Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review
Table 4
Conclusion on combination treatment as a new treatment of tegumentary leishmaniasis in the systematic review.
Treatment
Dose
Route of Administration/Time
Time
Efficacy
Safety
Practice/clinical implications
Study source
MA + IM
IM: Lesion ≤3 cm: 1 dose of 7.5% cream. Lesion > 3 cm: 2 doses of 7.5% cream. Each dose = 125 mg.
IM: topical - daily
20 days
Efficacious
Acceptable risk with specialized monitoring
Investigational
Arevalo et al., 2007
MA: 20 mg/kg/day.
MA: IV - daily
IM: 5% cream.
IM: topical- 3 times per day
IM: 28 days
Likely efficacious
Acceptable risk with specialized monitoring
Investigational
Firooz et al., 2006
MA: 20mg Sb5+/kg/day.
MA: IM daily
MA: 14 days
IM: 5% cream.
IM: Topical- daily.
IM: 20 days.
Efficacious
Acceptable risk without specialized monitoring
Clinically useful
Miranda- Verastegui et al., 2005
MA: 20mg/kg/day.
MA: IM daily in children, and IV infusion in older subjects.
MA: 20 days.
MA + PE
MA: 20mg5+/kg/day
MA: daily
MA: 30 days
Efficacious
Acceptable risk with specialized monitoring
Clinically useful
Machado et al., 2007
PE: 400mg
PE: oral – 3 times daily
PE: 30 days
MA: 20/Kg/day
MA: IV- daily
MA: 20 days
Not efficacious
Acceptable risk with specialized monitoring
Not useful
Brito et al., 2017
PE: 400m
PE: oral- 3 times daily
PE: 20 days
MA+ cryotherapy
Cryotherapy: freeze time (10-25 s)
Cryotherapy: on the lesion until 1-2 mm of surrounding normal tissue appeared frozen
Every two weeks
Likely efficacious
Acceptable risk without specialized monitoring
Possibly useful
Farajzadeh et al., 2015
MA: 15 mg/kg/day
Intramuscular
Every day for 3 weeks
MA + (LEISH-F1 + MPL-SE)
LEISH-F1: 5, 10 or 20 μg + 25 μg MPL-SE.
LEISH-F1: SUB – 3 times.
LEISH-F1: On day 0, 28 and 56.
Likely efficacious
Acceptable risk with specialized monitoring
Possibly useful
Nascimento et al., 2010
MA: 10 mg/ Sb5+kg/day.
MA: IV – 10-days cycles followed by 11 days of rest.
MA: The first 10-days cycle on Day 0. Additional cycles on days 21, 42, and 63
MA + GM-CSF
GM-CSF: 1-2 mL (10 µg/mL).
GM-CSF: topical – 3 times per week.
GM-CSF: 3 weeks
Efficacious
Acceptable risk without specialized monitoring
Investigational
Almeida et al., 2005
MA: 20 mg Sb5+/kg/day.
MA: IV – daily.
MA: 20 days
MA + OM
MA: 30mg/kg/day
MA: IM- daily
MA: 3 weeks
Likely efficacious
Acceptable risk with specialized monitoring
Clinically useful
Nilforoushzadeh et al., 2008
OM: 40mg
OM: oral - daily
OM: 3 weeks
il MA + silver PD
MA: il
MA: Intradermally in each one centimeter square of a lesion until blanching occurred intralesional, once weekly.
42 days
Not efficacious
Acceptable risk with specialized monitoring
Investigational
Khatami et al., 2013
Silver PD: on the lesion
Silver dressing: topical – once daily
il MA + topical honey
MA: il
MA: il enough to blanch the lesion and 1 mm rim of the surrounding normal skin, once weekly.
Until complete healing or for maximum 6 weeks
Not efficacious
Insufficient evidence
Investigational
Nilforoushzadeh et al., 2007
Honey: soaked gauze
Honey: topical – twice daily
il MA + cryotherapy
Cryotherapy: freeze time (10 - 25 s)
Cryotherapy: on the lesion until 2-3 mm halo forms around, weekly, before IL MA.
Until complete cure or for up to 12 weeks
Likely efficacious
Acceptable risk without specialized monitoring
Possibly useful
Meymandi et al., 2011
MA: (0.5 – 2 ml)
MA: intradermally, all directions, until the lesion had completely blanched, weekly.
SSG + (LEISH-F1+ MPL-SE)
LEISH- F1: 5, 10 or 20 µg + 25 µg MPL-SE.
LEISH-F1: SUB – 3 times.
LEISH-F1: On day 0, 28 and 56.
Efficacious
Acceptable risk with specialized monitoring
Investigational
Llanos Cuentas et al., 2010
SSG: 20mg/kg/day
SSG: IV – daily
SSG: day 0 to 27
SSG + IM
IM: 5% cream.
IM: Topical - 3 times per week.
IM: 20 days
Efficacious
Acceptable risk without specialized monitoring
Clinically useful
Miranda- Verastegui et al., 2009
SSG: 20 mg/kg/day
SSG: IV – daily.
SSG: 20 days
il SSG + im SSG
il SSG (100 mg/mL), the dose varied between 0.3-3.0 mL. Maximum dose 20mg/Kg/day.
il: Infiltrated in multiple sites until complete blanching and a 1-mm wide ring of the surrounding normal skin.
il SSG on days 1, 3, 5 in one session - up to 3 cycles.
Efficacious
Acceptable risk with specialized monitoring
Possibly useful
El-Sayed & Anwar, 2010
im SSG (a part of the dose 20mg/Kg/day already given provided to IL SSG in the same days).
im: one injection on days 1, 3, 5 - up to 3 cycles with 4 weeks interval.
il SSG + KE
il SSG (100mg/mL), the dose varied between 0.3-3.0 mL, maximum dose 20mg/Kg/day.
il: Infiltrated in multiple sites until complete blanching and a 1-mm wide ring of the surrounding normal skin.
il: on days 1, 3, 5 in one session - up to 3 cycles.
Efficacious
Acceptable risk with specialized monitoring
Possibly useful
El-Sayed & Anwar, 2010
KE: 200 mg.
KE: 3 times daily.
KE: 4 weeks.
il SSG + cryotherapy
il SSG: 1-2ml.
il SSG: into margin of each lesion, all around, until blanching with cryotherapy preceding the first injection.
il SSG: 3 injections SSG with intervals of 1-3 days.
Efficacious
Acceptable risk without specialized monitoring
Clinically useful
van Thiel et al., 2010
Cryotherapy: local with a double freeze-thaw cycle. 20 seconds for freezing cycle and thawing time between cycles of 45-90 seconds.
Cryotherapy: treatment was repeated until clinical improvement (range 1-163 days).
MA, meglumine antimoniate; PE, pentoxifylline; GM-CSF, granulocyte macrophage colony-stimulating factor; IM, imiquimod; il SSG, intralesional sodium stibogluconate; im SSG, intramuscular sodium stibogluconate; KE, ketoconazole; il MA (intralesional meglumine antimoniate); nonsilver PD, nonsilver containing polyester dressing; silver PD, silver containing polyester dressing; SSG, sodium stibogluconate; LEISH-F1, lyophilized LEISH-F1 protein; MPL-SE, adjuvant; OM, omeprazole; IV, intravenous; IM, intramuscular; SUB, subcutaneously.