Efficacy of a Paromomycin plus Chloroquine Combination Therapy in Experimental Cutaneous Leishmaniasis.

Wijnant, GJ; Van Bocxlaer, K; Yardley, V; Murdan, S; Croft, S; (2017) Efficacy of a Paromomycin plus Chloroquine Combination Therapy in Experimental Cutaneous Leishmaniasis. Antimicrobial agents and chemotherapy. ISSN 0066-4804 DOI: https://doi.org/10.1128/AAC.00358-17

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The 4-aminoquinoline chloroquine (CQ) is clinically used in combination with doxycycline to cure chronic Q-fever, as it enhances the activity of the antibiotic against the causative Coxiella burnetii bacteria residing within macrophage phagolysosomes. As there is a similar cellular host-pathogen biology for Leishmania parasites, this study aimed to determine whether such an approach could be also the basis for a new, improved treatment for cutaneous leishmaniasis (CL). We have evaluated the in vitro and in vivo activity of combinations of CQ with standard drugs paromomycin (PM), miltefosine and amphotericin B against Leishmania major and Leishmania mexicana In 72-hour intracellular anti-leishmanial assays, outcomes were variable for different drugs. Significantly, the addition of 10 μM CQ to PM reduced EC50 values by over 5-fold against L. major and against the normally insensitive L. mexicana In murine models of L. major and L. mexicana CL, daily co-administration of 50 mg/kg PM and 25 mg/kg CQ for 10 days resulted in significant reduction in lesion size but not in parasite load compared to mice given the same doses of PM alone. Overall, our data indicates that a PM plus CQ combination therapy is unlikely to be a potential candidate for further preclinical development.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
Neglected Tropical Diseases Network
PubMed ID: 28607026
Web of Science ID: 406259400037
URI: http://researchonline.lshtm.ac.uk/id/eprint/3962447


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