Topical Paromomycin with or without Gentamicin for Cutaneous Leishmaniasis

Salah, Afif Ben; Messaoud, Nathalie Ben; Guedri, Evelyn; Zaâtour, Amor; Alaya, Nissaf Ben; Bettaieb, Jihéne; Gharbi, Alya; Hamida, Nabil Belhadj; Boukthir, Aïcha; Chlif, Sadok; Kidar, A.; Ahmadi, Zaher El; Louzir, Hechmi; Mokni, M.; Morizot, Gloria; Buffet, Pierre; Smith, Philip L.; Kopydlowski, Karen M.; Kreishman-Deitrick, Mara; Smith, Kirsten S.; Nielsen, Carl J.; Ullman, Diane; Norwood, Jeanne A.; Thorne, George D.; McCarthy, William F.; Adams, Ryan C.; Rice, Robert M.; Tang, Douglas B.; Berman, Jonathan; Ransom, Janet H.; Magill, Alan J.; Grögl, Max

doi:10.1056/nejmoa1202657

Cited by 197 publications

(137 citation statements)

References 23 publications

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“…Topical antileishmanial treatments containing paramomycin daily for 20 days have proven effective for the treatment of CL caused by L. major. 32,33 Topical treatments that can be managed at the primary care level or even as home-based care could overcome many of the technical impediments for local treatment of CL in children. However, in addition to being an experimental formulation and hence, unavailable, the efficacy and effectiveness of paramomycin for New World CL have not been established.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Blanco¹,

Cossio²,

Martinez³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Treatment alternatives have seldom been evaluated in children with cutaneous leishmaniasis (CL). We examine the clinical/epidemiological profile of children with CL considering international guidelines for local treatment. Descriptive analyses were conducted using International Center for Medical Research and Training (CIDEIM) case reports of parasitologically diagnosed patients 14 years of age from 2004 to 2010. Eligibility for local treatment based on World Health Organization/Pan American Health Organization (WHO/PAHO) criteria was determined. Among 380 children, 90% presented lesions of 3 months duration, 54% presented single lesions 30 mm in diameter, and 45% were 5 years old. Lesions on the head and neck were more frequent among children 0-5 years, and lesions below the head/neck were more frequent among 11-to 14-year-old children (P = 0.004). Using PAHO and WHO criteria, 26% and 53% of children, respectively, were eligible for local treatment. Recommended local treatments for New World CL have potential but limited applicability in children. Individual risk-benefit assessment and effectiveness data in children may increase eligibility.

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Section: Discussionmentioning

confidence: 99%

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Blanco¹,

Cossio²,

Martinez³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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“…However, due to the emergence of pronounced parasite drug resistance in some regions, relatively high costs, and/or the severe toxic effects, there has been an extensive search over the last few years for new therapeutic agents. Paromomycin, a clinically approved AG for the treatment of various bacterial and parasitic infections, is the major component of a topical ointment (Leishcutan) used to treat cutaneous leishmaniasis caused by several species of parasites, and attempts have been made to further improve existing formulations (13)(14)(15). Paromomycin is also effective against visceral leishmaniasis, the fatal form of this disease (16), and it is registered in India and Nepal.…”

mentioning

confidence: 99%

Identification of the molecular attributes required for aminoglycoside activity against Leishmania

Shalev

Kondo

Kopelyanskiy³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Leishmaniasis, a parasitic disease caused by protozoa of the genus Leishmania , affects millions of people worldwide. Aminoglycosides are mostly known as highly potent, broad-spectrum antibiotics that exert their antibacterial activity by selectively targeting the decoding A site of the bacterial ribosome, leading to aberrant protein synthesis. Recently, some aminoglycosides have been clinically approved and are currently used worldwide for the treatment of leishmaniasis; however the molecular details by which aminoglycosides induce their deleterious effect on Leishmaina is still rather obscure. Based on high conservation of the decoding site among all kingdoms, it is assumed that the putative binding site of these agents in Leishmania is the ribosomal A site. However, although recent X-ray crystal structures of the bacterial ribosome in complex with aminoglycosides shed light on the mechanism of aminoglycosides action as antibiotics, no such data are presently available regarding their binding site in Leishmania . We present crystal structures of two different aminoglycoside molecules bound to a model of the Leishmania ribosomal A site: Geneticin (G418), a potent aminoglycoside for the treatment of leishmaniasis at a 2.65-Å resolution, and Apramycin, shown to be a strong binder to the leishmanial ribosome lacking an antileishmanial activity at 1.4-Å resolution. The structural data, coupled with in vitro inhibition measurements on two strains of Leishmania , provide insight as to the source of the difference in inhibitory activity of different Aminoglycosides. The combined structural and physiological data sets the ground for rational design of new, and more specific, aminoglycoside derivatives as potential therapeutic agents against leishmaniasis.

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“…3 Paramomycin has recently been shown to be an effective topical treatment of CL in adults. 12 Although we could not find any published trials recommending paramomycin for L. tropica CL in children, literature reports 80% response to paramomycin for Leishmania major CL in studies which included children. 12 Neal and others found that in mouse models, aminosidine (chemically identical to paromomycin) showed high activity against amastigotes of all strains of L. major and L. tropica.…”

Section: Discussionmentioning

confidence: 72%

Successful Treatment of Cutaneous Leishmaniasis with Topical Paramomycin in a Child After Treatment Failure with Systemic Fluconazole

Chacko

Joseph

Feltis³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. It is challenging to find safe, nonscarring and noninvasive treatment of facial cutaneous leishmaniasis (CL) in children. Herein, we report a child with CL from a region endemic for Leishmania tropica, whose lesion persisted after treatment with oral fluconazole but responded to topical paromomycin. Paromomycin should be considered early for treatment of Old World CL and is a well-tolerated and effective mode of therapy for facial lesions.

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Topical Paromomycin with or without Gentamicin for Cutaneous Leishmaniasis

Abstract: This trial provides evidence of the efficacy of paromomycin-gentamicin and paromomycin alone for ulcerative L. major disease. (Funded by the Department of the Army; ClinicalTrials.gov number, NCT00606580.).

Cited by 197 publications

References 23 publications

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Identification of the molecular attributes required for aminoglycoside activity against Leishmania

Successful Treatment of Cutaneous Leishmaniasis with Topical Paramomycin in a Child After Treatment Failure with Systemic Fluconazole

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