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.

[Clinical analysis of 11 cases of otogenic intracranial complications treated by multidisciplinary collaboration].

Objective:To analyze the clinical diagnosis, treatment ，and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University（Qingdao） from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.

Microbiologic and Clinical Description of Postoperative Central Nervous System Infection After Endoscopic Endonasal Surgery.

BACKGROUND: Consensus guidelines for antibiotic prophylaxis in endoscopic endonasal surgery (EES) have not been developed. The study objective was to define the microbiologic and clinical characteristics of post-EES central nervous system (CNS) infections. METHODS: This was a single-center retrospective study of patients >18 years of age who underwent EES between January 2010 and July 2021 at a high-volume skull base center. Patients with confirmed CNS infection within 30 days of EES were included. During the study period, the standard prophylaxis regimen was ceftriaxone 2 g every 12 hours for 48 hours. For patients with a documented penicillin allergy, vancomycin plus aztreonam was recommended. RESULTS: In total, 2440 EES procedures were performed on 2005 patients; the CNS infection rate was 1.8% (37/2005). CNS infections were more common among patients with a history of previous EES (6.5%; 20/307) compared with those who did not (1%; 17/1698; P < 0.001). The median time from EES to CNS infection was 12 (6-19) days. Thirty-two percent (12/37) of CNS infections were polymicrobic, which was more common among patients without previous EES (52.9%; 9/17) compared with those with previous EES (15%; 3/20; P = 0.03). Across all cases, Staphylococcus aureus (n = 10) and Pseudomonas aeruginosa (n = 8) were commonly isolated pathogens. Among those with confirmed methicillin-resistant Staphylococcus aureus (MRSA) nares colonization before EES, 75% (3/4) developed MRSA CNS infections compared with 6.1% (2/33) of noncolonized patients (P = 0.005). CONCLUSIONS: CNS infection after EES is rare and causative pathogens vary. Further studies are needed to identify the impact of MRSA nares screening on antimicrobial prophylaxis before EES.

Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study.

OBJECTIVES: To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation. METHODS: Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection. RESULTS: Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001). CONCLUSIONS: CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality.

Risks of central nervous system infections and related mortality in patients undergoing dialysis.

INTRODUCTION: This study aimed to investigate the risks of central nervous system (CNS) infections and related mortality in patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Incident dialysis patients were identified from 2000 to 2013. The risks of CNS infection and related mortality were analyzed. RESULTS: The adjusted hazard ratio (HR) of CNS infection in the ESRD group compared with the control group was 3.46 (95% confidence interval [CI] 2.75-4.35). The adjusted odds ratio (OR) of 90-day mortality following CNS infections in the ESRD group in comparison with the control group was 5.99 (95% CI 2.78-12.9). The adjusted HR of overall CNS infection for the peritoneal dialysis (PD) group in comparison with the hemodialysis (HD) group was 1.07 (95% CI 0.63-1.82). Influenza vaccination was associated with a lower risks of CNS infection in dialysis patients (adjusted HR: 0.38, 95% CI 0.30-0.48). The adjusted OR of 90-day mortality following CNS infection for the PD group in comparison with the HD group was 1.01 (95% CI 0.55-1.87). CONCLUSIONS: The risks of CNS infections and related mortality were remarkably high in dialysis patients with no significant difference between patients with ESRD under HD and PD treatment.

A clinical, aetiological, and public health perspective on central nervous system infections in Bolivia, 2017-2018.

Central nervous system (CNS) infections are important causes of morbidity and mortality worldwide. In Bolivia, aetiologies, case fatality, and determinants of outcome are poorly characterised. We attempted to investigate such parameters to guide diagnosis, treatment, prevention, and health policy. From Nov-2017 to Oct-2018, we prospectively enrolled 257 inpatients (20.2% HIV-positive patients) of all ages from healthcare centers of Cochabamba and Santa Cruz, Bolivia with a suspected CNS infection and a lumbar puncture performed. Biological diagnosis included classical microbiology, molecular, serological and immunohistochemical tests. An infectious aetiology was confirmed in 128/257 (49.8%) inpatients, including, notably among confirmed single and co-infections, Cryptococcus spp. (41.7%) and Mycobacterium tuberculosis (27.8%) in HIV-positive patients, and Mycobacterium tuberculosis (26.1%) and Streptococcus pneumoniae (18.5%) in HIV-negative patients. The total mortality rate was high (94/223, 42.1%), including six rabies cases. In multivariate logistic regression analysis, mortality was associated with thrombocytopenia (Odds ratio (OR) 5.40, 95%-CI 2.40-11.83) and hydrocephalus (OR 4.07, 95%-CI 1.35-12.23). The proportion of untreated HIV patients, late presentations of neurotuberculosis, the rate of pneumococcal cases, and rabies patients who did not benefit from a post-exposure prophylaxis, suggest that decreasing the burden of CNS infections requires reinforcing health policy regarding tuberculosis, rabies, S. pneumoniae vaccination, and HIV-infections.

[Neurological complications in haematopoietic stem cell transplant patients]. / Complicaciones neurológicas en pacientes sometidos a trasplante de progenitores hematopoyéticos.

INTRODUCTION: Neurological complications are some of the most important complications that can occur in a patient undergoing haematopoietic stem cell transplantation (HSCT), not only because of the high mortality rate, but also because of the sequelae that appear in survivors. The causes of such complications are manifold and very often coexist in the same patient: toxicity of the conditioning regimen, graft-versus-host disease and its treatment, infections and their treatment, platelets and coagulation disorders, liver failure or arterial hypertension with low platelet count. AIMS: The aim of the present study is to provide a clinical description and to describe the risk factors for complications involving the central nervous system that may occur during the course of HSCT, in order to assist in the early detection of these disorders that may have a negative influence on the morbidity and mortality of these patients. DEVELOPMENT: The following types of neurological complications are described: central nervous system infections, vascular complications, pharmacological toxicity, metabolic complications, immune-mediated disorders and post-HSCT carcinogenesis, and effects of graft-versus-host disease and thrombotic microangiopathy on the nervous system. CONCLUSIONS: The patient undergoing HSCT is at particular risk for the development of neurological complications. Early diagnosis and treatment are needed to try to reduce the high morbidity and mortality in these patients.

TITLE: Complicaciones neurológicas en pacientes sometidos a trasplante de progenitores hematopoyéticos.Introducción. Las complicaciones neurológicas son algunas de las más importantes que se pueden presentar en un paciente sometido a un trasplante de progenitores hematopoyéticos (TPH), no sólo porque conllevan una mortalidad elevada, sino también por las secuelas que aparecen en los supervivientes. Las causas de dichas complicaciones son múltiples y, muy frecuentemente, coexisten en el mismo paciente: toxicidad del régimen de acondicionamiento, enfermedad del injerto contra el hospedador y su tratamiento, infecciones y su tratamiento, plaquetopenia y trastornos de la coagulación, fallo hepático o hipertensión arterial con plaquetopenia. Objetivos. El objetivo del presente estudio es el de aportar una descripción clínica y de los factores de riesgo de las complicaciones sobre el sistema nervioso central que pueden presentarse en el curso de un TPH, para ayudar en la detección precoz de estos trastornos que pueden influir negativamente en la morbimortalidad de estos pacientes. Desarrollo. Se describen los siguientes tipos de complicaciones neurológicas: infecciones sobre el sistema nervioso central, complicaciones vasculares, toxicidad farmacológica, complicaciones metabólicas, trastornos inmunomediados y carcinogenia pos-TPH, y efectos de la enfermedad del injerto contra el hospedador y de la microangiopatía trombótica sobre el sistema nervioso. Conclusiones. El paciente sometido a TPH es de especial riesgo para el desarrollo de complicaciones neurológicas. Se precisan un diagnóstico y un tratamiento precoces para intentar disminuir la elevada morbimortalidad de estos pacientes.

Hypothalamus-Pituitary Dysfunction as an Independent Risk Factor for Postoperative Central Nervous System Infections in Patients With Sellar Region Tumors.

Objective: The purpose of this study was to verify that hypothalamus-pituitary dysfunction is one of the risk factors for postoperative central nervous system infections (PCNSIs). Method: We performed a retrospective analysis of all patients with sellar region lesions who underwent surgery between January 2016 and November 2019 at Peking Union Medical College Hospital. In total, 44 age- and sex-matched controls were enrolled. Univariate and multivariate analyses were performed to identify risk factors for PCNSIs. Result: We enrolled 88 patients, 44 of whom had PCNSIs. Surgical approach (TCS) (P<0.001), previous surgery on the same site (P=0.001), intraoperative cerebral spinal fluid (CSF) leakage (P<0.001), postoperative adrenal insufficiency (P=0.017), postoperative DI (P=0.004) and the maximum Na+ levels(<0.001) correlated significantly with PCNSIs. Multivariate analysis showed that Surgery approach (TCS)(OR: 77.588; 95%CI: 7.981-754.263; P<0.001), intraoperative CSF leakage (OR: 12.906; 95%CI: 3.499-47.602; P<0.001), postoperative DI (OR: 6.999; 95%CI:1.371-35.723; P=0.019) and postoperative adrenal insufficiency (OR: 6.115; 95%CI: 1.025-36.469; P=0.047) were independent influencing factors for PCNSIs. Conclusion: TCS, intraoperative CSF leakage, postoperative DI and postoperative adrenal insufficiency are risk factors for PCNSIs in patients with sellar region tumors.

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.

The epidemiology and clinical spectrum of infections of the central nervous system in adults in north India.

Infections of the central nervous system (CNS) are a leading cause of mortality in low- and middle-income countries. We studied the spectrum, aetiology and outcome of CNS infections in 401 consecutive patients aged ≥12 years admitted at the medical emergency centre of PGIMER, Chandigarh, India. An aetiological diagnosis was made in 365 (91.0%) patients, with 149 (40.8%) microbiologically confirmed cases. CNS tuberculosis was the most prevalent cause (51.5%), followed by viral meningoencephalitis (13.9%), community-acquired bacterial meningitis (9.7%), cryptococcal meningitis (6.2%), scrub typhus meningoencephalitis (1.7%), neurocysticercosis (1.7%) and fungal brain abscess (1.7%). Human immunodeficiency virus (11.0%) and diabetes mellitus (6.2%) remained the usual predisposing conditions. We found a mortality rate of 27.9%, highest in cases without an aetiology (64.5%). Tuberculosis remained the most common cause; however, an increasing number of scrub typhus, dengue, fungal infections and non-classical bacterial pathogens may indicate a change in the epidemiology of community-acquired CNS infections in India.

Central Nervous System Infections in the Immunocompromised Adult Presenting to the Emergency Department.

Over the past 2 decades, the population of immunocompromised patients has increased dramatically in the United States. These patients are at elevated risk for both community-acquired and opportunistic central nervous system infections. We review the most common and serious central nervous system pathogens affecting these patients and outline a diagnostic and therapeutic approach to their management in the emergency department. We recommend a broad diagnostic evaluation, including neuroimaging and cerebrospinal fluid studies where appropriate, empiric antimicrobial therapy, and early involvement of subspecialists to provide comprehensive care for these complex patients.

Cutibacterium acnes Central Nervous System Catheter Infection Induces Long-Term Changes in the Cerebrospinal Fluid Proteome.

Cutibacterium acnes is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is likely underdiagnosed due to the difficulty in culturing this pathogen. Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. Currently, the gold standard for identifying CSF shunt infections is microbiologic culture. However, C. acnes infection often results in falsely negative cultures; therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a rat model of CSF catheter infection to C. acnes. We found elevated levels of interleukin-1ß (IL-1ß), IL-6, chemokine ligand 2, and IL-10 in the CSF and brain tissues of animals implanted with C. acnes-infected catheters compared to sterile controls at day 1 postinfection. This coincided with modest increases in neutrophils in the CSF and, to a greater extent, in the brain tissues of animals with C. acnes infection, which closely mirrors the clinical findings in patients with C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of disease, typified at day 1 postinfection by an acute-phase and pathogen neutralization response evolving to a response consistent with wound resolution at day 28 compared to a sterile catheter placement. Collectively, these results demonstrate that it is possible to distinguish C. acnes infection from sterile postoperative inflammation and that CSF proteins could be useful in a diagnostic strategy for this pathogen that is difficult to diagnose.

Determination of Etiology and Epidemiology of Viral Central Nervous System Infections by Quantitative Real-Time Polymerase Chain Reaction in Central India Population.

INTRODUCTION: Viral infections of the central nervous system (CNS) are the most common cause of hospital admission in worldwide and remain a challenging disease for diagnosis and treatment. The most common infectious agents associated with viral CNS infections are cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), Japanese encephalitis virus (JEV), Dengue virus (DENV),West Nile virus(WNV), and Chandipura virus(CHPV). The aim of the present work was to find the etiology of CNS viral infection in the Central India population by transcriptase PCR (RT-PCR) comparing real-time polymerase chain reaction (PCR) method [one-step and two-step reverse transcriptase (RT-PCR)] in cerebrospinal fluid (CSF) and blood samples of CNS viral infections patients. MATERIALS AND METHODS: One-step and two-step real-time PCR assays were evaluated in CSF and parallel blood samples from patients with viral CNS infections for detection of DNA and RNA viruses. A comparative analysis was also done between gDNA, gRNA, cDNA, and plasmid-based real-time PCR methods for an efficient quantitation of viral particles in clinical samples for determination of viral etiology. RESULT: On evaluation of 150 CSF and 50 parallel blood samples from suspected cases of viral CNS infections, a viral etiology was confirmed in 21 (14%) cases, including 3% for EBV, 1% of CMV, and 5% for VZV and JEV. The one-step RT-PCR has a higher detection limit for detection and quantitation of viral RNA in comparison to two-step RT-PCR. CONCLUSION: Our result reveals that VZV and JEV are the most usual cases of CNS viral infection in hospitalized patients in the Central India population and one-step RT-PCR shows higher viral load detection limits for quantitation of viral genome and more sensitivity in comparison to two-step RT-PCR.

Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a highly contagious respiratory disease referred to as COVID-19. However, emerging evidence indicates that a small but growing number of COVID-19 patients also manifest neurological symptoms, suggesting that SARS-CoV-2 may infect the nervous system under some circumstances. SARS-CoV-2 primarily enters the body through the epithelial lining of the respiratory and gastrointestinal tracts, but under certain conditions this pleiotropic virus may also infect peripheral nerves and gain entry into the central nervous system (CNS). The brain is shielded by various anatomical and physiological barriers, most notably the blood-brain barrier (BBB) which functions to prevent harmful substances, including pathogens and pro-inflammatory mediators, from entering the brain. The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS. In this review, potential routes of viral entry and the possible mechanisms utilized by SARS-CoV-2 to penetrate the CNS, either by disrupting the BBB or infecting the peripheral nerves and using the neuronal network to initiate neuroinflammation, are briefly discussed. Furthermore, the long-term effects of SARS-CoV-2 infection on the brain and in the progression of neurodegenerative diseases known to be associated with other human coronaviruses are considered. Although the mechanisms of SARS-CoV-2 entry into the CNS and neurovirulence are currently unknown, the potential pathways described here might pave the way for future research in this area and enable the development of better therapeutic strategies.

Multi-assay investigation of viral etiology in pediatric central nervous system infections.

INTRODUCTION: In an attempt to identify a wide spectrum of viral infections, cerebrospinal fluid (CSF) specimens were collected from pediatric cases with the preliminary diagnosis of viral encephalitis/meningoencephalitis in two reference hospitals, from October 2011 to December 2015. METHODOLOGY: A combination of nucleic acid-based assays, including in house generic polymerase chain reaction (PCR) assays for enteroviruses, flaviviruses and phleboviruses, a commercial real-time PCR assay for herpesviruses and a commercial real time multiplex PCR, enabling detection of frequently-observed viral, bacterial and fungal agents were employed for screening. RESULTS: The microbial agent could be characterized in 10 (10%) of the 100 specimens. Viral etiology could be demonstrated in 7 (70%) specimens, which comprises Human Herpesvirus 6 (4/7), Herpes Simplex virus type1 (2/7) and Enteroviruses (1/7). In 3 specimens (30%), Streptococcus pneumoniae, Listeria monocytogenes and Staphylococcus aureus were detected via the multiplex PCR, which were also isolated in bacteriological media. All specimens with detectable viral nucleic acids, as well as unreactive specimens via nucleic acid testing remained negative in bacteriological cultures. CONCLUSIONS: Herpes and enteroviruses were identified as the primary causative agents of central nervous system infections in children. Enterovirus testing must be included in the diagnostic work-up of relevant cases.

AIDS-associated Talaromyces marneffei central nervous system infection in patients of southwestern China.

BACKGROUND: The clinical and laboratory characteristics of AIDS-associated Talaromyces marneffei infection, a rare but a fatal mycosis disease of the central nervous system, remain unclear. CASE PRESENTATION: Herein, we conducted a retrospective study of ten AIDS patients with cerebrospinal fluid culture-confirmed central nervous system infection caused by Talaromyces marneffei. All 10 patients were promptly treated with antifungal treatment for a prolonged duration and early antiviral therapy (ART). Among them, seven patients were farmers. Nine patients were discharged after full recovery, while one patient died during hospitalization, resulting in a mortality rate of 10%. All patients initially presented symptoms and signs of an increase in intracranial pressure, mainly manifesting as headache, dizziness, vomiting, fever, decreased muscle strength, diplopia or even altered consciousness with seizures in severe patients. Nine patients (90%) showed lateral ventricle dilatation or intracranial infectious lesions on brain CT. Cerebrospinal fluid findings included elevated intracranial pressure, increased leukocyte count, low glucose, low chloride and high cerebrospinal fluid protein. The median CD4+ T count of patients was 104 cells/µL (IQR, 36-224 cells/µL) at the onset of the disease. The CD4+ T cell counts of three patients who eventually died were significantly lower (W = 6.00, p = 0.020) than those of the patients who survived. CONCLUSIONS: The common clinical symptoms of T. marneffei central nervous system infection are associated with high intracranial pressure and intracranial infectious lesions. Earlier recognition and diagnosis and a prolonged course of amphotericin B treatment followed by itraconazole combined with early ART might reduce the mortality rate.

Central nervous system disorders after hematopoietic stem cell transplantation: a prospective study of the Infectious Diseases Working Party of EBMT.

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients.

Complications of Otitis Media and Sinusitis Caused by Streptococcus anginosus Group Organisms in Children.

BACKGROUND: The Streptococcus anginosus group (SAG, S. anginosus, S. intermedius and S. constellatus) are often associated with severe disease and abscess formation. In our institution, we observed an apparent increase in frequency of intraorbital and intracranial infections resulting from SAG at Texas Children's Hospital. We undertook a retrospective review to describe the frequency and clinical features of these infections. METHODS: We reviewed the database of the microbiology laboratory at Texas Children's Hospital from 2011 to 2018 for SAG-positive cultures. Cases included were those associated with (1) either otitis media or sinusitis and (2) Pott's puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging. The number of overall diagnoses were determined using diagnostic codes and used to estimate the proportion of disease caused by SAG. RESULTS: Ninety-five cases were identified meeting inclusion criteria. The median age of patients was 11.4 years, and 75.8% were previously healthy. S. intermedius was most commonly isolated (80%) followed by S. constellatus (12.6%) and S. anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention. 8.4% of patients experienced persistent neurologic deficits. We observed a significant increase in disease incidence during the study period; in addition, the overall proportion of all intracranial infections caused by SAG increased. CONCLUSIONS: Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity. These infections are becoming increasingly common at our center although the precise reason for this temporal trend is unclear.

Utilidad de las técnicas de biología molecular en neuroinfecciones / Usefulness of molecular biology techniques in neuroinfectious diseases / Utilidade das técnicas de biologia molecular em neuroinfecções

Resumen: Introducción: un porcentaje de las infecciones del sistema nervioso central permanece sin diagnóstico etiológico. Las técnicas de amplificación de ácidos nucleicos mediante reacción en cadena de la polimerasa en tiempo real pueden disminuir este porcentaje. Objetivo: describir la etiología de las neuroinfecciones y valorar la utilidad de las técnicas de biología molecular en el diagnóstico y su impacto en el tratamiento antimicrobiano. Metodología: estudio observacional, descriptivo, retrospectivo a partir de registros clínicos. Se incluyeron mayores de 18 años asistidos en un hospital público de Montevideo durante un período de 32 meses, a quienes que se les realizaron técnicas de biología molecular en líquido cefalorraquídeo por sospecha clínica de neuroinfección. Resultados: se incluyeron 109 pacientes. En pacientes sin infección por VIH ni antecedentes neuroquirúrgicos (67%), se identificó microorganismo responsable en 16 casos, 8 bacterias y 9 virus. Todos identificados por técnicas de biología molecular modificando el tratamiento antimicrobiano empírico en 25 casos (34,2%). En portadores de VIH (25,7%), se detectaron microorganismos en 14 pacientes (50%). Seis virus, 5 bacterias y 7 hongos (Cryptococcus neoformans). El estudio por técnicas de biología molecular determinó el diagnóstico de 17 microorganismos y modificó el plan antimicrobiano inicial en 12 casos (42,9%). En pacientes con antecedente de neurocirugía reciente (7,3%), se aislaron seis microorganismos, tres de ellos exclusivamente mediante cultivo. Se modificó el tratamiento en tres casos (37,5%). Conclusiones: las técnicas de biología molecular deben considerarse complementarias. El impacto que generan en el diagnóstico y tratamiento justifica el uso de estas técnicas a pesar de su mayor costo.

Summary: Introduction: a certain percentage of infections of the central nervous system have no etiological diagnosis. Nucleic acids amplification techniques by means of a polymerase chain reaction in real time may reduce this percentage. Objective: to describe etiology of neuroinfectious diseases and assess the usefulness of molecular biology techniques in their diagnosis, as well as its impact on antimicrobial treatment. Method: observational, descriptive, retrospective study based on clinical records which included patients older than 18 years old, who had been assisted in a public hospital in Montevideo for over 32 months and had undergone molecular biology techniques with cerebrospinal fluid (CSF) given the clinical suspicion of neuroinfection. Results: 109 patients were included in the study. Among non-HIV infected patients who had not undergone neurosurgeries the responsible microorganism was identified in 16 cases (8 bacteria and 9 virus). They were all identified by molecular biology techniques by modifying the empiric antimicrobial therapy in 25 cases (34.2%). In carriers of HIV (25.7%), microorganisms were identified in 14 patients (50%). Six virus, 5 bacteria and 7 fungi (Cryptococcus neoformans). Molecular biology techniques defined the diagnosis of 17 microorganisms and modified the initial antimicrobial plan in 12 cases (42.9%). In patients with a history of recent neurosurgery (7.3%), 6 microorganisms were isolated, 3 of them exclusively through cultures. Treatment was modified in 3 cases (37.5%). Conclusions: molecular biology techniques need to be regarded as a complement. The impact that have in diagnosis and therapy justify their use despite its higher cost.

Resumo: Introdução: uma proporção das infecções do sistema nervoso central permanece sem diagnóstico etiológico. As técnicas de ampliação de ácidos nucléicos por reação em cadeia da polimerase em tempo real, podem diminuir esta proporção. Objetivo: descrever a etiologia das neuro infecções e avaliar a utilidade das técnicas de biologia molecular no diagnóstico e seu impacto no tratamento antimicrobiano. Metodologia: estudo observacional, descritivo, retrospectivo de prontuários de pacientes. Foram incluídos pacientes maiores de 18 anos, atendidos em um hospital público de Montevidéu, durante um período de 32 meses. Foram realizadas técnicas de biologia molecular ao líquido cefalorraquidiano por suspeita clínica de neuroinfecção. Resultados: foram incluídos 109 pacientes. Em pacientes sem infecção por VIH e sem antecedentes neurocirúrgicos (67%), o microrganismo responsável em 16 casos, sendo 8 bactérias e 9 vírus. Todos foram identificados por técnicas de biologia molecular modificando el tratamento antimicrobiano empírico em 25 casos (34,2%). Em portadores de VIH (25,7%), foram detectados microrganismos em 14 pacientes (50%). Seis vírus, 5 bactérias e 7 leveduras (Cryptococcus neoformans). O estudo por técnicas de biologia molecular permitiu o diagnóstico de 17 microrganismos e modificou o tratamento antimicrobiano inicial em 12 casos (42,9%). Em pacientes com antecedentes de neurocirurgia recente (7,3%), foram isolados 6 microrganismos, em 3 casos exclusivamente por cultura. O tratamento foi modificado em 3 casos (37,5%). Conclusões: as técnicas de biologia molecular devem ser consideradas como complementares. O impacto que causam sobre o diagnóstico e o tratamento justifica seu uso apesar de seu maior custo.