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Guo et al. Diagnosis and treatment of cryptococcal meningitis

(LAmB)/amphotericin B lipid complexes (ABLC) with survival and reduction of fungal load in CSF. [47,50]
small renal toxicity are recommended in the induction
[24]
period. [11,24] In 2010, IDSA suggests induction therapy AmB is easy to combine with human cholesterol cell
with LAmB (3-4 mg/kg per day i.v.) or ABLC (5 mg/kg per membrane, [48,49] so the adverse reactions are more
day i.v.) plus 5-FC (100 mg/kg per day i.v.) for at least and serious. AmB has high toxicity, especially liver
2 weeks, consolidation therapy with FCZ 400-800 mg and kidney toxicity. Renal toxicity which could lead
(6-12 mg/kg) per day for 8 weeks. And maintenance to lowering glomerular filtration rate and electrolyte
therapy with FCZ 200-400 mg (3-6 mg/kg) per day disturbances is the most common. Renal function
lasts for 6-12 months [Table 2]. LAmB should be used can be restored by early termination of the use of
[11]
[51]
at least 4-6 weeks without the use of 5-FC in induction AmB or replacement of LamB. In addition, some
therapy. Increasing dosage (6 mg/kg per day) should studies [11,52,53] support that preemptive hydration and
be conducted when the fungal load is higher or electrolyte supplementation are the effective methods
palindromia. to minimize the toxicity in middle- and low-income
countries (MLICs). Anemia is another common side
[4]
[54]
Treatment for non-HIV associated or non-transplant patients effect of AmB, the reason is that the effect of the
includes induction therapy with AmB 0.7-1.0 mg/kg per day bone marrow on the synthesis of the erythropoietin.
[55]
or LAmB 3-4 mg/kg per day or ABLC 5 mg/kg per day 5-FC could get through the BBB easily and has slight
plus 5-FC 100 mg/kg per day for 4-6 weeks. IDSA also adverse reactions, such as gastrointestinal reaction,
recommends that it is essential to extend induction rash, erythropenia, light degree damage of liver and
period if treated with AmB/LAmB monotherapy or kidney function, etc. Symptoms can be relieved after
treatment interrupted. In addition, consolidation therapy stopping taking the drug. The incidence rate of adverse
with FCZ 400-800 mg (6-12 mg/kg) per day lasts for 8 reactions of FCZ is low, the symptoms mainly include
weeks, and maintenance therapy with FCZ 200 mg gastrointestinal reaction, rash, and so on. Liver and
(3 mg/kg) per day lasts for 6-12 months [Table 3]. kidney impairment are transient and would returned to
normal after drug withdrawal generally. [56]
It is difficult to achieve effective concentration in the
CSF for AmB or LAmB because of their poor ability Treatment of high intracranial pressure
to traverse BBB. Intravenous combined intrathecal The incidence of HICP in patients with cryptococcal
[50]
administration of AmB can improve the drug meningitis is more than 50%. HICP is the leading
[44]
concentration in CSF to inhibit the C. neoformans cause of death and complications. Therefore,
effectively, and observational studies suggest that effective control of intracranial pressure for improving
it could be associated with improved survival. clinical symptoms to gain enough time for the success
[45]
However, it is necessary to prevent the occurrence of of anti-fungal therapy is of crucial importance.
complications caused by intrathecal administration , Active treatment of HICP is crucial whether it is HIV-
such as paresthesias, radiculitis, or myelopathy. [46] associated patients or not. Methods used to reduce
[57]
intracranial pressure commonly as follows: (1) Drugs
[58]
Previous studies in humans and animals indicate that such as mannitol, glycerin fructose, corticosteroids,
intrathecal administration of lipid formulations of AmB acetazolamide and so on. While the long-term effect
is better tolerated than AmB. [47-49] Furthermore, there is of medical management is not clear that is not used
an animal experiment suggesting that the combination routinely; [57,59] (2) Lumbar puncture. Patients whose
of intravenous antifungal drugs with intrathecal intracranial pressure > 2.4 kPa are performed with
administration of LAmB could be beneficial in terms of regular lumbar paracentesis to maintain normal

Table 2: Antifungal therapeutic schedule for CM patients with renal dysfunction
Schedule Course
Induction period LAmB 3-4 mg/kg per day/ABLC 5 mg/kg per day + 5-FC 100 mg/kg per day ≥ 2 weeks
Consolidation period FCZ 400-800 mg/day or 6-12 mg/kg per day ≥ 8 weeks
Maintenance period FCZ 200-400 mg/day or 3-6 mg/kg per day 6-12 months
CM: cryptococcal meningitis; LAmB: liposome amphotericin B; ABLC: amphotericin B lipid complexes; 5-FC: 5-Flurocytosine; FCZ: fluconazole
Table 3: Antifungal therapeutic schedule for non-HIV associated or non-transplant patients
Schedule Course
Induction period AmB 0.7-1.0 mg/kg per day or LAmB 3-4 mg/kg per day or ABLC 5 mg/kg per day + 5-FC 100 mg/kg per day
4-6 weeks
Consolidation period FCZ 400-800 mg/day or 6-12 mg/kg per day 8 weeks
Maintenance period FCZ 200 mg or 6 mg/kg per day 6-12 months
HIV: human immunodeficiency virus; AmB: amphotericin B; LAmB: liposome amphotericin B; ABLC: amphotericin B lipid complexes; 5-FC:
5-Flurocytosine; FCZ: fluconazole
Neuroimmunology and Neuroinflammation ¦ Volume 3 ¦ November 18, 2016 253