Short-Course Rather Than Low-Dose Amphotericin B May Exert Potential Influence on Mortality in Cryptococcal Meningitis Patients Treated With Amphotericin B Plus Flucytosine Alone or in Combination With Fluconazole

Abstract

BackgroundThe influence of Amphotericin B (AmB) dose and the addition of fluconazole (Flu) on the AmB + 5-flucytosine (5FC) regimen for cryptococcal meningitis (CM) treatment remain debatable.MethodsA retrospective study was conducted to compare 44 CM patients treated with AmB + 5FC and 78 CM patients treated with AmB + 5FC + Flu using the propensity score matching method. The effects of AmB dosage, AmB course and Flu addition on the cerebrospinal fluid (CSF) chemical profile recovery, adverse effects, and 90-day mortality were compared between the groups.ResultsNo differences in adverse effects, the rate of the 14-day CSF chemical profile recovery and 90-day cumulative survival rate (91.2% vs. 87.5%, P = 0.637) were observed between the AmB + 5FC group and the AmB + 5FC + Flu group. However, the incidence rates of hypokalemia (33.9%) and creatinine elevation (7.1%) in patients treated with an AmB dosage of 0.4–0.5 mg/kg/d were less than those (53.0 and 22.7%, respectively) treated with an AmB dosage of 0.6–0.7 mg/kg/d (P = 0.034 and P = 0.018, respectively). The 90-day cumulative survival rate was 70.1% for patients treated with AmB for <14 days and 96.4% for patients treated with AmB for ≥14 days (log-rank P < 0.001). Multivariate Cox proportional hazards models suggested the hazard ratio was 26.8 (95% CI: 3.9–183.2) for patients treated with AmB < 14 days than those treated with AmB ≥ 14 days (P = 0.001).ConclusionTreatment with AmB less than 14 days was associated with a higher 90-day mortality in CM patients. A relative lower dosage but prolonged course of AmB in the +5FC ± Flu regimen led to favorable trends of fewer adverse effects and comparable clinical efficacy.

Establishment of a novel scoring model for mortality risk prediction in HIV-infected patients with cryptococcal meningitis

“…Confirmation of HIV infection was established by positivity of the HIV antibody test via Western Blot, and a positive HIV RNA polymerase chain reaction [ 13 ]. The diagnosis of CM was based on the identification of Cryptococcus neoformans in CSF via India ink staining, CSF culture or CSF cryptococcal antigen assay [ 14 , 15 ].…”

The clinical characteristics and outcome of cryptococcal meningitis with AIDS in a tertiary hospital in China: an observational cohort study

“…Initial intracranial pressure ≥ 250 mmH 2 O was found in 65% of CM patients, and consciousness disorder was an independent risk factor for death in CM patients [ 5 ]. Similarly, treatment with amphotericin B (AmB) for less than 14 days was associated with a higher 90-day mortality in CM patients [ 6 ]. Early internal drainage is the key factor for better prognosis, and cerebrospinal fluid (CSF) positive for cryptococcus before surgery is not a contraindication [ 3 ].…”

In Vitro Characterization of Twenty-One Antifungal Combinations against Echinocandin-Resistant and -Susceptible Candida glabrata

“…As far as we know, this the first report to confirm the fungicidal and synergistic action of 5FC-AMB combination against C. glabrata . Clinically, 5FC-AMB combination at lower dosage with a prolonged course has a potent role for treatment of cryptococcal meningitis patients with fewer adverse effects [ 35 ]. Furthermore, time-killing assay results of 5FC combinations with other antifungal agents showed promising results with decreasing log 10 CFU/mL in a range of 0.02–1.83 compared to that obtained when 5FC alone was tested.…”