Results Summary
What was the research about?
Children hospitalized for a severe infection often need to continue to take antibiotics after they go home. In this study, the research team wanted to learn if antibiotics taken by mouth work as well as those given through an IV peripherally inserted central catheter, or PICC. A PICC is a thin tube put into a vein in the upper arm. The PICC reaches into a large vein near the heart. The research team also wanted to
- See how often there were problems from the PICC. For example, the tube could break or become clogged or infected.
- Compare how often side effects occurred with each way of giving the antibiotics. Side effects could include a rash, stomach pain, or nausea.
The team looked at medical records from children who had been in the hospital for a bone infection, severe pneumonia, or a burst appendix.
What were the results?
Antibiotics taken by mouth worked as well as those given through a PICC. Problems from the PICC were common. Side effects also occurred more often with a PICC than with antibiotics taken by mouth.
Children with a PICC were more likely to go to the emergency department, or ED. They were also more likely to end up back in the hospital. The reason was usually problems from the PICC.
Who was in the study?
The research team looked at medical records from 8,762 children in the United States. The children were between 2 months and 18 years of age. They had been in the hospital with a severe infection: 2,060 had a bone infection, 2,123 had severe pneumonia, and 4,579 had a burst appendix. The research team didn’t look at records from children with these health problems who also had other serious health problems.
- Of the children with a bone infection, 51 percent were male, 63 percent were white, 18 percent were black, and 18 percent were Hispanic. Most were between the age of 5 and 13. The most common infection sites were the pelvis, thigh, lower leg, ankle, and foot.
- Of children with severe pneumonia, 59 percent were white, 16 percent were black, and 7 percent were Asian or Native American. The average age was five.
- Of children with a burst appendix, 61 percent were male. Fifty-five percent were less than 10 years of age.
What did the research team do?
The research team looked at medical records from 38 children’s hospitals over four years. The team compared children who took antibiotics by mouth after leaving the hospital with those who had a PICC. The team wanted to see
- How often the antibiotics did not get rid of the infection
- How often problems resulted from the PICC
- How often the children had side effects
- How often a child had to go to the ED or return to the hospital because of problems from the PICC or side effects
A parent from a hospital family advisory council helped the research team decide what to look for in the study.
What were the limits of the study?
The medical records only showed when children went to the ED of the original hospital or were put back in that hospital. They didn’t show when children went to a doctor’s office or another hospital. Thus, the study may not have counted all the times children taking antibiotics by mouth had side effects. Also, the type of antibiotic, not whether it was given by mouth or through a PICC, may affect whether there are side effects.
Future research could compare different types of antibiotics to see if one works better than others. Researchers could also look at how long children need to take the antibiotics.
How can people use the results?
When children have a severe infection, their doctors and families can use these results to decide whether to give antibiotics by mouth or through a PICC after leaving the hospital.
Professional Abstract
Objective
To compare the effectiveness and rates of adverse outcomes of postdischarge antibiotic therapy administered orally versus through a peripherally inserted central catheter (PICC) in children hospitalized for acute osteomyelitis, complicated pneumonia, or perforated appendicitis
Study Design
| Design Element | Description |
|---|---|
| Design | 3 retrospective cohort studies |
| Population | Medical records for 8,762 children ages 2 months to 18 years requiring prolonged (at least 1 week) home antibiotic therapy after hospitalization including 2,060 with acute osteomyelitis, 2,123 with complicated pneumonia, and 4,579 with perforated appendicitis |
| Interventions/ Comparators |
|
| Outcomes |
Primary: treatment failure Secondary: rates of PICC complications and adverse drug reactions requiring a return ED visit or hospital readmission |
| Timeframe | Up to 6 months for acute osteomyelitis, 14 days for complicated pneumonia, and 30 days for perforated appendicitis |
This retrospective study compared the effectiveness of oral and intravenous (IV) PICC postdischarge antibiotic therapy in three cohorts: children with acute osteomyelitis, complicated pneumonia, or perforated appendicitis. The research team examined the rates of treatment failure, PICC complications, and adverse drug reactions requiring a return emergency department (ED) visit or hospital readmission. The team defined treatment failure as follows:
- Acute osteomyelitis: Rehospitalization for change in antibiotic or dose; therapy prolongation; change from oral to IV antibiotics; bone, skin, or muscle abscess drainage; debridement; bone biopsy; arthrocentesis; or pathologic fracture
- Complicated pneumonia: Rehospitalization for change in antibiotic, therapy prolongation, or pleural drainage
- Perforated appendicitis: Rehospitalization for recurrent intra-abdominal infection documented by abdominal imaging
Researchers reviewed medical records for 8,762 children from 38 US children’s hospitals over four years. The study excluded records from children with concurrent or previous chronic cardiac, hematologic, immunologic, oncologic, or respiratory conditions. The study also excluded records from children with very short or prolonged hospital stays.
To reduce risk of bias, the study used within- and/or across-hospital matching. This matching linked each child in the PICC group to the most similar child in the oral group, or vice versa.
A parent representative of the Children’s Hospital of Philadelphia Family Advisory Council helped select study outcomes.
Results
Acute osteomyelitis. The oral antibiotics group did not experience more treatment failures than the PICC group in
- Across-hospital matched analyses (risk difference between PICC and oral administration [RD]=0.3%; 95% confidence interval [CI]: -0.1%, 2.5%)
- Within-hospital matched analyses (RD=0.6%; 95% CI: -0.2%, 3.0%)
Compared with the oral antibiotics group, the PICC group had a higher risk of return ED visits or hospital readmissions for any adverse outcome in
- Across-hospital matched analyses (RD=14.6%; 95% CI: 11%, 18%)
- Within-hospital matched analyses (RD=14.0%; 95% CI: 11%, 18%)
Complicated pneumonia. No statistically significant differences in treatment failures between the oral antibiotics and PICC groups occurred in across-hospital matched analyses (RD=1.8%; 95% CI: -0.4%, 3.9%).
The composite outcome of all return ED visits or hospital readmissions was significantly higher in the PICC group (RD=15%; 95% CI: 10%, 19%) than in the oral antibiotics group.
Perforated appendicitis. When compared with the oral antibiotics group in across-hospital matched analyses, the PICC group had significantly higher rates of
- Treatment failure (odds ratio [OR]=1.7; 95% CI: 1.05, 2.9; RD=4.0%; 95% CI: 0.4%, 7.6%).
- All-cause revisits (OR=2.1; 95% CI: 1.4, 3.1; RD=9.2%; 95% CI: 4.2%, 14%)
- Nontreatment-failure-related revisits (OR=2.2; 95% CI: 1.3, 3.7; RD=5.4%; 95% CI: 2.0%, 8.8%)
Limitations
Patient matching was limited to observed covariates. Unmeasured confounders, such as length of bacteremia or differences in home care, might have influenced treatment outcomes. For the complicated pneumonia and perforated appendicitis cohorts, researchers only used across-hospital matching because of the limited number of children with PICCs at some hospitals.
Differences in antibiotic type rather than route of delivery may have contributed to the higher rates of adverse events in the PICC group. This study only ascertained outcomes that occurred in the hospitals that provided the initial treatment. It is possible that treatment failures or adverse drug reactions may have been managed at a different hospital, in primary care settings, or by a provider in the home.
Conclusions and Relevance
Children receiving postdischarge oral antibiotics did not experience more treatment failures than those receiving PICC-administered antibiotics. PICC complications were relatively common and potentially serious. Higher rates of complications and adverse drug reactions in the PICC groups contributed to higher rates of ED revisits and hospital readmissions. These results suggest that when treating children with a serious bacterial infection postdischarge, clinicians should consider using oral antibiotics instead of IV antibiotics when an effective oral antibiotic is available.
Future Research Needs
Future research could include a randomized controlled trial to compare oral and IV PICC postdischarge antibiotic therapy. Researchers could examine the relative effectiveness of different oral antibiotic agents or investigate the ideal duration and endpoints of antibiotic treatment.
Final Research Report
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Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer review identified the following strengths and limitations in the report:
- The awardee addressed reviewers’ concerns about the generalizability of study results and the report’s inadequate emphasis on study population characteristics in the final report. Reviewers noted that the study population consisted of children considered low risk for reinfection or treatment failure, who only make up about 25-30 percent of all children requiring antibiotics for serious infections. The awardee responded that the study protocol and published papers clearly indicated that the children in this study were low risk.
- The awardee addressed comments from the statistical reviewer by referring the reader to previously published papers that have details on study methods and analyses.
- Responding to reviewer requests for more details on the methods for insuring consistency and limiting interrater variability, the awardee added language describing chart reviewers’ training. The awardee also noted that the team did not measure how often different raters disagreed in their reviews of medical charts.
- The investigator did not respond to reviewers’ questioning of the conclusion that there were no differences in treatment failure on oral antibiotics between hospitals that had low versus high use of peripherally inserted central catheters. The lack of sample sizes for this comparison and the wide confidence intervals for the odds ratio did not provide sufficient evidence to warrant this conclusion.