Duration of INtravenous antibiOticc therapy for Septic arthritis or acUte osteomyelitis in a paediatRic population - DINOSAUR

Currently there is no international & little UK consensus regarding the route or duration for antibiotic treatment of acute bone and joint infections in children. The suggested duration for IV antibiotic treatment ranges from 3 days to 6 weeks, resulting from several observational studies with relatively poor level of evidence. There is no current evidence to aid the clinical decision of when to switch from intravenous to oral therapy, which is widely accepted and usually occurs when the patient has shown a marked clinical improvement. In the past, the overall duration of antibiotic treatment has been considered an important factor to improve outcome & reduce relapse. Several paediatric texts recommend at least 4 to 6 weeks of treatment, but others advocate only 2 or 3 weeks of treatment. Bone and joint infections in children are uncommon and present with a range of clinical severity. The exact disease occurrence rate in UK practice has been estimated from recent audits at 3 regional centres to be 1.4-10 cases per 100,000 per year (bone more frequent than joint infections). Recent unpublished national data from England shows the admission rate for osteomyelitis in children 0-18 years of age has varied between 0.048 and 0.070 per 1000 child years, which equates to 5- 6 cases per month at large regional centres and 2-3 cases per month seen at large district general hospitals. Mild cases are often treated by paediatricians or orthopaedic surgeons with no surgical treatment, more severe cases require intervention. The exact microbiological diagnosis is consistently found in less than 15% of cases seen, despite a review of international literature (highly case selected) which suggests higher rates, and so the true range of bacteria-causing disease is also unknown. Our study has 2 clear stages. Firstly, we will mimic an established, validated electronic paediatric infection surveillance system (familiar to many of our team) to conduct a service evaluation of the current case spectrum seen in the UK and the exact diagnostic and treatment regimens that are carried out. This part of the study will allow us to establish the current NHS practice on which to design a randomised clinical trial to assess the safety of reduced intravenous antibiotic therapy compared with longer intravenous courses, and to gain consensus on the total length of therapy to be used in a clinical trial. In a representative sample, we will use a new, extremely cheap test recently validated at a Heath Protection Agency regional laboratory to identify better the range of bacteria-causing disease in order to inform the antimicrobial choice in a randomised trial. NHS REC Ethics applications currently in place will be amended and replicated to capture, store and analyse all data. In the second stage, we will: a) conduct a formal survey of clinical stakeholders (paediatric generalists & specialists in secondary & tertiary care, orthopaedic surgeons, paediatric microbiologists & radiologists) to identify: 1. the willingness of clinicians to randomise to a protocol finalised using the results of our service evaluation; 2. the clinical and laboratory criteria on which to base the intravenous to oral antibiotic switch and total length of antibiotic therapy; and 3. with experts in study methodology &design we will identify the outcome measures to be used in a randomised trial and the statistical parameters to inform the RCT design. b) In addition we will conduct a formal qualitative survey of 30 children (and their parents) who have been treated for bone and joint infections to assess the willingness of patients & parents to be randomised & consumer perceptions of the relevant study outcomes. The study team are ideally placed to carry out this research, as we are a partnership of all national clinical groups involved in the clinical care of children with bone and joint infections and the NIHR clinical research networks (Medicines for Children Research Network and Comprehensive Local Research Networks) including: methodologists/statisticians (MCRN), national representative groups for paediatric infections, orthopaedics and microbiology, MCRN clinical studies groups for general paediatrics and paediatric allergy, immunology and infection; and qualitative researchers. The costs of research provide for validated electronic disease surveillance & data analysis, formal qualitative research and methodological analysis in order to inform the design of a possible randomised trial and assess the detailed statistical issues specified by the brief (non-inferiority margins). NIHR networks ensure maximum economy of scale. Minimal NHS costs have been identified for this feasibility study.