The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding) and by indirectness (differences in studied interventions).
A Cochrane review [Abstract] 1 included 45 studies (53 comparisons) with a total of 4 486 subjects. Studies included systemic antibiotics (5 studies) and different topical preparations: cadexomer iodine (11 studies); povidone iodine (6 studies); peroxide-based preparations (4 studies); honey-based preparations (2 studies); silver-based preparations (12 studies); other topical antibiotics (3 studies); and other topical antiseptics (2 studies).
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 (for complete healing RR 1.31, 95% CI 1.06 to 1.62; 1 study, n=59). 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.
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: 4 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 4 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.
The authors state that 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.
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