High-dose vs. Standard-dose Cephalexin for Cellulitis

Summary

Cellulitis is a painful bacterial infection of the skin and underlying tissue that needs antibiotic treatment. There are approximately 193,000 visits to Canadian emergency departments (EDs) each year for cellulitis. Emergency doctors who treat patients with cellulitis must decide on the correct antibiotic agent, dose, duration and frequency. Cellulitis is most commonly treated with the oral antibiotic cephalexin. However, there has been little research to guide doctors with respect to cellulitis treatment, which has led to an overuse of intravenous antibiotics. In addition, the current treatment failure rate of 20% is unacceptably high. When compared to standard-dose oral cephalexin, high-dose oral cephalexin may reduce treatment failure, which would help decrease the need for intravenous antibiotics and subsequent hospitalization. A well-designed clinical trial is necessary to determine if high-dose oral cephalexin reduces treatment failure for cellulitis patients. This pilot trial will determine the feasibility and design of such a clinical trial.

Timeline

Start

2021-08-16

Primary completion

2022-02-23

Completion

2022-02-23

Publications

• Results Stevens DL, Eron LL. In the clinic. Cellulitis and soft-tissue infections. Ann Intern Med. 2009 Jan 6;150(1):ITC11. doi: 10.7326/0003-4819-150-1-200901060-01001.
• Results Stenstrom R, Grafstein E, Romney M, Fahimi J, Harris D, Hunte G, Innes G, Christenson J. Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus skin and soft tissue infection in a Canadian emergency department. CJEM. 2009 Sep;11(5):430-8. doi: 10.1017/s1481803500011623.
• Results Yadav K, Suh KN, Eagles D, MacIsaac J, Ritchie D, Bernick J, Thiruganasambandamoorthy V, Wells G, Stiell IG. Predictors of Oral Antibiotic Treatment Failure for Nonpurulent Skin and Soft Tissue Infections in the Emergency Department. Acad Emerg Med. 2019 Jan;26(1):51-59. doi: 10.1111/acem.13492. Epub 2018 Jul 4.
• Results Pollack CV Jr, Amin A, Ford WT Jr, Finley R, Kaye KS, Nguyen HH, Rybak MJ, Talan D. Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital. J Emerg Med. 2015 Apr;48(4):508-19. doi: 10.1016/j.jemermed.2014.12.001. Epub 2015 Jan 17.
• Results Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. doi: 10.1093/cid/ciu444.
• Results Kwak YG, Choi SH, Kim T, Park SY, Seo SH, Kim MB, Choi SH. Clinical Guidelines for the Antibiotic Treatment for Community-Acquired Skin and Soft Tissue Infection. Infect Chemother. 2017 Dec;49(4):301-325. doi: 10.3947/ic.2017.49.4.301.
• Results Li HK, Agweyu A, English M, Bejon P. An unsupported preference for intravenous antibiotics. PLoS Med. 2015 May 19;12(5):e1001825. doi: 10.1371/journal.pmed.1001825. eCollection 2015 May.
• Results Cyriac JM, James E. Switch over from intravenous to oral therapy: A concise overview. J Pharmacol Pharmacother. 2014 Apr;5(2):83-7. doi: 10.4103/0976-500X.130042.
• Results Yadav K, Gatien M, Corrales-Medina V, Stiell I. Antimicrobial treatment decision for non-purulent skin and soft tissue infections in the emergency department. CJEM. 2017 May;19(3):175-180. doi: 10.1017/cem.2016.347. Epub 2016 Aug 17.
• Results Chow M, Quintiliani R, Cunha BA, Thompson M, Finkelstein E, Nightingale CH. Pharmacokinetics of high-dose oral cephalosporins. J Clin Pharmacol. 1979 Apr;19(4):185-94. doi: 10.1002/j.1552-4604.1979.tb01650.x. No abstract available.
• Results Wise R. The pharmacokinetics of the oral cephalosporins--a review. J Antimicrob Chemother. 1990 Dec;26 Suppl E:13-20. doi: 10.1093/jac/26.suppl_e.13.
• Results Murray H, Stiell I, Wells G. Treatment failure in emergency department patients with cellulitis. CJEM. 2005 Jul;7(4):228-34. doi: 10.1017/s1481803500014342.
• Results Peterson D, McLeod S, Woolfrey K, McRae A. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014 May;21(5):526-31. doi: 10.1111/acem.12371.
• Results Yadav K, Nath A, Suh KN, Sikora L, Eagles D. Treatment failure definitions for non-purulent skin and soft tissue infections: a systematic review. Infection. 2020 Feb;48(1):75-83. doi: 10.1007/s15010-019-01347-w. Epub 2019 Aug 5.
• Yadav K, Eagles D, Perry JJ, Taljaard M, Sandino-Gold G, Nemnom MJ, Corrales-Medina V, Suh KN, Stiell IG. High-dose cephalexin for cellulitis: a pilot randomized controlled trial. CJEM. 2023 Jan;25(1):22-30. doi: 10.1007/s43678-022-00433-7. Epub 2023 Jan 2.

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