level confounders.
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Effect Modification
– Age, culture-verified presence of methicillin-resistant Staphylococcus
aureus (MRSA), ie, is the effectiveness different in younger children, or
children with MRSA?
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Results
Flowchart of the
Study Cohort
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Results
Scatterplot of Hospital Volume
of Osteomyelitis, Proportion of
Children With Postdischarge
Antibiotic Therapy Via the
PICC Route, and Their Crossclassification Across Hospitals
• Large and evenly
distributed variation in use
of PICCs.
• No correlation between
hospital volume of
osteomyelitis and use of
PICCs.
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Results
Clinical and Demographic
Characteristics of the
Study Population
• Small differences
between the oral and
PICC routes in a few
key variables.
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Results
Clinical and Demographic
Characteristics of
Treatment Groups After
Within- and AcrossHospital Matching
• Matching reduces
differences.
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Results
Adverse Outcomesa
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Results
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Effect Modification
– No clinically relevant difference in rates of treatment failure for children
5 years and younger.
• Across-hospital risk difference = −1.3% (95% CI, −4.7% to 2.1%).
• Within-hospital risk difference = −2.8% (95% CI, −7.4% to 1.7%).
– Risk for treatment failure increased in children older than 5 years who
had received antibiotics via the PICC route.
• Across-hospital risk difference = 3.8% (95% CI, 1.3%-6.3%).
• Within-hospital risk difference = 4.6% (95% CI, 2.2%-7%).
– Isolation of MRSA as the causative organism did not modify the effect of
the treatment route on the outcome of treatment failure.
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Comment
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Children discharged to complete antibiotic course via oral route did NOT
have a higher rate of treatment failure.
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Children with MRSA infections did not have more treatment failures.
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High rate of serious complications of PICC line (15% requiring ED revisit
or rehospitalization): bloodstream infections, thromboembolism, line
displacement or breakage.
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Comment
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Likely to be strongest evidence available to answer question.
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Randomized clinical trial not feasible.
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Confirms results of prior study that used only administrative data.
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Results consistent, even with increase in MRSA prevalence (study period
2009-2012).
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Stop using PICC lines to treat acute osteomyelitis in otherwise healthy
children who can tolerate oral route.
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Oral route is equally effective, has fewer complications, is less expensive,
and is more convenient.
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Contact Information
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If you have questions, please contact the corresponding author:
– Ron Keren, MD, MPH, Division of General Pediatrics, Center for
Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia,
Abramson Research Building, Room 1347, Philadelphia, PA 19104
(keren@email.chop.edu).
Funding/Support
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This study was supported by the Patient Centered Outcomes Research
Institute.
Conflict of Interest Disclosures
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None reported.
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