What is the role of sodium stibogluconate and itraconazole in the treatment of leishmaniasis?

Role of Sodium Stibogluconate and Itraconazole in the Treatment of Leishmaniasis

Sodium stibogluconate is recommended as first-line therapy for leishmaniasis in areas with low antimony resistance (<10%), while itraconazole has insufficient evidence to support its routine use for leishmaniasis treatment. 1

Sodium Stibogluconate (SSG)

Indications and Efficacy

• Pentavalent antimonials (including sodium stibogluconate) have been the mainstay of leishmaniasis treatment for approximately 7 decades, showing good efficacy against most Leishmania species in most geographic regions 1
• For visceral leishmaniasis (VL), SSG is recommended at 20 mg SbV/kg/day IV or IM for 28 days in areas with low antimony resistance 1
• Efficacy rates exceed 90-95% for both L. infantum-chagasi and L. donovani infection in East Africa, Brazil, and Greece 1
• For cutaneous leishmaniasis (CL), the traditional regimen is 20 mg SbV/kg/day for 20 days 1
• Intralesional SSG has shown effectiveness for localized cutaneous leishmaniasis with cure rates of 58.3-91% when used alone 2, 3

Administration Routes

• Intravenous (IV) and intramuscular (IM) routes are most common in North America 1
• Intralesional administration is effective for cutaneous leishmaniasis, typically injected at 0.5 mL per lesion (50 mg) every 2-3 weeks for up to 12 weeks 3
• Alternative day or weekly intralesional treatments have shown better efficacy (97% and 91% respectively) compared to daily treatments (67%) 4

Limitations and Resistance

• Therapeutic failures have been reported, especially in northeast India, Bangladesh, Nepal, and Bhutan 1
• In Bihar, India, unresponsiveness to SSG was reported in 43% of patients at the end of treatment, increasing to 58% after 6 months follow-up 5
• Concerns about toxicity have led to the emergence of liposomal amphotericin B (L-AmB) and miltefosine as first-line drugs in some regions 1

Adverse Effects

• Common adverse effects include arthralgias and myalgias (58%), pancreatitis (97%), elevated transaminases (67%), headache (22%), hematologic suppression (44%), and rash (9%) 6
• These side effects necessitate interruption of treatment in approximately 28% of cases, but they are generally reversible 6
• Intralesional administration has milder side effects, mostly pain during injection and occasional mild local site reactions 3

Itraconazole

Evidence for Use in Leishmaniasis

• There are only published case reports and small clinical series with imidazole antifungals (fluconazole or itraconazole) with/without allopurinol in persons with VL 1
• The available data are insufficient to recommend itraconazole's use for visceral leishmaniasis 1
• When combined with intralesional SSG for cutaneous leishmaniasis, oral ketoconazole (another azole antifungal) showed 92.3% cure rate compared to 58.3% with intralesional SSG alone 2
• However, specific data on itraconazole's efficacy in leishmaniasis is limited in the available guidelines 1

Treatment Algorithm

1. For Visceral Leishmaniasis:

   • First-line in areas with low antimony resistance (<10%): Sodium stibogluconate 20 mg SbV/kg/day IV or IM for 28 days 1
   • First-line in areas with high antimony resistance or when SSG is contraindicated: Liposomal amphotericin B (L-AmB) 1
   • Itraconazole is not recommended as monotherapy due to insufficient evidence 1

2. For Cutaneous Leishmaniasis:

   • Small, uncomplicated lesions: Intralesional SSG (0.5 mL per lesion every 2-3 weeks) 3, 4
   • Multiple or complex lesions: Systemic SSG (20 mg SbV/kg/day for 20 days) 1
   • Combination therapy (intralesional SSG + systemic therapy) may be more effective than intralesional SSG alone 2

Important Caveats

• Monitor for adverse effects with systemic SSG therapy, particularly pancreatitis, hepatotoxicity, and hematologic abnormalities 6
• Do not use intralesional SSG on fingers, nose, ears, eyelids, near lips, or areas where vascular compromise could be concerning 1
• Avoid switching to amphotericin B deoxycholate in persons with contraindications to or substantial toxicity with L-AmB, as it is almost always associated with more toxicity 1
• Consider alternative therapies (miltefosine or amphotericin B) in patients with factors associated with non-response to SSG 5
• Clinical parameters correlate well with parasitologic responses to VL treatment and should be used to monitor the response 1