Hélène Pailhoriès, Rachel Chenouard, Matthieu Eveillard, Marie Kempf, Sabine Pereyre, Cécile Bébéar, Carole Lemarié

Abstract Background Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts. Case presentation We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status. Conclusions Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.…

Abstract Background Ruxolitinib is a highly potent janus kinase inhibitor that places its users at risk for various bacterial infections and viral reactivation. However new reports are also emerging that suggest greater immunosuppression and risk for fungal disease. Case presentation We report the case of a 51 year-old veteran from Guam, treated with ruxolitinib for polycythemia vera, who developed disseminated histoplasmosis and concurrent cryptococcal meningitis. Conclusion This case draws attention to the degree of immunosuppression that may be seen with this drug and the need for heightened vigilance for opportunistic infections in those treated with inhibitors of janus kinase/signal transducers and activators of transcription (JAK/STAT) such as ruxolitinib.…

Verajit Chotmongkol and Sittichai Khamsai

Abstract Background Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject. Methods Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values. Results A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases. Conclusions Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.…

Abstract Background Ischemic stroke is a common complication in patients with tuberculous meningitis (TBM), which is associated with poor clinical outcome. However, risk factors of stroke in TBM patients were not fully understood, especially in those young adults. Therefore, the aim of our study was to identify risk factors for acute ischemic stroke in young adults with TBM. Methods TBM patients (18 to 50 years) without cerebral vascular risk factors were prospective recruited between Feb 2014 and Dec 2017. Patients were defined as stroke group and non-stroke group by brain magnetic resonance imaging (MRI). Demographic characteristics, clinical presentations, cerebrospinal fluid (CSF) examination, basal meningeal enhancement, hydrocephalus, tuberculoma and clinical outcome were compared between two groups. Binary logistic regression was performed to determine risk factors for acute ischemic stroke in young TBM patients. Results Fifty-two patients with TBM were included and 12 (23.1%) patients were in stroke group. Patients in stroke group were older. Clinical presentations were comparable between two groups except headache was more common in TBM patients with stroke. In CSF examination, TBM patients with stroke had higher CSF white blood cell. By MRI, patients in stroke group were more likely to have basal meningeal enhancement but less likely to present tuberculoma. Compared to non-stroke group, patients in stroke group had worse short-term clinical outcome. In logistic regression, age (OR = 1.297; 95%CI 1.067, 1.576), CSF white blood cell (OR = 1.023; 95%CI 1.005, 1.042) and basal meningeal enhancement (OR = 23.913; 95%CI 1.398, 408.975) were independent risk factors for stroke. However, tuberculoma (OR = 0.005; 95%CI 0.000, 0.254) was negative related with stroke. Conclusions About a quarter of young adults with TBM have acute ischemic stroke which may lead to poor clinical outcome. Age, CSF white blood cell and basal meningeal enhancement are risk factors for acute ischemic stroke in young adults with TBM.…

Shiri T, Loyse A, Mwenge L, et al.

AbstractBackgroundMortality from cryptococcal meningitis remains very high in Africa. In the ACTA trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2-week amphotericin-based regimens. However, many African settings treat with FLU monotherapy and the cost effectiveness of adding 5FC to FLU is uncertain. MethodsEffectiveness and costs of FLU+5FC were taken from ACTA, which included costing analysis at the Zambian site. Effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtraction of 5FC drug and monitoring costs.Cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis assessed uncertainties, and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER.ResultsMean costs per patient were US$847 (95%CI:776-927) for FLU+5FC, and US$628 (95%CI:557-709) for FLU. 10 week mortality was 35.1% (95%CI 28.9-41.7) with FLU+5FC and 53.8% (95%CI: 43.1–64.1) with FLU. At the current 5FC price of $US1.30 per 500mg tablet, the ICER of 5FC+FLU versus FLU alone was US$65 (95%CI: 28-208) per life year saved. Reducing 5FC cost to between US$0.80 and US$0.40 per 500mg resulted in an ICER between US$44 and US$28 per life year saved.Conclusions Addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and if made available widely could substantially reduce mortality rates among HIV-infected persons in Africa.

Houlihan, Catherine F.; Bharucha, Tehmina; Breuer, Judith

Purpose of review Central nervous system (CNS) infections present an ongoing diagnostic challenge for clinicians, with an aetiological agent remaining unidentified in the majority of cases even in high-income settings. This review summarizes developments in a range of diagnostic methods published in the past 18 months. Recent findings Several commercial assays exist for the detection of viral, bacterial and fungal pathogens using single multiplex PCR. Multicentre validation of the Biofire FilmArray panel illustrated high sensitivity for bacterial and fungal pathogens, but poor results for Cryptococcus species detection. The development of microarray cards for bacterial CNS pathogens shows promise but requires further validation. Few developments have been made in proteomics and transcriptomics, contrasted with significant increase in the use of metagenomic (or unbiased) sequencing. Novel viruses causing CNS infection have been described using this technique but contamination, cost, expertise and turnaround time requirements remain restrictive. Finally, the development of Gene Xpert and Ultra has revolutionized tuberculosis meningitis diagnostics with newly released recommendations for their use from the WHO. Summary Progress has been made in the clinical validation and international recommendation of PCR-based tests for CNS infections. Sequencing techniques present the most dynamic field, although significant ongoing challenges persist. Correspondence to Professor Judith Breuer, Division of Infection and Immunity, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK. Tel: +44 20 3108 2130 (internal 52130); fax: +44 20 3108 2123; e-mail: j.breuer@ucl.ac.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alyssa Mezochow, Kiran Thakur, Isaac Zentner, Selvakumar Subbian, Leonid Kagan, Christopher Vinnard

Abstract Background Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM. Methods Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay. Results The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01). Conclusions The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis. Trial registration The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center (0378–17-TLV, 10/17/2017) and Rabin Medical Center (0270–18-RMC, 11/11/2018) Ethics committees and conforms to recognized standards.…

Muri, L., Perny, M., Zemp, J., Grandgirard, D., Leib, S. L.

Despite available antibiotic therapy, pneumococcal meningitis (PM) is associated with a case fatality rate of up to 30% in high-income countries. Survivors often suffer from severe lifelong disabilities. An excessive inflammatory reaction drives the pathophysiology leading to brain damage and neurologic sequelae. We aimed to improve the outcome of experimental PM by simultaneously targeting different pathophysiological mechanisms with combined adjunctive therapies previously shown to be neuroprotective. In vitro, the anti-inflammatory effect of doxycycline and daptomycin were evaluated on primary rat astroglial cells stimulated with S. pneumoniae. Eleven day old infant Wistar rats were infected intracisternally with S. pneumoniae and randomized for treatment with ceftriaxone or combination adjuvant therapy consisting of ceftriaxone, daptomycin and doxycycline. During acute PM, combined adjuvant therapy with ceftriaxone, daptomycin and doxycycline increased survival rate from 64.1% to 85.8% (p

ter Horst L, Brouwer M, van der Ende A, et al.

AbstractBackgroundCerebrospinal fluid (CSF) leakage is a risk factor for developing bacterial meningitis.Materials/methodsWe analyzed episodes of community-acquired bacterial meningitis associated with CSF leakage from a prospective nationwide cohort study.ResultsCSF leakage was identified in 65 episodes of 2022 episodes (3%) in 53 patients. The cause of CSF leakage was identified in 49 of 65 episodes (75%), most and most commonly consisted of ear-nose-throat surgery (19 of 49 episodes [29%]) and remote head trauma (15 of 49 episodes [23%]). The episode was a recurrent meningitis episode in 38 patients (59%). Of the recurrent episodes, 27 had known CSF leakage (71%) of whom 20 (53%) had previous surgery aiming to close the leak. Nine patients (38%) with known CSF leakage had been vaccinated (23-valent pneumococcal vaccine in 9 patients, meningococcal serogroup C vaccine in 2, meningococcal serogroup A and Haemophilus influenzae type b vaccine each in 1 patient). Streptococcus pneumoniae was cultured in 33 episodes (51%) and H. influenzae in 11 episodes (17%). Most common pneumococcal serotype were 3 (4 episodes), 35B, 9N, 38 and 15C (each 2 episodes). H. influenzae was unencapsulated in all 10 episodes with known capsule type. The outcome was unfavorable in 8 episodes (12%) and no patient died.ConclusionBacterial meningitis in patients with CSF leakage have a high recurrence rate, despite surgical repair or vaccination, and outcome is generally favorable. CSF leakage should be suspected in patients with bacterial meningitis presenting with liquorrhoea, recurrent meningitis or with disease caused by H. influenzae.

Kimaro G, Guinness L, Shiri T, et al.

AbstractBackgroundA randomised trial demonstrated that among late-stage HIV-infected patients initiating ART, screening serum for cryptococcal antigen (CrAg) combined with community -based adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness estimates.MethodsHIV-infected adults with CD4 count

Wake R, Govender N, Omar T, et al.

AbstractBACKGROUNDCryptococcal antigen (CrAg) screening and treatment with pre-emptive fluconazole reduces the incidence of clinically-evident cryptococcal meningitis in individuals with advanced HIV-disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts.METHODSWe conducted a cohort study to investigate causes of morbidity and mortality during six-months follow-up, among asymptomatic CrAg-positive and CrAg–negative (ratio of 1:2) HIV-infected patients with CD4 counts

Tucker, E. W., Pieterse, L., Zimmerman, M. D., Udwadia, Z. F., Peloquin, C. A., Gler, M. T., Ganatra, S., Tornheim, J., Chawla, P., Caoili, J. C., Ritchie, B., Jain, S. K., Dartois, V., Dooley, K. E.

Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug (MDR-) and extensively drug resistant-tuberculous meningitis (TBM), specifically, is nearly uniformly fatal, with little information to guide treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated TB drug with a low minimal inhibitory concentration (1-12 ng/mL) against Mycobacterium tuberculosis. It is used for pulmonary MDR-TB, but CNS pharmacokinetic (PK) data in TBM are not available. In the present study, we measured DLM concentrations in the brain and cerebrospinal fluid (CSF) of six rabbits, with and without experimentally-induced TBM, receiving single-dose DLM. We report steady-state CSF concentrations from three patients receiving DLM as part of multidrug-treatment who underwent therapeutic drug monitoring. Drug was quantified using LCMS/MS. In rabbits and humans, mean CSF concentrations (rabbit [1.26 ng/mL at 9h, 0.47 ng/mL at 24h]; human [48 ng/mL at 4h]) were significantly lower than plasma (rabbits [124 ng/mL at 9h, 14.5 ng/mL at 24h]; human [726 ng/mL at 4h]), but estimated free CSF/plasma ratio were >1. In rabbits, brain DLM concentrations were 5-fold higher than in plasma (mean 518 ng/mL at 9h, 74.0 ng/mL at 24h). All patients with XDR-TBM receiving DLM experienced clinical improvement and survival. Collectively, these results suggest that DLM achieves adequate concentrations in brain tissue. Despite relatively low total CSF drug levels, free drug may be sufficient and DLM may have a role in treating TBM. More studies are needed to develop a fuller understanding of its distribution over time with treatment, and clinical effectiveness.…

Abstract Background Purulent meningitis (PM) is a serious life-threatening infection of the central nervous system (CNS) by bacteria or fungi and associated with high mortality and high incidence of CNS sequelae in children. However, the conventional cerebrospinal fluid (CSF) culture method is time-consuming and has a low sensitivity. Methods Our study developed a real-time PCR-based purulent meningitis-TaqMan array card (PM-TAC) that targeted 21 PM-related pathogens and could produce results within 3 h. Primers and probes were adapted from published sources possibly. The performance of them were evaluated and optimized and then they were spotted on TAC. Results The PM-TAC showed a sensitivity and specificity of 95 and 96%, respectively. For all of the 21 targeted pathogens, the PM-TAC assay had a LOD ranging from 5 copies/reaction to 100 copies/reaction, an intra-assay variation of 0.07–4.45%, and an inter-assay variation of 0.11–6.81%. Of the 15 CSF samples collected from patients with PM after empiric antibiotic therapies, the positive rate was 53.3% (8/15) for our PM-TAC assay but was only 13.3% (2/15) for the CSF culture method. Of the 17 CSF samples showing negative CSF culture, the PM-TAC assay identified a case of Neisseria meningitidis infection. Furthermore, all of the 10 CSF samples from patients without CNS infection showed negative for the PM-TAC assay. Conclusions Our PM-TAC assay also demonstrated that the pathogen loads in the CSF samples correlated with the severity of PM. Thus, the PM-TAC may be helpful to improve the prognosis of PM and clinical outcomes from antibiotic therapies.…

Zihui Li, Liping Pan, Lingna Lv, Jing Li, Hongyan Jia, Boping Du, Qi Sun, Zongde Zhang

Tuberculous meningitis (TBM) is still difficult to diagnose. Digital PCR (dPCR) is a novel method which can quantify trace nucleic acids. This study sought to evaluate the diagnostic accuracy of dPCR analysis of cerebrospinal fluid (CSF) for TBM.

Ji-Soo Kwon, Joung Ha Park, Ji Yeun Kim, Hye Hee Cha, Min-Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Yong Seo Koo, Sang-Beom Jeon, Sang-Ahm Lee and Sung-Han Kim

Abstract. In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows: ADA > 6.95 U/L, 70% and 81%; IL-12p40 > 52.04 pg/mL, 80% and 73%; IL-13 > 0.44 pg/mL, 90% and 47%; MIP-1α > 8.83 pg/mL, 80% and 62%; soluble PD-1 > 35.87 pg/mL, 80% and 63%; soluble PD-L1 > 24.19 pg/mL, 80% and 61%; CSF-MC ELISPOT > 13.5 spots/250,000 CSF-MC, 30% and 91%; and PBMC ELISPOT > 14 spots/250,000 PBMCs, 50% and 78%, respectively. Therefore, CSF IL-12p40, IL-13, MIP-1α, and soluble PD-1 and PD-L1 concentrations appear to be useful adjuncts for diagnosing TBM.…

Brechje de Gier, Merel N. van Kassel, Elisabeth A. M. Sanders, Diederik van de Beek, Susan J. M. Hahné, Arie van der Ende, Merijn W. Bijlsma

by Brechje de Gier, Merel N. van Kassel, Elisabeth A. M. Sanders, Diederik van de Beek, Susan J. M. Hahné, Arie van der Ende, Merijn W. Bijlsma Background Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis worldwide. We aimed to estimate the current burden of neonatal invasive GBS disease in the Netherlands, as a first step in providing an evidence base for policy makers on the potential benefits of a future maternal GBS vaccine. Methods Surveillance of neonatal invasive GBS occurs at the National Reference Laboratory for Bacterial Meningitis, where culture isolates from cerebrospinal fluid and blood are sent by diagnostic laboratories. From the number of cultures we estimated the incidence of neonatal (age 0–90 days) GBS meningitis and sepsis. We constructed a disease progression model informed by literature and expert consultation to estimate the disease burden of neonatal invasive GBS infection. As many neonates with a probable GBS sepsis are never confirmed by blood culture, we further estimated the disease burden of unconfirmed cases of probable GBS sepsis in sensitivity analyses. Results An estimated 97 cases and 6.5 deaths occurred in the Netherlands in 2017 due to culture positive neonatal invasive GBS infection. This incidence comprised 15 cases of meningitis and 42 cases of sepsis per 100.000 births, with an estimated mortality of 3.8 per 100.000 live births. A disease burden of 780 disability-adjusted life years (DALY) (95% CI 650–910) or 460 DALY per 100.000 live births was attributed to neonatal invasive GBS infection. In the sensitivity analysis including probable neonatal GBS sepsis the disease burden increased to 71 cases and 550 DALY (95% CI 460–650) per 100.000 live births. Conclusion In conclusion, neonatal invasive GBS infection currently causes a substantial disease burden in the Netherlands. However, important evidence gaps are yet to be filled. Furthermore, cases of GBS sepsis lacking a positive blood culture may contribute considerably to this burden potentially preventable by a future GBS vaccine.…

A. Balkhair, H.B. Taher, I. Al Busaidi, M. Al Amin, A. Al-Khirbash, B. Al Adawi, T. Al-Siyabi

We presented a patient with disseminated strongyloidiasis post chemotherapy for lymphoblastic lymphoma.

Joseph M Ryan, Henry M Feder

A 12-day-old baby was admitted to our hospital with a fever, irritability, and poor feeding. His temperature was 39° C. On physical examination, he was irritable but consolable. His anterior fontanelle was full but not bulging. Laboratory tests included a complete blood cell count, which showed a white blood cell count of 4·8 × 109 per L, with 72% neutrophils. Analysis of the infant's cerebrospinal fluid (CSF) showed 3 050 white blood cells per μL, with 94% neutrophils, protein concentration was 110 mg/dL, and glucose concentration 49 mg/dL (normal 60–80).

Thao L, Wolbers M, Heemskerk A, et al.

AbstractBackgroundPre-treatment predictors of death from tuberculous meningitis (TBM) are well-established, but whether outcome can be predicted more accurately after the start of treatment by updated clinical variables is unknown. Hence, we developed and validated models that dynamically predict mortality using time-updated Glasgow coma score (GCS) and plasma sodium measurements, together with patient baseline characteristics.MethodsWe included 1048 adults from four TBM studies conducted in southern Vietnam from 2004-2016. We used a landmarking approach to predict death within 120 days after treatment initiation using time-updated data during the first 30 days of treatment. Separate models were built for patients with and without human immunodeficiency virus (HIV) infection. We used the area under the receiver operating characteristic curve (AUC) to evaluate performance of the models at day 10, 20 and 30 of treatment to predict mortality by 60, 90 and 120 days. Our internal validation was corrected for over-optimism using bootstrap. We provide a web-based application that computes mortality risk within 120 days.ResultsHigher GCS indicated better prognosis in all patients. In HIV-infected patients, higher plasma sodium was uniformly associated with good prognosis, whereas in HIV-uninfected patients the association was heterogeneous over time. The bias-corrected AUC of the models ranged from 0.82-0.92 in HIV-uninfected, and 0.81-0.85 in HIV-infected individuals. The models outperformed the previously published baseline models.ConclusionsTime-updated GCS and plasma sodium measurements improved predictions based solely on information obtained at diagnosis. Our models may be used in practice to define those with poor prognosis during treatment.

Ravi Shekhar Jaipuriar, Ravindra Kumar Garg, Imran Rizvi, Hardeep Singh Malhotra, Neeraj Kumar, Amita Jain, Rajesh Verma, Praveen Kumar Sharma, Shweta Pandey and Ravi Uniyal

Abstract. Most deaths in tuberculous meningitis occur in the early part of the illness. We assessed the determinants of early deaths, occurring within 2 months of intensive therapy. We prospectively included consecutive newly diagnosed adults with HIV-negative tuberculous meningitis. Patients were given WHO-recommended antituberculosis treatment and were followed up for 9 months. We enrolled 152 patients. A total of 26 deaths were recorded during 2 months. The logistic regression analysis revealed that papilledema (P = 0.029, odds ratio (OR) = 4.8 [1.2–19.8]), increasing age (P = 0.001, OR = 1.07 [1.03–1.1]), stage-III disease (Glasgow coma scale score ≤ 10; P = 0.01, OR = 4.2 [1.4–12.3]), and hydrocephalus (P = 0.003, OR = 8.4 [2.1–33.6]) were independently associated with death. In addition, cerebral infarcts (P = 0.012, OR = 5.6 [1.5–21.3]), paraparesis (P = 0.004, OR = 8.8 [2.02–38.1]), and age (P = 0.005, OR = 1.05 [1.02–1.09]) were associated with poor functional outcome. In conclusion, disease severity predicts early deaths in tuberculous meningitis.…

Abstract Purpose Many patients with suspected meningitis do not require hospitalization yet are admitted, often resulting in unnecessary care and additional cost. We assessed the possible economic impact of a rapid multiplex test for suspected adult community-acquired meningitis/encephalitis. Methods A model simulated diagnosis, clinical decisions, resource use/costs of standard of care (SOC) and two cerebrospinal fluid (CSF) testing strategies using the FDA-cleared BioFire® FilmArray® System (FA) which provides results in approximately one hour. Results Pathogens detected by FA caused approximately 74% of cases, 97% of which would be accurately diagnosed with FA. False positives and false negatives more often led to extended/unnecessary admission than inappropriate discharge/missed admission. Mean cost per case ranged from 16829 to 20791. A strategy of testing all suspected cases yielded greater savings (2213/case) than testing only those with abnormal CSF (812/case) and both were less expensive than SOC. Conclusion This economic analysis demonstrates that FA can inform more appropriate clinician decisions resulting in cost savings with greater economic benefits achievable with syndromic testing of all cases, rather than SOC or targeted syndromic testing.…

G. Oligbu et al.

Abstract Background Group B Streptococcus (GBS) is an important pathogen that causes high mortality and morbidity in young infants. However, data on clinical manifestations between different GBS serotypes and correlation with molecular epidemiology are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, clinical features and molecular characteristics of invasive GBS isolates recovered from Taiwanese infants. Methods From 2003 to 2017, 182 non-duplicate GBS isolates that caused invasive disease in infants less than one year of age underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. The clinical features of these infants with GBS disease were also reviewed. Results Of the 182 patients with invasive GBS disease, 41 (22.5%) were early-onset disease, 121 (66.5%) were late-onset disease and 20 (11.0%) were late late-onset disease (> 90 days of age). All these patients were treated with effective antibiotics on time. Among them, 51 (28.0%) had meningitis, 29 (16.0%) had neurological complications, 12 (6.6%) died during hospitalization, and 15 (8.8%) out of 170 patients who survived had long-term neurological sequelae at discharge. Serotype III GBS strains accounted for 64.8%, followed by serotype Ia (18.1%) and Ib (8.2%). MLST analysis revealed 11 different sequence types among the 182 isolates and ST-17 was the most dominant sequence type (56.6%). The correlation between serotype III and ST17 was evident, as ST17 accounted for 87.3% of all serotype III isolates. There was an obvious increasing trend of type III/ST-17 GBS that caused invasive disease in infants. All isolates were susceptible to penicillin, cefotaxime, and vancomycin, while 68.1 and 65.9% were resistant to erythromycin and clindamycin, respectively. Conclusions Despite timely and appropriate antibiotic treatment, a significant proportion of invasive GBS disease still inevitably causes adverse outcomes. Further study to explore preventive strategies and development of serotype-based vaccines will be necessary in the future.…

M. Rebelo et al.

Anna Marchese, Luisa Santoriello, Giovanni Riccio, Erika Coppo, Giuliana Carrega

We report the case of a man who presented with acute otomastoiditis and subsequent meningitis. Cerebrospinal fluid yielded Gram-negative bacteria identified by amplification and 16S rRNA sequencing as Thalassospira profundimaris. To the best of our knowledge, this is the first description of human invasive disease due to Thalassospira genus.

Abstract Staphylococcus condimenti (S. condimenti) is a coagulase-negative bacterium, generally regarded as not pathogenic. Indeed, S. condimenti owes its name to having been isolated from starter cultures of fermented sausage, as well as from fish and soy sauces. To the best of our knowledge, only two cases of human infection caused by this bacterium have been reported. Here, we present a case of meningitis by S. condimenti in a 65-year-old woman who was brought to hospital after having been found unconscious at home. At her arrival, she had a Glasgow coma scale = 3, fever, and hypoxic–normocapnic respiratory failure. Examination of her cerebrospinal fluid showed a slightly increased white blood cell count, normal glucose and protein concentrations. Paired cultures on blood and liquor samples yielded S. condimenti. Targeted antibiotic treatment with ceftriaxone led to a complete recovery. This unique case expands our knowledge on S. condimenti as a pathogenic bacterium.…

Wang M, Wang L, Wu P, et al.

AbstractCronobacter sakazakii causes meningitis and necrotizing enterocolitis in premature infants. However, its virulence determinants, especially those specific for strains associated with neonate infections, remain largely unknown. Here, we performed a comparative genomic analysis of 209 C. sakazakii genomes, and eight clonal groups (CGs) were revealed. CG1 and CG2 were found to be significantly associated with neonate infections, and significantly prevalent genes in these two CGs were identified. Of these, a gene encoding the LysR-type regulator CklR, was shown to contribute to bacterial pathogenicity based on animal experiments. We found that CklR directly binds and activates the suf Fe-S cluster biosynthesis operon and high expression of the suf operon increases bacterial resistance to oxidative stress, which increases survival within the host. This leads to a high degree of bacteremia, which contributes to the development of meningitis. Our work revealed a novel virulence factor specific to predominant pathogenic C. sakazakii strains.

Chen T, Mwenge L, Lakhi S, et al.

AbstractBackgroundMortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses.MethodsParticipants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done.ResultsTotal costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91–1210) per life-year saved.ConclusionsBoth 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.

Gregoire, M., Dailly, E., Turnier, P. L., Garot, D., Guimard, T., Bernard, L., Tattevin, P., Vandamme, Y.-M., Hoff, J., Lemaitre, F., Verdier, M.-C., Deslandes, G., Bellouard, R., Sebille, V., Chiffoleau, A., Boutoille, D., Navas, D., Asseray, N.

High dosages of ceftriaxone are used to treat central nervous system infections (CNSI). Dosage adaptation according to the glomerular filtration rate is currently not recommended. Ceftriaxone pharmacokinetics (PK) was investigated by a population approach in patients enrolled in a French multicenter, prospective cohort study who received high-dose ceftriaxone for CNSI as recommended by the French guidelines (75-100 mg/Kg/day without upper limit). Only suspected bacterial meningitis were included in the PK analysis. A population model was developed using Pmetrics. Based on this model, dosing nomogram was developed, using the estimated glomerular filtration rate (eGFR) and the total body weight as covariates to determine the optimal dosage allowing achieving targeted plasma trough concentrations. Efficacy and toxicity endpoints were based on previous reports as follows: total plasma ceftriaxone greater than or equal to 20 mg/L in more than 90% of patients for efficacy and less than or equal to 100 mg/L in more than 90% of patients for toxicity. Based on 153 included patients, a two-compartment model including eGFR and total body weight as covariates was developed. The median value of unbound fraction was 7.57 % and the median value of CSF/plasma ratio 14.39 %. A nomogram was developed according to a twice-daily regimen. High-dose ceftriaxone administration schemes, used to treat meningitis, should be adapted to the eGFR and the weight especially to avoid underdosing using current guidelines.…

Andrew Black, Freddy Sitas, Trust Chibrawara, Zoe Gill, Mmamapudi Kubanje, Brian Williams

by Andrew Black, Freddy Sitas, Trust Chibrawara, Zoe Gill, Mmamapudi Kubanje, Brian Williams Introduction Data on the association between HIV infection and deaths from underlying medical conditions are needed to understand and assess the impact of HIV on mortality. We present data on mortality in the Chris Hani Baragwanath Hospital (CHBH) South Africa and analyse the relationship between each cause of death and HIV. Methods From 2006 to 2009 data were collected on 15,725 deaths including age, sex, day of admittance and of death, HIV status, ART initiation and CD4+ cell counts. Causes of death associated with HIV were cases, causes of death not associated with HIV were controls. We calculate the odds-ratios (ORs) for being HIV-positive and for each AIDS related condition the disease-attributable fraction (DAF) and the population-attributable fraction (PAF) due to HIV for cases relative to controls. Results Among those that died, the prevalence of HIV was 61% and of acquired immune deficiency syndrome (AIDS) related conditions was 69%. The HIV-attributable fraction was 36% in the whole sample and 60% in those that were HIV-positive. Cryptococcosis, Kaposi’s sarcoma and Pneumocystis jirovecii, TB, gastroenteritis and anaemia were highly predictive of HIV with odds ratios for being HIV-positive ranging from 8 to 124, while genito-urinary conditions, meningitis, other respiratory conditions and sepsis, lymphoma and conditions of skin and bone were significantly associated with HIV with odds ratios for being HIV-positive ranging from 3 to 8. Most of the deaths attributable to HIV were among those dying of TB or of other respiratory conditions. Conclusions The high prevalence of HIV among those that died, peaking at 70% in those aged 30 years but still 7% in those aged 80 years, demonstrates the impact of the HIV epidemic on adult mortality and on hospital services and the extent to which early anti-retroviral treatment would have reduced the burden of both. These data make it possible to better assess mortality and morbidity due to HIV in this still high prevalence setting and, in particular, to identify those causes of death that are most strongly associated with HIV.…

Concetta Beninati, Agata Famà, Giuseppe Teti

Streptococcus agalactiae meningitis is a frequent neonatal disease associated with high mortality and permanent neurological damage. Deng et al. (PLoS Pathog., 2019) now show that interactions between the bacterial protein BspC and host cell vimentin participate in the process of invasion of the meninges by this bacterial pathogen.

Hung-Chin Tsai, Yu-Hsin Chen, Chuan-Min Yen, Susan Shin-Jung Lee, Yao-Shen Chen

by Hung-Chin Tsai, Yu-Hsin Chen, Chuan-Min Yen, Susan Shin-Jung Lee, Yao-Shen Chen The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after infection. The Evans blue method and BBB junctional protein expressions were used to measure changes in the BBB. Hematoxylin and eosin staining was used to analyze pathological changes in the mice brains following 1–3 weeks of infection with A. cantonensis. The levels of 14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different isoform distributions of 14-3-3 proteins and changes in BBB junctional proteins in the mice brain meninges. Dexamethasone was injected intraperitoneally from the seventh day post infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional proteins. The amounts of Evans blue, tight junction and 14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in 14-3-3 protein isoforms β and γ in the CSF in the second and third weeks after infection compared to the controls and first week of infection, which were correlated with the severity of BBB damage in brain histology, and Evans blue extravasation. Using IHC to assess the distribution of 14-3-3 protein isoforms and changes in BBB junctional proteins in the mice brain meninges, the expressions of isoforms β, γ, ε, and θ and junctional proteins occludin and claudin-5 in the brain meninges increased over a 3-week period after infection compared to the controls and 1 week after infection. The administration of dexamethasone decreased the expressions of BBB junctional proteins occludin and claudin-5 in the mice brain meninges. Our findings support that 14-3-3 proteins β and γ can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic meningitis caused by A. cantonensis.

Xing X, Bi S, Fan X, et al.

AbstractBackgroundStreptococcus suis is an emerging zoonotic agent. Its natural habitat is the tonsils, which are the main portals of S. suis entry into the bloodstream of pigs. The remarkable variability of the bacteria and complex pathogenic mechanisms make the development of a vaccine a difficult task.MethodFive conserved virulence factors involved in critical events of S. suis pathogenesis were combined and used as an intranasal vaccine (V5). The effect of V5 was investigated with intranasal and systemic challenge models.ResultsV5 immunization induced antibody and T cell responses at the mucosal site and systemically. The immunity promoted clearance of S. suis from the nasopharynx independent of S. suis serotypes and reduced lethality after systemic challenge with S. suis serotype 2. Moreover, mice that survived sepsis from intravenous infection developed meningitis, whereas, none of these mice showed neuropathological symptoms after V5 immunization.ConclusionIntranasal immunization with multiple conserved virulence factors decreases S. suis colonization at the nasopharynx across serotypes and inhibits the dissemination of the bacteria in the host. The protective mucosal immunity effects would potentially reduce S. suis reservoir and prevent S. suis disease in pigs.

Abstract Background Cryptococcosis is a common opportunistic infection in patients infected by Human Immunodeficiency Virus (HIV) and is the second leading cause of mortality in Acquired Immunodeficiency Syndrome (AIDS) patients worldwide. The most frequent presentation of cryptococcal infection is subacute meningitis, especially in patients with a CD4+ T Lymphocytes count below 100 cells/μL. However, in severely immunosuppressed individuals Cryptococcus neoformans can infect virtually any human organ, including the bone marrow, which is a rare presentation of cryptococcosis. Case presentation A 45-year-old HIV-infected male patient with a CD4+ T lymphocyte count of 26 cells/μL who presented to the emergency department with fever and pancytopenia. Throughout the diagnostic evaluation, the bone marrow aspirate culture yielded encapsulated yeasts in budding, identified as Cryptococcus sp. The bone marrow biopsy revealed a hypocellularity for age and absence of fibrosis. It was observed presence of loosely formed granuloma composed of multinucleated giant cells encompassing rounded yeast like organisms stained with mucicarmine, compatible with Cryptococcus sp. Then, the patient underwent a lumbar puncture to investigate meningitis, although he had no neurological symptoms and neurological examination was normal. The cerebrospinal fluid culture yielded Cryptococcus sp. The species and genotype identification step showed the infection was caused by Cryptococcus neoformans var. grubii (genotype VNI). The patient was initially treated with amphotericin B deoxycholate plus fluconazole for disseminated cryptococcosis, according to guideline recommendations. However, the patient developed acute kidney injury and the treatment was switched for fluconazole monotherapy. The symptoms disappeared completely with recovery of white blood cells and platelets counts. Cerebrospinal fluid cultures for fungi at one and two-weeks of treatment were negative. Conclusions Bone marrow infection caused by Cryptococcus neoformans is a rare presentation of cryptococcosis. The cryptococcal infection should be included for differential diagnosis in HIV-infected patients with fever and cytopenias, especially when CD4+ T lymphocytes count is below 100 cells/μL.…

Abstract Background Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited. Methods A retrospective study identifying all children aged

Sühs K, Novoselova N, Kuhn M, et al.

AbstractBackgroundThe tryptophan-kynurenine-NAD+ pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in CNS infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers.MethodsWe measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 220 cerebrospinal fluid samples from patients with bacterial and viral (herpes simplex, varicella zoster, enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (anti-NMDA-R encephalitis, multiple sclerosis), and noninflamed controls (Bell’s palsy, normal pressure hydrocephalus, Tourette syndrome).ResultsKyn concentrations correlated strongly with CSF markers of neuroinflammation (leukocyte count, lactate, and blood-CSF-barrier dysfunction) and were highly increased in bacterial and viral CNS infections, but were low or undetectable in anti-NMDA-R encephalitis, multiple sclerosis, and controls. Trp was decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed combinations of Kyn, Trp and Kyn/Trp ratio with leukocyte count or lactate as accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation. ConclusionsThe Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation.

Abstract Background Amphotericin-induced phlebitis is a common infusion-related reaction in patients managed for cryptococcal meningitis. High-quality nursing care is critical component to successful cryptococcosis treatment. We highlight the magnitude and main approaches in the management of amphotericin-induced phlebitis and the challenges faced in resource-limited settings. Methods We prospectively determined the incidence of amphotericin-induced phlebitis during clinical trials in Kampala, Uganda from 2013 to 2018. We relate practical strategies and challenges faced in clinical management of phlebitis. Results Overall, 696 participants were diagnosed with HIV-related cryptococcal meningitis. Participants received 7–14 doses of intravenous (IV) amphotericin B deoxycholate 0.7–1.0 mg/kg/day for induction therapy through peripheral IV lines at a concentration of 0.1 mg/mL in 5% dextrose. Overall, 18% (125/696) developed amphotericin-induced phlebitis. We used four strategies to minimize/prevent the occurrence of phlebitis. First, after every dose of amphotericin, we gave one liter of intravenous normal saline. Second, we rotated IV catheters every three days. Third, we infused IV amphotericin over 4 h. Finally, early ambulation was encouraged to minimize phlebitis. To alleviate phlebitis symptoms, warm compresses were used. In severe cases, treatment included topical diclofenac gel and oral anti-inflammatory medicines. Antibiotics were used only when definite signs of infection developed. Patient/caregivers’ education was vital in implementing these management strategies. Major challenges included implementing these interventions in participants with altered mental status and limited access to topical and oral anti-inflammatory medicines in resource-limited settings. Conclusions Amphotericin-induced phlebitis is common with amphotericin, yet phlebitis is a preventable complication even in resource-limited settings. Trial registration The ASTRO-CM trial was registered prospectively. ClincalTrials.gov: NCT01802385; Registration date: March 1, 2013; Last verified: February 14, 2018.…

Abstract Background We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. Case presentation The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. Conclusions This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis.…

McAlpine, Alastair; Sadarangani, Manish

Purpose of review This review highlights the recent impacts of vaccines against the major bacterial causes of meningitis in children, and the challenges for further prevention of bacterial meningitis, with a focus on Streptococcus pneumoniae, Neisseria meningitidis and group B Streptococcus. Recent findings Conjugate vaccines against S. pneumoniae and N. meningitidis have resulted in dramatic reductions in bacterial meningitis globally where they have been used. Recent licensure and use of capsular group B meningococcal protein vaccines have further reduced meningococcal meningitis in infants, young children and adolescents for countries with endemic disease and during outbreaks. Summary Existing vaccines to prevent bacterial meningitis in children should be utilized in countries with significant numbers of cases of pneumococcal and/or meningococcal meningitis. Vaccines, which are able to protect against more than 13 serotypes of S. pneumoniae are in clinical trials and should be able to further reduce pneumococcal meningitis cases. Cost effective meningococcal vaccines against non-A capsular groups are needed for low-resource countries. There remains an urgent need for a vaccine against group B Streptococcus, which is a major cause of neonatal meningitis globally and for which no vaccine currently exists. Correspondence to Manish Sadarangani, Vaccine Evaluation Center, BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver BC, Canada V5Z 4H4. Tel: +1 604 875 2422; e-mail: msadarangani@bcchr.ubc.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Lisa Malincarne, Elisabetta Schiaroli, Alessandra Ciervo, Vittoria Scaglione, Maurizio Paciaroni, Fabiola Mancini, Maria Grazia Paglia, Salvatore Cardaci, Maria Bruna Pasticci, Daniela Francisci, Franco Baldelli

Linder KA, Malani PN.

This JAMA Patient Page describes meningococcal meningitis, its causes, risk factors, and prevention measures.

Abstract Background During fulminant meningococcal septicaemia, meningococci are often observed in the cerebrospinal fluid (CSF) although the patients have frequently no meningeal symptoms. Meningococcal meningitis, by contrast, usually features clinical meningeal signs and biochemical markers of inflammation with elevated white blood cell count (pleiocytosis) in the CSF. Cases of typical symptomatic meningitis without these biochemical features are uncommon in adults. Case presentation A 21-year-old male presented with meningococcal purpura fulminans and disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome requiring hospitalization in the Intensive Care Unit. Despite typical meningeal clinical signs, lumbar puncture showed no pleiocytosis, normal glycorachia and normal proteinorachia, whereas the lactate concentration in the CSF was high (5.8 mmol/L). CSF culture showed a high inoculum of serogroup C meningococci. On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week. During the hospitalization, distal ischemic and necrotic lesions were observed, predominantly on the fingertips, which were treated with local and systemic vasodilators. Conclusions We report a rare case of adult meningococcal disease characterized by an intermediate form of meningitis between purulent meningitis and meningeal inoculation from fulminant meningococcal septicaemia, without classical signs of biological inflammation. It highlights the diagnostic value of CSF lactate, which may warrant administration of a meningeal dosing regimen of beta-lactam antibiotics. This case also demonstrates the potential severity of meningococcal myocarditis; we discuss its pathophysiology, which is distinct from other sepsis-related cardiomyopathies. Finally, the observed effects of vasodilators on the meningococcal skin ischemia in this case encourages future studies to assess their efficacy in DIC-associated necrosis.…

Abstract Background Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations. Methods A cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2–59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression. Results Among 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups. Conclusion This study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.…

Sullivan, Kaede V.; Dien Bard, Jennifer

Purpose of review The current review summarizes advances in rapid diagnostic testing that impacts infection prevention and antimicrobial stewardship programs. Recent findings A variety of rapid diagnostic technologies to identify organisms in cultured blood are now available. When coupled with antimicrobial stewardship (ASP), these rapid technologies can optimize antimicrobial utilization and patient outcomes. Two rapid molecular panels that detect organisms related to pneumonia are available and may impact infection prevention surveillance definitions. Three molecular tests are available for the detection of meningitis and encephalitis pathogens. Still, the clinical impact of these broad, multiplexed panels need additional clarification. For Clostridioides difficile infections, ultrasensitive toxin A/B assays may provide enhanced sensitivity and specificity compared with enzyme immunoassay and molecular testing respectively. Finally, the adoption of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI TOF MS) for rapid organism identification is growing. Recent US Food and Drug Administration-clearance of a MALDI TOF MS platform for identification of Nocardia, Mycobacteria, and molds may expedite antimicrobial decisions for infections that traditionally required days to weeks for an identification. Summary Tests with broad diagnostic scope and swift turnaround time are rapidly entering the market. Many impact infection prevention and ASP programs. Collaboration with the microbiology laboratory is crucial to ensure that new tests successfully optimize patient care. Correspondence to Kaede V. Sullivan, MD, Department of Pathology and Laboratory Medicine, Temple University Hospital, 3401 N. Broad St., Room A2 F329, Philadelphia, PA 19140, USA. E-mail: kaede.ota@tuhs.temple.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Kanyama C, Molloy S, Chan A, et al.

AbstractIn Malawi, 236 participants from the ACTA cryptococcal meningitis treatment trial were followed-up for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericinB plus flucytosine was associated with the lowest 1 year mortality (27.5% [95%CI: 16.3 to 44.1]).

Abstract Background Streptococcus agalactiae or Group B Streptococcus (GBS) is the leading cause of neonatal morbidity and mortality resulting in septicaemia, bacteraemia and meningitis. Long term problems in children range from loss of hearing to mental retardation. While Intrapartum Antibiotic Prophylaxis (IAP) has reduced the incidence of S. agalactiae infection, it still remains the leading cause of disease in neonates. GBS has ten capsular types whose distribution varies across the world. Therefore, this study sought to determine the prevalence of GBS in Namibia and South Africa amongst pregnant women between 35 and 37 weeks gestation and elucidate the capsular types. Methods Lower vaginal and rectal swabs were collected from pregnant women between 35 and 37 weeks gestation. Five hundred and thirty pregnant women were recruited into the study in Windhoek, Namibia while one hundred pregnant women were recruited in the Eastern Cape, South Africa. The swabs were cultured on 5% sheep blood agar (Biomerieux, New Jersey, USA) for isolation of GBS. Presumptive isolates were confirmed using both the Vitek (2) and molecular techniques targeting the scpB gene. Capsular typing was performed in a multiplex PCR with capsular specific primer pairs. Results The prevalence of GBS in Namibia was 13.6 and 37% in South Africa respectively. In both countries most women were dually colonised with GBS. Capsular types II, III and V were the most prevalent. Conclusions The prevalence of GBS in Namibia was lower than in South Africa in this study. The prevalence in both countries was not different from those reported in other African countries and around the world. The predominant capsular types in this study are the ones commonly associated with adverse maternal outcomes.…

Abstract Background Group B streptococcus (GBS) is reported as the leading cause of neonatal sepsis and meningitis. Newborns from GBS colonized pregnant women are at high risk of infection. Method A Hospital based cross-sectional study was conducted at Hawassa University Comprehensive Specialized Hospital from November 05, 2014 to March 25, 2015. A total of 280 pregnant women along with their newborns were screened for GBS using standard method recommended by Center of Disease Control and Prevention. GBS strains were serotyped by using serotype specific antisera. A structured questionnaire was used to collect sociodemographic, obstetrics and clinical data of pregnant women and newborns. Data was analyzed by using chi-square and logistic regression to determine factors associated with prevalence of GBS among pregnant women and newborns. Descriptive statistics was used to determine prevalence of GBS among pregnant women and newborns. P value less than 0.05 was considered statistically significant. Result Prevalence of GBS among pregnant women, newborns and vertical transmission rate at Hawassa University Comprehensive Specialized Hospital were 44(15.7%), 26(8.9%) and 59.1% respectively. Among 26 GBS colonized newborns one developed sign and symptoms of early onset disease. Serotype distribution of GBS isolates collected from pregnant women and newborns was Ia 13(18.6%), Ib 9(12.9%), II 24(34.3%), III 8(11.4%), V 14(20%), and NT 2 (2.9%). Conclusion In our study we found relatively high prevalence of GBS among pregnant women and vertical transmission rate. The most prevalent GBS serotypes identified in this study were serotype II followed by V, Ia and Ib. Therefore, appropriate prevention strategies such as intrapartum antibiotic prophylaxis and vaccine development should be considered.…