Short high-dose liposomal amphotericin B ((L-Amb) for cryptococcal meningitis (CM)

80 HIV-positive patients with CM in Tanzania and Botswana
were randomized to three different regimens of short course
high-dose L-Amb or to standard therapy with L-Amb of 3 mg/
kg for 14 days. In all the three different high-dose arms, 10 mg
L-Amb was given on day 1, in the second and third arm another
5 mg/kg was given on day 3, and in the third arm another 5 mg/
kg was given on day 7. All patients received fluconazole 1200mg/
day for 14 days. Primary endpoint was mean rate of clearance
of cerebrospinal fluid cryptococcal infection (EFA). All three
arms with short course high-dose L-Amb were non-inferior
to the control arm. Actually, clearance was non-significantly
faster in all three arms with high dose L-Amb. There was no
evidence of improved efficacy with additional doses of L-Amb
compared to the initial 10 mg/kg dose. Total 10 week mortality
was 29 % without any difference between the arms. The high
dose L-Amb was well tolerated with overall low rates of adverse
events.

Ref; Jarvis et al. Clin Infect Dis;68:393-401

Comment: The mortality in HIV-associated cryptococcal meningitis
is still high. In this study a single high dose of liposomal
amphotericin B was at least as effective as standard dose of 3
mg/kg per day for 2 weeks in combination with fluconazole.
Perhaps could outcome improve further if fluconazole is replaced
by flucytosin?