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.