Neuroinfektioner

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.

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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.

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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.

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: 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”.

New England Journal of Medicine, Volume 387, Issue 4, Page 380-381, July 2022. …

AbstractBackgroundIt is unknown whether persons with symptomatic cryptococcal meningitis detected during routine blood cryptococcal antigen (CrAg) screening have better survival than persons presenting with overt meningitis.MethodsWe prospectively enrolled HIV-infected Ugandans with cryptococcal meningitis from December 2018 to December 2021. Participants were treated with amphotericin-based combination therapy. We compared outcomes between persons who were CrAg screened then referred to hospital versus those presenting directly to the hospital with symptomatic meningitis.ResultsAmong 489 participants with cryptococcal meningitis, 40% (194/489) received blood CrAg screening and were referred to hospital (median time to referral 2 days, IQR 1-6). CrAg screened persons referred to hospital had lower 14-day mortality than non-CrAg screened persons who presented directly to hospital with symptomatic meningitis (12% vs. 21%; Hazard Ratio = .51; 95%CI, .32–.83; p = .006). Fewer CrAg screened participants had altered mental status versus non-CrAg screened participants (29% vs. 41%; p = .03). CrAg screened persons had lower quantitative CSF culture burden (median 4,570 CFU/mL [IQR, 11–100,000] vs. 26,900 CFU/mL [IQR, 182–324,000]; p = .01) and lower CSF opening pressures (median 190 mmH2O [IQR, 120–270] vs. 225 mmH2O [IQR, 140–340]; p = .004) compared with non-CrAg screened persons.ConclusionsSurvival from cryptococcal meningitis was higher in persons with prior CrAg screening than those without CrAg screening. Altered mental status was the most potent predictor for mortality in a multivariate model. We suggest that CrAg screening detects cryptococcal meningitis at an earlier stage, as evidenced by a favorable baseline risk profile and notably fewer persons with altered mental status.

Abstract

Background

Meningitis is considered a life-threatening infection with high mortality all over the world. Hemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae) are regarded as the two most common infectious agents causing bacterial meningitis. This study aimed to identify H. influenzae and S. pneumoniae serotypes in blood and cerebrospinal fluid (CSF) of pediatric patients with meningitis, using polymerase chain reaction (PCR).

Methods

This multi-center cross-sectional study included 284 children with suspected meningitis referred to 4 target hospitals. Overall, 412 samples (128 blood and 284 CSF samples) were obtained from the patients from November 14, 2016 to November 15, 2017. The extracted DNA was examined using multiplex real time PCR to screen for S. pneumoniae and H. influenzae. S. pneumoniae serotyping was also done by multiplex PCR.

Results

Out of 284 CSF specimens, 22 were positive for ply S. pneumoniae. Of 20 DNA samples meeting the Quality Control (QC) standards for serotyping, 7 (35%), 6 (30%), 2 (10%), 2 (10%), 2 (10%), 1 (5%), 1 (5%), 1 (5%), 1 (5%) and 1 (5%) were positive for serotypes 3, 11A, 6A, 14, 7C, 23F, 23B, 19A, and 19F and 5, respectively. Overall, nine samples were positive for two serotypes, of whom 3 and 11A were the most common from Tehran province. Of note, one of these CSF samples showed a new co-infection with serotypes 7C and 14. Also, 6 samples (30%) were positive for H. influenzae detected by bexA primer. None of the blood samples were positive for S. pneumoniae or H. influenzae.

Conclusion

Co-infection with S. pneumoniae serotypes can occur in bacterial meningitis and it might be missed if all serotypes are not evaluated in CSF specimens.

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Abstract

Background

Meningitis is considered a life-threatening infection with high mortality all over the world. Hemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae) are regarded as the two most common infectious agents causing bacterial meningitis. This study aimed to identify H. influenzae and S. pneumoniae serotypes in blood and cerebrospinal fluid (CSF) of pediatric patients with meningitis, using polymerase chain reaction (PCR).

Methods

This multi-center cross-sectional study included 284 children with suspected meningitis referred to 4 target hospitals. Overall, 412 samples (128 blood and 284 CSF samples) were obtained from the patients from November 14, 2016 to November 15, 2017. The extracted DNA was examined using multiplex real time PCR to screen for S. pneumoniae and H. influenzae. S. pneumoniae serotyping was also done by multiplex PCR.

Results

Out of 284 CSF specimens, 22 were positive for ply S. pneumoniae. Of 20 DNA samples meeting the Quality Control (QC) standards for serotyping, 7 (35%), 6 (30%), 2 (10%), 2 (10%), 2 (10%), 1 (5%), 1 (5%), 1 (5%), 1 (5%) and 1 (5%) were positive for serotypes 3, 11A, 6A, 14, 7C, 23F, 23B, 19A, and 19F and 5, respectively. Overall, nine samples were positive for two serotypes, of whom 3 and 11A were the most common from Tehran province. Of note, one of these CSF samples showed a new co-infection with serotypes 7C and 14. Also, 6 samples (30%) were positive for H. influenzae detected by bexA primer. None of the blood samples were positive for S. pneumoniae or H. influenzae.

Conclusion

Co-infection with S. pneumoniae serotypes can occur in bacterial meningitis and it might be missed if all serotypes are not evaluated in CSF specimens.

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Objectives

To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.

Design

Retrospective cohort study.

Setting

64 UK and Irish hospitals.

Participants

1471 adults with community-acquired meningitis of any aetiology in 2017.

Results

None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3–9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10).

Conclusion

This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.

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: Cytomegalovirus (CMV) viremia is associated with increased mortality in persons with HIV. We previously demonstrated that CMV viremia was a risk factor for 10-week mortality in antiretroviral therapy (ART)-naïve persons with cryptococcal meningitis. We investigated whether similar observations existed over a broader cohort of HIV-associated meningitis at 18 weeks.

LETTER…

To study the clinical features of bacterial meningitis in myeloma patients.

Fungal meningitis is typically diagnosed by culture, sometimes by molecular diagnosis or histology. However, cultures lack sensitivity and require several days to grow. A sensitive biomarker that could rapidly identify a fungal central nervous system (CNS) infection could be one step among several towards improving diagnosis and treatment.

Cryptococcal meningitis, a major cause of meningitis in adults living with HIV infection, accounts for 15% of global HIV-associated mortality.1 Treatment of cryptococcal meningitis involves three phases: induction, consolidation, and maintenance. The induction phase, which aims at reducing cerebral and meningeal fungal burden crucial for early survival, requires combination antifungal therapy and management of increased cerebrospinal fluid intracranial pressure. WHO in 2018 recommended at induction either 1-week amphotericin B deoxycholate plus flucytosine followed by high-dose fluconazole or 2-week oral fluconazole plus flucytosine.

In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit.

Abstract

Purpose

In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the “meningitis/encephalitis panel” (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP’s efficacy in paediatric patients.

Methods

Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children’s Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics.

Results

Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [−1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397).

Conclusions

The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients.

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Abstract

Purpose

In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the “meningitis/encephalitis panel” (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP’s efficacy in paediatric patients.

Methods

Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children’s Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics.

Results

Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [−1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397).

Conclusions

The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients.

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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.