India ink-negative and culture-negative cryptococcal meningitis in HIV-negative patients.

BACKGROUND: The clinical features of India ink-negative and culture-negative cryptococcal meningitis (CM) in HIV-negative patients remain unclear. METHODS: A total of 395 antifungal-naïve HIV-negative CM patients were enrolled in this retrospective study. The 90-day poor outcome and associated risk factors were compared between patients with positive and negative India ink, and those with positive and negative culture in cerebrospinal fluid (CSF). RESULTS: India ink-negative patients had a high level of glucose [mmol/L; 2.6 ± 1.5 vs. 2.1 ± 1.4, P = 0.005], total protein level [g/L; 1.1 (0.7–1.8) vs. 0.9 (0.6–1.2), P = 0.002] and WBC count [×106/L; 121.9 (36.5–210.0) vs. 67.5 (18.0-140.0), P = 0.001] in CSF but lower intracranial pressure (ICP) (mmH2O; 185.0 (130.0-250.0) vs. 270.0 (191.0-397.5), P < 0.001) at the time of CM diagnosis. Culture-negative patients showed a high CSF glucose level (mmol/L; 2.9 ± 1.6 vs. 2.1 ± 1.3, P < 0.001) and low ICP [mmH2O; 215.0 (150.0-277.3) vs. 250.0 (180.0-360.0), P = 0.006]. The 90-day poor outcome was 9.3% for India ink-negative patients, 24.5% for India ink-positive patients (log-rank P = 0.003), 21.7% for culture-negative patients and 19.8% for culture-positive patients (log-rank P = 0.579). ICP ≥ 300.0 mmH2O [adjusted odds ratio (AOR) (95% confidence interval): 4.6 (1.0-20.7), P = 0.045] and not going CrAg Assay [AOR:4.4(1.0-18.4), P = 0.045] were independent risk factors for India ink-negative patients. Low CSF count (< 20.0 × 106/L) [AOR: 2.7 (1.0-7.2), P = 0.047] and and positive India ink [AOR:5.3(1.2–23.5), P = 0.028] were independent risk factors for 90-day poor outcome in culture negative patients. CONCLUSIONS: India ink-/culture-negative CM patients had mild CSF profile changes. The CrAg assay was associated with an increased survival rate of India ink- negative CM patients and positive India ink was associated with poor outcome of culture-negative CM patients. The mortality of patients with a positive India ink was significantly increased.