Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials

Abstract

Background: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting.

Methodology/principal findings: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled using a random-effects model. Fourteen trials including 1,221 patients were included. In placebo-controlled trials, topical PR appeared to have therapeutic activity against the old world and new world CL, with increased local reactions, when used with methylbenzethonium chloride (MBCL) compared to when used alone (risk ratio [RR] for clinical cure, 2.58 versus 1.01: RR for local reactions, 1.60 versus 1.07). In SbV-controlled trials, the efficacy of topical PR was not significantly different from that of intralesional SbV in the old world CL (RR, 0.70; 95% confidence interval, 0.26-1.89), whereas topical PR was inferior to parenteral SbV in treating the new world CL (0.67; 0.54-0.82). No significant difference in efficacy was found between parenteral PR and parenteral SbV in the new world CL (0.88; 0.56-1.38). Systemic side effects were fewer with topical or parenteral PR than parenteral SbV.

Conclusions/significance: Topical PR with MBCL could be a therapeutic alternative to SbV in selected cases of the old world CL. Development of new formulations with better efficacy and tolerability remains to be an area of future research.

Figure 1. Flow Diagram of the Study Selection Process.

Abbreviations: CENTRAL, Cochrane Central Register of Controlled Trials; RCT, randomized controlled trials. * When a trial involved a second-line treatment as well as placebo or pentavalent antimony compounds, the data on placebo or pentavalent antimony compounds were included.

Figure 2. Meta-analysis of the Efficacy of Paromomycin Compared with Placebo*.

Abbreviations: CI, confidence interval; CL, cutaneous leishmaniasis; MBCL, methylbenzethonium chloride; PR, paromomycin; RR, risk ratio. * Pooled RRs and 95% CIs of clinical cure were calculated using an inverse-variance weighted random-effects model and displayed in diamonds in the figure. The I² statistic describes the percentage of total variation across the studies that is attributable to heterogeneity rather than chance.

Figure 3. Meta-analysis of the Efficacy of Paromomycin Compared with Pentavalent Antimony Compounds*†.

Abbreviations: CI, confidence interval; CL, cutaneous leishmaniasis; MA, meglumine antimoniate; MBCL, methylbenzethonium chloride; PR, paromomycin; RR, risk ratio; SB, sodium stibogluconate. * Pooled RRs and 95% CIs of clinical cure were calculated using an inverse-variance weighted random-effects model and displayed in diamonds in the figure. The I² statistic describes the percentage of total variation across the studies that is attributable to heterogeneity rather than chance. † Parenteral antimony compounds include parenteral MA and parenteral SB.

Figure 4. Influence of Study Quality Criteria on Pooled Estimates*.

* Pooled RRs and 95% CIs of clinical cure were calculated by study quality components, using an inverse-variance weighted random-effects model. † Adjusted for paromomycin regimen among trials with placebo control group and for antimony regimen among trials with pentavalent antimony compound control group.