Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their life. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. There are two main strategies used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics.
The objective of the review is to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers.
The following databases were searched up to October 2007: the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; and CINAHL. In addition, the reference lists of included studies and relevant review articles were examined.
Randomised controlled trials recruiting people with venous leg ulceration that evaluated at least one systemic antibiotic, topical antibiotic or topical antiseptic and 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 three authors working independently.
Data collection and analysis
Information on the characteristics of participants, interventions and outcomes were recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including methods of randomisation and allocation concealment, use of blinded outcome assessment, intention-to-treat analysis, reporting of patient follow-up and study group comparability at baseline. Data extraction and validity assessment were conducted by one author and checked by a second.
Twenty two trials were identified of different antibiotics and antiseptics, including systemic antibiotics (5 trials). The remainder were topical preparations: cadexomer iodine (10 trials); povidone iodine (2 trials); peroxide-based preparations (3 trials); ethacridine lactate (1 trial); and mupirocin (1 trial). For the systemic antibiotics, the only comparison where a statistically significant between-group difference was detected was that in favour of the antihelminthic levamisole when compared with placebo. This trial, in common with the other evaluations of systemic antibiotics, was small and so the observed effect could have occurred by chance. In terms of topical preparations, there is some evidence to suggest that cadexomer iodine generates higher healing rates than standard care. One study showed a statistically significant result in favour of cadexomer iodine when compared with standard care (not involving compression) in terms of frequency of complete healing at six weeks (RR 2.29, 95% CI 1.10 to 4.74). The intervention regimen used was intensive, involving daily dressing changes, and so these findings may not be generalisable to most everyday clinical settings. When cadexomer iodine was compared with standard care with all patients receiving compression, the pooled estimate from two trials for frequency of complete healing at 4 to 6 weeks indicated significantly higher healing rates for cadexomer iodine (RR 6.72, 95% CI 1.56 to 28.95). Surrogate healing outcomes such as change in ulcer surface area and daily or weekly healing rate showed favourable results for cadexomer iodine, peroxide-based preparations and ethacridine lactate in some studies. These surrogate outcomes may not be valid proxies for complete healing of the wound. Most of the trials were small and many had methodological problems such as poor baseline comparability between groups, failure to use (or report) true randomisation, adequate allocation concealment, blinded outcome assessment and analysis by intention-to-treat.
At present, there is no existing evidence to support the routine use of systemic antibiotics to promote healing in 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, there is some evidence to support the use of cadexomer iodine. Further good quality research is required before definitive conclusions can be made about the effectiveness of systemic antibiotics and topical preparations such as povidone iodine, peroxide-based preparations, ethacridine lactate and mupirocin in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should only be used in cases of defined infection and not for bacterial colonisation.