Title: Adjunctive Clindamycin For Cellulitis: Clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis (C4C Trial).
Funder: Department of Health (England)

Abstract: Protein inhibiting antibiotics such as clindamycin are used as adjunctive therapy alongside beta-lactams for the treatment of severe skin and soft tissue infections caused by group A streptococci (GAS). It is thought that these antibiotics reduce the production of toxins which are responsible for local tissue damage and systemic features of sepsis. Cellulitis is a very common condition caused by GAS. A study from 2006 found a cellulitis incidence rate of 24.6/1000 person-years. The most common site of infection was the lower extremity (39.9%). There were 62,000 admissions to UK hospitals in 2011 with an average length of stay of 6.8 days and an estimated cost in excess of £100 million. There has been an increase of 20% in the number of hospital inpatient days from 2001 to 2011. If clindamycin is an effective adjuvant in streptococcal infections, its benefit should be detectable in cellulitis. A reduction in toxin production should lead to a reduction in the local and systemic severity of infection. A reduction in systemic features of severity would allow more patients to be treated confidently at home and there would be less perceived need for intravenous therapy. A reduction in local skin damage would result in less pain, more rapid resolution and a more rapid return to normal activity. We propose a randomised blinded controlled trial to assess whether the addition of clindamycin to the treatment of limb cellulitis results in less tissue damage and a more rapid resolution of systemic features, and is a cost-effective treatment alternative. Patients would be recruited from adults presenting to the medical assessment unit, emergency department or hospital-based general practice support unit with cellulitis. On diagnosis of cellulitis patients will start treatment with flucloxacillin; they will then be invited to enter the trial and randomised to either additional clindamycin or placebo. Patients must be in the trial within 24 hours of first dose of flucloxacillin. They will receive clindamycin, or placebo, for 48 hours and flucloxacillin for at least 5 days. Primary outcome is: Improvement at days 5 range (4-6) based on a composite of systemic and local features (temperature less than 37.5C and a reduction in limb swelling). Secondary outcomes include: Decrease in pain using a visual analogue score (VAS) at 5, 10 and 30 days, resolution of systemic features, resolution of composite inflammatory markers, recovery of renal function and return to work or normal activities. Data will be collected at enrolment (just before the study drug is given to the patient), after 5 days of treatment (range 4-6), after 10 days of treatment (range 9-11), with a patient questionnaire by telephone or visit at 30 days The data will be collected by the study nurse either in hospital or at home depending whether the patient was admitted or not. A reasonable estimate of improvement in the placebo group at 5 days is 80%. An improvement to 90% would have clinical significance. A sample size in each group is 219 (total 438) will have 80% power to detect the difference between the two groups. Apart from the potential benefits of adjunctive clindamycin as described above, we think that patients enrolled in the study will be more likely to have optimum treatment and be discharged earlier than at present. They will be less likely to have intravenous therapy and if started will have a shorter duration. We also think, within this study, that we can develop a nurse-led care pathway that would, in future allow most patients to remain out of hospital or shorten their hospital stay.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION