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Resistance to antimony and treatment failure in human Leishmania (Viannia) infection.
J Infect Dis. 2006 May 15; 193(10):1375-83.JI

Abstract

BACKGROUND

Failure of antimonial therapy has been increasingly reported in anthroponotic visceral leishmaniasis and in cutaneous disease. The role of drug resistance in treatment failure has been difficult to ascertain because therapeutic response is multifactorial, and the efficacy of antimonial drugs depends on an effective immune response. In this study, we sought to determine whether standard treatment selects for resistant organisms and whether drug resistance contributes to treatment failure.

METHODS

We evaluated the susceptibility to antimony of 19 strains isolated before treatment with meglumine antimoniate and 21 strains isolated at treatment failure from 20 patients. The 50% effective dose (ED50) of antimony in the form of additive-free meglumine antimoniate was determined for intracellular amastigotes in human promonocytic U-937 cells.

RESULTS

Before treatment, 16% of strains (3/19) showed primary resistance (ED50 of >128 microg Sb/mL), whereas 84% (16/19) were susceptible (ED50 of <20 microg Sb/mL). However, 88% of susceptible strains (14/16) had ED90 values of >128 microg Sb/mL. At treatment failure, 40% of strains (8/20) were resistant. Secondary resistance was documented in 4 patients.

CONCLUSIONS

Primary and secondary resistance to antimony can contribute to treatment failure in American cutaneous leishmaniasis. Selection for resistance to antimony occurs during standard treatment with antimonial drugs, and primary resistance to antimony supports the plausibility of anthroponotic transmission.

Authors+Show Affiliations

Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, Colombia, and Centre Hospitalier Universitaire Laval, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16619185

Citation

Rojas, Ricardo, et al. "Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection." The Journal of Infectious Diseases, vol. 193, no. 10, 2006, pp. 1375-83.
Rojas R, Valderrama L, Valderrama M, et al. Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis. 2006;193(10):1375-83.
Rojas, R., Valderrama, L., Valderrama, M., Varona, M. X., Ouellette, M., & Saravia, N. G. (2006). Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. The Journal of Infectious Diseases, 193(10), 1375-83.
Rojas R, et al. Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection. J Infect Dis. 2006 May 15;193(10):1375-83. PubMed PMID: 16619185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. AU - Rojas,Ricardo, AU - Valderrama,Liliana, AU - Valderrama,Mabel, AU - Varona,Maria X, AU - Ouellette,Marc, AU - Saravia,Nancy G, Y1 - 2006/04/07/ PY - 2005/09/29/received PY - 2005/12/09/accepted PY - 2006/4/19/pubmed PY - 2006/6/2/medline PY - 2006/4/19/entrez SP - 1375 EP - 83 JF - The Journal of infectious diseases JO - J Infect Dis VL - 193 IS - 10 N2 - BACKGROUND: Failure of antimonial therapy has been increasingly reported in anthroponotic visceral leishmaniasis and in cutaneous disease. The role of drug resistance in treatment failure has been difficult to ascertain because therapeutic response is multifactorial, and the efficacy of antimonial drugs depends on an effective immune response. In this study, we sought to determine whether standard treatment selects for resistant organisms and whether drug resistance contributes to treatment failure. METHODS: We evaluated the susceptibility to antimony of 19 strains isolated before treatment with meglumine antimoniate and 21 strains isolated at treatment failure from 20 patients. The 50% effective dose (ED50) of antimony in the form of additive-free meglumine antimoniate was determined for intracellular amastigotes in human promonocytic U-937 cells. RESULTS: Before treatment, 16% of strains (3/19) showed primary resistance (ED50 of >128 microg Sb/mL), whereas 84% (16/19) were susceptible (ED50 of <20 microg Sb/mL). However, 88% of susceptible strains (14/16) had ED90 values of >128 microg Sb/mL. At treatment failure, 40% of strains (8/20) were resistant. Secondary resistance was documented in 4 patients. CONCLUSIONS: Primary and secondary resistance to antimony can contribute to treatment failure in American cutaneous leishmaniasis. Selection for resistance to antimony occurs during standard treatment with antimonial drugs, and primary resistance to antimony supports the plausibility of anthroponotic transmission. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/16619185/Resistance_to_antimony_and_treatment_failure_in_human_Leishmania__Viannia__infection_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/503371 DB - PRIME DP - Unbound Medicine ER -