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In spite of decades of investigation of alternatives to antimony, pentavalent antimony (Sb) remains the treatment of first choice for South American and much of Central American cutaneous leishmaniasis. The standard regimen is 20 mg of Sb/kg/day for 20 days administered intramuscularly or intravenously. In clinical trials with groups of 16–56 patients, the cure rates with this regimen were 84–93% for Colombian adults primarily infected with Leishmania panamensis,1,2 79–96% for Guatemalan adults infected with L. braziliensis,3,4, only 51% for L. braziliensis and 26% for L. guyanensis in Brazil,5 and only 25% for 5–15-year-old children in Colombia.6
A larger experience with any one of these patient groups would be of value. It is also valuable to report the results of re-treatment of those who failed initial treatment with antimony.
In 1999–2000, 226 consecutive cases of cutaneous leishmaniasis in Colombian soldiers were treated with pentavalent antimony in the form of Glucantime (treatment course 1). The diagnosis was made by visualization of the parasite in approximately 90% of the patients in Giemsa-stained lesion slit smears, and in 10% of the patients in hematoxylin and eosin–stained lesion biopsy specimens. The patients were members of four units who acquired the disease consequent to duty in Urabá and Magdalena Medio Valley Provinces. These regions are endemic for L. panamensis and have shown a few cases of L. braziliensis. For 126 of the patients, the initial course of therapy was administered by medical staff in field facilities; 100 patients were transported to Bogota Military Dispensary and the initial course was administered at this location.
Glucantime is packaged in 5-mL ampules containing a total of 425 mg of Sb. Because Glucantime was administered intramuscularly by study personnel, patient compliance with medication was not an issue. The recommended treatment regimen is 20 mg of Sb/kg/day for 20 days. In field facilities, drug availability can be a problem, and when available, the total contents are administered so as not to waste the product. A 60-kg person should receive 1,200 mg of Sb per day (2.8 ampules), but the patient could instead receive 2 ampules (850 mg = 14 mg/kg) or 3 ampules (1,275 mg = 21 mg/kg). A 70-kg patient might receive 3 ampules (18 mg/kg) per day instead of the recommended 3.3 ampules.
Cure was defined as complete re-epithelialization of the lesion. Treatment failures (patients who had a lesion that was not completely re-epithelialized) were sent to the Bogota Military Dispensary, with a transfer note listing the treatment that the patient had been given, where re-treatment (treatment courses 2, 3, and 4) was performed.
Table 1
shows that of the 226 initial courses of Sb, 42 (19%) were clinical failures. The mean total dose of Sb actually received by patients that were cured was 405 mg/kg (20.2 mg/kg/day if administered over a 20-day period). The mean total dose for failures was 354 mg (17.7 mg/kg/day). Although the mean dose for patients that failed treatment was only 11% less than the intended dose of 20 mg/kg/day (which was administered to cured patients), the large number of patients in each group made the difference statistically significant (P = 0.002, by t-test).
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In this large experience of more than 200 consecutive Colombian adults, the initial Sb failure rate was approximately 20%. This percentage is compatible with, although at the low end of, the results found in formal clinical trials, and therefore is likely to represent the initial failure rate attendant to routine clinical treatment. There are no standard recommendations for re-treatment of initial antimonial treatment failures. The experience of 39 patients reported here suggests that if initial Sb failures are re-treated with antimony, approximately 40% will fail this treatment. The clinical failure rate after the second course of Sb was significantly higher than the failure rate after the first course of Sb (P = 0.003, by Fischer’s exact test). Although clinical resistance can be due to relative deficiencies in host immunity or in distribution of drug to the lesion, the statistical difference between the total dose of antimony administered to initial Sb failures versus the dose administered to initial Sb cures suggests a parasitologic basis for clinical resistance. Relatively low amounts of Sb could select for resistant parasites in the initial parasite inoculum or lead to generation of resistant parasites.
Pentamidine was administered to 20 cases of Sb failure. Six (30%) of the 20 pentamidine treatments failed. Although the pentamidine experience is smaller than the Sb experience, this figure of 30% may be a good guide to the likely percentage of failures if pentamidine is administered after Sb failure.
Received February 4, 2004. Accepted for publication May 5, 2004.
Financial support: This study was supported by the AB Foundation.
Authors’ addresses: J. Soto, J. Toledo, and J. Vega, Consorcio de Investigaciones Bioclínicas, Calle 60 A 5-54, Suite 201, Bogota, Colombia. J. Berman, 6205 Poindexter Lane, North Bethesda, MD 20852, Telephone/Fax: 301-230-7138/0427, E-mail: JBe9320457{at}aol.com.
Reprint requests: J. Soto, Consorcio de Investigaciones Bioclínicas, Calle 60 A 5-54, Suite 201, Bogota, Colombia, Telephone: 57-1-348-2171, Fax: 57-1-347-6093, E-mail: Jaime.Soto{at}medplus.org.co.
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