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Background Increased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs. Methods We prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days. Results Our analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P  < .001), seizures (P  < .01), and higher quantitative cryptococcal cultures (P  < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P  < .001) and CSF white blood cell count ≥5 cells/µL (P  = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P  = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P  = .04), irrespective of baseline ICP. Conclusions Management of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP. [ABSTRACT FROM AUTHOR]

Background Sodium abnormalities are frequent in central nervous system infections and may be caused by cerebral salt wasting, syndrome of inappropriate antidiuretic hormone secretion, or medication adverse events. In cryptococcal meningitis (CM), the prevalence of baseline hyponatremia and whether hyponatremia adversely impacts survival is unknown. Methods We conducted a secondary analysis of data from 2 randomized trials of human immunodeficiency virus–infected adult Ugandans with CM. We grouped serum sodium into 3 categories: <125, 125–129, and 130–145 mmol/L. We assessed whether baseline sodium abnormalities were associated with clinical characteristics and survival. Results Of 816 participants with CM, 741 (91%) had a baseline sodium measurement available: 121 (16%) had grade 3–4 hyponatremia (<125 mmol/L), 194 (26%) had grade 2 hyponatremia (125–129 mmol/L), and 426 (57%) had a baseline sodium of 130–145 mmol/L. Hyponatremia (<125 mmol/L) was associated with higher initial cerebrospinal fluid (CSF) quantitative culture burden (P  < .001), higher initial CSF opening pressure (P  < .01), lower baseline Glasgow Coma Scale score (P  < .01), and a higher percentage of baseline seizures (P  = .03). Serum sodium <125 mmol/L was associated with increased 2-week mortality in unadjusted and adjusted survival analyses (adjusted hazard ratio, 1.87 [95% confidence interval, 1.26–2.79]; P  < .01) compared to those with sodium 130–145 mmol/L. Conclusions Hyponatremia is common in CM and is associated with excess mortality. A standardized management approach to correctly diagnose and correct hyponatremia in CM needs to be developed and tested. [ABSTRACT FROM AUTHOR]

Background Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. Methods We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Results Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P  < .0001), seizures (P  = .0005), elevated intracranial opening pressure (P  = .03), higher CSF white cells (P  = .007), and lower CSF glucose (P  = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P  =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55–7.51; P  = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Conclusions Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate. [ABSTRACT FROM AUTHOR]

Background C-reactive protein (CRP) is an acute phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker used for following the progression and resolution of infection. We aimed to determine the association of baseline CRP level and the temporal change in CRP over time with cryptococcal meningitis outcome. Methods We reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline plasma CRP collected within 5 days of meningitis diagnosis was categorized into quartiles. We compared baseline CRP with 18-week survival using time-to-event analysis. Results Of 168 participants, the baseline first quartile of serum CRP was <29.0 mg/L, second quartile 29.0–49.5 mg/L, third quartile 49.6–83.6 mg/L, and fourth quartile >83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by CRP quartile. Participants with CRP >49.5 mg/L more likely presented with Glasgow Coma Scale (GCS) <15 (P  = .03). The 18-week mortality rate was 55% (46/84) in the highest 2 quartile CRP groups (>49.5 mg/L), 41% (17/42) in the mid-range CRP group (29.0–49.5 mg/L), and 14% (6/42) in the low-CRP group (<29.0 mg/L; P  < .001). After adjustment for possible confounding factors including GCS <15, CRP remained significantly associated with mortality (adjusted hazard ratio, 1.084 per 10 mg/L; 95% CI, 1.031–1.139; P  = .0016). Conclusions Higher baseline CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. CRP could be a surrogate marker for undiagnosed coinfections or may reflect immune dysregulation, leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis. [ABSTRACT FROM AUTHOR]

Background Cryptococcus is the commonest cause of adult meningitis in Africa, with 50%–70% experiencing increased intracranial pressure. Cerebral oximetry is a noninvasive near-infrared spectroscopy technology to monitor percent regional cerebral tissue oxygenation (rSO2). We assessed if cerebral oximetry predicts meningitis mortality. Methods We performed cerebral oximetry within 14 days of cryptococcal meningitis diagnosis on 121 Ugandans from April 2016 to September 2017. We evaluated baseline rSO2 association with mortality by multivariable logistic regression and correlation with other clinical factors. We compared groups formed by initial rSO2 <30% vs ≥30% for longitudinal change with mixed effects models. We measured change in %rSO2 before and after lumbar puncture (LP). Results The median initial rSO2 (interquartile range) was 36% (29%–42%), and it was <30% in 29% (35/121). For 30-day mortality, the unadjusted odds ratio (per 5% increase in rSO2) was 0.73 (95% confidence interval [CI], 0.58 to 0.91; P =.005). Those with initial rSO2 <30% had 3.4 (95% CI, 1.5 to 8.0) higher odds of 30-day mortality than those with initial rSO2 ≥30%. Hemoglobin correlated with initial rSO2 (rho =.54; P <.001), but rSO2 did not correlate with pulse oximetry, intracranial pressure, cerebral perfusion pressure, or quantitative cerebrospinal fluid culture, and rSO2 was unchanged pre/post–lumbar punctures. The longitudinal rSO2 measurements change was 15% (95% CI, 12% to 18%) lower in the group with initial rSO2 <30%. Conclusions Individuals with cryptococcal meningitis and low cerebral oximetry (rSO2 < 30%) have high mortality. Cerebral oximetry may be useful as a prognostic marker of mortality. Targeted interventions to improve rSO2 should be tested in trials to try to decrease mortality in meningitis. [ABSTRACT FROM AUTHOR]