Microbiome Manipulation: Antibiotic Effects on Cutaneous Leishmaniasis Presentation and Healing

Abstract

Background. Cutaneous ulcers of leishmanial infection are chronic wounds with an anaerobe-predominant microbiome, further impacted by the immunomodulatory effects of Leishmania and superinfecting bacteria. Leveraging a policy to give presumptive pyoderma treatment prior to evaluation for leishmaniasis, we assessed the efect of antibiotic therapy upon clinical presentation or treatment outcome among those with cutaneous leishmaniasis. Methods. Data were obtained from a 418-patient open label study of 10 or 20 days of sodium stibogluconate (SSG) therapy conducted at Walter Reed Army Medical Center. Subjects with parasitologically confirmed leishmaniasis were included if this was their first treatment course. We assessed clinical presentation by number and aggregate size of lesions, appearance, and lymphatic involvement. Treatment outcome was evaluated by patient report of healing at 2, 6, and 12 months post SSG. We divided subjects into those with and without prior antibiotic treatment for analysis of clinical presentation and further subdivided the antibiotic group (outcome analysis) into those receiving antibiotics during or prior to SSG. We performed two-group comparisons of clinical presentation with Mann-Whitney and Fisher's Exact tests and three-group comparisons of SSG treatment outcomes with Kruskal-Wallis and χ2 tests. Results. The cohort was 360 mainly young white males, with median four lesions in both groups. Most commonly used antibiotics were doxycycline (n = 29 courses), cephalexin (33), and amoxicillin-clavulanate (127). Of those interviewed, prior antibiotic-treated patients had greater heal rates (49/58 vs. 50/74) at 2 months follow-up (P = 0.03). Further analysis found no significant Differences between the groups in clinical severity at presentation or in consolidated 6-12 month treatment outcomes (167/195 antibiotic, 139/165 no antibiotic, P = 0.77). Conclusion. Systemic antibiotics given prior to, but not during SSG therapy, may modestly hasten healing of leishmanial skin lesions. This observation was not associated with any specifc antibiotic (e.g., better anaerobic spectrum). No antibiotic efect on number or size of lesions at presentation for treatment or upon long-term (6-12 months) lesion healing outcome was seen.