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Abstract Background Bacterial meningitis (BM) causes significant morbidity and mortality. We investigated predisposing factors, clinical characteristics, spectrum of etiological bacteria, and clinical outcome of community-acquired and nosocomial BM. Methods In this retrospective study we analyzed data of 148 adults (age > 16 years) with BM treated in Turku University Hospital, Southwestern Finland, from 2011 to 2018. Besides culture- or polymerase chain reaction (PCR)-positive cases we also included culture-negative cases with laboratory parameters strongly suggestive of BM and those with meningitis-related findings in imaging. We used Glasgow Outcome Scale (GOS) score 1–4 to determine unfavorable outcome. Results The median age of patients was 57 years and 48.6% were male. Cerebrospinal fluid (CSF) culture for bacteria showed positivity in 50 (33.8%) cases, although pre-diagnostic antibiotic use was frequent (85, 57.4%). The most common pathogens in CSF culture were Streptococcus pneumoniae (11, 7.4%), Staphylococcus epidermidis (7, 4.7%), Staphylococcus aureus (6, 4.1%) and Neisseria meningitidis (6, 4.1%). Thirty-nine patients (26.4%) presented with the triad of fever, headache, and neck stiffness. A neurosurgical procedure or an acute cerebral incident prior BM was recorded in 74 patients (50%). Most of the patients had nosocomial BM (82, 55.4%) and the rest (66, 44.6%) community-acquired BM. Ceftriaxone and vancomycin were the most used antibiotics. Causative pathogens had resistances against the following antibiotics: cefuroxime with a frequency of 6.8%, ampicillin (6.1%), and tetracycline (6.1%). The case fatality rate was 8.8% and the additional likelihood of unfavorable outcome 40.5%. Headache, decreased general condition, head computed tomography (CT) and magnetic resonance imaging (MRI), hypertension, altered mental status, confusion, operative treatment, neurological symptoms, pre-diagnostic antibiotic use and oral antibiotics on discharge were associated with unfavorable outcome. Conclusions The number of cases with nosocomial BM was surprisingly high and should be further investigated. The usage of pre-diagnostic antibiotics was also quite high. Headache was associated with unfavorable outcome. The frequency of unfavorable outcome of BM was 40.5%, although mortality in our patients was lower than in most previous studies. …

Tropical Medicine &International Health, Accepted Article.

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 107 Issue: 6 Pages: 1288-1294 …

AbstractBackgroundDrug regimens which include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in Tuberculous Meningitis (TBM). Safety data on their use in combination and in the context of HIV is needed to inform clinical trial design.MethodsWe conducted a phase 2 open-label parallel-design RCT to assess safety of high-dose rifampicin, linezolid and high-dose aspirin in HIV-associated TBM. Participants were randomised (1.4:1:1) to three treatment arms (arm 1, standard of care (SOC); arm 2 SOC + additional rifampicin (up to 35mg/kg/day)) + linezolid 1200mg/day reducing after 28/7 to 600mg/day; arm 3, as per arm 2 + aspirin 1000mg/day) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed.Results52 participants with HIV-associated TBM were randomised. 59% had mild disease (MRC Grade 1) vs 39% (Grade 2) vs 2% (Grade 3). 33% had microbiologically-confirmed TBM; 41% ‘possible’, 25% ‘probable’. AESI or death occurred in 10/16 (63%) (arm 3) vs 4/14 (29%) (arm 2) vs 6/20 (30%) (arm 1) (p = 0.083). The cumulative proportion of AESI or death (Kaplan-Meier) demonstrated worse outcomes in arm 3 vs arm 1 (p = 0.04), however only one event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) at day 56 between arms.ConclusionsHigh-dose rifampicin and adjunctive linezolid can safely be added to SOC in HIV-associated TBM. Larger studies are required to evaluate whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit.

Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately.

This JAMA Patient Page explains the symptoms, spread, diagnosis, treatment, and prevention of bacterial meningitis, an infection that causes inflammation of the tissues surrounding the brain and spinal cord.

This review summarizes current evidence on the epidemiology, diagnosis, and treatment of bacterial meningitis.

Abstract Background Descriptions of the patterns of acute/subacute cerebral infarction (ASCI) in HIV-negative patients with cryptococcal meningitis (CM) are scarce, and the predictors of ischemic stroke and outcomes following ASCI remain unclear. Aim To study the clinical characteristics and evaluate the predictors of ASCI in HIV-negative patients with CM and assess the impact of ischemic stroke on the outcomes of the patients. Methods We retrospectively analyzed the data of 61 HIV-negative patients with CM treated between January, 2016 and February, 2022, and among them, 53 patients with complete neuroimaging and cerebrospinal fluid (CSF) data were enrolled in this study. The cohort was stratified by the occurrence of ASCI diagnosed based on MRI evidences for comparison of the clinical characteristics (consciousness disturbance, GCS score, duration of symptoms, and treatment), CSF parameters, imaging findings (meningeal inflammation, hydrocephalus, posterior fossa exudates) and outcomes of the patients. A favorable outcome was defined as a modified Rankin scale (mRS) score ≤ 2 and a poor outcome as a mRS score > 2. Logistic regression analysis was used to identify the risk factors of ASCI in the HIV-negative patients with CM. Results Of the 53 HIV-negative patients with CM, 14 (26.4%) had ASCI. The incidences of fever, headache, neck stiffness, duration of symptoms, CSF parameters, meningeal enhancement in brain MRI and the treatment regimens were similar between the patients with and those without ASCI. Most of the infarcts (92.9%) were of the lacunar type, involving both the anterior and posterior territories. Basal ganglia-corona radiata and the brainstem-cerebellum were the most frequently involved sites. Univariate logistic regression analysis suggested that consciousness disturbance (P = 0.002), MRI evidence of hydrocephalus (P = 0.042) and posterior fossa exudates (P = 0.028) were predictors of ASCI in these HIV-negative patients with CM. Multivariate analysis identified consciousness disturbance as a significant predictor of ASCI (P = 0.020). Compared with the patients without ASCI, the HIV-negative patients with CM and ASCI had poorer outcomes (P = 0.001). Conclusion ASCI can occur in HIV-negative patients with CM, presented commonly as multiple lacunar infarctions involving all the cerebrovascular territories. The presence of consciousness disturbance, hydrocephalus and posterior fossa exudates may increase the risk of ASCI in patients with CM. ASCI is associated with a poor outcome of the HIV-negative patients with CM. …

Antimicrobial Agents and Chemotherapy, Ahead of Print. …

Proceedings of the National Academy of Sciences, Volume 119, Issue 45, November 2022.

Abstract

Background

The Meningitis/Encephalitis FilmArray® Panel (ME panel) was approved by the U.S. Food and Drug Administration in 2015 and provides rapid results when assessing patients with suspected meningitis or encephalitis. These patients are evaluated by various subspecialties including pediatric hospital medicine (PHM), pediatric emergency medicine (PEM), pediatric infectious diseases, and pediatric intensive care unit (PICU) physicians. The objective of this study was to evaluate the current use of the ME panel and describe the provider and subspecialty practice variation.

Methods

We conducted an online cross-sectional survey via the American Academy of Pediatrics Section of Hospital Medicine (AAP-SOHM) ListServe, Brown University PEM ListServe, and PICU Virtual pediatric system (VPS) Listserve.

Results

A total of 335 participants out of an estimated 6998 ListServe subscribers responded to the survey. 68% reported currently using the ME panel at their institutions. Among test users, most reported not having institutional guidelines on test indications (75%) or interpretation (76%). 58% of providers self-reported lack of knowledge of the test’s performance characteristics. Providers from institutions that have established guidelines reported higher knowledge compared to those that did not (51% vs. 38%; p = 0.01). More PHM providers reported awareness of ME panel performance characteristics compared to PEM physicians (48% vs. 27%; p = 0.004); confidence in test interpretation was similar between both groups (72 vs. 69%; p = 0.80).

Conclusion

Despite the widespread use of the ME panel, few providers report having institutional guidelines on test indications or interpretation. There is an opportunity to provide knowledge and guidance about the ME panel among various pediatric subspecialties.

…

AbstractBackgroundCognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence is not described.MethodsA cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with HIV-associated TBM 6 months post-diagnosis. Cognitive performance was compared to a comparator group of 66 people living with HIV (PLWH) without a history of TB. A secondary comparison was made between TBM cases and 26 participants with HIV 6-months post diagnosis of TB outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence.ResultsIn TBM, 16/34 (47%) of participants had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in TBM cases compared to PLWH (mean T-score 41 vs 48, p < 0.001). TBM cases also had lower global cognition compared to those with non-CNS TB (mean global T score 41 vs 46, p = 0.016). Functional outcomes did not significantly correlate with cognitive performance in the sub-group of participants where this was assessed (n = 19).ConclusionsLow cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS TB disease. Further studies are needed to understand longer term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties to improve outcomes in TBM.

Journal of Medical Virology, Accepted Article.

We aimed to derive and validate a risk score to differentiate patients with bacterial meningitis from those with viral meningitis or encephalitis, among patients presenting with CSF leukocytosis and a negative Gram stain.

AbstractThe AMBITION-cm phase III randomized controlled trial, conducted in east and southern Africa, showed that a single high dose (10 mg/kg) of liposomal amphotericin B, given with an optimized oral backbone of fluconazole and flucytosine, was non-inferior to the World Health Organization (WHO)-recommended regimen of seven days of amphotericin B deoxycholate plus flucytosine for treatment of HIV-associated cryptococcal meningitis, and has been incorporated into updated WHO treatment guidelines. We believe the trial findings also have important implications for the treatment of HIV-associated cryptococcal meningitis in high-income settings. We advance the arguments, supported by evidence where available, that the AMBITION-cm study regimen is likely to be (i) as fungicidal as the currently recommended 14-day liposomal amphotericin based treatments, (ii) better tolerated with fewer adverse effects, and (iii) confer significant economic and practical benefits, therefore should be included as a treatment option in guidance for HIV-associated cryptococcal treatment in high-income country settings.

Abstract

Background

To investigate the clinical features and risk factors of ventriculoperitoneal shunt (VPS) associated surgical site infections (SSIs) in HIV-negative patients with cryptococcal meningitis (CM).

Methods

We retrospectively reviewed the medical records of HIV-negative patients with CM underwent VPS operation admitted to The Third Affiliated Hospital of Sun Yat-sen University in Southwest China over the past 7 years.

Results

193 patients were included, of whom 25 (12.95%) had SSIs in 6 (median duration, 1–48 days) days after operation. Compared with patients without SSIs, patient with SSIs tended to be shorter preoperative stay. 52% patients in SSIs group and 25% patients in no-SSIs group underwent VPS operations within 3 days after admission (p = 0.017). Although body temperature and infectious indicators slightly elevated postoperative in both groups. The patients with SSIs experienced more fever; more central nervous system symptoms; higher PCT value and lower cerebrospinal fluid (CSF) glucose in contrast to the no-SSIs group. Multivariate regression analysis found a 2.653 fold increase in the risk of infection for every 1 °C increase in postoperative body temperature. Among the 25 patients, 9 patients had positive culture results, three samples reported to be oxacillin resistant coagulase-negative Staphylococci.

Conclusions

SSIs was one of the serious surgical complications after VPS operation. High body temperature, the occurrence of dizziness and headache, low postoperative hemoglobin are risk factors. Postoperative patients with high fever, high PCT and low CSF glucose should be paid more attention to.

…

Neurological symptoms of COronaVIrus Disease-2019 (COVID-19) are highly frequent and disabling. [Wan D et al, 2021] Severe neurological disorders such as encephalitis, meningitis, Guillain-Barré syndrome, and vascular events have been described as anecdotal reports or in case series. Here, we describe the first case of a female patient infected with Omicron SARS-CoV-2 BA.2 Variant of Concern (VoC) meningitis with newly diagnosed central demyelinating disease.

by Fangyu Shi, Xia Qiu, Mingjing Yu, Yan Huang

Objective Tuberculous meningitis (TBM) is one of the most devastating TB. Accurate identification of TBM is helpful to eliminate TB. Therefore, we assessed the performance of TBAg stimulated IFN-γ (IGRA) and unstimulated IFN-γ in blood and cerebrospinal fluid (CSF) for diagnosing TBM. Methods We searched Web of Science, PubMed, Embase and the Cochrane Library databases until March 2022. Bivariate and hierarchical summary receiver operating characteristic models were employed to compute summary estimates for diagnostic accuracy parameters of IGRA and unstimulated IFN-γ in blood and CSF for diagnosing TBM. Results 28 studies including 1,978 participants and 2,641 samples met the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of blood IGRA were separately as 0.73, 0.83, 4.32, 0.33, 13.22 and 0.86, indicating a good diagnostic accuracy of blood IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IGRA were separately as 0.77, 0.91, 8.82, 0.25, 34.59 and 0.93, indicating good diagnostic accuracy of CSF IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IFN-γ were separately as 0.86, 0.92, 10.27, 0.16, 65.26 and 0.95, suggesting CSF IFN-γ provided excellent accuracy for diagnosing TBM. Conclusions For differentiating TBM from non-TBM individuals, blood and CSF IGRA are good assays and unstimulated CSF IFN-γ is an auxiliary excellent marker.…

Abstract

Background

The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.

Methods

A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.

Results

Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.

Conclusion

Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.

Clinical Trials: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

…

: Providing country-specific estimates of case-fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress towards the World Health Organisation's roadmap to “Defeating meningitis by 2030”.

Coagulopathy may deter physicians from performing a lumbar puncture.

To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.

To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.

To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM).

The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome.

The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.

To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections.

Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.

Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.

Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.

Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse.