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Background: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure. Methods: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome. Results: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22–24.16). Conclusions: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes. Author summary: American cutaneous leishmaniasis is a skin disease caused by parasites that are transmitted through the bite of sandflies. It is considered as a neglected tropical disease. In non-endemic countries like Germany, this disease is rarely seen and is imported by migrants or travellers who have been infected in tropical or subtropical areas of the Americas. Experts suggest that the treatment should be given depending on the specific parasite species found in the affected skin, but there is still a scarcity of information on the optimal management strategy. We analysed 75 American cutaneous leishmaniasis cases seen between 2000 and 2023 at our German medical centre. Most patients were men, around 35 years of age, who most commonly travelled to the Americas for tourism. We found that when using systemic medications (i.e., given by mouth, injection or drip into a vein), that were recommended for the specific parasite type, patients were more likely to be cured, with a 73% success rate, compared to a mere 35% success rate when those recommendations were not followed. This highlights the importance of identifying the species that is causing the disease, and suggests that tailoring treatment to the specific parasite species increases the chances of cure. [ABSTRACT FROM AUTHOR]