BACKGROUND: Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up. METHODS: Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality. RESULTS: Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks. CONCLUSION This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.
China ; HIV ; HIV Infections/drug therapy* ; Humans ; Meningitis, Cryptococcal/drug therapy* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To evaluate the time and effect of shunt operation on cryptococcal meningitis.
 METHODS: A total 7 patients received shunt operation for the therapy of cryptococcal meningitis patients and the data was retrospectively analyzed.
 RESULTS: Intracranial hypertension-caused symptoms were resolved immediately. There was no complication, no infection dissemination and no recrudescence of cryptococcal meningitis. 
 CONCLUSION Shunt operation is effective for intracranial hypertension caused by cryptococcal meningitis. It does not affect the antifungal treatment.
Antifungal Agents ; therapeutic use ; Drainage ; Humans ; Intracranial Hypertension ; surgery ; Meningitis, Cryptococcal ; drug therapy ; surgery ; Recurrence ; Retrospective Studies

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.
Antifungal Agents/therapeutic use ; Antiviral Agents/*adverse effects ; Cryptococcus neoformans/immunology/*pathogenicity ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy/immunology ; Humans ; Immunocompromised Host ; Interferon-alpha/*adverse effects ; Meningitis, Cryptococcal/drug therapy/immunology/*microbiology ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*microbiology ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Ribavirin/*adverse effects ; Time Factors ; Treatment Outcome

Amphotericin B ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Humans ; Male ; Meningitis, Cryptococcal ; diagnosis ; drug therapy

BACKGROUNDAmphotericin B (0.7 mg/kg) with flucytosine is the standard treatment for cryptococcal meningitis. However, the long treatment course can induce adverse reactions in patients; therefore, reducing the dose may decrease such reactions. We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B (0.4 mg/kg or 0.7 mg/kg per day) and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.

METHODSRetrospective analysis was conducted on inpatients at the First Affiliated Hospital, College of Medicine, Zhejiang University (January 2005 to December 2009). Low- or high-dose amphotericin B (0.4 or 0.7 mg/kg per day, respectively) plus flucytosine was used. The negative conversion rate of Cryptococcus in the cerebrospinal fluid (CSF), patient mortality, and the incidence of side effects for the two groups (low- vs. high-dose) were compared immediately after treatment and 2 and 10 weeks later. Data were analyzed by the Student's t test, chi-square tests using SPSS 12.0 statistical software.

RESULTSTwo weeks post-treatment, Cryptococcus negative CSF rates were 78% (18/23) in the low-dose group and 87% (13/15) in the high-dose group (P = 0.28). Ten weeks post-treatment, both groups were negative. The mortality rate was 8% (2/25) in the low-dose group and 17% (3/18) in the high-dose group (P = 0.25). There was a statistically significant difference in the incidence of adverse events between the groups, 48% (12/25) and 78% (14/18) in the low- and high-dose groups, respectively (P = 0.04). Adverse events that required a change in treatment program in the low-dose group were 12% (3/25) compared to 39% (7/18) in the high-dose group (P = 0.04).

CONCLUSIONLow-dose treatment regimens were better tolerated than high-dose ones.

Adolescent ; Adult ; Aged ; Amphotericin B ; adverse effects ; therapeutic use ; Antifungal Agents ; adverse effects ; therapeutic use ; Female ; Flucytosine ; adverse effects ; therapeutic use ; Humans ; Male ; Meningitis, Cryptococcal ; drug therapy ; microbiology ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo explore the pharmacokinetics of amphotericin B (AMB) in the cerebrospinal fluid (CSF) during continuous intrathecal administration of AMB for treatment of cryptococcal neoformans meningitis (CNM).

METHODSThe concentration of AMB in the CSF was measured using reversed phase high performance liquid chromatography (RP-HPLC) in 3 patients receiving continuous intrathecal infusion of AMB for CNM.

RESULTSAMB concentrations in the CSF of the 3 patients exceeded the minimal inhibitory concentration (MIC) of AMB against Cryptococcus neoformans. The concentration-time curve showed that AMB concentration in the CSF underwent obvious variations on the first day of intrathecal infusion and after additional AMB doses, but maintained a stable level (0.61-1.21 µg/ml) on the next day.

CONCLUSION[corrected] Continuous intrathecal administration of AMB can enhance the drug concentration in the CSF and maintain a stable and effective drug level for treatment of CNM.

Adolescent ; Amphotericin B ; administration & dosage ; pharmacokinetics ; Antifungal Agents ; administration & dosage ; pharmacokinetics ; Cerebrospinal Fluid ; metabolism ; Cryptococcus neoformans ; isolation & purification ; Female ; Humans ; Infusions, Spinal ; methods ; Male ; Meningitis, Cryptococcal ; drug therapy ; metabolism

OBJECTIVETo evaluate the value of cryptococcal latex agglutination test in the diagnosis and treatment of cryptococcal meningitis in children.

METHODSThe clinical data of 10 children with cryptococcal meningitis were retrospectively studied. Cryptococcal meningitis was confirmed based on clinical manifestations, India ink stain, cryptococcal latex agglutination test or cryptococcal culture. The outcome of antifungal treatment and the changes of latex agglutination test titer were followed up for 2 to 4 years.

RESULTSLatex agglutination test and/or India ink stain were positive (titer 1 : 64-1 : 1024) in 8 patients in the first examination of cerebrospinal fluid. In the other 2 patients, latex agglutination test was positive (titer 1 : 256) in the fourth examination of cerebrospinal fluid in one, and India ink stain was positive in the eleventh examination in the other. After antifungal treatment, six patients were cured, two patients died, and two patients were lost to follow-up. The positive cryptococcal latex agglutination test (titer 1 : 2-1 : 16) was seen respectively in six, three, two and one cured patients 6 months, 1 year, 2 years and 4 years later.

CONCLUSIONSThe cryptococcal latex agglutination test of cerebrospinal fluid is valuable for the quick and early diagnosis of cryptococcal meningitis; however, the decision of withdrawal of antifungal treatment should not rely on the results of the test.

Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Latex Fixation Tests ; methods ; Male ; Meningitis, Cryptococcal ; cerebrospinal fluid ; diagnosis ; drug therapy

Antifungal Agents ; therapeutic use ; Humans ; Infant ; Meningitis, Cryptococcal ; drug therapy ; Pyrimidines ; adverse effects ; therapeutic use ; Triazoles ; adverse effects ; therapeutic use ; Voriconazole

Amphotericin B ; administration & dosage ; Antifungal Agents ; administration & dosage ; Child ; Cryptococcus neoformans ; drug effects ; pathogenicity ; Diagnosis, Differential ; Drug Delivery Systems ; instrumentation ; methods ; Humans ; Injections, Intraventricular ; Injections, Spinal ; Intracranial Hypertension ; complications ; drug therapy ; etiology ; Male ; Meningitis, Cryptococcal ; diagnosis ; drug therapy ; physiopathology ; Treatment Outcome

Cryptococcosis is a relatively common mycosis of human caused by a worldwide Cryptococcus neoformans. Cryptococcosis occurs more frequently in immuno-compromised hosts such as patients with lymphoma, AIDS, leukemia and other debilitating diseases which manifest a condition of altered cell mediated immunity. Also cancer patients with anticancer chemotherapy are at high risk. Cryptococcosis is primarily a pulmonary disease that remains asymptomatic and unrecognised in most cases. Meningitic and meningoencephalitc forms are more frequently diagnosed because of their striking clinical symptoms.Meningoencephalitis is an uncommon form of cryptoccocosis that often leads to coma and death within a short time, if it is not quickly diagnosed and treated properly. The treatment of choice for the cryptococcosis consists of intravenous amphotericin B and 5-fluorocytocine. We report a case of cryptococcal meningitis in 47-year-old female breast cancer patient with liver metastasis after systemic chemotherapy. She complained headach, fever and diagnosed as cryptococcal meningitis after the India ink smear and culture of CSF. After treated with amphotericin B, her conditions were improved.
Amphotericin B ; Breast Neoplasms ; Coma ; Cryptococcosis ; Cryptococcus neoformans ; Drug Therapy ; Female ; Fever ; Herpes Zoster* ; Humans ; Immunity, Cellular ; India ; Ink ; Leukemia ; Liver* ; Lung Diseases ; Lymphoma ; Meningitis, Cryptococcal* ; Middle Aged ; Neoplasm Metastasis* ; Strikes, Employee