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Short‐course amphotericin B in addition to sertraline and fluconazole for treatment of HIV‐associated cryptococcal meningitis in rural Tanzania
Author(s) -
Katende Andrew,
Mbwanji Gladys,
Faini Diana,
Nyuri Amina,
Kalinjuma Aneth Vedastus,
Mnzava Dorcas,
Hullsiek Katherine H.,
Rhein Joshua,
Weisser Maja,
Meya David B.,
Boulware David R.,
Letang Emilio
Publication year - 2019
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/myc.12995
Subject(s) - amphotericin b , amphotericin b deoxycholate , fluconazole , sertraline , medicine , gastroenterology , indinavir , pharmacology , immunology , antifungal , human immunodeficiency virus (hiv) , antidepressant , sida , dermatology , viral disease , caspofungin , hippocampus
Summary Background Cryptococcal meningitis accounts for 15% of all AIDS mortality globally. Most cases in low‐ and middle‐income countries are treated with fluconazole monotherapy, which is associated with a high mortality. New available therapies are needed. Short‐course amphotericin B has been shown to be a safe and efficient therapeutic option. Sertraline has in vitro fungicidal activity against Cryptococcus and bi‐directional synergy with fluconazole. Methods We conducted an open‐label clinical trial to assess the safety and efficacy of sertraline 400 mg/day and fluconazole 1200 mg/day (n = 28) vs sertraline, fluconazole and additional 5 days of amphotericin B deoxycholate 0.7‐1 mg/kg (n = 18) for cryptococcal meningitis. Results Two‐week survival was 64% (18/28) without amphotericin and 89% (16/18) with amphotericin, and 10‐week survival was 21% (6/28) vs 61% (11/18), respectively ( P = .012). The cerebrospinal fluid (CSF) Cryptococcus clearance rate was 0.264 log 10 colony‐forming units (CFU)/mL of CSF/day (95% CI: 0.112‐0.416) without amphotericin and 0.473 log 10 CFU/mL/day (95% CI: 0.344‐0.60) with short‐course amphotericin ( P = .03). Sertraline was discontinued in one participant due to side effects. Four participants receiving amphotericin B experienced hypokalemia <2.4 mEq/L. Conclusions Short‐course amphotericin substantially increased CSF clearance and 10‐week survival. Adjunctive sertraline improved 2‐week CSF fungal clearance but did not improve 10‐week mortality compared with published data using fluconazole 1200 mg/day monotherapy (early fungicidal activity 0.15 log 10 CFU/mL/day).