Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial

Duncan R Cranendonk, Brent C Opmeer, Jan M Prins, W Joost Wiersinga, Duncan R Cranendonk, Brent C Opmeer, Jan M Prins, W Joost Wiersinga

Abstract

Background: Recommended therapy duration for patients hospitalized with cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days.

Methods/design: In a multicenter, randomized, double-blind, non-inferiority trial, adult patients admitted with cellulitis will be included. Cellulitis is defined as warmth, erythema, and induration of the skin and/or subcutaneous tissue, with or without pain (including erysipelas). All patients will initially be treated with intravenous flucloxacillin, and will be evaluated after 5-6 days. Those who have improved substantially (defined as being afebrile, and having a lower cellulitis severity score) will be randomized at day 6 between additional 6 days of oral flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as resolution of cellulitis on day 14 (disappearance of warmth and tenderness, improvement of erythema and edema), without the need of additional antibiotics for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90), speed of recovery (using a cellulitis severity score until day 28, and VAS scores on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D questionnaires) and costs (associated with total antibiotic use and health-care resource utilization up to day 90).

Discussion: Inclusion is planned to start in Q2 2014.

Trial registration: ClinicalTrials.gov (NCT02032654) and the Netherlands Trial Register (NTR4360).

References

    1. Swartz MN. Cellulitis. N Engl J Med. 2004;14:904–912. doi: 10.1056/NEJMcp031807.
    1. Kilburn S, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010;14:1–64.
    1. Chira S, Miller LG. Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review. Epidemiol Infect. 2010;14:313–317. doi: 10.1017/S0950268809990483.
    1. Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas. J Infect. 2012;14:148–155. doi: 10.1016/j.jinf.2011.11.004.
    1. Christensen KLY, Holman RC, Steiner CA, Sejvar JJ, Stoll BJ, Schonberger LB. Infectious disease hospitalizations in the United States. Clin Infect Dis. 2009;14:1025–1035. doi: 10.1086/605562.
    1. Phoenix G, Das S, Joshi M. Diagnosis and management of cellulitis. Br Med J. 2012;14:e4955. doi: 10.1136/bmj.e4955.
    1. Goettsch WG, Bouwes Bavinck JN, Herings RMC. Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands. J Eur Acad Dermatol Venereol. 2006;14:834–839.
    1. Wielink G, Koning S, Oosterhout R, Wetzels R, Nijman F, Draijer L. Dutch College of General Practitioners Guideline on bacterial skin infections. Huisarts Wet. 2007;14:426–444.
    1. Bergkvist PI, Sjöbeck K. Relapse of erysipelas following treatment with prednisolone or placebo in addition to antibiotics: a 1-year follow-up. Scand J Infect Dis. 1998;14:206–207. doi: 10.1080/003655498750003708.
    1. Jenkins TC, Sabel AL, Sarcone EE, Price CS, Mehler PS, Burman WJ. Skin and soft-tissue infections requiring hospitalization at an academic medical center: opportunities for antimicrobial stewardship. Clin Infect Dis. 2010;14:895–903. doi: 10.1086/656431.
    1. Ellis Simonsen SM, van Orman ER, Hatch BE, Jones SS, Gren LH, Hegmann KT, Lyon JL. Cellulitis incidence in a defined population. Epidemiol Infect. 2006;14:293–299.
    1. Cox NH, Colver GB, Paterson WD. Management and morbidity of cellulitis of the leg. J R Soc Med. 1998;14:634–637.
    1. Jorup-Rönström C, Britton S. Recurrent erysipelas: predisposing factors and costs of prophylaxis. Infection. 1987;14:105–106. doi: 10.1007/BF01650206.
    1. Perelló-Alzamora M-R, Santos-Duran J-C, Sánchez-Barba M, Cañueto J, Marcos M, Unamuno P. Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis. Eur J Clin Microbiol Infect Dis. 2012;14:2147–2152. doi: 10.1007/s10096-012-1549-2.
    1. Morris AD. Cellulitis and erysipelas. Clin Evid (Online) 2008;14:1–8.
    1. Stevens DL, Eron LL. Cellulitis and soft-tissue infections. Ann Intern Med. 2009;14:ITC11.
    1. Clinical Resource Efficiency Support Team (CREST) Guidelines on the Management of Cellulitis in Adults. Belfast, Ireland; 2005.
    1. Conceptrichtlijn cellulitis en erysipelas van de onderste extremiteiten [Concept guideline cellulitis and erysipelas of the lower extremities] [ ]
    1. Antimicrobial resistance interactive database. [ ]
    1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak MJ, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;14:e18–e55. doi: 10.1093/cid/ciq146.
    1. Bruns AHW, Oosterheert JJ, El Moussaoui R, Opmeer BC, Hoepelman AIM, Prins JM. Pneumonia recovery: discrepancies in perspectives of the radiologist, physician and patient. J Gen Intern Med. 2010;14:203–206. doi: 10.1007/s11606-009-1182-7.
    1. Eron LJ, Lipsky BA, Low DE, Nathwani D, Tice AD, Volturo GA. Managing skin and soft tissue infections: expert panel recommendations on key decision points. J Antimicrob Chemother. 2003;14(Suppl 1):i3–i17.
    1. Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004;14:1669–1674. doi: 10.1001/archinte.164.15.1669.
    1. Milo G, Katchman E, Paul M, Christiaens T, Baerheim A, Leibovici L. Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane Database Syst Rev. 2009;14:1–81.
    1. Michael M, Hodson EM, Craig JC, Martin S, Moyer V. Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children. Cochrane Database Syst Rev. 2010;14:1–29.
    1. Sandberg T, Skoog G, Hermansson AB, Kahlmeter G, Kuylenstierna N, Lannergård A, Otto G, Settergren B, Ekman GS. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;14:484–490. doi: 10.1016/S0140-6736(12)60608-4.
    1. Falagas ME, Karageorgopoulos DE, Grammatikos AP, Matthaiou DK. Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials. Br J Clin Pharmacol. 2009;14:161–171. doi: 10.1111/j.1365-2125.2008.03306.x.
    1. Altamimi S, Khalil A, Khalaiwi KA, Milner RA, Pusic MV, Al Othman MA. Short-term late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis in children. Cochrane Database Syst Rev. 2012;14:1–56.
    1. Pugh R, Grant C, Cooke RPD, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2012;14:72.
    1. el Moussaoui R, de Borgie CA, van den Broek P, Hustinx WN, Bresser P, van den Berk GE, Poley JW, van den Berg B, Krouwels FH, Bonten MJM, Weenink C, Bossuyt PM, Speelman P, Opmeer BC, Prins JM. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ. 2006;14:1355. doi: 10.1136/bmj.332.7554.1355.
    1. Havey TC, Fowler RA, Daneman N. Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Crit Care. 2011;14:R267. doi: 10.1186/cc10545.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;14:834–840. doi: 10.1016/j.jclinepi.2010.02.005.
    1. Calandra GB, Norden C, Nelson JD, Mader JT. Evaluation of New Anti-Infective Drugs for the Treatment of Selected Infections of the Skin and Skin Structure. Clin Infect Dis. 1992;14(Suppl 1):S148–54.
    1. Gunderson CG. Cellulitis: definition, etiology, and clinical features. Am J Med. 2011;14:1113–1122. doi: 10.1016/j.amjmed.2011.06.028.
    1. Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, LeFrock JL, Lew DP, Mader JT, Norden C, Tan JS. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004;14:885–910. doi: 10.1086/424846.
    1. Lipsky BA, Itani KMF, Weigelt JA, Joseph W, Paap CM, Reisman A, Myers DE, Huang DB. The role of diabetes mellitus in the treatment of skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: results from three randomized controlled trials. Int J Infect Dis. 2011;14:e140–e146. doi: 10.1016/j.ijid.2010.10.003.
    1. Garau J, Ostermann H, Medina J, Avila M, McBride K, Blasi F. Current management of patients hospitalized with complicated skin and soft tissue infections across Europe (2010–2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics from the REACH study. Clin Microbiol Infect. 2013;14:e377–e385. doi: 10.1111/1469-0691.12235.
    1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, Vlieghe E, Hara GL, Gould IM, Goossens H, Greko C, So AD, Bigdeli M, Tomson G, Woodhouse W, Ombaka E, Peralta AQ, Qamar FN, Mir F, Kariuki S, Bhutta ZA, Coates A, Bergstrom R, Wright GD, Brown ED, Cars O. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013;14:1057–1098. doi: 10.1016/S1473-3099(13)70318-9.
    1. Niederman MS. Antimicrobial Agents Principles of appropriate antibiotic use. Antimicrob Agents. 2005;14:170–175.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa