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.
Highlights
The current treatment using antifungal drugs against cryptococcosis involves three categories of drugs, namely, amphotericin B (AmB), triazoles, and 5-flucytosine (5FC)
The diagnosis of cryptococcal meningitis (CM) was defined as the presence of at least one of the following criteria: (1) culture of cerebrospinal fluid (CSF) positive for Cryptococcus neoformans, (2) CSF India ink smear of centrifuged sediment positive for Cryptococcus, (3) histopathology compatible with Cryptococcus (5- to 10μm encapsulated yeasts observed in brain tissue using silver and/or PAS stain), or (4) probable CM with the clinical syndrome of meningitis and positive cryptococcal antigen titer ≥1:4 or positive CrAg lateral flow assay in CSF even without microbiological or pathological documentation
Cryptococcal meningitis was diagnosed in 55 individuals via the method of CSF India ink staining and culture after admission, 20 by sole CSF Cryptococcus culture positivity, 4 by CSF Cryptococcus culture positivity combined with either cryptococcal antigen titer ≥1:4 or CrAg lateral flow assay in CSF, 24 by India ink staining combined with either cryptococcal antigen titer ≥1:4 or CrAg lateral flow assay in CSF, and 19 patients by cryptococcal antigen titer ≥1:4 or positive CrAg lateral flow assay in CSF but without the finding of Cryptococcus
Summary
The current treatment using antifungal drugs against cryptococcosis involves three categories of drugs, namely, amphotericin B (AmB), triazoles, and 5-flucytosine (5FC). The standard protocol for the treatment of cryptococcal meningitis (CM) is divided into three phases: AmB (0.7–1 mg/kg/d) + 5FC (100 mg/kg/d) as an initial 2- to 4-week induction therapy, followed by fluconazole (Flu) 400–800 mg/d for 8 weeks as consolidation therapy and fluconazole 200 mg/d for at least 6 months as subsequent maintenance therapy (Perfect et al, 2010; Perfect and Bicanic, 2015). The effects of shortening the duration or reducing the dose of the induction treatment with AmB in CM patients remains controversial. The 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
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