Efficacy and safety of Pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review.

RATIONALE FOR REVIEW We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human visceral and tegumentary leishmaniasis. KEY FINDINGS Six hundred and sixteen papers were evaluated, and 88 studies reporting data on 3108 cases of leishmaniasis (2082 patients with tegumentary leishmaniasis and 1026 with visceral leishmaniasis) were finally included. The majority of available studies were on New World cutaneous leishmaniasis and visceral leishmaniasis caused by Leishmania donovani. At the same time, few data are available for Old World cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis caused by L. infantum. Pooled cure rate for tegumentary leishmaniasis was 78.8% (CI95% 76.9-80.6%) and 92.7% (CI95% 88.3-97.1%) according to controlled randomized trial and observational studies and case report and case series respectively. Pooled cure rate for visceral leishmaniasis was 84.8% (CI95% 82.6-87.1%) and 90.7% (CI95% 84.1-97.3%) according to controlled randomized trial and observational studies and case report and case series respectively. Comparable cure rate was observed in recurrent and refractory cases of visceral leishmaniasis. Concerning the safety profile, among almost 2000 treated subjects with some available information, the most relevant side effects were six cases of arrhythmia (including four cases of fatal ventricular fibrillation), 20 cases of irreversible diabetes, 26 cases of muscular aseptic abscess following intramuscular administration. CONCLUSIONS/RECOMMENDATIONS Pentamidine isethionate is associated with a similar cure rate of the first line antileishmanial drugs. Severe and irreversible adverse effect appear to be rare. The drug may still have a role in the treatment of any form of human leishmaniasis when the first-line option has failed or in patients who cannot tolerate other drugs also in the context of travellers or migrants. In difficult cases, the drug can also be considered as a component of a combination treatment regimen.