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Intervenciones para la prevención de la erisipela y celulitis recurrentes

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Referencias

Chakroun 1994 {published and unpublished data}

Chakroun M, Ben‐Romdhane F, Battikh R, Souki A, Bouzouaia N. Benzathine penicillin prophylaxis in recurrent erysipelas [Intérêt de la benzathine pénicilline dans la prévention des récidives d'érysipèle]. Médecine et Maladies Infectieuses 1994;24(10):894‐7. [CENTRAL: CN‐00169390; EMBASE: 1994338740]CENTRAL

Kasseroller 1998 {published data only (unpublished sought but not used)}

Kasseroller R. Prophylaxis of erysipelas in secondary lymphedema with selenium [Erysipelprophylaxe beim sekundären Lymphödem mit Selen]. Der Allgemeinarzt 1996;18(3):244‐7. CENTRAL
Kasseroller R. Sodium selenite as prophylaxis against erysipelas in secondary lymphedema. Anticancer Research 1998;18(3C):2227‐30. [CENTRAL: CN‐00153878; EMBASE: 1998283262]CENTRAL

Kremer 1991 {published data only (unpublished sought but not used)}

Kremer M, Zuckerman R, Avraham Z, Raz R. Long‐term antimicrobial therapy in the prevention of recurrent soft‐tissue infections. Journal of Infection 1991;22(1):37‐40. [CENTRAL: CN‐00073794; PUBMED: 2002231]CENTRAL

Sjöblom 1993 {published and unpublished data}

Sjöblom AC, Eriksson B, Jorup‐Rönström C, Karkkonen K, Lindqvist M. Antibiotic prophylaxis in recurrent erysipelas. Infection 1993;21(6):390‐3. [CENTRAL: CN‐00099842; PUBMED: 8132369]CENTRAL

Thomas 2012 {published and unpublished data}

Centre of Evidence Based Dermatology. Prophylactic Antibiotics for the Treatment of Cellulitis at Home (PATCH). www.nottingham.ac.uk/research/groups/cebd/projects/patch.aspx (accessed 6th June 2017). CENTRAL
Mason JM, Thomas KS, Crook AM, Foster KA, Chalmers JR, Nunn AJ, et al. Prophylactic antibiotics to prevent cellulitis of the leg: economic analysis of the PATCH I & II Trials. PLoS One 2014;9(2):e82694. [DOI: 10.1371/journal.pone.0082694; PUBMED: 24551029]CENTRAL
Thomas KS, UK Dermatology Clinical Trials Network's PATCH study group. Studying a disease with no home‐‐lessons in trial recruitment from the PATCH II study. Trials 2010;11(22):1‐5. [DOI: 10.1186/1745‐6215‐11‐22; PUBMED: 20196846]CENTRAL
UK Dermatology Clinical Trials Network’s PATCH Trial Team, Thomas K, Crook A, Foster K, Mason J, Chalmers J, Bourke J, et al. Prophylactic antibiotics for the prevention of cellulitis (erysipelas) of the leg: results of the UK Dermatology Clinical Trials Network's PATCH II trial. British Journal of Dermatology 2012;166(1):169‐78. [CENTRAL: CN‐00836571; PUBMED: 21910701]CENTRAL

Thomas 2013 {published and unpublished data}

Centre of Evidence Based Dermatology. Prophylactic Antibiotics for the Treatment of Cellulitis at Home (PATCH). www.nottingham.ac.uk/research/groups/cebd/projects/patch.aspx (accessed 6th June 2017). CENTRAL
Mason JM, Thomas KS, Crook AM, Foster KA, Chalmers JR, Nunn AJ, et al. Prophylactic antibiotics to prevent cellulitis of the leg: economic analysis of the PATCH I & II Trials. PLoS One 2014;9(2):e82694. [DOI: 10.1371/journal.pone.0082694; PUBMED: 24551029]CENTRAL
Thomas KS, Crook AM, Nunn AJ, Foster KA, Mason JM, Chalmers JR, et al. Penicillin to prevent recurrent leg cellulitis. New England Journal of Medicine 2013;368(18):1695‐703. [CENTRAL: CN‐00859316; PUBMED: 23635049]CENTRAL
Williams HC, Crook AM, Mason JM, UK Dermatology Clinical Trials Network’s PATCH I Trial Team. Penicillin to prevent recurrent leg cellulitis. New England Journal of Medicine 2013;369(9):881‐2. [DOI: 10.1056/NEJMc1307321; PUBMED: 23984744]CENTRAL

Duvanel 1986 {published data only (unpublished sought but not used)}

Duvanel T, Harms M, Merot Y, Saurat JH. Les récidives d’érysipèle et leur prévention par la benzathine‐penicilline. Annales de Dermatologie et de Vénéréologie 1986;113:174‐6. CENTRAL

Ferrieri 1973 {published data only}

Ferrieri P, Dajani AS, Wannamaker LW. Benzathine penicillin in the prophylaxis of streptococcal skin infections: a pilot study. Journal of Pediatrics 1973;83(4):572‐7. [CENTRAL: CN‐00009022; PUBMED: 4581016]CENTRAL

Fritz 2011 {published and unpublished data}

Fritz SA, Camins BC, Eisenstein KA, Fritz JM, Epplin EK, Burnham CA, et al. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community‐associated skin and soft‐tissue infections: a randomized trial. Infection Control and Hospital Epidemiology 2011;32(9):872‐80. [CENTRAL: CN‐00804495; PUBMED: 21828967]CENTRAL

Haustein 1989 {published data only}

Haustein UF, Biella U, Tausch I, Knöll H. Treatment of chronic recurrent erysipelas with streptococcal vaccine [Die behandlung des chronisch rezidivierenden erysipels mit Streptokokkenvakzine]. Hautarzt 1989;40(4):215‐21. [PUBMED: 2659550]CENTRAL

Klempner 1988 {published data only}

Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin infections with low‐dose oral clindamycin therapy. JAMA 1988;260(18):2682‐5. [CENTRAL: CN‐00056409; PUBMED: 3184334]CENTRAL

Maddox 1985 {published data only}

Maddox JS, Ware JC, Dillon HC. The natural history of streptococcal skin infection: prevention with topical antibiotics. Journal of the American Academy of Dermatology 1985;13(2 Pt 1):207‐12. [CENTRAL: CN‐00039750; PUBMED: 2995463]CENTRAL

Raz 1996 {published data only}

Raz R, Miron D, Colodner R, Staler Z, Samara Z, Keness Y. A 1‐year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection. Archives of Internal Medicine 1996;156(10):1109‐12. [CENTRAL: CN‐00124903; PUBMED: 8638999]CENTRAL

Wang 1997 {published data only}

Wang JH, Liu YC, Cheng DL, Yen MY, Chen YS, Wang JH, et al. Role of benzathine penicillin G in prophylaxis for recurrent streptococcal cellulitis of the lower legs. Clinical Infectious Diseases 1997;25(3):685‐9. [CENTRAL: CN‐00143909; PUBMED: 9314462]CENTRAL

References to studies awaiting assessment

Ratnikova 1991 {published data only}

Ratnikova LI. Effectiveness of bemitil in recurrent erysipelas [Эффективность бемитила при рецидивирующей роже]. Klinicheskaia Meditsina 1991;69(7):89‐90. [CENTRAL: CN‐00079309; EMBASE: 1942990]CENTRAL

Addis 2011

Addiss DG, Michel MC, Michelus A, Radday J, Billhimer W, Louis‐Charles J, et al. Evaluation of antibacterial soap in the management of lymphoedema in Leogane, Haiti. Transactions of the Royal Society of Tropical Medicine and Hygiene 2011;105(1):58‐60.

ALA 2015

Australasian Lymphology Association (ALA). Consensus Guideline: Management of Cellulitis in Lymphoedema. www.lymphoedema.org.au/public/7/files/ALA%20CELLULITIS%20IN%20LYMPHOEDEMA%202015.pdf (accessed May 2017).

Allard 1999

Allard P, Stücker M, Von Kobyletzki G, el Gammal S, Altmeyer P. Cyclical intravenous antibiosis as an effective therapy concept in chronic recurrent erysipelas [Zyklische intravenöse Antibiose als effizientes Therapiekonzept des chronisch‐rezidivierenden Erysipels]. Hautarzt 1999;50(1):34‐8. [PUBMED: 10068929]

Arakaki 2014

Arakaki RY, Strazzula L, Woo E, Kroshinsky D. The impact of dermatology consultation on diagnostic accuracy and antibiotic use among patients with suspected cellulitis seen at outpatient internal medicine offices: a randomized clinical trial. JAMA Dermatology 2014;150(10):1056‐61. [PUBMED: 25143179]

Arasaratnam 2013

Arasaratnam R. Penicillin to prevent recurrent leg cellulitis. New England Journal of Medicine 2013;369(9):881. [DOI: 10.1056/NEJMc1307321#SA2; PUBMED: 23984746]

Arsenault 2011

Arsenault K, Rielly L, Wise H. Effects of complete decongestive therapy on the incidence rate of hospitalization for the management of recurrent cellulitis in adults with lymphedema. Rehabilitation Oncology 2011;29(3):14‐20. [EMBASE: 2011656495]

Arumugam 2012

Arumugam D, Atherton JJ, Martin PT. A lethal injection?. Lancet 2012;379(9814):492. [PUBMED: 22305227]

Babb 1966

Babb RR, Spittell JA, Martin WJ, Schirger A. Prophylaxis of recurrent lymphangitis complicating lymphedema. JAMA 1966;195(10):871‐3. [PUBMED: 12608187]

Baddour 2000

Baddour LM. Cellulitis syndromes: an update. International Journal of Antimicrobial Agents 2000;14(2):113‐6. [PUBMED: 10720800]

Bartholomeeusen 2007

Bartholomeeusen S, Vandenbroucke J, Truyers C, Buntinx F. Epidemiology and comorbidity of erysipelas in primary care. Dermatology 2007;215(2):118‐22. [PUBMED: 17684373]

Bernard 1987

Bernard P, Toty L, Mounier M, Denis F, Bonnetblanc JM. Early detection of streptococcal group antigens in skin samples by latex particle agglutination. Archives of Dermatology 1987;123(4):468‐70. [PUBMED: 3827278]

Biosyn 2015

Biosyn Selenase®. Selenium as a beacon of hope [Selen als Hoffnungsträge]. www.biosyn.de/innovation/selen‐als‐hoffnungstraeger(accessed January 2015).

Bisno 1996

Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. New England Journal of Medicine 1996;334(4):240‐5. [PUBMED: 8532002]

Bitnun 1985

Bitnun S. Prophylactic antibiotics in recurrent erysipelas. Lancet 1985;1(8424):345. [PUBMED: 2857399]

Bjornsdottir 2005

Bjornsdottir S, Gottfredsson M, Thorisdottir AS, Gunnarsson GB, Rikardsdottir H, Kristjansson M, et al. Risk factors for acute cellulitis of the lower limb: a prospective case‐control study. Clinical Infectious Diseases 2005;41(10):1416‐22. [PUBMED: 16231251]

BLS 2016

British Lymphology Society (BLS). Consensus Document on the Management of Cellulitis in Lymphoedema. Revised Cellulitis Guidelines 2016. www.lymphoedema.org/images/pdf/CellulitisConsensus.pdf(accessed May 2017).

Bowler 2001

Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clinical Microbiology Reviews 2001;14(2):244‐69. [PUBMED: 11292638]

Brook 1995

Brook I, Frazier EH. Clinical features and aerobic and anaerobic microbiological characteristics of cellulitis. Archives of Surgery 1995;130(7):786‐92. [PUBMED: 7611872]

Brorson 2000

Brorson H. Liposuction gives complete reduction of chronic large arm lymphedema after breast cancer. Acta Oncologica 2000;39(3):407‐20. [PUBMED: 10987239]

Bruun 2015

Bruun T, Oppegaard O, Kittang BR, Mylvaganam H, Langeland N, Skrede S. Etiology of cellulitis and clinical prediction of streptococcal disease: a prospective study. Open Forum Infectious Diseases 2015;31(1):ofv181. [PUBMED: 26734653]

Campisi 2015

Campisi CC, Ryan M, Boccardo F, Campisi C. A single‐site technique of multiple lymphatic‐venous anastomoses for the treatment of peripheral lymphedema: long‐term clinical outcome. Journal of Reconstructive Microsurgery 2016;32(1):42‐9. [PUBMED: 26029991]

Carratala 2003

Carratala J, Roson B, Fernandez‐Sabe N, Shaw E, Del Rio O, Rivera A, et al. Factors associated with complications and mortality in adult patients hospitalized for infectious cellulitis. European Journal of Clinical Microbiology & Infectious Diseases 2003;22(3):151‐7. [PUBMED: 12649712]

Chaniotakis 2016

Chaniotakis I, Gartzonika CG, Gaitanis G, Levidiotou‐Stefanou S, Bassukas ID. Causality evaluation of bacterial species isolated from patients with community‐acquired lower leg cellulitis. Journal of the European Academy of Dermatology and Venereology 2016;30(9):1583‐9. [PUBMED: 27400752]

Chen 2015

Chen HM, Li YL, Liu YM, Liu CE, Cheng YR, Chen CH, et al. The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study. Journal of Microbiology, Immunology, & Infection 2015;S1684‐1182(15):00831‐2. [PUBMED: 26475200]

Chira 2010

Chira S, Miller LG. Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review. Epidemiology and Infection 2010;138(3):313‐7. [PUBMED: 19646308]

Corey 2014

Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS, Porwal A, et al. Single‐dose oritavancin in the treatment of acute bacterial skin infections. New England Journal of Medicine 2014;370(23):2180‐90. [PUBMED: 24897083]

Cox 1998

Cox NH, Colver GB, Paterson WD. Management and morbidity of cellulitis of the leg. Journal of The Royal Society of Medicine 1998;91(12):634‐7.

Cox 2006

Cox NH. Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow‐up. British Journal of Dermatology 2006;155(5):947‐50. [PUBMED: 17034523 ]

CREST 2005

CREST. Clinical Resource Efficiency Support Team (CREST). Guidelines on the management of cellulitis in adults. www.acutemed.co.uk/docs/Cellulitis%20guidelines,%20CREST,%2005.pdf 2005 (accessed 6th June 2017).

Crisp 2015

Crisp JG, Takhar SS, Moran GJ, Krishnadasan A, Dowd SE, Finegold SM, et al. Inability of polymerase chain reaction, pyrosequencing, and culture of infected and uninfected site skin biopsy specimens to identify the cause of cellulitis. Clinical Infectious Diseases 2015;61(11):1679‐87. [PUBMED: 26240200]

Damstra 2008

Damstra RJ, Van Steensel MA, Boomsma JH, Nelemans P, Veraart JC. Erysipelas as a sign of subclinical primary lymphoedema: a prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg. British Journal of Dermatology 2008;158(6):1210‐5. [PUBMED: 18363756]

Damstra 2009

Damstra RJ, Voesten HG, Van Schelven WD, Van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Research & Treatment 2009;113(2):199‐206. [PUBMED: 18270813]

David 2011

David CV, Chira S, Eells SJ, Ladrigan M, Papier A, Miller LG, et al. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatology Online Journal 2011;17(3):1. [PUBMED: 21426867]

De Godoy 2000

De Godoy JM, De Godoy MF, Valente A, Camacho EL, Paiva EV. Lymphoscintigraphic evaluation in patients after erysipelas. Lymphology 2000;33(4):177‐80. [PUBMED: 11191659]

Didem 2005

Didem K, Ufuk YS, Serdar S, Zümre A. The comparison of two different physiotherapy methods in treatment of lymphedema after breast surgery. Breast Cancer Research & Treatment 2005;93(1):49‐54. [PUBMED: 16184458]

Draijer 2008

Draijer LW, Koning S, Wielink G, Boukes FS, Goudswaard AN. Summary of the practice guideline 'Bacterial skin infections' (first revision) from the Dutch College of General Practitioners [Samenvatting van de standaard ‘Bacteriële huidinfecties’(eerste herziening) van het Nederlands Huisartsen Genootschap]. Nederlands Tijdschrift voor Geneeskunde 2008;152(29):1619‐25. [PUBMED: 18998269]

Duodecim 1999

Finnish Medical Society Duodecim and the Finnish Dermatological Society. Bacterial skin infections (online). Current care guideline. October 1999 [updated November 2010] [Ihon bakteeri‐infektiot]. www.kaypahoito.fi (accessed 11 February 2016):1‐3 (accessed December 2013).

Dupuy 1999

Dupuy A, Benchikhi H, Roujeau JC, Bernard P, Vaillant L, Chosidow O, et al. Risk factors for erysipelas of the leg (cellulitis): case‐control study. BMJ 1999;318(7198):1591‐4. [PUBMED: 10364117]

Durand 2013

Durand M, Wistaff R, Lelorier J. Penicillin to prevent recurrent leg cellulitis. New England Journal of Medicine 2013;369(9):880. [DOI: 10.1056/NEJMc1307321#SA1; PUBMED: 23984745]

Duvanel 1985

Duvanel T, Merot Y, Harms M, Saurat JH. Prophylactic antibiotics in erysipelas. Lancet 1985;1(8442):1401. [PUBMED: 2861358]

Duvanel 1989

Duvanel T, Auckenthaler R, Rohner P, Harms M, Saurat JH. Quantitative cultures of biopsy specimens from cutaneous cellulitis. Archives of Internal Medicine 1989;149(2):293‐6. [PUBMED: 2644902]

Egger 1997

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34. [PUBMED: 9310563]

Ellis 2006

Ellis Simonsen SM, Van Orman ER, Hatch BE, Jones SS, Gren LH, Hegmann KT, et al. Cellulitis incidence in a defined population. Epidemiology & Infection 2006;134(2):293‐9. [PUBMED: 16490133]

Eriksson 1996

Eriksson B, Jorup‐Rönström C, Karkkonen K, Sjöblom AC, Holm SE. Erysipelas: clinical and bacteriologic spectrum and serological aspects. Clinical Infectious Diseases 1996;23(5):1091‐8. [PUBMED: 8922808]

Eron 2003

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. Journal of Antimicrobial Chemotherapy 2003;52(Suppl 1):i3‐17. [PUBMED: 14662806]

Esposito 2011

Esposito S, Bassetti M, Borre S, Bouza E, Dryden M, Fantoni M, et al. Diagnosis and management of skin and soft‐tissue infections (SSTI): a literature review and consensus statement on behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy. Journal of Chemotherapy 2011;23(5):251‐62. [PUBMED: 22005055]

Ezzo 2015

Ezzo J, Manheimer E, McNeely ML, Howell DM, Weiss R, Johansson KI, et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database of Systematic Reviews 2015, Issue 5. [DOI: 10.1002/14651858.CD003475.pub2]

Finlay 1994

Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)‐‐a simple practical measure for routine clinical use. Clinical & Experimental Dermatology 1994;19(3):210‐6. [PUBMED: 8033378]

Garau 2015

Garau J, Blasi F, Medina J, McBride K, Ostermann H, REACH study group. Early response to antibiotic treatment in European patients hospitalized with complicated skin and soft tissue infections: analysis of the REACH study. BMC Infectious Diseases 2015;15(78):1‐9. [PUBMED: 25879713]

Gerber 1995

Gerber MA. Antibiotic resistance in group A streptococci. Pediatric Clinics of North America 1995;42(3):539‐51. [PUBMED: 7761140]

Goettsch 2006

Goettsch WG, Bouwes Bavinck JN, Herings RM. Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands. Journal of the European Academy of Dermatology and Venereology 2006;20(7):834‐9. [PUBMED: 16898907]

Goscinski 2006

Goscinski G, Tano E, Thulin P, Norrby‐Teglund A, Sjölin J. Release of SpeA from Streptococcus pyogenes after exposure to penicillin: dependency on dose and inhibition by clindamycin. Scandinavian Journal of Infectious Diseases 2006;38(11‐12):983‐7. [PUBMED: 17148065]

Granzow 2014

Granzow JW, Soderberg JM, Kaji AH, Dauphine C. Review of current surgical treatments for lymphedema. Annals of Surgical Oncology 2014;21(4):1195‐201. [PUBMED: 24558061]

Guillemot 1998

Guillemot D, Carbon C, Balkau B, Geslin P, Lecoeur H, Vauzelle‐Kervroëdan F, et al. Low dosage and long treatment duration of beta‐lactam: risk factors for carriage of penicillin‐resistant Streptococcus pneumoniae. JAMA 1998;279(5):365‐70. [PUBMED: 9459469]

Halpern 2008

Halpern J, Holder R, Langford NJ. Ethnicity and other risk factors for acute lower limb cellulitis: a UK‐based prospective case‐control study. British Journal of Dermatology 2008;158(6):1288‐92. [PUBMED: 18341662]

Harris 2001

Harris SR, Hugi MR, Olivotto IA, Levine M. Clinical practice guidelines for the care and treatment of breast cancer: 11. Lymphedema. CMAJ: Canadian Medical Association Journal 2001;164(2):191‐9. [PUBMED: 11332311]

Higgins 2011

Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Hook 1986

Hook EW, Hooton TM, Horton CA, Coyle MB, Ramsey PG, Turck M. Microbiologic evaluation of cutaneous cellulitis in adults. Archives of Internal Medicine 1986;146(2):295‐7. [PUBMED: 3947189]

Horn 1998

Horn DL, Zabriskie JB, Austrian R, Cleary PP, Ferretti JJ, Fischetti VA. Why have group A streptococci remained susceptible to penicillin? Report on a symposium. Clinical Infectious Diseases 1998;26(6):1341‐5. [PUBMED: 9636860]

ILF 2006

International Lymphoedema Framework (ILF). Best Practice for the Management of Lymphoedema. International consensus 2006. http://www.lympho.org/portfolio/best‐practice‐for‐the‐management‐of‐lymphoedema/ (accessed 6th June 2017):1‐60.

Inghammar 2014

Inghammar M, Rasmussen M, Linder A. Recurrent erysipelas‐risk factors and clinical presentation. BMC Infectious Diseases 2014 May;14:270. [DOI: 10.1186/1471‐2334‐14‐270; PUBMED: 24884840]

ISL 2013

International Society of Lymphology (ISL). The diagnosis and treatment of peripheral lymphedema: Consensus document. Lymphology 2013;46(1):1‐11. [PUBMED: 23930436]

Israeli Ministry of Health 2015

Israeli Ministry of Health. Safety warning over the use of intramuscular Benzathine benzylpenicillin February 2015 [הנחיות המשך להפחתת הסיכון לתופעות לוואי במתן תוך שרירי של תכשירים המכילים בנזתין בנזילפניצלין]. www.health.gov.il/newsandevents/recall_drugs/doclib1/benzathine_benzylpenicillin.pdf(accessed August 2015).

Jeng 2010

Jeng A, Beheshti M, Li J, Nathan R. The role of beta‐hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine (Baltimore) 2010;89(4):217‐26. [PUBMED: 20616661]

Jorup‐Rönström 1986

Jorup‐Rönström C. Epidemiological, bacteriological and complicating features of erysipelas. Scandinavian Journal of Infectious Diseases 1986;18(6):519‐24. [PUBMED: 3810046]

Jorup‐Rönström 1987

Jorup‐Rönström C, Britton S. Recurrent erysipelas: predisposing factors and costs of prophylaxis. Infection 1987;15(2):105‐6. [PUBMED: 3110071]

Jüni 2001

Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6. [PUBMED: 11440947 ]

Karimkhani 2014a

Karimkhani C, Boyers LN, Margolis DJ, Naghavi M, Hay RJ, Williams HC, et al. Comparing cutaneous research funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease results. PLoS One 2014;9(7):e102122. [PUBMED: 25003335]

Karimkhani 2014b

Karimkhani C, Boyers LN, Prescott L, Welch V, Delamere FM, Nasser M, et al. Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews. JAMA Dermatology 2014;150(9):945. [PUBMED: 24807687]

Karppelin 2010

Karppelin M, Siljander T, Vuopio‐Varkila J, Kere J, Huhtala H, Vuento R, et al. Factors predisposing to acute and recurrent bacterial non‐necrotizing cellulitis in hospitalized patients: a prospective case‐control study. Clinical Microbiology & Infection 2010;16(6):729‐34. [PUBMED: 19694769]

Karppelin 2013

Karppelin M, Siljander T, Huhtala H, Aroma A, Vuopio J, Hannula‐Jouppi K, et al. Recurrent cellulitis with benzathine penicillin prophylaxis associated with diabetes and psoriasis. European Journal of Clinical Microbiology & Infectious Diseases 2013;32(3):369‐72. [PUBMED: 23007460]

Karppelin 2014

Karppelin M, Siljander T, Aittoniemi J, Hurme M, Huttunen R, Huhtala H, et al. Predictors of recurrent cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP. Journal of Infection 2015;70(5):467‐73. [DOI: 10.1016/j.jinf.2014.11.002; PUBMED: 25447714]

Kasseroller 1996

Kasseroller R. Erysipelprophylaxe beim sekundären Lymphödem mit Selen. Der Allgemeinartzt 1996;3:244‐7.

Kilburn 2010

Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database of Systematic Reviews 2010, Issue 6. [DOI: 10.1002/14651858.CD004299.pub2]

Ko 1998

Ko DS, Lerner R, Klose G, Cosimi AB. Effective treatment of lymphedema of the extremities. Archives of Surgery 1998;133(4):452‐8. [PUBMED: 9565129]

Kotloff 2004

Kotloff KL, Corretti M, Palmer K, Campbell JD, Reddish MA, Hu MC, et al. Safety and immunogenicity of a recombinant multivalent group a streptococcal vaccine in healthy adults: phase 1 trial. JAMA 2004;292(6):709‐15. [PUBMED: 15304468]

Koutkia 1999

Koutkia P, Mylonakis E, Boyce J. Cellulitis: evaluation of possible predisposing factors in hospitalized patients. Diagnostic Microbiology & Infectious Disease 1999;34(4):325‐7. [PUBMED: 10459485]

Kouyos 2014

Kouyos RD, Metcalf CJ, Birger R, Klein EY, Abel zur Wiesch P, Ankomah P, et al. The path of least resistance: aggressive or moderate treatment?. Proceedings. Biological Sciences / the Royal Society 2014;281(1794):1‐8. [PUBMED: 25253451]

Kunkel 2015

Kunkel A, Colijn C, Lipsitch M, Cohen T. How could preventive therapy affect the prevalence of drug resistance? Causes and consequences. Philosopical Transactions of the Royal Society B 2015;370(1670):1‐9. [DOI: 10.1098/rstb.2014.0306; PUBMED: 25918446]

Lazzarini 2005

Lazzarini L, Conti E, Tositti G, De Lalla F. Erysipelas and cellulitis: clinical and microbiological spectrum in an Italian tertiary care hospital. Journal of Infection 2005;51(5):383‐9. [PUBMED: 16321649]

Levell 2011

Levell NJ, Wingfield CG, Garioch JJ. Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care. British Journal of Dermatology 2011;164(6):1326‐8. [PUBMED: 21564054]

Lewis 2006

Lewis SD, Peter GS, Gomez‐Marin O, Bisno AL. Risk factors for recurrent lower extremity cellulitis in a U.S. Veterans Medical Center population. American Journal of the Medical Sciences 2006;332(6):304‐7. [PUBMED: 17170620]

Lum 2002

Lum GR. Cellulitis among active duty service members, US Armed Forces, 1998‐2001. Medical Surveillance Monthly Report (MSMR) 2002;8:6‐9.

Mallon 1997

Mallon E, Powell S, Mortimer P, Ryan TJ. Evidence for altered cell‐mediated immunity in postmastectomy lymphoedema. British Journal of Dermatology 1997;137(6):928‐33. [PUBMED: 9470909]

Mandell 2010

Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7. Vol. 1, Philadelphia: Churchill Livingstone, 2010.

Mason 2014

Mason JM, Thomas KS, Crook AM, Foster KA, Chalmers JR, Nunn AJ, et al. Prophylactic antibiotics to prevent cellulitis of the leg: economic analysis of the PATCH I & II Trials. PLoS One 2014;9(2):e82694. [DOI: 10.1371/journal.pone.0082694; PUBMED: 24551029]

Massell 1969

Massell BF, Honikman LH, Amezcua J. Rheumatic fever following streptococcal vaccination. Report of three cases. JAMA 1969;207(6):1115‐9. [PUBMED: 5818242 ]

McNamara 2007

McNamara DR, Tleyjeh IM, Berbari EF, Lahr BD, Martinez J, Mirzoyev SA, et al. A predictive model of recurrent lower extremity cellulitis in a population‐based cohort. Archives of Internal Medicine 2007;167(7):709‐15. [PUBMED: 17420430]

McNeil 2005

McNeil SA, Halperin SA, Langley JM, Smith B, Warren A, Sharratt GP, et al. Safety and immunogenicity of 26‐valent group a streptococcus vaccine in healthy adult volunteers. Clinical Infectious Diseases 2005;41(8):1114‐22. [PUBMED: 16163629]

Mertz 1998

Mertz KR, Baddour LM, Bell JL, Gwin JL. Breast cellulitis following breast conservation therapy: a novel complication of medical progress. Clinical Infectious Diseases 1998;26(2):481‐6. [PUBMED: 9502474]

Miller 1998

Miller SR, Mondry T, Reed JS, Findley A, Johnstone PA. Delayed cellulitis associated with conservative therapy for breast cancer. Journal of Surgical Oncology 1998;67(4):242‐5. [PUBMED: 9579371]

Mokni 2006

Mokni M, Dupuy A, Denguezli M, Dhaoui R, Bouassida S, Amri M, et al. Risk factors for erysipelas of the leg in Tunisia: a multicenter case‐control study. Dermatology 2006;212(2):108‐12. [PUBMED: 16484815]

Moreland 2014

Moreland NJ, Waddington CS, Williamson DA, Sriskandan S, Smeesters PR, Proft T, et al. Working towards a group A streptococcal vaccine: report of a collaborative Trans‐Tasman workshop. Vaccine 2014;32(30):3713‐20. [PUBMED: 24837510]

Morris 2008

Morris AD. Cellulitis and erysipelas. Clinical Evidence 2008;01(1708):1‐8. [PUBMED: 19450336]

Mortimer 2014

Mortimer PS, Rockson SG. New developments in clinical aspects of lymphatic disease. Journal of Clinical Investigation 2014;124(3):915‐21. [PUBMED: 24590276]

Nathwani 2001

Nathwani D. The management of skin and soft tissue infections: outpatient parenteral antibiotic therapy in the United Kingdom. Chemotherapy 2001;47(Suppl 1):17‐23. [PUBMED: 11096185]

NICE 2005

National Institute for Health and Care Excellence (NICE). Cellulitis ‐ acute 2005. //cks.nice.org.uk/cellulitis‐acute#!topicsummary(accessed March 2015).

Oh 2014

Oh CC, Ko HC, Lee HY, Safdar N, Maki DG, Chlebicki MP. Antibiotic prophylaxis for preventing recurrent cellulitis: A systematic review and meta‐analysis. Journal of Infection 2014;69(1):26‐34. [DOI: 10.1016/j.jinf.2014.02.011; PUBMED: 24576824]

Ostermann 2014

Ostermann H, Blasi F, Medina J, Pascual E, McBride K, Garau J, REACH study group. Resource use in patients hospitalized with complicated skin and soft tissue infections in Europe and analysis of vulnerable groups: the REACH study. Journal of Medical Economics 2014;17(10):719‐29. [PUBMED: 24983206]

Parmar 1998

Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta‐analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815‐34. [PUBMED: 9921604]

Pauszek 1991

Pauszek ME. Prophylaxis for recurrent cellulitis complicating venous and lymphatic insufficiency. Indiana Medicine 1991;84(4):252‐3. [PUBMED: 2037773]

Pavlotsky 2004

Pavlotsky F, Amrani S, Trau H. Recurrent erysipelas: risk factors. Journal Der Deutschen Dermatologischen Gesellschaft 2004;2(2):89‐95. [PUBMED: 16279242]

Pierce 1992

Pierce RP, Daugird AJ. Recurrent leg cellulitis: pathogenesis, treatment, and prevention. Journal of the American Board of Family Medicine 1992;5(1):85‐7. [PUBMED: 1561927]

Quirke 2016

Quirke M, Ayoub F, McCabe A, Boland F, Smith B, O'Sullivan R, et al. Risk factors for non‐purulent leg cellulitis: a systematic review and meta‐analysis. British Journal of Dermatology 2016 Nov 18 [Epub ahead of print]. [DOI: 10.1111/bjd.15186]

Raff 2016

Raff AB, Kroshinsky D. Cellulitis: a review. JAMA 2016;316(3):325‐37. [PUBMED: 27434444]

Read 2011

Read AF, Day T, Huijben S. The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy. Proceedings of the National Academy of Sciences of the United States of America 2011;108(Suppl 2):10871‐7. [PUBMED: 21690376 ]

Roldan 2000

Roldan YB, Mata‐Essayag S, Hartung C. Erysipelas and tinea pedis. Mycoses 2000;43(5):181‐3. [PUBMED: 10948816]

Roujeau 2004

Roujeau JC, Sigurgeirsson B, Korting HC, Kerl H, Paul C. Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case‐control study. Dermatology 2004;209(4):301‐7. [PUBMED: 15539893]

Sawai 2007

Sawai J, Hasegawa T, Kamimura T, Okamoto A, Ohmori D, Nosaka N, et al. Growth phase‐dependent effect of clindamycin on production of exoproteins by Streptococcus pyogenes. Antimicrobial Agents & Chemotherapy 2007;51(2):461‐7. [DOI: 10.1128/AAC.00539‐06; PUBMED: 17101685]

Schünemann 2013

Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for grading quality of evidence and strength of recommendation. The GRADE Working Group, 2013. Available from:http://gdt.guidelinedevelopment.org/app/handbook/handbook.html.

Semel 1996

Semel JD, Goldin H. Association of athlete's foot with cellulitis of the lower extremities: diagnostic value of bacterial cultures of ipsilateral interdigital space samples. Clinical Infectious Diseases 1996;23(5):1162‐4. [PUBMED: 8922818]

SFD 2000

French Society of Dermatology [Société Française de Dermatologie]. Management of erysipelas and necrotizing fasciitis [Erysipèle et fasciite nécrosante:prise en charge]. Annales de Dermatologie et de Vénéréologie 2000;127(12):1118‐37. [PUBMED: 11173699]

Shenoy 1999

Shenoy RK, Kumaraswami V, Suma TK, Rajan K, Radhakuttyamma G. A double‐blind, placebo‐controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis. Annals of Tropical Medicine & Parasitology 1999;93(4):367‐77. [PUBMED: 10656038]

Siljander 2008

Siljander T, Karppelin M, Vahakuopus S, Syrjanen J, Toropainen M, Kere J, et al. Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clinical Infectious Diseases 2008;46(6):855‐61. [PUBMED: 18260753]

Simon 1992

Simon MS, Cody RL. Cellulitis after axillary lymph node dissection for carcinoma of the breast. American Journal of Medicine 1992;93(5):543‐8. [PUBMED: 1364813]

Soo 2008

Soo JK, Bicanic TA, Heenan S, Mortimer PS. Lymphatic abnormalities demonstrated by lymphoscintigraphy after lower limb cellulitis. British Journal of Dermatology 2008;158(6):1350‐3. [PUBMED: 18241266]

Stalbow 2004

Stalbow J. Preventing cellulitis in older people with persistent lower limb oedema. British Journal of Nursing 2004;13(12):725‐32. [PUBMED: 15284636]

Stevens 2005

Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, et al. Practice guidelines for the diagnosis and management of skin and soft‐tissue infections. Clinical Infectious Diseases 2005;41(10):1373‐406. [PUBMED: 16231249]

Stevens 2014

Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical Infectious Diseases 2014;59(2):e10‐52. [DOI: 10.1093/cid/ciu444; PUBMED: 24973422]

Stoberl 1987

Stoberl C, Partsch H. Erysipelas and lymphedema‐‐egg or hen?. Zeitschrift für Hautkrankheiten 1987;62(1):56‐62. [PUBMED: 3577282]

Strazzula 2015

Strazzula L, Cotliar J, Fox LP, Hughey L, Shinkai K, Gee SN, et al. Inpatient dermatology consultation aids diagnosis of cellulitis among hospitalized patients: A multi‐institutional analysis. Journal of the American Academy of Dermatology 2015;73(1):70‐5. [PUBMED: 26089048]

Swartz 2004

Swartz MN. Clinical practice. Cellulitis. New England Journal of Medicine 2004;350(9):904‐12. [PUBMED: 14985488]

Szolnoky 2014

Szolnoky G, Dobozy A, Kemény L. Towards an effective management of chronic lymphedema. Clinics in Dermatology 2014 Sep‐Oct;32(5):685‐91. [PUBMED: 25160111]

Tay 2015

Tay EY, Fook‐Chong S, Oh CC, Thirumoorthy T, Pang SM, Lee HY. Cellulitis Recurrence Score: A tool for predicting recurrence of lower limb cellulitis. Journal of the American Academy of Dermatology 2015;72(1):140‐5. [DOI: 10.1016/j.jaad.2014.08.043; PUBMED: 25443627]

Thind 1985

Thind P. Prophylactic antibiotics in recurrent erysipelas. Lancet 1985;1(8435):986. [PUBMED: 2859444]

Thomas 2010

Thomas KS, UK Dermatology Clinical Trials Network's PATCH study group. Studying a disease with no home‐‐lessons in trial recruitment from the PATCH II study. Trials 2010;11(2):1‐5. [DOI: 10.1186/1745‐6215‐11‐22; PUBMED: 20196846]

Tierney 2007

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time‐to‐event data into meta‐analysis. Trials 2007;8:16. [PUBMED: 17555582]

Van Zuuren 2014

Van Zuuren EJ, Fedorowicz Z, Alper B, Mitsuma SF. Penicillin to prevent recurrent leg cellulitis: a critical appraisal. British Journal of Dermatology 2014;171(6):1300‐3. [DOI: 10.1111/bjd.13461; PUBMED: 25523263]

Vinh 2005

Vinh DC, Embil JM. Rapidly progressive soft tissue infections. Lancet Infectious Diseases 2005;5(8):501‐13. [PUBMED: 16048719]

Weng 2016

Weng QY, Raff AB, Cohen JM, Gunasekera N, Okhovat JP, Vedak P, et al. Costs and consequences associated with misdiagnosed lower extremity cellulitis. JAMA Dermatology 2016 Nov 2 [Epub ahead of print]. [DOI: 10.1001/jamadermatol.2016.3816; PUBMED: 27806170]

WHO 2000

World Health Organization. Benzathine penicillin: three fatal reports following mega unit injections. Drug Information Bulletin 2000;4(2):1.

Woo 2000

Woo PC, Lum PN, Wong SS, Cheng VC, Yuen KY. Cellulitis complicating lymphoedema. European Journal of Clinical Microbiology & Infectious Diseases 2000;19(4):294‐7. [PUBMED: 10834819]

Yamamoto 2015

Yamamoto T, Koshima I. Supermicrosurgical anastomosis of superficial lymphatic vessel to deep lymphatic vessel for a patient with cellulitis‐induced chronic localized leg lymphedema. Microsurgery 2015;35(1):68‐71. [PUBMED: 25197031]

Young 1960

Young JR, Dewolfe VG. Recurrent lymphangitis of the leg associated with dermatophytosis. Report of 25 consecutive cases. Cleveland Clinic quarterly 1960;27:19‐24. [PUBMED: 13846637]

References to other published versions of this review

Dalal 2012

Dalal A, Eskin‐Shwartz M, Mimouni D, Ray S, Days W, Hodak E, et al. Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD009758]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Chakroun 1994

Methods

A randomised controlled, open‐label, parallel‐group trial

Participants

1. Setting: the trial recruited participants admitted to the infectious diseases service of the central university hospital in Monastir, Tunisia
2. Number of participants randomised: 58

3. Sex (men/women): 15/29 (14 participants were lost to follow‐up)

4. Mean age ± SD: 46.2 ± 19.4

5. Area of body involved: leg

6. Number of episodes of cellulitis prior to intervention: NR

Interventions

Study groups:

  • Intramuscular injection of benzathine penicillin 1.2 million units every 15 days (participants who had allergy to penicillin were excluded)

  • No treatment

Duration of treatment: between 1 month and 38 months (average = 11.6 months)

Follow‐up: during treatment phase‐ every 3 months; after treatment phase‐ NF

Outcomes

1. The number of participants with repeat episodes of cellulitis

2. The number of repeat episodes of cellulitis

3. Costs

Notes

Criteria for diagnosis of cellulitis: fever + signs of local inflammation confirmed by a single infectious diseases specialist

Funding source and Declaration of interest: NC and NR.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "A la sortie du service, un tirage au sort est effactué afin de classer le patient dans l'un des 2 groupes suivants".

Comment: Randomisation was done by drawing lots

Allocation concealment (selection bias)

Low risk

The author reported using sealed enveloped in a separate email correspondence (Table 2)

Blinding of participants and personnel (performance bias)
All outcomes

High risk

This was an open‐label study

Blinding of outcome assessment (detection bias)
All outcomes

High risk

This was an open‐label study

Incomplete outcome data (attrition bias)
All outcomes

High risk

76% of participants were followed up (75% of the intervention group‐ 18/24, and 76% of the control group‐ 26/34) with low number of participants and events and 'per protocol' analysis (Table 1)

Selective reporting (reporting bias)

Unclear risk

There was insufficient information

Similarity of groups at baseline (baseline imbalance bias)

Low risk

Quote: "Les deux groupes sont statistiquement comparables pour les critères sus‐cités (tableau I)".

Comment: Baseline characteristics were reported and balanced

Early termination (early stopping bias)

Unclear risk

Termination criteria or stopping rule were not reported

Other bias

Low risk

No other sources of potential bias were found

Kasseroller 1998

Methods

A randomised, double‐blind, placebo‐controlled parallel‐group trial

Participants

1. Setting: participants with lymphoedema following mastectomy admitted to Wittlinger's therapy centre in Walchsee, Austria (private rehabilitation clinic)
2. Number of participants randomised: 60

3. Sex (men/women): presumably all women

4. Mean age: 60.5

5. Area of body involved: upper limb

6. Number of episodes of cellulitis prior to intervention: ≥ 4

Interventions

Study groups:

  • Sodium selenite solution taken by mouth: week 1‐ 1000 μg/d; week 2 ‐ 3‐ 300 μg/d ; week 4 ‐ 15‐ 200 μg/d (body weight > 70 kg), 100 μg/d (body weight < 70 kg)

  • Physiological salt solution

Concomitant treatment: 3 weeks of inpatient care (Table 1) of congestion relief for both groups including daily treatment with manual lymph drainage; bandaging; exercise; skin care and high voltage therapy

Duration of treatment:15 weeks: 3 weeks of intensive congestion relief treatment and 3 months of oral solution

Follow‐up: during intensive treatment phase‐ inpatient care follow‐up, afterwards‐ NR

Outcomes

1.The number of participants with repeat episodes of cellulitis

2. Blood selenium levels before and after treatment

Notes

1. Criteria for diagnosis of cellulitis: prior to study enrolment diagnosis was made in general and university hospitals; after enrolment diagnosis was based on clinical examination and blood test markers of inflammation (erythrocyte sedimentation rate and CRP) but exact criteria are NR

2. No details reported on high voltage therapy

Funding source and Declaration of interest: NR but on further examination we confirmed industrial sponsorship (Biosyn Arzneimittel GmbH ‐ Biosyn 2015, also in Table 2)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The paper did not detail the randomisation process

Allocation concealment (selection bias)

Unclear risk

The paper did not provide details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "double‐blind study".

Comment: the paper did not provide details on randomisation process, including similarity of treatment characteristics (possible different taste or colour of selenium solution versus physiological salt solution) or allocation schedule control (breaking of the code for analysis or for medical reasons)

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "double‐blind study"

Comment: the investigator did not identify those blinded in the trial or other necessary data (specified above) to allow judgement of blinding of the participants, care‐givers, outcome assessors or others

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote: "During the treatment, some of the patients were excluded from the study since they did not meet the criteria for study inclusion, namely, too short period of stay".

Comment: 3 participants were omitted from analyses. The study did not specify exclusion criteria nor the group to which these participants belonged or the reason for their short period of stay in the trial

Selective reporting (reporting bias)

High risk

The study report failed to include results for outcomes that would be expected to have been reported for such a study, such as number of episodes of cellulitis, severity of lymphoedema, adverse events. In addition, the investigator reported measurements of selenium blood levels, which had not been proposed prior to the results

Similarity of groups at baseline (baseline imbalance bias)

Unclear risk

The investigator did not report on baseline differences between study groups including previous treatment with radiation or other oncological treatment

Early termination (early stopping bias)

Unclear risk

The trial ended after 15 weeks but the investigator did not prespecify termination criteria nor did he explain the study's duration

Other bias

High risk

1. Criteria for the diagnosis of cellulitis are unclear, especially in the ambulatory (Table 1) phase of the trial (this might cause differences in diagnosis of cellulitis between the intensive care phase and the ambulatory phase)

2.The investigator did not answer queries (sent by emails, post and professional website ‐ drkasseroller.at (accessed February 2014))

Kremer 1991

Methods

A randomised controlled, open‐label, parallel‐group trial

Participants

1. Setting: the trial was conducted in an outpatient (Table 1) setting in northern Israel. The recruitment process of participants was NR
2. Number of participants randomised: 40

3. Sex (men/women): 14/18 (8 participants were lost to follow‐up and their details are NR)

4. Mean age (range): treatment group‐ 63.2 (42 ‐ 75), control group‐ 65.5 (32 ‐ 75)

5. Area of body involved: leg. 2 participants from the control group suffered upper extremity infections

6. Number of episodes of cellulitis prior to intervention: ≥ 2

Interventions

Study groups:

  • Oral erythromycin base 250 mg X 2/d (3 participants changed treatment to penicillin V‐K 250 mg X 2/d due to nausea and vomiting)

  • No treatment except for local treatment

Concomitant treatment: local antifungal treatment for tinea pedis

Duration of treatment: 18 months

Follow‐up:during treatment phase‐monthly, after treatment phase‐ NR

Outcomes

1. The number of participants with repeat episodes of cellulitis

2. The number of repeat episodes of cellulitis

3. The number of participants requiring hospitalisation

4. The number of adverse drug reactions

Notes

Criteria for diagnosis of cellulitis: NR.
Comment: the report mentioned that during follow‐up participants with "a relapse" came to the clinic and were treated according to "clinical findings"

Funding source and Declaration of interest: NR.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The paper did not provide details

Allocation concealment (selection bias)

Unclear risk

The paper did not provide details

Blinding of participants and personnel (performance bias)
All outcomes

High risk

This was an open‐label study

Blinding of outcome assessment (detection bias)
All outcomes

High risk

This was an open‐label study

Incomplete outcome data (attrition bias)
All outcomes

High risk

8 participants were lost to follow‐up (20% of participants in the study) and the paper did not detail to which groups they were assigned; we conducted a 'per protocol' analysis

Selective reporting (reporting bias)

Unclear risk

There was insufficient information

Similarity of groups at baseline (baseline imbalance bias)

Low risk

Baseline characteristics were reported and balanced (Table 1 in the article).

Early termination (early stopping bias)

High risk

Quote: "After I8 months' follow‐up the differences between the two groups were dramatic, and led us to conclude the study"

Comment: the study was terminated based on results and did not report sample size calculation, formal interim analysis or a formal stopping rule

Other bias

Low risk

No other sources of potential bias were found

Sjöblom 1993

Methods

A randomised controlled, open‐label, parallel‐group trial

Participants

1. Setting: the trial recruited participants admitted to the infectious diseases department of Roslagstull hospital in Stockholm, Sweden
2. Number of participants randomised: 40

3. Sex (men/women): 20/20

4. Mean age (range): treatment group‐ 67.5 (36 ‐ 87), control group‐ 62.6 (25 ‐ 84)

5. Area of body involved: leg. 1 participant from the control group suffered upper limb lymphoedema after having a mastectomy

6. Number of episodes of cellulitis prior to intervention: ≥ 2

Interventions

Study groups:

  • Oral phenoxymethylpenicillin 1 g x 2/d if body weight < 90 kg; 1 g + 2 g/d if 90 ‐ 120 kg; 2 g x 2/d if > 120 kg

5 participants that were allergic to penicillin received oral erythromycin 250 mg X 2/d; 250 mg + 500 mg/d and 500 mg X 2/d for the corresponding weight groups

  • No treatment except for medical advice

Concomitant treatment:local skin care and compression stockings or elastic bandages

Duration of treatment (mean (range), days) ‐ treatment group‐ 443 (50 ‐ 1047), control group‐ 436 (25 ‐ 84)

Follow‐up: during treatment phase ‐ every 3 months, after treatment phase ‐ NF

Outcomes

1. The number of participants with repeat episodes of cellulitis

2. The number of participants with adverse drug reactions requiring the interruption of treatment and other adverse events of interest (changes in blood cell count, liver enzyme disturbances, gastrointestinal symptoms, e.g. nausea, diarrhoea and rash)

3. Colonisation with streptococci and staphylococci (from blood, skin, nasopharynx and throat cultures)

Notes

Criteria for diagnosis of cellulitis:a febrile infection of acute onset with a sharply demarcated, warm, indurated and painful erythema (Table 1) accompanied by a temperature of at least 38° C. The diagnosis was made by 2 infectious diseases specialists

Funding source and Declaration of interest: NC and NR.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The investigators described using stratified block randomisation (Table 1) in a separate email correspondence (Table 2)

Allocation concealment (selection bias)

Low risk

Quote: "The patients were randomly assigned to treatment or control groups using sealed envelopes".

Comment: investigators mentioned in correspondence that envelopes were sequentially numbered

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "This was an open study"

Comment: trial was not blinded

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote: "This was an open study"

Comment: trial was not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 participants stopped treatment due to adverse drug reactions (95% follow‐up) and ITT analysis was performed

Selective reporting (reporting bias)

Low risk

The publication reported findings on all outcomes listed in the Methods section

Similarity of groups at baseline (baseline imbalance bias)

Low risk

Quote: "No major differences concerning predisposing factors were found between the groups".

Comment: Baseline characteristics were reported and balanced

Early termination (early stopping bias)

Unclear risk

The trial stopped after a mean time of 14.4 months and the paper did not report sample size calculation, a formal stopping rule or results of an interim analysis (stated to be conducted every 6 months for at least 20 participants followed up for a minimum of 1 year)

Other bias

High risk

Randomisation included fixed‐size blocks (of 10) and the trial was open, thus allowing predictability

Thomas 2012

Methods

A multicentre, randomised, double‐blind, placebo‐controlled trial

Participants

1. Setting: the trial recruited participants from 20 hospitals in the UK and Ireland, either in hospital setting or retrospectively via medical coding in records or poster adverts
2. Number of participants randomised: 123

3. Sex (men/women): 42/81

4. Mean age (range): treatment group‐ 56.7 (18 ‐ 81), placebo group‐ 59.5 (23 ‐ 84)

5. Area of body involved: leg

6. Number of episodes of cellulitis prior to intervention: ≥ 1

Interventions

Study groups:

  • Oral penicillin V (phenoxymethylpenicillin) 250 mg X 2/d

  • Oral Placebo tablets 250 mg X 2/d

Duration of treatment: 6 months

Follow‐up: on‐prophylaxis phase‐ telephone calls from co‐ordinating centre every 3 months , post‐prophylaxis phase‐ phone calls at 6‐month intervals. In addition participants were asked to complete a study diary and to immediately inform the trial staff of a repeat episode

Outcomes

Primary outcomes:

1. Time to next episode of cellulitis

Secondary outcomes:

1. The proportion of participants with repeat episodes of cellulitis at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase

2. The number of repeat episodes of cellulitis
3. The proportion of participants with new oedema and/or ulceration at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase

4. The number of nights in hospital for the treatment of repeat episodes of cellulitis

5. The number of adverse drug reactions and/or adverse events of interest (death, nausea, diarrhoea, thrush, rash)

6. Cost effectiveness

7. Predictors of response model to explore the impact of known risk factors in predicting the efficacy of prophylaxis (stated to be conducted only if a significant treatment effect was found)

Notes

1. Criteria for diagnosis of cellulitis:

‐ Criteria for an episode of cellulitis for study eligibility (index episode): a confirmed diagnosis of cellulitis by the recruiting dermatologist; if the patient was not seen by the recruiting clinician, validation of diagnosis was sought from the medical records and interview with the patient. In this case specific criteria were required consistent with clinical signs and symptoms of cellulitis (specified in the report). Any doubt over the certainty of the diagnosis was grounds for exclusion

‐ Criteria for a repeat episode of cellulitis during treatment or follow‐up phases: next episode of cellulitis in either leg that had been reported by the participant and confirmed by a medical practitioner (sensitivity analysis was performed for patient‐reported cases that required antibiotic treatment and were not confirmed as stated)

2. The paper reported good and balanced adherence in both groups: "From self‐reported tablet counts, 97 (79%) patients fully adhered to treatment, defined as at least 75% of tablets taken.This was similar across treatment groups".

Funding source and Declaration of interest: NC (The BUPA Health Foundation) and no conflicts of interests.

The Thomas 2012 and Thomas 2013 report on 2 studies that were led by the same group of researchers under the title of: Prophylactic Antibiotics for the Treatment of Cellulitis at Home ‐ The PATCH trials (The PATCH II and PATCH I studies, respectively). Similar study designs were reported for both trials including randomisation process, allocation, blinding, definitions of outcomes, monitoring and analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "participants were randomised by staff at the coordinating centre using a web‐based randomisation service provided by the Clinical Trials Unit (CTU)...".

Comment: investigators used computer‐generated random list

Allocation concealment (selection bias)

Low risk

Quote: "Treatment allocations were concealed from all members of the trial team".

Comments: central block randomisation was conducted with varying block sizes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Participants and all members of the study team were blinded to treatment allocation throughout the trial, and analysis was performed prior to breaking of the randomization code...Although the treatments were packaged in an identical way, and the placebo tablets were of the same size and shape as penicillin V, the tablets were not identical due to difficulties in obtaining a matched placebo product. Nevertheless, there was a low risk of unblinding...".

Comment: The trial included placebo, randomisation list was held by the CTU, breaking of the allocation code was allowed according to decisions by the data monitoring committee and as prespecified in the protocol of the trial

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

As detailed for blinding of the participants and personnel: there was blinding, and it was unlikely that the blinding could have been broken

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "Of the 123 participants randomized, 20 (16%) participants (11 penicillin V and nine placebo) did not reach the end of the study... Participants in both groups had a similar study time experience, and approximately 80% had at least 2 years of follow‐up".

Comment: most of participants completed follow‐up (84%); their number is balanced between groups; the reasons for withdrawal from study are probably not related to treatment or outcome;and ITT was performed

Selective reporting (reporting bias)

Low risk

Changes to outcomes, as prespecified in the protocol, were explained. Other outcomes were reported as mentioned in the protocol, that had been registered and available online (via ongoing trials registries and the trial website ‐Thomas 2012)

Similarity of groups at baseline (baseline imbalance bias)

Low risk

Quote:"...these stratification factors and other baseline variables were broadly similar across the two treatment groups".

Comment: Baseline characteristics were reported and balanced

Early termination (early stopping bias)

Low risk

Quote:"...the identification of suitable participants was much slower than anticipated, and recruitment was therefore stopped after 2 years due to funding limitations. The possible reasons for this failure to recruit have been reported elsewhere" (Thomas 2010).

Comment: Sample size calculation was stated (a sample of 400 participants) and the goal of recruitment was not achieved but carefully examined. Nevertheless, the study ended according to the protocol (see Thomas 2012)

Other bias

Low risk

No other sources of potential bias were found

Thomas 2013

Methods

A multicentre, randomised, double‐blind, placebo‐controlled trial

Participants

1. Setting:the trial recruited participants from 28 hospitals in the UK and Ireland, either in hospital setting or retrospectively via medical coding in records or poster adverts
2. Number of participants randomised: 274

3. Sex (men/women):109/165

4. Mean age ± SD: treatment group ‐ 58.1 ± 12.6, placebo group ‐ 57.4 ± 14.4

5. Area of body involved: leg

6. Number of episodes of cellulitis prior to intervention: ≥ 2

Interventions

Study groups:

  • Oral penicillin V (phenoxymethylpenicillin) 250 mg X 2/d

  • Oral Placebo tablets 250 mg X 2/d

Concomitant treatment: "normal clinical practice" for predisposing factors such as tinea pedis

Duration of treatment‐ 12 months

Follow‐up:on‐prophylaxis phase‐ telephone calls from co‐ordinating centre every 3 months, post‐prophylaxis phase‐ phone calls at 6‐month intervals. In addition participants were asked to complete a study diary and to immediately inform the trial staff on a repeat episode

Outcomes

Primary outcomes:

1. Time to next episode of cellulitis

Secondary outcomes:

1. The proportion of participants with repeat episodes of cellulitis at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase

2. The number of repeat episodes of cellulitis
3. The proportion of participants with new oedema and/or ulceration at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase

4. The number of nights in hospital for the treatment of repeat episodes of cellulitis

5. The number of adverse drug reactions and/or adverse events of interest (death, nausea, diarrhoea, thrush, rash, severe skin reactions, sepsis, and renal failure)

6. Cost effectiveness

7. Predictors of response model to explore the impact of known risk factors in predicting the efficacy of prophylaxis

Notes

1. Criteria for diagnosis of cellulitis:

‐ Criteria for an episode of cellulitis for study eligibility (index episode):a confirmed diagnosis of cellulitis by the recruiting dermatologist; if the patient was not seen by the recruiting clinician, validation of diagnosis was sought from the medical records and interview with the patient. In this case specific criteria were required consistent with clinical signs and symptoms of cellulitis (specified in the report). Any doubt over the certainty of the diagnosis was grounds for exclusion

‐ Criteria for a repeat episode of cellulitis during treatment or follow‐up phases: next episode of cellulitis in either leg that had been reported by the participant and confirmed by a medical practitioner (sensitivity analysis was performed for patient‐reported cases that required antibiotic treatment and were not confirmed as stated).

2. The paper reported good and balanced adherence in both groups: "A total of 214 participants (78%) reported taking at least 75% of the study tablets; the proportion of patients who reported taking at least 75% of the tablets was similar in the two groups".

Funding source and Declaration of interest: NC (Action Medical Research‐ medical research charity) and no conflicts of interests

The Thomas 2012 and Thomas 2013 report on 2 studies that were led by the same group of researchers under the title of: Prophylactic Antibiotics for the Treatment of Cellulitis at Home ‐ The PATCH trials (The PATCH II and PATCH I studies, respectively). Similar study designs were reported for both trials including randomisation process, allocation, blinding, definitions of outcomes, monitoring and analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The coordinating center randomly assigned the participants with the use of the Nottingham Clinical Trials Unit (NCTU) Web‐based randomization service".

Comment: Investigators used computer‐generated random list

Allocation concealment (selection bias)

Low risk

Quote: "The computer‐generated randomization list was produced before the start of recruitment, with the use of randomly varying block sizes, and was held by the NCTU".

Comment: Central block randomisation was conducted with varying block sizes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Participants and all members of the study team were unaware of the treatment assignments throughout the trial, and the analysis was performed before the breaking of the randomization code".

Comment: The trial included placebo, randomisation list was held by the CTU, breaking of the allocation code was allowed according to decisions by the data monitoring committee and as prespecified in the protocol of the trial

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

As detailed for blinding of the participants and personnel: there was blinding, and it was unlikely that the blinding could have been broken

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "A total of 247 patients (90%) underwent at least 18 months of follow‐up (median, 25)"

Comment: attrition was low

Selective reporting (reporting bias)

Low risk

All the outcomes prespecified in the protocol were reported and any changes to its plan were explained (see Thomas 2013)

Similarity of groups at baseline (baseline imbalance bias)

Low risk

Quote: "The baseline characteristics of the participants were well balanced between the groups".

Comment: Baseline characteristics were reported and balanced

Early termination (early stopping bias)

Low risk

Sample size calculation was stated (a sample of 260 participants), the goal of recruitment was achieved (274 participants randomised), and the study did not terminate prematurely

Other bias

Low risk

No other sources of potential bias were found.

Abbreviations:

d ‐ Day
g ‐ Microgram
ITT ‐ Intention‐to‐treat (Table 1)
NC ‐ Non‐commercial
NF ‐ No follow‐up
NR ‐ Not reported
SD ‐ Standard deviation

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Duvanel 1986

This was a retrospective cohort study (Table 1)

Ferrieri 1973

Participants were children (ages 1 to 14)

Fritz 2011

The study mainly investigated recurrent purulent abscesses in children

Haustein 1989

This was a retrospective cohort study

Klempner 1988

This study investigated prophylaxis for recurrent skin abscesses

Maddox 1985

Participants were children (ages 2 to 5)

Raz 1996

This study investigated prophylaxis for recurrent furunculosis and folliculitis (Table 1)

Wang 1997

This was a non‐randomised study

Characteristics of studies awaiting assessment [ordered by study ID]

Ratnikova 1991

Methods

Interventional study, exact methods are unclear

Participants

66 participants with recurrent erysipelas, probably from Russia

Interventions

Study groups:

  • "conventional treatment" with bemitil 0.25 g/day to 0.5 g/day by mouth for 5 to 7 days

  • "placebo"

Outcomes

Not reported

Notes

  • Only abstract was available

  • The bemitil group was free of intoxication symptoms and local manifestations and discharged from hospital sooner than the controls

  • The investigator considers bemitil as an immunostimulator that promotes activation of mononuclear phagocytes

Data and analyses

Open in table viewer
Comparison 1. Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

5

513

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.13, 0.72]

Analysis 1.1

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 1 Recurrence of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 1 Recurrence of cellulitis.

2 Incidence rate of recurrence of cellulitis Show forest plot

4

4375

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.22, 0.89]

Analysis 1.2

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

3 Time to next episode of cellulitis Show forest plot

3

Hazard Ratio (Random, 95% CI)

0.51 [0.34, 0.78]

Analysis 1.3

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 3 Time to next episode of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 3 Time to next episode of cellulitis.

4 Hospitalisation Show forest plot

3

429

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.37, 1.57]

Analysis 1.4

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 4 Hospitalisation.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 4 Hospitalisation.

5 Any adverse reactions Show forest plot

4

469

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.58, 1.30]

Analysis 1.5

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 5 Any adverse reactions.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 5 Any adverse reactions.

5.1 Penicillin

3

437

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.60, 1.10]

5.2 Erythromycin

1

32

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 125.44]

6 Mortality Show forest plot

3

437

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.32, 3.91]

Analysis 1.6

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 6 Mortality.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 6 Mortality.

Open in table viewer
Comparison 2. Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

2

287

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.59, 1.31]

Analysis 2.1

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 1 Recurrence of cellulitis.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 1 Recurrence of cellulitis.

2 Incidence rate of recurrence of cellulitis Show forest plot

2

4566

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.65, 1.36]

Analysis 2.2

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

3 Time to next episode of cellulitis Show forest plot

2

Hazard Ratio (Random, 95% CI)

0.78 [0.39, 1.56]

Analysis 2.3

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 3 Time to next episode of cellulitis.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 3 Time to next episode of cellulitis.

Open in table viewer
Comparison 3. Antibiotic prophylaxis versus no treatment/placebo, overall

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

2

397

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.59, 0.95]

Analysis 3.1

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 1 Recurrence of cellulitis.

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 1 Recurrence of cellulitis.

2 Incidence rate of recurrence of cellulitis Show forest plot

2

7854

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.56, 0.85]

Analysis 3.2

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 2 Incidence rate of recurrence of cellulitis.

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 2 Incidence rate of recurrence of cellulitis.

Study selection flow diagram.
Figuras y tablas -
Figure 1

Study selection flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 1 Recurrence of cellulitis.
Figuras y tablas -
Analysis 1.1

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 1 Recurrence of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.
Figuras y tablas -
Analysis 1.2

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 3 Time to next episode of cellulitis.
Figuras y tablas -
Analysis 1.3

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 3 Time to next episode of cellulitis.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 4 Hospitalisation.
Figuras y tablas -
Analysis 1.4

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 4 Hospitalisation.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 5 Any adverse reactions.
Figuras y tablas -
Analysis 1.5

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 5 Any adverse reactions.

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 6 Mortality.
Figuras y tablas -
Analysis 1.6

Comparison 1 Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis, Outcome 6 Mortality.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 1 Recurrence of cellulitis.
Figuras y tablas -
Analysis 2.1

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 1 Recurrence of cellulitis.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.
Figuras y tablas -
Analysis 2.2

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 2 Incidence rate of recurrence of cellulitis.

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 3 Time to next episode of cellulitis.
Figuras y tablas -
Analysis 2.3

Comparison 2 Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis, Outcome 3 Time to next episode of cellulitis.

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 1 Recurrence of cellulitis.
Figuras y tablas -
Analysis 3.1

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 1 Recurrence of cellulitis.

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 2 Incidence rate of recurrence of cellulitis.
Figuras y tablas -
Analysis 3.2

Comparison 3 Antibiotic prophylaxis versus no treatment/placebo, overall, Outcome 2 Incidence rate of recurrence of cellulitis.

Summary of findings for the main comparison. Antibiotic prophylaxis compared to no treatment/placebo for the prevention of recurrent erysipelas and cellulitis

Antibiotic prophylaxis compared to no treatment/placebo for the prevention of recurrent erysipelas and cellulitis ‐ on prophylaxis

Patient or population: People with recurrent erysipelas or cellulitis
Intervention: Antibiotic prophylaxis
Comparison: No treatment/Placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

no treatment/placebo

Antibiotic prophylaxis

Recurrence of cellulitis

Study population

RR 0.31
(0.13 to 0.72)

513
(5 RCTs)

⊕⊕⊕⊝
MODERATE 1

Number needed to treat for 1 additional beneficial outcome (NNTB) is 6

316 per 1000

98 per 1000
(41 to 227)

Incidence rate of cellulitis

Study population

RR 0.44 (0.22 to 0.89)

473

(4 RCTs)

⊕⊕⊕⊝
MODERATE 1

43 fewer episodes of cellulitis per 1000 person‐months in treatment group

(from 8 fewer to 60 fewer)

Time to next episode of cellulitis

Not estimable

HR 0.51
(0.34 to 0.78)

437
(3 RCTs)

⊕⊕⊕⊝
MODERATE 1

Hospitalisation

Study population

RR 0.77
(0.37 to 1.57)

429
(3 RCTs)

⊕⊕⊝⊝
LOW 2

74 per 1000

57 per 1000
(27 to 116)

Any adverse reactions

Study population

RR 0.87
(0.58 to 1.30)

469
(4 RCTs)

⊕⊕⊝⊝
LOW 3

287 per 1000

250 per 1000
(166 to 373)

Quality of life

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: risk ratio; HR: hazard ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1We downgraded by one level because of imprecision due to the low number of events and the small sample size (optimal information size ‐ OIS).

2 We downgraded by two levels because of imprecision due to the low number of events and the small sample size (OIS) and the 95% confidence interval overlapping the line of no effect and ranging from benefit to harm.

3We downgraded by two levels because of imprecision due to the considerable low number of events and the small sample size (OIS).

We decided not to downgrade any of the outcomes for risk of bias as we decided it was not serious enough to affect the overall quality of the outcome.

Figuras y tablas -
Summary of findings for the main comparison. Antibiotic prophylaxis compared to no treatment/placebo for the prevention of recurrent erysipelas and cellulitis
Table 1. Glossary of terms

Medical term

Explanation

Ambulatory

Ambulatory is when the patient can walk and is not bedridden. When referring to medical care it means that it is being provided to patients that are not hospitalised (outpatients)

Block randomisation

A method of randomisation that ensures allocation of participants into roughly equal sizes of comparison groups

Clostridium difficile

A bacterium that causes inflammation of the colon (colitis), typically resulting in diarrhoea, and is strongly associated with the use of antibiotics

Comorbidity

The presence of one or more diseases or conditions other than those of primary interest

Contralateral

On the opposite side of the body (e.g. a repeat episode of leg cellulitis can recur in the same leg [see 'ipsilateral'] or the other, contralateral leg

Control event rate (CER)

The rate at which events of interest (i.e. episodes of cellulitis in our review) occur in the control group of the study

Diuretics

Commonly known as "water pills" these are drugs that help the body to eliminate unneeded water and salt through the urine

Epidemiology

The study of the health of populations and communities, not just particular individuals

Erythema

Redness of the skin caused by increased blood flow. Often a sign of inflammation or infection

Filariasis

A disease caused by infection with worms, usually in tropical and subtropical areas of the world. The worms reside in the lymphatic system of the affected person and interfere with the drainage of the lymph, subsequently causing a significant swelling of the involved limb

Filarial lymphoedema

see Filiariasis

Folliculitis

Inflammation of hair follicles

Furunculosis

Deep form of inflammation of the hair follicles resulting in lumps caused by the accumulation of pus (boils)

Gastrointestinal

Relating to the stomach and the intestines

Incidence rate/Incidence rate ratio

The number of new occurrences of events in a population divided by its time period at risk; Incidence rate ratio is the ratio of two incidence rates

Ipsilateral

On the same side of the body; as opposed to 'contralateral'

Mastectomy

Surgical removal of one or both breasts

Outpatient/Inpatient

Outpatient is a person that is being treated without being hospitalised overnight and visits the physician in the clinic, hospital or other facility; compared with an inpatient who requires an overnight stay in hospital for medical treatment

Person‐months

The sum of the number of months each participant in the trial has been under observation (treated/followed)

'Per protocol'/Intention‐to‐treat (ITT) analyses

'Per protocol' analysis compares participants in a study based on the treatment they actually took and includes only those patients who completed the treatment originally allocated, as opposed to intention‐to‐treat analysis that compares participants on the basis of their random assignment to groups (treatment or placebo), regardless of adherence to treatment

Prophylaxis

Preventive treatment for disease

Retrospective cohort study

An observational study in which a defined group of people (the cohort) is followed over time. A retrospective cohort study identifies persons from past medical records and follows them from the time of those records to the present

Sensitivity analysis

An analysis used to determine how sensitive the results of a study or systematic review are to changes in how it was done

Tinea pedis

Fungal infection of the foot (athlete's foot)

Tonsillectomy

Surgical removal of tonsils

Figuras y tablas -
Table 1. Glossary of terms
Table 2. Contact with investigators of included studies

Study

Way of communication

Date

Information provided

Notes

Chakroun 1994

email

12/2013

‐ Allocation concealment

‐ Participants follow‐up

‐ Criteria for diagnosis

‐ Adherence

‐ Adverse reactions

‐ Informed consent

‐ Ethical committee approval

‐ Source of funding

Full information was not available for all queries, but investigators responded to all of them

Kasseroller 1998

airmail, email, website

2013 ‐ 2014

Investigator did not reply to our queries

We also contacted a potential sponsor, not reported by the author, who confirmed their financial support for the conduct of this study (email correspondence with the head of medical‐scientific department of 'biosyn

Arzneimittel GmbH' from January 2015)

Kremer 1991

email and telephone

12/2013 and 1/2014

Data were not available and the investigator did not remember any details

Sjöblom 1993

email

12/2013

‐ Allocation concealment

‐ Participants follow‐up

‐ By whom cellulitis was diagnosed

‐ Adherence

‐ Source of funding

Full information was not available for all queries, but investigators responded to all of them

Thomas 2012

email

1/2014

‐ Episodes of recurrent cellulitis

per person‐months (incidence rate)

‐Time to next episode

‐ Adverse events by study arm

‐ Duration of hospitalisation

‐ Quality of life

Thomas 2013

email

1/2014

‐ Episodes of recurrent cellulitis

per person‐months (incidence rate)

‐ Quality of life

Hospitalisation and quality of life were not evaluated directly in this trial but were reported by indirect evaluation in Mason 2014

Figuras y tablas -
Table 2. Contact with investigators of included studies
Table 3. Clinical guidelines on antibiotic prophylaxis for the prevention of recurrent cellulitis

Guideline

Organisation

Recommended antibiotic

Duration of Px

No of episodes

to initiate Px

Adjunctive Tx

Quality of evidence †

BLS 2016

BLS

penicillin by mouth;

alternatives: cephalexin,

erythromycin, clarithromycin,

clindamycin, doxycycline

2 y; life‐long Px

if recurrence after Px stopped

2 ≥/y

skin care, decongestive Tx, antifungal Tx, alcohol

wipes; SIT

NS

ALA 2015

ALA

penicillin by mouth;

alternatives: cephalexin,

erythromycin, clindamycin

2 y; life‐long Px

if recurrence after

Px stopped

2 ≥/y

skin care, decongestive Tx, bacterial decolonisation Tx; SIT

NS

Stevens 2014

IDSA

penicillin by mouth/IM;

alternatives:erythromycin

as long as

RF persist

3 – 4 /y

skin care, Tx of oedema, weight reduction

antibiotic Px ‐weak, moderate ‡

duration of Px ‐ strong,

moderate ‡

skin care ‐ strong,

moderate ‡

Stevens 2005

penicillin by mouth/IM;

alternatives:erythromycin

NS

frequent

skin care, Tx of oedema

compression stockings,

diuretics; SIT

grade IIB §

ISL 2013

ISL

penicillin;

alternatives: broad spectrum

antibiotic

NS

repeat despite

physical Tx

skin care, antifungal Tx

NS

Esposito 2011

SIMIT and ISC

penicillin or macrolide

NS

recurrent

skin hygiene and

compression stockings

NS

Draijer 2008

NHG

penicillin by mouth/IM

1 ‐ 2 y

2 ≥/y

skin care, compression

stockings; SIT

NS

ILF 2006

ILF

penicillin by mouth;

alternatives:erythromycin,

clindamycin, clarithromycin

2 y; life‐long Px

if recurrence after

Px stopped

2 ≥/y

skin care, decongestive Tx,

antifungal Tx; SIT

NS

CREST 2005

CREST

penicillin or erythromycin by mouth

2 y

2 ≥/y

SIT may be preferable

weak and inconclusive

NICE 2005

NICE

a trial should be considered

NS

> 2/y

skin care, Tx of oedema,

compression stockings,

weight reduction

weak and inconclusive

Eron 2003

Other*

antibiotic may be needed;

type of antibiotic NS

long term

NS

skin care, Tx of oedema,

antifungal Tx; SIT

NS

SFD 2000

SFD

penicillin by mouth/IM;

alternatives: macrolide

prolonged,

probably indefinitely

several/poorly

controlled RF

skin care, Tx of oedema

NS

Duodecim 1999

FMSD

antibiotic should be considered;

type of antibiotic NS

long term

frequent

skin care

NS

† Assessement of quality of evidence as defined and graded by the authors of the document.

‡ Strong recommendation, moderate quality ‐ desirable effects clearly outweigh undesirable effects; evidence from RCTs with important limitations or exceptionally strong evidence from unbiased observational studies; recommendation can apply to most patients in most circumstances and further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate.

Weak recommendation, moderate quality ‐ desirable effects closely balanced with undesirable effects; evidence from RCTs with important limitations;recommendation may change when higher‐quality evidence becomes available; and further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate.

§ Moderate evidence ‐ should generally be offered; II ‐ evidence from one well‐designed clinical trial.

Abbreviations

IM injections into the muscle (intramuscular)
No ‐ number
NS ‐ not specified
Px ‐ preventive treatment (prophylaxis)
RF‐ risk factors
SIT ‐ self‐initiated treatment
Tx ‐ treatment
y ‐ year/s

Medical organisations

BLS ‐ British Lymphology Society
ALA ‐ Australasian Lymphology Association
IDSA ‐ Infectious Diseases Society of America
ISL ‐ International Society of Lymphology
SIMIT ‐ Società Italiana di Malattie Infettive e Tropicali ‐ Italian Society of Infectious Diseases
ISC ‐ International Society of Chemotherapy
NHG ‐ Nederlands Huisartsen Genootschap ‐ The Dutch College of General Practitioners
ILF ‐ International Lymphoedema Framework
CREST ‐ Clinical Resources Efficiency Support Team (UK)
NICE ‐ National Institute for Health and Clinical Excellence (England)
SFD ‐ La Société Française de Dermatologie ‐ The French Society of Dermatology
MSD ‐ The Finnish Medical Society Duodecim

* 5 of 6 experts in this consensus paper were from North America; published in the Journal of the British Society for Antimicrobial Chemotherapy

Figuras y tablas -
Table 3. Clinical guidelines on antibiotic prophylaxis for the prevention of recurrent cellulitis
Comparison 1. Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

5

513

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.13, 0.72]

2 Incidence rate of recurrence of cellulitis Show forest plot

4

4375

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.22, 0.89]

3 Time to next episode of cellulitis Show forest plot

3

Hazard Ratio (Random, 95% CI)

0.51 [0.34, 0.78]

4 Hospitalisation Show forest plot

3

429

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.37, 1.57]

5 Any adverse reactions Show forest plot

4

469

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.58, 1.30]

5.1 Penicillin

3

437

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.60, 1.10]

5.2 Erythromycin

1

32

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 125.44]

6 Mortality Show forest plot

3

437

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.32, 3.91]

Figuras y tablas -
Comparison 1. Antibiotic prophylaxis versus no treatment/placebo, on prophylaxis
Comparison 2. Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

2

287

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.59, 1.31]

2 Incidence rate of recurrence of cellulitis Show forest plot

2

4566

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.65, 1.36]

3 Time to next episode of cellulitis Show forest plot

2

Hazard Ratio (Random, 95% CI)

0.78 [0.39, 1.56]

Figuras y tablas -
Comparison 2. Antibiotic prophylaxis versus no treatment/placebo, post‐prophylaxis
Comparison 3. Antibiotic prophylaxis versus no treatment/placebo, overall

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Recurrence of cellulitis Show forest plot

2

397

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.59, 0.95]

2 Incidence rate of recurrence of cellulitis Show forest plot

2

7854

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.56, 0.85]

Figuras y tablas -
Comparison 3. Antibiotic prophylaxis versus no treatment/placebo, overall