Adjunctive clindamycin for cellulitis: a clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis

Richard Brindle, O Martin Williams, Paul Davies, Tim Harris, Heather Jarman, Alastair D Hay, Peter Featherstone, Richard Brindle, O Martin Williams, Paul Davies, Tim Harris, Heather Jarman, Alastair D Hay, Peter Featherstone

Abstract

Objective: To compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis.

Design: Parallel, double-blinded, randomised controlled trial.

Setting: Emergency department attendances and general practice referrals within 20 hospitals in England.

Interventions: Flucloxacillin, at a minimum of 500 mg 4 times per day for 5 days, with clindamycin 300 mg 4 times per day for 2 days given orally versus flucloxacillin given alone.

Main outcome measures: The primary outcome was improvement at day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side effects.

Results: 410 patients were included in the trial. No significant difference was seen in improvement at day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%)-OR 1.55 (95% CI 0.81 to 3.01), p=0.174. There was a significant difference in the number of patients with diarrhoea at day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%)-OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%)-adjusted OR 0.90 (95% CI 0.44 to 1.84).

Conclusions: The addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days.

Trial registration number: NCT01876628, Results.

Keywords: cellulitis; clindamycin; diarrhoea; erysipelas; flucloxacillin; limb.

Conflict of interest statement

Competing interests: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Flow chart summarising the numbers of patients screened for eligibility and numbers present at each follow-up.

References

    1. Hirschmann JV, Raugi GJ. Lower limb cellulitis and its mimics: part I. Lower limb cellulitis. J Am Acad Dermatol 2012;67:163.e1–12; quiz 175–6.
    1. Office of Population Censuses and Surveys. Morbidity statistics from general practice Fourth National Study. Her Majesty's Stationery Office Series MB5(272), 1992.
    1. United Kingdom Department of Health. Hospital Episode Statistics. 2012. (accessed May 2015).
    1. Bernard P, Toty L, Mounier M et al. . Early detection of streptococcal group antigens in skin samples by latex particle agglutination. Arch Dermatol 1987;123:468–70. 10.1001/archderm.1987.01660280070025
    1. Brook I, Frazier EH. Clinical features and aerobic and anaerobic microbiological characteristics of cellulitis. Arch Surg 1995;130:786–92. 10.1001/archsurg.1995.01430070108024
    1. Johnson KE, Kiyatkin DE, An AT et al. . PCR offers no advantage over culture for microbiologic diagnosis in cellulitis. Infection 2012;40:537–41. 10.1007/s15010-012-0289-7
    1. Karppelin M, Siljander T, Haapala AM et al. . Evidence of streptococcal origin of acute non-necrotising cellulitis: a serological study. Eur J Clin Microbiol Infect Dis 2015;34:669–72. 10.1007/s10096-014-2274-9
    1. Toleman MS, Vipond IB, Brindle R. Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis. J Med Microbiol 2016;65:44–7. 10.1099/jmm.0.000191
    1. Pallin DJ, Binder WD, Allen MB et al. . Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis 2013;56:1754–62. 10.1093/cid/cit122
    1. Brindle R, Williams OM, Bennett C et al. . Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev 2016;(3):CD004299 10.1002/14651858.CD004299.pub2
    1. Sawai J, Hasegawa T, Kamimura T et al. . Growth phase-dependent effect of clindamycin on production of exoproteins by Streptococcus pyogenes. Antimicrob Agents Chemother 2007;51:461–7. 10.1128/AAC.00539-06
    1. Gemmell CG, Peterson PK, Schmeling D et al. . Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin. J Clin Invest 1981;67:1249–56. 10.1172/JCI110152
    1. Bryant AE, Stevens DL. Chapter 199: streptococcus pyogenes. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas and Bennett's principles and practices of infectious diseases. 8th edn. Elsevier Inc, 2015. 2285–2299, ISBN 978-1-4557-4801-3.
    1. Mulla ZD, Leaverton PE, Wiersma ST. Invasive group A streptococcal infections in Florida. South Med J 2003;96:968–73. 10.1097/01.SMJ.0000051060.95210.9A
    1. Mehta S, McGeer A, Low DE et al. . Morbidity and mortality of patients with invasive group A streptococcal infections admitted to the ICU. Chest 2006;130:1679–86. 10.1378/chest.130.6.1679
    1. Mascini EM, Jansze M, Schouls LM et al. . Penicillin and clindamycin differentially inhibit the production of pyrogenic exotoxins A and B by group A streptococci. Int J Antimicrob Agents 2001;18:395–8. 10.1016/S0924-8579(01)00413-7
    1. Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J 1999;18:1096–100. 10.1097/00006454-199912000-00014
    1. Carapetis JR, Jacoby P, Carville K et al. . Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections. Clin Infect Dis 2014;59:358–65. 10.1093/cid/ciu304
    1. Joint Formulary Committee. British National Formulary. 17th edn. London: BMJ Group and Pharmaceutical Press, 2016.
    1. Dong SL, Kelly KD, Oland RC et al. . ED management of cellulitis: a review of five urban centers. Am J Emerg Med 2001;19:535–40. 10.1053/ajem.2001.28330
    1. Williams OM, Brindle RJ, South West Regional Microbiology Group (SWRMG). Audit of guidelines for antimicrobial management of cellulitis across English NHS hospitals reveals wide variation. J Infect 2016;73:291–3. 10.1016/j.jinf.2016.06.002
    1. Thomas KS, Crook AM, Nunn AJ et al. . Penicillin to prevent recurrent leg cellulitis. N Engl J Med 2013;368:1695–703. 10.1056/NEJMoa1206300
    1. Blaszczyk-Kostanecka M, Dobozy A, Dominguez-Soto L et al. . Comparison of two regimens of oral clindamycin versus dicloxacillin in the treatment of mild-to-moderate skin and soft-tissue infections. Curr Ther Res Clin Exp. 1998;59:341–53. 10.1016/S0011-393X(98)85036-4
    1. (accessed 1 Apr 2016).
    1. Montalto M, Davies F, Marijanovic N et al. . Skin surface temperature: a possible new outcome measure for skin and soft tissue infection. Aust Fam Physician 2013;42:653–7.
    1. Björnsdóttir S, Gottfredsson M, Thórisdóttir AS et al. . Risk factors for acute cellulitis of the lower limb: a prospective case-control study. Clin Infect Dis 2005;41:1416–22. 10.1086/497127
    1. Leman P, Mukherjee D. Flucloxacillin alone or combined with benzylpenicillin to treat lower limb cellulitis: a randomised controlled trial. Emerg Med J 2005;22:342–6. 10.1136/emj.2004.019869
    1. Carter K, Kilburn S, Featherstone P. Cellulitis and treatment: a qualitative study of experiences. Br J Nurs 2007;16:S22–4, S26–8 10.12968/bjon.2007.16.Sup1.27089
    1. Thomas KS, Cox NH, Savelyich BS et al. . Feasibility study to inform the design of a UK multi-centre randomised controlled trial of prophylactic antibiotics for the prevention of recurrent cellulitis of the leg. Trials 2007;8:3 10.1186/1745-6215-8-3
    1. Warrell DA. 2015. Envenoming: Consequences and Management. eLS. 1–10. DOI: 10.1002/9780470015902.a0002188.pub3. 10.1002/9780470015902.a0002188.pub3
    1. Leigh DA, Simmons K, Williams S. Gastrointestinal side effects following clindamycin and lincomycin treatment—a follow up study. J Antimicrob Chemother 1980;6:639–45. 10.1093/jac/6.5.639

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