Background:

There is little current consensus regarding the route or duration of antibiotic treatment for acute osteomyelitis (OM) and septic arthritis (SA) in children.

Objective:

To assess the overall feasibility and inform the design of a future randomised controlled trial (RCT) to reduce the duration of intravenous (i.v.) antibiotic use in paediatric OM and SA.

Design:

(1) A prospective service evaluation (cohort study) to determine the current disease spectrum and UK clinical practice in paediatric OM/SA; (2) a prospective cohort substudy to assess the use of targeted polymerase chain reaction (PCR) in diagnosing paediatric OM/SA; (3) a qualitative study to explore families’ views and experiences of OM/SA; and (4) the development of a core outcome set via a systematic review of literature, Delphi clinician survey and stakeholder consensus meeting.

Setting:

Forty-four UK secondary and tertiary UK centres (service evaluation).

Participants:

Children with OM/SA.

Interventions:

PCR diagnostics were compared with culture as standard of care. Semistructured interviews were used in the qualitative study.

Results:

Data were obtained on 313 cases of OM/SA, of which 218 (61.2%) were defined as simple disease and 95 (26.7%) were defined as complex disease. The epidemiology of paediatric OM/SA in this study was consistent with existing European data. Children who met oral switch criteria less than 7 days from starting i.v. antibiotics were less likely to experience treatment failure (9.6%) than children who met oral switch criteria after 7 days of i.v. therapy (16.1% when switch was between 1 and 2 weeks; 18.2% when switch was > 2 weeks). In 24 out of 32 simple cases (75%) and 8 out of 12 complex cases (67%) in which the targeted PCR was used, a pathogen was detected. The qualitative study demonstrated the importance to parents and children of consideration of short- and long-term outcomes meaningful to families themselves. The consensus meeting agreed on the following outcomes: rehospitalisation or recurrence of symptoms while on oral antibiotics, recurrence of infection, disability at follow-up, symptom free at 1 year, limb shortening or deformity, chronic OM or arthritis, amputation or fasciotomy, death, need for paediatric intensive care, and line infection. Oral switch criteria were identified, including resolution of fever for ≥ 48 hours, tolerating oral food and medicines, and pain improvement.

Limitations:

Data were collected in a 6-month period, which might not have been representative, and follow-up data for long-term complications are limited.

Conclusions:

A future RCT would need to recruit from all tertiary and most secondary UK hospitals. Clinicians have implemented early oral switch for selected patients with simple disease without formal clinical trial evidence of safety. However, the current criteria by which decisions to make the oral switch are made are not clearly established or evidence based.

Future work:

A RCT in simple OM and SA comparing shorter- or longer-course i.v. therapy is feasible in children randomised after oral switch criteria are met after 7 days of i.v. therapy, excluding children meeting oral switch criteria in the first week of i.v. therapy. This study design meets clinician preferences and addresses parental concerns not to randomise prior to oral switch criteria being met.

Funding:

The National Institute for Health Research Health Technology Assessment programme.

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 10/146/01. The contractual start date was in March 2013. The draft report began editorial review in January 2016 and was accepted for publication in November 2016. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Saul N Faust was UK chief investigator and University Hospital Southampton NHS Foundation Trust principal investigator for a Cubist-sponsored clinical trial of daptomycin against standard of care antibiotic therapy in paediatric osteomyelitis. All funds were paid into accounts within the NHS trust or university and not paid as personal fees. He reports consultancy fees for advisory board participation paid into accounts within the NHS trust or university (not personal fees) from vaccine manufacturers and antimicrobial agent manufacturers, including AstraZeneca, Cubist, Merck, GlaxoSmithKline (GSK) and Pfizer, outside the submitted work. He acts as principal investigator for clinical trials and other studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers and antimicrobial agents, and has participated in advisory boards for vaccine manufacturers. Adam Finn reports grants and personal fees from Sanofi Pasteur MSD Ltd (SPMSD), and grants and personal fees from GSK, outside the submitted work. In addition, prior to October 2014, the University of Bristol and University Hospitals Bristol NHS Foundation Trust received funding for research conducted by Adam Finn and for consultancy and lectures from Pfizer, GSK, SPMSD and Novartis, who manufacture licensed and developmental meningococcal vaccines. Stuart C Clarke acts as principal investigator for clinical trials and other studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers but receive no personal payments from them. He has participated in advisory boards for vaccine manufacturers and has received financial assistance from vaccine manufacturers to attend conferences, but receives no personal payments for this work. All grants and honoraria are paid into accounts within the respective NHS trusts or universities. Jethro Herberg reports that he was an investigator for a Cubist-sponsored clinical trial of daptomycin against standard of care antibiotic therapy in paediatric osteomyelitis; he received no personal payments. Andrew Riordan reports that the trust, but not he, has received funding for research sponsored by vaccine manufacturers and antimicrobial agents. He was lead editor for an e-learning package on meningitis produced by the Royal College of Paediatric and Child Health, funded by an unrestricted grant from Novartis Vaccines. Marieke Emonts was Newcastle upon Tyne Hospitals Foundation Trust’s principal investigator for a Cubist-sponsored clinical trial of daptomycin against standard of care antibiotic therapy in paediatric osteomyelitis. All grants and honoraria are paid into accounts within the NHS trust or university; she received no personal payment of any kind. Marieke Emonts reports acting as site principle investigator on behalf of the Newcastle upon Tyne Hospitals Foundation Trust/Newcastle University for clinical trials sponsored by Merck Sharp & Dohme Corp. and SPMSD outside the submitted work. Claire Ballinger is currently a member of the Health Technology Assessment (HTA) Primary Care, Community and Preventive Interventions (PCCPI) Panel and the HTA PCCPI Methods group. She was a former member of the Research for Patient Benefit London committee. Claire Ballinger is supported by the National Institute for Health Research (NIHR) Collaboration for Applied Health Research and Care Wessex. Catherine Spowart reports grants from NIHR during the conduct of the study. Philip Henman reports working as an investigator in a commercial clinical trial sponsored by Merck Sharpe & Dohme, on behalf of his employer, outside the submitted work.