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 antisepticsCadexomer
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.