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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 The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. Methods We prospectively enrolled 102 human immunodeficiency virus (HIV)–positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters. Results Subjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality—worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra–negative (30%) probable TBM cases (P  = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P  = .48). Ct tertile was significantly associated with baseline CSF lactate (P  = .03). Conclusions High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care. [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]

Background: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda., Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites., Results: During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144)., Conclusion: The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)