Solid organ transplant-related central nervous system infections.

PURPOSE OF REVIEW: Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause. RECENT FINDINGS: New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations. SUMMARY: The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients.

Development and Validation of a Risk Score to Differentiate Viral and Autoimmune Encephalitis in Adults.

BACKGROUND: Encephalitis represents a challenging condition to diagnose and treat. To assist physicians in considering autoimmune encephalitis (AE) sooner, we developed and validated a risk score. METHODS: The study was conducted as a retrospective cohort of patients with a diagnosis of definite viral encephalitis (VE) and AE from​​ February 2005 to December 2019. Clinically relevant and statistically significant features between cases of AE and VE were explored in a bivariate logistic regression model and results were used to identify variables for inclusion in the risk score. A multivariable logistic model was used to generate risk score values and predict risk for AE. Results were externally validated. RESULTS: A total of 1310 patients were screened. Of the 279 enrolled, 36 patients met criteria for definite AE and 88 criteria for definite VE. Patients with AE compared with VE were more likely to have a subacute to chronic presentation (odds ratio [OR] = 22.36; 95% confidence interval [CI], 2.05-243.7), Charlson comorbidity index <2 (OR = 6.62; 95% CI, 1.05-41.4), psychiatric and/or memory complaints (OR = 203.0; 95% CI, 7.57-5445), and absence of robust inflammation in the cerebrospinal fluid defined as <50 white blood cells/µL and protein <50 mg/dL (OR = 0.06; 95% CI, .005-0.50). Using these 4 variables, patients were classified into 3 risk categories for AE: low (0-1), intermediate (2-3), and high (4). Results were externally validated and the performance of the score achieved an area under the curve of 0.918 (95% CI, .871-.966). DISCUSSION: This risk score allows clinicians to estimate the probability of AE in patients presenting with encephalitis and may assist with earlier diagnosis and treatment.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Viral meningitis and encephalitis: an update.

PURPOSE OF REVIEW: The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide. RECENT FINDINGS: Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis. SUMMARY: We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.

Undetectable JC virus CSF PCR in patients with JC virus-induced progressive multifocal leukoencephalopathy.

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.

US Hospitalizations and 60-Day Readmission Rates Associated With Herpes Simplex Virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions.

BACKGROUND: Herpes simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. METHODS: HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. RESULTS: There were 10 272 HSE cases in the US between 2010 and 2017, resulting in a national rate of 4.95 per 100 000 hospitalizations. A total of 23.7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62.4 vs 57.9, P < .001), had a greater number of procedures at the index hospitalization (adjusted odds ratio [aOR] 1.03, P < .001) and have a higher Charlson comorbidity score (aOR 1.11, P < .001). Among those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over 8 years, the rate of encephalopathy associated readmissions increased from 0.12 to 0.20. Encephalopathy specific readmissions were found to be associated with greater age (mean age 65.9 vs 61.7, P = .004) and findings of cerebral edema at index hospitalization (aOR 2.16, P < .001). CONCLUSIONS: HSE readmissions are relatively common, particularly among older and sicker individuals. However, early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions.

Diagnostic approach and update on encephalitis.

PURPOSE OF REVIEW: The present article gives an update and outlines the fundamental principles of clinical reasoning and a diagnostic approach to a patient suspected to have acute encephalitis. RECENT FINDINGS: Encephalitis remains to be associated with significant mortality and neurological morbidity. Unfortunately, the etiologic diagnosis remains elusive for the majority of the patients with encephalitis preventing targeted therapies. Clinicians could utilize clues such as duration of symptoms, exposure history, cerebrospinal fluid profile, neuroimaging findings and locations, and entertain certain opportunistic infections in immunosuppressed individuals. A comprehensive diagnostic for the most common viral and autoimmune etiologies should be systematically done and prompt empiric antiviral therapy should be started. Evaluation and therapy for autoimmune etiologies should be done for patients with a negative viral work up. Brain biopsy and metagenomic sequencing should be considered for patients with unknown etiologies that are clinically worsening. SUMMARY: Encephalitis remains with unacceptable mortality and morbidity with the most common etiologies being idiopathic. A comprehensive diagnostic work up and prompt antiviral and autoimmune therapies are of paramount importance to improve the outcomes of this devastating disease.

A pilot study of cognition and creativity among persons with HIV disease referred for neuropsychological evaluation.

Creativity can help people to innovate, overcome obstacles, and successfully navigate challenges in daily life. Some aspects of creativity rely on the prefrontostriatal loops and executive functions, which can be compromised in persons with HIV (PWH). This pilot study examined whether neuropsychological functioning plays a role in creativity in PWH. A consecutive series of 41 PWH who were referred to an urban neuropsychology clinic in southeastern Texas were enrolled. Participants completed the Abbreviated Torrance Test for Adults (ATTA) to measure creativity, from which standardized creativity scores of fluency, originality, elaboration, and flexibility were derived. Participants also completed several measures of everyday functioning and a brief clinical neuropsychological battery measuring executive functions, motor skills, memory, and visuoconstruction. Global neuropsychological functioning showed a large, positive association with ATTA creativity performance that did not vary meaningfully by creativity domain and was independent of premorbid IQ. ATTA creativity scores were not associated with any measure of everyday functioning. Findings from this pilot study suggest that higher levels of neuropsychological functioning may support multiple dimensions of creativity in adults with HIV disease. Future studies might examine whether creativity moderates the association between HIV-associated neurocognitive impairment and various health behaviors (e.g., adherence, appointment attendance).

Progress and Challenges in Bacterial Meningitis: A Review.

Importance: Bacterial meningitis is a worldwide health problem, with incidence rates ranging from approximately 0.9 per 100 000 individuals per year in high-income countries to 80 per 100 000 individuals per year in low-income countries. In low-income countries, bacterial meningitis has a mortality rate of up to 54%. Up to 24% of those who survive develop chronic neurological sequelae, such as hearing loss or focal neurological deficits. Observations: Streptococcus pneumoniae causes about 72% and Neisseria meningitidis causes about 11% of cases of bacterial meningitis in people older than 16 years. Escherichia coli and Streptococcus agalactiae cause about 35% of cases of early-onset neonatal meningitis. In adults, risk factors for bacterial meningitis include older age and immunosuppressive conditions. The most common symptoms are headache (84%), fever (74%), stiff neck (74%), altered mental status (median [IQR] Glasgow Coma Scale score of 11 [9-14] on a scale ranging from 3-15), and nausea (62%). Brain imaging should be performed before lumbar puncture if patients present with altered mental status, focal neurological deficits, papilledema, or history of immunocompromising conditions or central nervous system disease. Bacterial meningitis should be suspected if any of the following are present on admission: serum leukocytes greater than 10.0 ×109/L, cerebrospinal fluid (CSF) leukocytes greater than 2000/µL, CSF granulocytes greater than 1180/µL, CSF protein greater than 2.2 g/L, CSF glucose less than 34.23 mg/dL, or fever. A positive Gram stain result for bacteria is diagnostic, but the sensitivity of a positive Gram stain result for bacterial meningitis ranges from 50% to 90%. In countries in which the prevalence of ceftriaxone-resistant Streptococcus pneumoniae exceeds 1%, vancomycin and ceftriaxone are the empirical antibiotics of choice, with the addition of ampicillin in neonates, older patients, and immunocompromised patients. Adjunctive dexamethasone should be used in patients with bacterial meningitis but stopped if Listeria monocytogenes is confirmed. Conclusions and Relevance: Bacterial meningitis affects approximately 0.9 per 100 000 individuals to 80 per 100 000 individuals per year and has a mortality rate as high as 54%. First-line therapy is prompt empirical intravenous antibiotic therapy and adjunctive dexamethasone.

Central nervous system infections associated with neurologic devices.

PURPOSE OF REVIEW: To review recent data on the epidemiology, microbiology, diagnosis, and management of central nervous system (CNS) infections associated with neurologic devices. RECENT FINDINGS: The increasing use of implanted neurologic devices has led to an increase in associated infections. Cerebrospinal fluid (CSF) inflammation may be present after a neurosurgical procedure, complicating the diagnosis of CNS infection. Newer biomarkers such as CSF lactate and procalcitonin show promise in differentiating infection from other causes of CSF inflammation. Molecular diagnostic tests including next-generation or metagenomic sequencing may be superior to culture in identifying pathogens causing healthcare-associated ventriculitis and meningitis. SUMMARY: Neurologic device infections are serious, often life-threatening complications. Rapid recognition and initiation of antibiotics are critical in decreasing morbidity. Device removal is usually required for cure.

Neuroradiology of infectious diseases.

PURPOSE OF REVIEW: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions. RECENT FINDINGS: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed. SUMMARY: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.

Clinical Epidemiology, Risk Factors, and Outcomes of Encephalitis in Older Adults.

BACKGROUND: Encephalitis is associated with significant morbidity and mortality, with unknown etiologies in the majority of patients. Large prognostic studies evaluating elderly patients are currently lacking. METHODS: We performed a retrospective cohort of encephalitis cases in 19 hospitals from New Orleans, Louisiana, and Houston, Texas, between the years 2000 and 2017. RESULTS: A total of 340 adult (aged ≥17 years) patients with confirmed encephalitis were enrolled, and 194 (57%) had unknown etiologies. A cerebrospinal fluid polymerase chain reaction (PCR) for herpes simplex virus (HSV) and varicella zoster virus was done in 237 (69%) and 82 (24%) patients, respectively. Furthermore, an arboviral serology was done in 169 (49%) patients and measurements of anti-N-methyl-D-aspartate receptor antibodies were taken in 49 (14%) patients. A total of 172 out of 323 patients (53%) had adverse clinical outcomes (ACOs) at discharge. Older individuals (>65 years of age) had a lower prevalence of human immunodeficiency virus, had a higher number of comorbidities, were less likely to receive adjuvant steroids, were more likely to have a positive arbovirus serology, were more likely to have a positive HSV PCR, were more likely to have abnormal computerized tomography findings, and were more likely to have to have an ACO (all P values < .05). Prognostic factors independently associated with an ACO were age ≥65, fever, Glasgow Coma Scale (GCS) score <13, and seizures (all P values ≤0.01). CONCLUSIONS: Encephalitis in adults remain with unknown etiologies and adverse clinical outcomes in the majority of patients. Independent prognostic factors include age ≥65 years, fever, GCS score <13, and seizures.

Case Commentary: Delayed Cerebral Vasculitis Associated with the Development of Ceftriaxone-Resistant Pneumococcal Meningitis.

Mizrahi and colleagues present a well-described case of the emergence of drug resistance in Streptococcus pneumoniae meningitis during therapy with ceftriaxone monotherapy with a low bactericidal concentration in the cerebrospinal fluid. Adherence to international guidelines could possibly have prevented the emergence of this resistant isolate and the adverse outcome.

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis-evidence from an in vivo PET study.

BACKGROUND: Bacterial meningitis is a devastating central nervous system (CNS) infection with acute and long-term neurological consequences, including cognitive impairment. The aim of this study was to understand the association between activated microglia-induced neuroinflammation and post-meningitis cognitive impairment. METHOD: Meningitis was induced in male Wistar rats by injecting Streptococcus pneumoniae into the brain through the cisterna magna, and rats were then treated with ceftriaxone. Twenty-four hours and 10 days after meningitis induction, rats were imaged with positron emission tomography (PET) using [11C]PBR28, a specific translocator protein (TSPO) radiotracer, to determine in vivo microglial activation. Following imaging, the expression of TSPO, cardiolipin, and cytochrome c, inflammatory mediators, oxidative stress markers, and glial activation markers were evaluated in the prefrontal cortex and hippocampus. Ten days after meningitis induction, animals were subjected to behavioral tests, such as the open-field, step-down inhibitory avoidance, and novel object recognition tests. RESULTS: Both 24-h (acute) and 10-day (long-term) groups of rats demonstrated increased [11C]PBR28 uptake and microglial activation in the whole brain compared to levels in the control group. Although free from infection, 10-day group rats exhibited increased expression levels of cytokines and markers of oxidative stress, microglial activation (IBA-1), and astrocyte activation (GFAP) similar to those seen in the 24-h group. Acute meningitis induction also elevated TSPO, cytochrome c, and caspase-3 levels with no change in caspase-9 levels. Furthermore, upregulated levels of TSPO, cytochrome c, and caspase-3 and caspase-9 were observed in the rat hippocampus 10 days after meningitis induction with a simultaneous reduction in cardiolipin levels. Animals showed a cognitive decline in all tasks compared with the control group, and this impairment may be at least partially mediated by activating a glia-mediated immune response and upregulating TSPO. CONCLUSIONS: TSPO-PET could potentially be used as an imaging biomarker for microglial activation and long-term cognitive impairment post-meningitis. Additionally, this study opens a new avenue for the potential use of TSPO ligands after infection-induced neurological sequelae.

Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

Impact of the Film Array Meningitis/Encephalitis panel in adults with meningitis and encephalitis in Colombia.

The Biofire® Film Array Meningitis Encephalitis (FAME) panel can rapidly diagnose common aetiologies but its impact in Colombia is unknown. A retrospective study of adults with CNS infections in one tertiary hospital in Colombia. The cohort was divided into two time periods: before and after the implementation of the Biofire® FAME panel in May 2016. A total of 98 patients were enrolled, 52 and 46 were enrolled in the Standard of Care (SOC) group and in the FAME group, respectively. The most common comorbidity was human immunodeficiency virus infection (47.4%). The median time to a change in therapy was significantly shorter in the FAME group than in the SOC group (3 vs. 137.3 h, P < 0.001). This difference was driven by the timing to appropriate therapy (2.1 vs. 195 h, P < 0.001) by identifying viral aetiologies. Overall outcomes and length of stay were no different between both groups (P > 0.2). The FAME panel detected six aetiologies that had negative cultures but missed identifying one patient with Cryptococcus neoformans. The introduction of the Biofire FAME panel in Colombia has facilitated the identification of viral pathogens and has significantly reduced the time to the adjustment of empirical antimicrobial therapy.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Update and advances in community acquired bacterial meningitis.

PURPOSE OF REVIEW: Community-acquired bacterial meningitis continues to occur and be associated with significant morbidity and mortality despite the availability of effective conjugate vaccines for the three most important meningeal pathogens. RECENT FINDINGS: Indications for cranial imaging in suspected bacterial meningitis varies significantly between guidelines. Cranial imaging is of no clinical utility in those patients without indications and fosters delays in performing a lumbar puncture. Delaying lumbar puncture is associated with increased costs in both adults and children with meningitis and previous antibiotic therapy impacts the yield of microbiological results. Delaying antibiotic therapy is associated with worse clinical outcomes. Adjunctive steroids have reduced the mortality of adults with pneumococcal meningitis but have been associated with increased adverse outcomes in Listeria monocytogenes and Cryptococcus neoformans. SUMMARY: Community-acquired bacterial meningitis remains a global health concern with high morbidity and mortality especially in low-income countries. Cranial imaging should be done only in patients with an indication with an attempt to do a prompt lumbar puncture and to initiate antibiotic therapy and adjunctive steroids as soon as possible to improve clinical outcomes.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Economic analysis of rapid multiplex polymerase chain reaction testing for meningitis/encephalitis in adult patients.

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.