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Meta-Analysis
. 2014 Jan 10;2014(1):CD003557.
doi: 10.1002/14651858.CD003557.pub5.

Antibiotics and antiseptics for venous leg ulcers

Susan O'Meara  1 , Deyaa Al-Kurdi, Yemisi Ologun, Liza G Ovington, Marrissa Martyn-St James, Rachel Richardson
Affiliations
Meta-Analysis

Antibiotics and antiseptics for venous leg ulcers

Susan O'Meara et al. Cochrane Database Syst Rev. .

Abstract

Background: Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics.

Objectives: The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers.

Search methods: In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied.

Selection criteria: Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently.

Data collection and analysis: Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate.

Main results: Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antiseptics Cadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care.

Authors' conclusions: At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.

PubMed Disclaimer

Conflict of interest statement

Susan O'Meara receives funding from the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP‐PG‐0407‐10428). The views expressed in this review are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Liza G Ovington is an employee of Ethicon, USA. This company does not have any commercial products that are considered in this review.

Deyaa Al‐Kurdi, Yemisi Ologun, Marrissa Martyn‐St James, Rachel Richardson: none.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
4
4
Forest plot of comparison: 8 Cadexomer iodine versus standard care, outcome: 8.1 Frequency of complete healing at 4 to 12 weeks.
5
5
Forest plot of comparison: 18 Honey products versus alternatives, outcome: 18.1 Complete healing at 12 weeks.
6
6
Forest plot of comparison: 23 Silver dressing versus non‐antimicrobial dressing, outcome: 23.1 Complete healing at 4 to 12 weeks.
1.1
1.1. Analysis
Comparison 1 Systemic antibiotic given according to sensitivities versus standard care, Outcome 1 Complete healing at 3 weeks.
1.2
1.2. Analysis
Comparison 1 Systemic antibiotic given according to sensitivities versus standard care, Outcome 2 Complete healing—eventual, assessment point not stated.
1.3
1.3. Analysis
Comparison 1 Systemic antibiotic given according to sensitivities versus standard care, Outcome 3 Bacterial eradication.
2.1
2.1. Analysis
Comparison 2 Ciprofloxacin versus standard care/placebo, Outcome 1 Frequency of complete healing.
2.2
2.2. Analysis
Comparison 2 Ciprofloxacin versus standard care/placebo, Outcome 2 Emergence of antibiotic‐resistant strains.
2.3
2.3. Analysis
Comparison 2 Ciprofloxacin versus standard care/placebo, Outcome 3 Bacterial eradication.
3.1
3.1. Analysis
Comparison 3 Ciprofloxacin versus trimethoprim, Outcome 1 Frequency of complete healing.
3.2
3.2. Analysis
Comparison 3 Ciprofloxacin versus trimethoprim, Outcome 2 Emergence of antibiotic‐resistant strains.
4.1
4.1. Analysis
Comparison 4 Trimethoprim versus placebo, Outcome 1 Frequency of complete healing.
4.2
4.2. Analysis
Comparison 4 Trimethoprim versus placebo, Outcome 2 Emergence of antibiotic‐resistant strains.
5.1
5.1. Analysis
Comparison 5 Amoxicillin plus compression verus povidone‐iodine alone, Outcome 1 Frequency of complete healing.
6.1
6.1. Analysis
Comparison 6 Amoxicillin plus compression verus povidone‐iodine plus compression, Outcome 1 Frequency of complete healing.
7.1
7.1. Analysis
Comparison 7 Levamisole versus placebo, Outcome 1 Frequency of complete healing.
8.1
8.1. Analysis
Comparison 8 Cadexomer iodine versus standard care, Outcome 1 Frequency of complete healing at 4 to 12 weeks.
8.2
8.2. Analysis
Comparison 8 Cadexomer iodine versus standard care, Outcome 2 Adverse events.
9.1
9.1. Analysis
Comparison 9 Cadexomer iodine versus dextranomer, Outcome 1 Frequency of complete healing.
10.1
10.1. Analysis
Comparison 10 Cadexomer iodine versus hydrocolloid dressing, Outcome 1 Frequency of complete healing.
11.1
11.1. Analysis
Comparison 11 Cadexomer iodine versus paraffin gauze, Outcome 1 Frequency of complete healing.
12.1
12.1. Analysis
Comparison 12 Cadexomer iodine dressing versus silver dressing, Outcome 1 Frequency of complete healing.
12.2
12.2. Analysis
Comparison 12 Cadexomer iodine dressing versus silver dressing, Outcome 2 Participant satisfaction.
13.1
13.1. Analysis
Comparison 13 Povidone‐iodine plus sugar versus growth factor, Outcome 1 Frequency of complete healing at 4 weeks.
14.1
14.1. Analysis
Comparison 14 Povidone‐iodine plus compression versus hydrocolloid plus compression, Outcome 1 Frequency of complete healing.
15.1
15.1. Analysis
Comparison 15 Povidone‐iodine plus compression versus moist or foam dressings plus compression, Outcome 1 Complete healing at 4 weeks.
16.1
16.1. Analysis
Comparison 16 Peroxide‐based topical preparation versus control, Outcome 1 Mean percentage ulcer area remaining.
17.1
17.1. Analysis
Comparison 17 Honey products versus alternatives, Outcome 1 Complete healing at 12 weeks.
17.2
17.2. Analysis
Comparison 17 Honey products versus alternatives, Outcome 2 Incidence of ulcer infection during the 12‐week trial period.
17.3
17.3. Analysis
Comparison 17 Honey products versus alternatives, Outcome 3 Participants with MRSA eradication at 4 weeks.
17.4
17.4. Analysis
Comparison 17 Honey products versus alternatives, Outcome 4 Participants reporting at least 1 adverse event.
18.1
18.1. Analysis
Comparison 18 1% silver sulphadiazine cream versus placebo cream, Outcome 1 Complete healing at 4 weeks.
19.1
19.1. Analysis
Comparison 19 1% silver sulphadiazine cream versus 0.4% tripeptide copper complex cream, Outcome 1 Complete healing at 4 weeks.
20.1
20.1. Analysis
Comparison 20 1% silver sulphadiazine cream versus non‐adherent dressing, Outcome 1 Complete healing at 12 weeks.
21.1
21.1. Analysis
Comparison 21 Silver dressing (Avance) versus silver dressing (Acticoat 7), Outcome 1 Complete healing at 12 weeks.
22.1
22.1. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 1 Complete healing at 4 to 12 weeks.
22.2
22.2. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 2 Complete healing at 6 months.
22.3
22.3. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 3 Complete healing at 12 months.
22.4
22.4. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 4 Ulcer recurrence within first year.
22.5
22.5. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 5 Change in ulcer surface area (cm squared) at 4 weeks.
22.6
22.6. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 6 Change in ulcer surface area (%) at 4 weeks.
22.7
22.7. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 7 Healing rate (cm squared per day).
22.8
22.8. Analysis
Comparison 22 Silver dressing versus non‐antimicrobial dressing, Outcome 8 Proportion of participants reporting any type of adverse event.
23.1
23.1. Analysis
Comparison 23 Chloramphenicol‐containing ointment versus enzymatic cleanser, Outcome 1 Complete healing at 4 weeks.
23.2
23.2. Analysis
Comparison 23 Chloramphenicol‐containing ointment versus enzymatic cleanser, Outcome 2 Participants discontinuing treatment because of ineffectiveness or allergy.
24.1
24.1. Analysis
Comparison 24 Framycetin sulphate‐containing ointment versus enzymatic cleanser, Outcome 1 Complete healing at 4 weeks.
24.2
24.2. Analysis
Comparison 24 Framycetin sulphate‐containing ointment versus enzymatic cleanser, Outcome 2 Participants discontinuing treatment because of ineffectiveness or allergy.
25.1
25.1. Analysis
Comparison 25 Chloramphenicol‐containing ointment versus framycetin sulphate‐containing ointment, Outcome 1 Complete healing at 4 weeks.
25.2
25.2. Analysis
Comparison 25 Chloramphenicol‐containing ointment versus framycetin sulphate‐containing ointment, Outcome 2 Participants discontinuing treatment because of ineffectiveness or allergy.
26.1
26.1. Analysis
Comparison 26 Mupirocin versus control, Outcome 1 Frequency of complete healing.
26.2
26.2. Analysis
Comparison 26 Mupirocin versus control, Outcome 2 Eradication of gram‐positive bacteria.
27.1
27.1. Analysis
Comparison 27 Topical antibiotics versus herbal ointment, Outcome 1 Complete healing at 7 weeks.
27.2
27.2. Analysis
Comparison 27 Topical antibiotics versus herbal ointment, Outcome 2 Participants with bacterial eradication at 7 weeks.
28.1
28.1. Analysis
Comparison 28 Ethacridine lactate versus control, Outcome 1 Number of responsive ulcers.
28.2
28.2. Analysis
Comparison 28 Ethacridine lactate versus control, Outcome 2 Participants reporting at least 1 adverse event.
28.3
28.3. Analysis
Comparison 28 Ethacridine lactate versus control, Outcome 3 Participant satisfaction (treatment rated as excellent).
See this image and copyright information in PMC

Update of

Comment in

References

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    1. Palfreyman S, Walker N. Venous leg ulcers and the VULCAN trial. British Journal of Nursing 2007;16(8):442‐3. - PubMed
Miller 2010 {published data only}
    1. Carville K, Kapp S, Newall N, Saflekas S, Lewin G, Gliddon T, et al. Predicting covert and overt infection in venous leg ulcers: a randomised controlled trial. Australian Wound Management Association 7th National Conference: Dreams, Diversity, Disasters, 2008 May 7‐10, Darwin, Australia. 2008.
    1. Kapp S, Carville K, Saflekas S, Newall N, Lewin G, Flowers C, et al. The Angior initiative: results of a randomised controlled trial comparing the effectiveness of two antimicrobials. 3rd Congress of the World Union of Wound Healing Societies Meeting, 2008 June 4‐8, Toronto, Canada. 2008.
    1. Kapp S, Carville K, Saflekas S, Newall N, Lewin G, Flowers C, et al. The Angior Initiative: results of a randomised controlled trial comparing the effectiveness of two antimicrobials. Australian Wound Management Association 7th National Conference: Dreams, Diversity, Disasters, 2008 May 7‐10, Darwin, Australia. 2008.
    1. Miller C, Kapp S, Newall N, Lewin G, Karimi L, Carville K, et al. Predicting concordance with multilayer compression bandaging. Journal of Wound Care 2011;20(2):101‐12. - PubMed
    1. Miller C, Karimi L, Kapp S, Newall N, Lewin G, Carville K, et al. Client perceptions of two types of antimicrobial dressings and compression bandaging. Wound Practice and Research 2010;18(3):124‐32.
Morias 1979 {published data only}
    1. Morias J, Peremans W, Campaert H, Mertens RL. Levamisole treatment in ulcus cruris. A double‐blind placebo‐controlled. Arzneimittel‐Forschung 1979;29(7):1050‐2. - PubMed
Moss 1987 {published data only}
    1. Moss C, Taylor A, Shuster S. Controlled trial of Iodosorb in chronic venous ulcers. BMJ 1985;297(6499):902. - PMC - PubMed
    1. Moss C, Taylor AEM, Shuster S. Comparison of cadexomer iodine and dextranomer for chronic venous ulcers. Clinical and Experimental Dermatology 1987;12(6):413‐8. - PubMed
    1. Moss C, Taylow A, Shuster S. Comparative study of cadexomer iodine and dextranomer in chronic leg ulcers. Scottish Medical Journal 1984;25:54.
Münter 2006 {published data only}
    1. Münter K‐C, Beele H, Russell L, Basse PB, Groechenig E, Crespi A, et al. The CONTOP Study: a large‐scale, comparative, randomised study in patients treated with a sustained silver‐releasing foam dressing. European Wound Management Association Conference, 2005 September 15‐17, Stuttgart, Germany. 2005:Poster abstracts P193 292.
    1. Münter KC, Beele H, Russell L, Basse PB, Groechenig E, Crespi A, et al. The CONTOP Study: a large‐scale, comparative, randomized study in patients treated with a sustained silver‐releasing foam dressing. Symposium on Advanced Wound Care & Medical Research Forum on Wound Repair, 2006 April 30 ‐ May 3, San Antonio, Texas. 2006:Poster 11.
    1. Münter KC, Beele H, Russell L, Basse PB, Gröchenig E, Crespi A, et al. The CONTOP Study: improved healing of delayed healing ulcers with sustained silver‐releasing foam dressing versus other silver dressings. 16th Conference of the European Wound Management Association, 2006 May 18‐20, Prague, Czech Republic. 2006:210, Abstract No.P068.
    1. Münter KC, Beele H, Russell L, Crespi A, Gröchenig E, Basse P, et al. Effect of a sustained silver‐releasing dressing on ulcers with delayed healing: the CONTOP study. Journal of Wound Care 2005;15(5):199‐206. - PubMed
    1. Russell L (on behalf of the UK investigators). The CONTOP multinational study: preliminary data from the UK arm. Wounds UK 2005;1(1):44‐54.
Ormiston 1985 {published data only}
    1. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox JA. A randomised comparison of cadexomer iodine and a standard treatment in out‐patients with chronic venous ulcers. Cadexomer Iodine. Stuttgart: Schattauer Verlag, 1983:63‐9.
    1. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox JA. Controlled trial of Iodosorb in chronic venous ulcers. BMJ 1985;291(6491):308‐10. - PMC - PubMed
Skog 1983 {published data only}
    1. Hillstrom L. Iodosorb compared to standard treatment in chronic venous leg ulcers‐‐a multicenter study. Acta Chirurgica Scandinavica ‐ Supplementum 1988;544:53‐6. - PubMed
    1. Skog E, Arnesjö B, Troëng T, Gjöres JE, Bergljung L, Gundersen J, et al. A randomized trial comparing cadexomer iodine and standard treatment in the out‐patient management of chronic venous ulcers. British Journal of Dermatology 1983;109(1):77‐83. - PubMed
    1. Troëng T, Skog E, Arnesjö B, Gjöres JE, Bergljung L, Gundersen J, et al. A randomised multicentre trial to compare the efficacy of cadexomer iodine and standard treatment in the management of chronic venous ulcers in out‐patients. Unpublished report 43‐50. - PubMed
Smith 1992 {published data only}
    1. Smith JM, Dore CJ, Charlett A, Lewis JD. A randomized trial of biofilm dressing for venous leg ulcers. Phlebology 1992;7(3):108‐13.
Steele 1986 {published data only}
    1. Steele K, Irwin G, Dowds N. Cadexomer iodine in the management of venous leg ulcers in general practice. The Practitioner 1986;230(1411):63‐8. - PubMed
Valtonen 1989 {published data only}
    1. Valtonen V, Karppinen L, Kariniemi AL. A comparative study of Ciprofloxacin and conventional therapy in the treatment of patients with chronic lower leg ulcers infected with Pseudomonas aeruginosa or other gram‐negative rods. Scandinavian Journal of Infectious Diseases Supplement 1989;60:79‐83. - PubMed
Wunderlich 1991 {published data only}
    1. Wunderlich U, Orfanos CE. Treatment of venous ulcera cruris with dry wound dressings. Phase overlapping use of silver impregnated activated charcoal xero‐dressing [Bedhandlung der ulcera cruris venosa mit trockenen wundauflagen. Phasenübergreifende anwendung eines silber‐imprägnierten aktivkohle‐xerodressings]. Der Hautarzt 1991;42(7):446‐50. - PubMed

References to studies excluded from this review

Allen 1980 {published data only}
    1. Allen S, Cooper J. The effect of an antibacterial on pain ulcerated legs. British Journal of Clinical Practice 1980;10:284‐5. - PubMed
Allen 1996 {published data only}
    1. Allen RB, Kerstein M, Klassen H, Friedmann PS, Pryce DW, Lawrence JC, et al. Prospective study of clinical infections in wounds dressed with occlusive versus conventional dressings. 9th Annual Symposium on Advanced Wound Care and 6th Annual Medical Research Forum on Wound Repair, 20‐24 April 1996, Atlanta, Georgia, USA. 1996.
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Altman 1976 {published data only}
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Anonymous 1982 {published data only}
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Bazzigaluppi 1991 {published data only}
    1. Bazzigaluppi F, Biraghi MG, Fano M, Moschin AM, Toscani P, Cervone C, et al. Cadexomer iodine in the treatment of cutaneous ulcers: open, multicentric trial. Gazetta Medica Italiana ‐ Archivo per le Scienze Mediche 1991;150(11):471‐80.
Beele 2010 {published data only}
    1. Beele H, Meuleneire F, Nahuys M, Percival SL. A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing. International Wound Journal 2010;7(4):262‐70. - PMC - PubMed
Beitner 1985c {published data only}
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Bender 1982 {published data only}
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Bourgeois 1963 {published data only}
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Brauman 2008 {published data only}
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Brzeziska 1990 {published data only}
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Castellano 2007 {published data only}
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Chaparro 2003 {published data only}
    1. Chaparro M, Alvarez de los Heros F, Novo E, Rodriguez‐Alvarez J, Stolle D, Losada A. Effectiveness of topical treatment of chronic varicose ulcers with sterile single‐dose ciprofloxacin ampoules versus physiologic serum. Revista Espanola de Geriatria y Gerontologia 2003;38(3):145‐52.
Chaudhary 2008 {published data only}
    1. Chaudhary M, Kumar Dwivedi V, Naithani V. Clinical trial survey report of ampucare done on patients with different wounds. Journal of Ecophysiology and Occupational Health 2008;8(1‐2):89‐97.
Cherry 2003 {published data only}
    1. Cherry GW. Comparison of Syerilox with tap water in the treatment of chronic venous ulcers of the leg. National Research Register 2003.
Chirwa 2010 {published data only}
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Colombo 1993 {published data only}
    1. Colombo P. Topical chloroxidating solution in wounds treatment: a controlled trial. Acta Toxicologica Therapeutica 1993;24:65‐71.
Colonna 2004 {published data only}
    1. Colonna MR, Amadeo G, Giofre C, Strano A, Stagno D'Alcontres F. Are nanocristalline silver dressings effective in reducing both secretions and bacterial colonization in necrotic infected wounds. 2nd World Union of Wound Healing Societies Meeting, 8‐13 July 2004, Paris. 2004:91.
Contretas‐Ruiz 2004 {published data only}
    1. Contretas‐Ruiz J, Fuentes‐Suarez S, Arroyo‐Escalante S, Sosa‐De‐Martinez C, Maravilla‐Franco E, Dominguez‐Cherit J. Larval debridement therapy to control infection in venous leg ulcers. A comparative study. 2nd World Union of Wound Healing Societies Meeting, 8‐13 July 2004, Paris. 2004:103.
Coutts 2005 {published data only}
    1. Coutts P, Sibbald RG. The effect of a silver‐containing Hydrofibre® dressing on superficial wound bed and bacterial balance of chronic wounds. International Wound Journal 2005;2(4):348‐56. - PMC - PubMed
Daltrey 1981 {published data only}
    1. Daltrey DC, Cunliffe WJ. A double‐blind study of the effects of benzoyl peroxide 20% and eusol and liquid paraffin on the microbial flora of leg ulcers. Acta Dermatologica Venereologica 1981;61(6):575‐7. - PubMed
Danielsen 1997 {published data only}
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Dharap 2008 {published data only}
    1. Dharap SB, Ghag GS, Kulkarni KP, Venkatesh V. Efficacy and safety of oxum in treatment of the venous ulcer. Journal of the Indian Medical Association 2008;106(5):326‐9. - PubMed
Ferra 2007 {published data only}
    1. Ferrara F, Meli F, Raimondi F, Amato C, Bonura F, Mulè G. The treatment of venous leg ulcers, a new therapeutic use of iloprost. Annals of Surgery 2007;246(5):860‐4. - PubMed
Fox 1966 {published data only}
    1. Fox DB. Trial of betamethasone 17‐valerate with neomycin tulle in the treatment of gravitational eczema and ulceration of the leg. British Journal of Clinical Practice 1966;20:183‐9.
Friedman 1984 {published data only}
    1. Friedman SJ, Su WP. Management of leg ulcers with hydrocolloid occlusive dressing. Archives of Dermatology 1984;120(10):1329‐36. - PubMed
Garcia 1984 {published data only}
    1. Garcia HGG, Cobian RR, Martin JR, Konaizeh S, Rahola JG. The effect on the reparation process of dextranomer (Debrisan) in perimalleolar ulcers due to chronic venous insufficiency. Clinical Trials Journal 1984;21(3):121‐34.
Gottrup 2003 {published data only}
    1. Gottrup F, Aabenhus A, Holt R and the Contreet Study Group. Evaluation of clinical results from 4 studies on two new antibacterial silver containing dressings. 13th Conference of the European Wound Management Association, 22‐24 May 2003, Pisa, Italy. 2003.
Haler 1964 {published data only}
    1. Haler D. Polynoxylin: a new antiseptic. British Journal of Clinical Practice 1964;May 18:267‐9. - PubMed
Hanft 2006 {published data only}
    1. Hanft J, Serena T, Snyder R. Evaluation of the clinical effectiveness of a collagen‐orc antimicrobial matrix in venous leg ulcers. 16th Conference of the European Wound Management Association, 18‐20 May 2006, Prague, Czech Republic. 2006.
    1. Hanft JR, Serena T, Snyder R. A study to evaluate the clinical effectiveness of a Collagen‐ORC Antimicrobial Matrix in venous leg ulcers. Wound Repair and Regeneration 2006;14(2):A64.
Heggers 2003 {published data only}
    1. Heggers JP. Assessing and controlling wound infection. Clinics in Plastic Surgery 2003;30(1):25‐35. - PubMed
Howell‐Jones 2005 {published data only}
    1. Howell Jones RS, Wilson MJ, Hill KE, Howard AJ, Price PE, Thomas DW. A review of the microbiology, antibiotic usage and resistance in chronic skin wounds. Journal of Antimicrobial Chemotherapy 2005;55(2):143‐9. - PubMed
Hutchinson 1993 {published data only}
    1. Hutchinson JJ. A prospective clinical trial of wound dressings to investigate the rate of infection under occlusion. 3rd European Conference on Advances in Wound Management, 19‐22 October 1993, Harrogate, UK. 1993.
    1. Hutchinson JJ. Influence of occlusive dressings on wound microbiology—interim results of a multi‐centre clinical trial of an occlusive hydrocolloid dressing. 1st European Conference on Advances in Wound Management, 4‐6 September 1991, Cardiff, UK. 1991.
Ivins 2006 {published data only}
    1. Ivins N, Harding KG, Price P, Jørgensen B, Lohmann M, Gottrup F, et al. Safety and efficacy in long‐term use of a sustained silver‐releasing foam dressing: a randomized, controlled trial on venous leg ulcers. SAWC 2006, April 30 ‐ May 3, 2006, San Antonio, Texas. 2006.
    1. Ivins N, Jørgensen B, Lohmann M. Safety and efficacy in long term use of a sustained silver‐releasing foam dressing: a randomised, controlled trial on venous leg ulcers. European Wound Management Association Conference, 15‐17 September 2005, Stuttgart, Germany. 2005.
Karap 2008 {published data only}
    1. Karap Z. Significant difference in pain levels of delayed‐healing wounds during applying an ionic silver hydrofibre dressing. Poster 281. EWMA Journal. Proceedings of the 18th Conference of the European Wound Management Association, 2008, Lisbon, Portugal. 2008.
Karas 1984 {published data only}
    1. Karas Z, Zabel J, Erenski P. Treatment of chronic crural ulcers with Pseudomonilia. Przeglad Dermatologiczny 1984;71(1):78‐9. - PubMed
Katelaris 1987 {published data only}
    1. Katelaris PM, Fletcher JP, Little JM, McEntyre RJ, Jeffcoate KW. Electrical stimulation in the treatment of chronic venous ulceration. Australian and New Zealand Journal of Surgery 1987;57(9):605‐7. - PubMed
Kordestani 2008 {published data only}
    1. Kordestani S, Shahrezaee M, Tahmasebi MN, Hajimahmodi H, Haji Ghasemali D, Abyaneh MS. A randomised control trial on the effectiveness of an advanced wound dressing used in Iran. Journal of wound care July 2008;17(7):323‐7. - PubMed
Kosicek 2004 {published data only}
    1. Kosicek M, Planinsek Rucigaj T. A comparative clinical trial: microbial colonisation of venous leg ulcers treated with hydrofibre dressings or with ointments. 2nd World Union of Wound Healing Societies Meeting, 8‐13 July 2004, Paris. 2004.
Lanzara 2008 {published data only}
    1. Lanzara S, Tacconi G, Gianesini S, Menegatti E, Federici F, Liboni A, et al. A pilot randomized trial to determine the effects of a new active dressing on wound healing of venous leg ulcers. EWMA Journal 2008;8(2 Suppl):76.
Lischka 1980 {published data only}
    1. Lischka G, Wolff HH. Benzoyl peroxide for the treatment of badly healing leg ulcers: a double‐blind study. Munchener Medizinische Wochenschrift 1980;122(49):1781‐4. - PubMed
Locati 1994 {published data only}
    1. Locati F, Rozzoni M, Reseghetti A, Sena P. Evaluation of the efficacy and tolerability of a new cutaneous antiseptic combination. Giornale Italiano di Dermatologia e Venereologia 1994;129(5):XXVII‐XXX.
Magana Lozano 1980 {published data only}
    1. Magana Lozano M. Ulcer leg complex: double blind study of bromelins alone or associated to tetracyclines. Compendium de Investigaciones Clinicas Latinoamericanas 1980;1(2):6‐12.
Maiques Nadal 1976 {published data only}
    1. Maiques Nadal V, Zambrano Zambrano A. Trial of an enzymatic preparation in the treatment of various ulcerative processes. Revista Clinica Espanola 1976;141(1):67‐72. - PubMed
Mancuso 1994 {published data only}
    1. Mancuso G, Staffa M, Errani A. Acetic acid in the treatment of superficial dermic burns and venous leg ulcers infected by Pseudomonas aeruginosa. Chronica Dermatologica 1994;4(3):473‐8.
Markoishvili 2002 {published data only}
    1. Markoishvili K, Tsitlanadze G, Katsarava R, Morris JG Jr, Sulakvelidze A. A novel sustained‐release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. International Journal of Dermatology 2002;41(7):453‐8. - PubMed
Marzin 1982 {published data only}
    1. Marzin L, Rouveix B. An evaluation of collagen gel in chronic leg ulcers. Schweizerische Rundschau fur Medizin Praxis 1982;71(36):1373‐8. - PubMed
McKnight 1965 {published data only}
    1. McKnight AG. A clinical trial of povidone‐iodine in the treatment of chronic leg ulcers. Practitioner 1965;195:230‐4. - PubMed
Mehtar S 1988 {published data only}
    1. Mehtar S, Fox D. A double‐blind comparative study with Mupirocin vs placebo base in the treatment of chronic leg ulcers. British Journal of Clinical Practice 1988;42(8):324‐8. - PubMed
Mogabgab 1984 {published data only}
    1. Mogabgab WJ. Treatment of skin and soft‐tissue infections with cefsulodin. Reviews of Infectious Diseases 1984;6(Suppl 3):S721‐7. - PubMed
Morely de Benzaquen 1990 {published data only}
    1. Morely de Benzaquen S, Cirelli N, Halmai O, Sanjuan E, Piquero Martín J, Arbona J, et al. Argentic sulfadiazine in lower limbs ulcers: double‐blinded study. Archivos Venezolanos de Farmacología y Terapéutica 1990;9(2):116‐9.
Motta 2004 {published data only}
    1. Motta GJ, Milne CT, Corbett LQ. Impact of antimicrobial gauze on bacterial colonies in wounds that require packing. Ostomy/Wound Management 2004;50(8):48‐62. - PubMed
Nakagawa 1997 {published data only}
    1. Nakagawa K, Kobayashi H, Kono T, Hayashi A, Tsuruta D, Ishii M. Evaluation of the effects of cadexomer iodine ointment (Decrat(TM) ointment) in the treatment of skin Ulcer. Skin Research 1997;39(3):364‐78.
Ouvry 1989 {published data only}
    1. Ouvry PA. A trial of silver sulfadiazine in the local treatment of venous ulcer [Essai de la sulfadiazine argentique dans le traitement local de l'ulcѐre veineux]. Phlebologie 1989;42(4):673‐9. - PubMed
Pardes 1993 {published data only}
    1. Pardes JB, Carson PA, Eaglstein WH, Falanga V. Mupirocin treatment of exudative venous ulcers. Journal of the American Academy of Dermatology 1993;29(3):497‐8. - PubMed
Paul 1990 {published data only}
    1. Paul E. Wound healing with Iruxol. Results of a multicenter study. Fortschritte der Medizin 1990;108(35):679‐81. - PubMed
Pegum 1968 {published data only}
    1. Pegum JM, Fegan WG. Polynoxylin in the treatment of varicose ulcers. Irish Journal of Medical Science 1968;7(7):299‐302. - PubMed
Pereira 2004 {published data only}
    1. Pereira M, Baudrier T, Cotta F, Mota A, Fonseca C. Influence of 0.5% sodium hypochlorite solution on bacterial countings in leg ulcers. 2nd World Union of Wound Healing Societies Meeting, 8‐13 July 2004, Paris. 2004.
Pierard‐Franchimont 1997 {published data only}
    1. Pierard‐Franchimont C, Paquet P, Arrese JE, Pierard GE. Healing rate and bacterial necrotizing vasculitis in venous leg ulcers. Dermatology 1997;194(4):383‐7. - PubMed
Planinsek 2006 {published data only}
    1. Planinsek TR. Treatment of venous leg ulcers with different alginate dressings: their effects on healing rate and pain. 16th Conference of the European Wound Management Association, 18‐20 May 2006, Prague, Czech Republic. 2006:154.
Pollice 1989 {published data only}
    1. Pollice F, D'Agostino D, Mirizzi F. Treatment of varicose ulcer with iodine cadexomere in powder form. Phlebologie 1989:1184‐7.
Privat 1979 {published data only}
    1. Privat Y. Clinical trial of Pulvo 47 Neomycin in the treatment of leg ulcer. Semaine des Hopitaux 1979;55(13‐14):711‐3. - PubMed
Robson 2009 {published data only}
    1. Robson V, Dodd S, Thomas S. Standardized antibacterial honey (MedihoneyTM) with standard therapy in wound care: randomized clinical trial. Journal of Advanced Nursing 2009;65(3):565‐75 doi: 10.1111/j.1365‐2648.2008.04923.x. - PubMed
Rogers 2000 {published data only}
    1. Rogers RR, Alvarez OM, Patel M. Effect of a silver ion‐containing wound dressing on the bacterial burden of chronic venous ulcers. 13th Annual Symposium on Advanced Wound Care and 10th Annual Medical Research Forum on Wound Repair, 1‐4 April 2000, Dallas, Texas. 2000:D35‐D36.
Romanelli 2010 {published data only}
    1. Romanelli M, Dini V, Barbanera S, Bertone MS. Evaluation of the efficacy and tolerability of a solution containing propyl betaine and polihexanide for wound irrigation. Skin Pharmacology and Physiology 2010;23(Suppl 1):41‐4. - PubMed
    1. Romanelli M, Dini V, Bertone MS. Evaluation of the efficacy and tolerability of a cleansing solution with propil betaine and polyhexanide in reducing the bacterial load of venous wounds in lower limbs (poster presentation). 17th Conference of the European Wound Management Association, 2‐4 May 2007, Glasgow, Scotland. 2007.
Rubisz Brzeziska 87 {published data only}
    1. Rubisz‐Brzezińska J, Szarmach H, Filipiuk J, Brzezińska‐Wcisło L, Wilkowska A. Benzoyl peroxide in the treatment of crural ulcerations [Nadtlenek benzoilu w leczeniu owrzodzeń podudzi]. Przeglad Dermatologiczny 1987;74(4‐5):363‐9. - PubMed
Rucigaj 2007a {published data only}
    1. Rucigaj TP. Comparative effects of honey based and silver/charcoal based dressings on the healing of venous leg ulcers: a randomized clinical study. 17th Conference of the European Wound Management Association, 2‐4 May 2007, Glasgow, Scotland. 2007.
Rucigaj 2007b {published data only}
    1. Rucigaj TP. Effectiveness of non alcohol film forming skin protector on skins isles inside the ulcers and the healing rate of venous leg ulcers. EWMA Journal 2007;7(1):23‐5.
Salim 1991 {published data only}
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Sanchez‐Vasquez 2008 {published data only}
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Serra 2005 {published data only}
    1. Serra N, Torres OG, Romo MI, Llovera JM, Vigil‐Escalera LJ, Soto MA, et al. Hydro‐colloidal dressings which liberate hydro‐active silver [Apósitos hidrocoloides liberadores de plata hidroactiva: estudio clínico comparativo en el tratamiento de úlceras crónicas]. Revista de Enfermeria 2005;28(2):13‐8. - PubMed
Sibbald 2007 {published data only}
    1. Sibbald RG, Coutts P, Fierheller M, Woo K. A pilot (real‐life) randomised clinical evaluation of a pain‐relieving foam dressing: (Ibuprofen‐foam versus local best practice). International Wound Journal 2007;4(Suppl 1):16‐23. - PMC - PubMed
Sibbald 2011 {published data only}
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Steenvoorde 2007 {published data only}
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Subrahmanyam 1993 {published data only}
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Thebbe 1996 {published data only}
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Thorne 1965 {published data only}
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Wuite 1974 {published data only}
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Additional references

AAWC 2010
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