Successful therapy was often limited by severe nephrotoxicity, electrolyte abnormalities, and infusion-related adverse events
13
Landmark therapy
Two major randomized clinical trials addressing the treatment of cryptococcal meningitis were conducted in the late 1970s and mid- 1980s
Lumbar puncture showed a WBC count of 58×106/L with 0.94 monocytes, protein was 176mg/dL, and glucose was 1.5mmol/L
Failed for treating with broad spectrum antibiotics including ceftazidime, levofloxacin, etc.
Antifungal Treatment for Cryptococcal Meningitis
1
Challenge for Cryptococcal Meningitis
Cryptococcus neoformans is the most common cause of fungal meningitis in HIV and non-HIV-infected patients
neoformans CSF cryptococcal antigen titres 1:160
5
Cranial MRI
6
Past History of Hepatitis B
In 2019 he was diagnosed with decompensated hepatitis B cirrhosis, presenting with fatigue, anorexia and bloating
10
Roadmap
Clinical studies in the pre-HIV Era Clinical studies in the AIDS Era Recent studies for cryptococcal meningitis
11
Clinical studies in the pre-HIV Era
CSF: WBC28×106/L，multinucleated cells 15/28，monocytes 13/28，protein 1169mg/L， glucose1.3mmol/L
CSF smear for fungi was negative CSF culture was positive for Cryptococcus
Since then he had several episodes of jaundice, liver enzyme elevation, ascites and spontaneous bacterial peritonitis. Symptoms were relieved each time after anti-infective and supportive therapy
HBVM: HBsAg(+), HBeAg(+), HBcAB(+) HBV DNA was 2.2×107 copies/mL
7
Past History of Hepatitis B
He took Lamivudine 100mg/d，and witnessed a reduction of viral load to 3.8×103 copies/mL. 15 months later he developed YMDD mutation and viral load rebounded to 1.0×107copies/mL
HBV DNA was 6.19×108 copies/mL in July 2019. Adefovir 10mg/d was added to lamivudine
8

Liver CT
9
How can I initially treat this patient?
AmB L-AmB Fluconazole Itraconazole Posaconazole Flucytosine
Found in 7%-10% patients with AIDS Remain high mortality rate (10%-44%),
especially in immunocompromised patients
2
Case Study
3
Present History
A 46-year-old man was admitted to our hospital because of fevers and headache for over 2 months
12
AmB
Prior to the availability of AmB, cryptococcal meningitis was considered to be uniformly fatal
When AmB became available in the late 1950s, it became the drug of choice for crypotococcal meningitis with success rates of up to 60%
His temperature continued to climb up to 39˚C, and his headache developed into an intolerable one. He was then transferred to our hospital
4
Lab Examinations