AUTHOR=Xu Lijun , Tao Ran , Wu Jingjing , Dai Xiahong , Hu Caiqin , Huang Ying , Chen YaoKai , Zhu Biao , He Jianqin 

TITLE=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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02082

DOI=10.3389/fmicb.2019.02082

ISSN=1664-302X

ABSTRACT=Abstract
Background 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. 
Method A 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. 
Results No differences in adverse effects, the rate of the 14-day CSF chemical profile recovery and 90-day cumulative survival rate (91.2± 5.1% vs. 87.5 ± 4.7%, 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 ± 10.0% for patients treated with AmB for < 14 days and 96.4 ± 2.6% 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).
Conclusion Treatment 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.