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Abstract Background Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%–30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival.Methods Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers.Results 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60–3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011).Conclusions Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes.Clinical Trials Registration Clinicaltrials.gov (NCT03945448).

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for more than one year in serum from 38 of 44 (86%) patients and in CSF from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a two fold drop in titer to occur, was slower in serum than in CSF. Speed of decline of antigen titers was much slower in serum and CSF for patients infected with C. gattii than C. neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure.

Abstract Objective To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). Methods This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. Results In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015–1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589–0.814; P 

by Carol S. Palackdharry, Stephanie Wottrich, Erin Dienes, Mohamad Bydon, Michael P. Steinmetz, Vincent C. Traynelis …

Abstract Objective To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). Methods This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. Results In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015–1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589–0.814; P 

Abstract Background Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.Methods We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7–1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality.Results We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355–0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360–0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44–1.25; P = 0.26).Conclusions Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.

ObjectiveThis study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF). DesignSingle-centre retrospective study. SettingThe Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital. ParticipantsWe enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023. MethodsWe calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM. ResultsAmong these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively. ConclusionThe diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM. …

Nigeria will be the first country in the world to vaccinate residents aged 1 through 29 years with Men5CV, a novel 1-dose vaccine that protects people from 5 major strains of the meningococcus bacteria (Neisseria meningitidis), the World Health Organization (WHO) announced. The news comes amid a 50% surge in meningitis cases in Africa last year, as well as an uptick in the disease worldwide, including in the US.

A 57-year-old man with a 2-day history of a fever and sudden onset of bilateral hearing loss was admitted to our local infectious diseases unit. The patient had no medical history.

Abstract Purpose To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. Methods In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. Results We included 1,699 patients in 2006–2020, 50 patients in 2020–2021, and 182 patients in 2021–2023. After March 2020 relatively more alcoholism was reported (2006–2020, 6.1%; 2020–2021, 18%; 2021–2023, 9.7%; P = 0.002) and otitis–sinusitis was less frequently reported (2006–2020, 45%; 2020–2021, 22%; 2021–2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006–2020, 89%; 2020–2021, 74%; 2021–2022, 86%; P = 0.002) and outcomes were worse (‘good recovery’, 2020–2021, OR 0.5, 95% CI 0.3–0.8). Conclusion During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality. …

Abstract Purpose To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. Methods In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. Results We included 1,699 patients in 2006–2020, 50 patients in 2020–2021, and 182 patients in 2021–2023. After March 2020 relatively more alcoholism was reported (2006–2020, 6.1%; 2020–2021, 18%; 2021–2023, 9.7%; P = 0.002) and otitis–sinusitis was less frequently reported (2006–2020, 45%; 2020–2021, 22%; 2021–2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006–2020, 89%; 2020–2021, 74%; 2021–2022, 86%; P = 0.002) and outcomes were worse (‘good recovery’, 2020–2021, OR 0.5, 95% CI 0.3–0.8). Conclusion During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality. …

Abstract Background and objectives Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. Methods This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients’ cerebrospinal fluid was accomplished through the utilization of ELISA. Results We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P 

Abstract Background and objectives Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. Methods This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients’ cerebrospinal fluid was accomplished through the utilization of ELISA. Results We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P 

Abstract Background and objectives Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. Methods This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients’ cerebrospinal fluid was accomplished through the utilization of ELISA. Results We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P 

by Mark Okwir, Abigail Link, Bosco Opio, Fred Okello, Ritah Nakato, Betty Nabongo, Jimmy Alal, Joshua Rhein, David Meya, Yu Liu, Paul R. Bohjanen Background Cryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival. Methods We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival (≥1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders. Results We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03–0.53], p…

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. Methods Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. Results Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: 

Abstract Background Otitis is commonly associated with community-acquired bacterial meningitis but role of ear surgery as treatment is debated. In this study, we investigated the impact of otitis and ear surgery on outcome of adults with community-acquired bacterial meningitis.Methods We analyzed episodes of adults with community-acquired bacterial meningitis from a nationwide prospective cohort study in the Netherlands, between March 2006 to July 2021.Results A total of 2,548 episodes of community-acquired bacterial meningitis were evaluated. Otitis was present in 696 episodes (27%). In these patients the primary causative pathogen was Streptococcus pneumoniae (615 of 696 [88%]), followed by Streptococcus pyogenes (5%) and Haemophilus influenzae (4%). In 519 of 632 otitis episodes (82%) an ear-nose-throat specialist was consulted, and surgery was performed in 287 of 519 (55%). The types of surgery performed were myringotomy with ventilation tube insertion in 110 of 287 episodes (38%), mastoidectomy in 103 of 287 (36%) and myringotomy alone in 74 of 287 (26%). Unfavorable outcome occurred in 210 of 696 episodes (30%) and in 65 of 696 episodes was fatal (9%). Otitis was associated with a favorable outcome in a multivariable analysis (odds ratio 0.74; 95% CI 0.59-0.92; p =0.008). There was no association between outcome and ear surgery.Conclusions Otitis is a common focus of infection in community-acquired bacterial meningitis in adults, with S. pneumoniae being the most common causative pathogen. Presence of otitis is associated with a favorable outcome. Ear surgery’s impact on the outcome of otogenic meningitis patients remains uncertain.