• 1

    Velez I, Agudelo S, Hendrickx E, Puerta J, Grogl M, Modabber F, Berman J, 1997. Inefficacy of allopurinol for Colombian cutaneous leishmaniasis: a randomized, controlled trial. Ann Intern Med 126 :232–236.

    • Search Google Scholar
    • Export Citation
  • 2

    Soto J, Fuya P, Herrera R, Berman J, 1998. Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study. Clin Infect Dis 26 :56–58.

    • Search Google Scholar
    • Export Citation
  • 3

    Navin TR, Arana BA, Arana FE, de Merida AM, Castillo AL, Pozuelos JL, 1990. Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala. Am J Trop Med Hyg 42 :43–50.

    • Search Google Scholar
    • Export Citation
  • 4

    Navin TR, Arana BA, Arana FE, Berman JD, Chajon JF, 1992. Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala. J Infect Dis 165 :528–534.

    • Search Google Scholar
    • Export Citation
  • 5

    Romero GA, Guerra MV, Paes MG, Macedo VO, 2001. Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate. Am J Trop Med Hyg 65 :456–465.

    • Search Google Scholar
    • Export Citation
  • 6

    Palacios R, Osorio LE, Grajalew LF, Ochoa MT, 2001. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg 64 :187–193.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

SHORT REPORT: EFFICACY OF PENTAVALENT ANTIMONY FOR TREATMENT OF COLOMBIAN CUTANEOUS LEISHMANIASIS

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  • 1 Consorcio de Investigaciones Bioclínicas, Bogota, Colombia; North Bethesda, Maryland

Two hundred twenty-six consecutive adult patients with cutaneous leishmaniasis in Colombia were treated with Glucantime and 81% were cured. The 19% who failed treatment had received a statistically significant lower total amount of antimony (354 mg/kg) than those who were cured (405 mg/kg) (P = 0.002). Thirty-nine of the failures were re-treated with Glucantime and 59% were cured. This large experience on initial and re-treatment cure rates probably represents the values found in clinical practice. In this series, parasite resistance may have been induced by the relatively low initial dose of antimony administered to some patients.

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).

Thirty-nine of the initial patients who failed treatment with Sb were treated with a second course of Sb, and 16 of them failed (41%). Four of the 16 secondary failures were treated with a third course of Sb and 2 of them failed (50%). Pentamidine was especially used for repeated failures of treatment with Sb.

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.

Table 1

Efficacy of initial and subsequent therapy for 226 Colombian adults with cutaneous leishmaniasis*

RXTotal no.of patientsNo. of patients per groupTreatment regimenNo. of patients curedNo. of patients failed% cured
* RX = treatment; Sb = antimony in the form of Glucantime; Pent = pentamidine.
† Intended treatment regimen of 400 mg/kg total dose.
‡ One of the four patients treated with Pentamidine and the one patient treated with Sb were the two patients who failed their third treatment with Sb.
1226226Sb: 20 mg/kg/day × 20 day†1844281
24239Sb: 20 mg/kg/day × 20 days221659
3Pent: 4 mg/kg/day × 4 days30100
31610Pent: 4 mg/kg/day × 4 days6460
2Pent: 4 mg/kg/day × 7 days20100
4Sb: 20 mg/kg/day × 20 days2250
461Pent: 4 mg/kg/day × 4 days10100
4‡Pent: 4 mg/kg/day × 7 days40100
1‡Sb: 20 mg/kg/day × 20 days10100

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@aol.com.

Financial support: This study was supported by the AB Foundation.

REFERENCES

  • 1

    Velez I, Agudelo S, Hendrickx E, Puerta J, Grogl M, Modabber F, Berman J, 1997. Inefficacy of allopurinol for Colombian cutaneous leishmaniasis: a randomized, controlled trial. Ann Intern Med 126 :232–236.

    • Search Google Scholar
    • Export Citation
  • 2

    Soto J, Fuya P, Herrera R, Berman J, 1998. Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study. Clin Infect Dis 26 :56–58.

    • Search Google Scholar
    • Export Citation
  • 3

    Navin TR, Arana BA, Arana FE, de Merida AM, Castillo AL, Pozuelos JL, 1990. Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala. Am J Trop Med Hyg 42 :43–50.

    • Search Google Scholar
    • Export Citation
  • 4

    Navin TR, Arana BA, Arana FE, Berman JD, Chajon JF, 1992. Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala. J Infect Dis 165 :528–534.

    • Search Google Scholar
    • Export Citation
  • 5

    Romero GA, Guerra MV, Paes MG, Macedo VO, 2001. Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate. Am J Trop Med Hyg 65 :456–465.

    • Search Google Scholar
    • Export Citation
  • 6

    Palacios R, Osorio LE, Grajalew LF, Ochoa MT, 2001. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg 64 :187–193.

    • Search Google Scholar
    • Export Citation

Author Notes

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@medplus.org.co.
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