Publications by authors named "Rodrigo Hasbun"

111 Publications

Future and past autobiographical memory in persons with HIV disease.

Neuropsychology 2021 Jul 22;35(5):461-471. Epub 2021 Apr 22.

Department of Psychology, University of Houston.

While HIV disease is associated with impairment in declarative memory, the ability of people with HIV (PWH) to describe past and future autobiographical events is not known. Participants included 63 PWH and 28 seronegative individuals ages 50-78 who completed standardized neurocognitive and everyday functioning assessments. Participants described four events from the recent past and four imagined events in the near future, details from which were classified as internal or external to the main event. PWH produced fewer autobiographical details with small-to-medium effect sizes but did not differ from seronegative participants in meta-cognitive ratings of their performance. Performance of the study groups did not vary across past or future probes or internal versus external details; however, within the entire sample, past events were described in greater detail than future events, and more external than internal details were produced. Within the PWH group, the production of fewer internal details for future events was moderately associated with poorer prospective memory, executive dysfunction, and errors on a laboratory-based task of medication management. Older PWH may experience difficulty generating autobiographical details from the past and simulated events in the future, which may be related to executive dyscontrol of memory processes. Future studies might examine the role of future thinking in health behaviors such as medication adherence and retention in healthcare among PWH. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000727DOI Listing
July 2021

US Hospitalizations and 60-Day Readmission Rates Associated with Herpes simplex virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions.

Clin Infect Dis 2021 Jul 8. Epub 2021 Jul 8.

Division of Infectious Disease, Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX.

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<0.001), had a greater number of procedures at the index hospitalization (aOR 1.03, p<0.001) and have a higher Charlson comorbidity score (aOR 1.11, p<0.001). Amongst those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over eight 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 = 0.004) and findings of cerebral edema at index hospitalization (aOR 2.16, p <0.001).

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.
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http://dx.doi.org/10.1093/cid/ciab613DOI Listing
July 2021

The Epidemiology of Meningitis in Infants under 90 Days of Age in a Large Pediatric Hospital.

Microorganisms 2021 Mar 4;9(3). Epub 2021 Mar 4.

Department of Pediatrics, Section of Pediatric Tropical Medicine, William T. Shearer Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.

Background: Meningitis is associated with substantial morbidity and mortality, particularly in the first three months of life.

Methods: We conducted a retrospective review of patients <90 days of age with meningitis at Texas Children's Hospital from 2010-2017. Cases were confirmed using the National Healthcare Safety Network (NHSN) definition of meningitis.

Results: Among 694 infants with meningitis, the most common etiology was viral ( = 351; 51%), primarily caused by enterovirus ( = 332; 95%). A quarter of cases were caused by bacterial infections ( = 190; 27%). The most common cause of bacterial meningitis was group B (GBS, = 60; 32%), followed by Gram-negative rods other than ( = 40; 21%), and ( = 37; 19%). The majority of Gram-negative organisms (63%) were resistant to ampicillin, and nearly one-fourth of Gram-negative rods (23%) other than and 2 (6%) isolates were resistant to third-generation cephalosporins. Significant risk factors for bacterial meningitis were early preterm birth and the Black race.

Conclusions: Enteroviruses most commonly caused viral meningitis in infants; GBS was the most common bacterial cause despite universal screening and intrapartum prophylaxis. The emergence of MRSA and resistance to third-generation cephalosporins in Gram-negative bacterial meningitis challenges the options for empirical antimicrobial therapy.
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http://dx.doi.org/10.3390/microorganisms9030526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999219PMC
March 2021

Neuroradiology of infectious diseases.

Curr Opin Infect Dis 2021 Jun;34(3):228-237

Section of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1097/QCO.0000000000000725DOI Listing
June 2021

Central nervous system infections associated with neurologic devices.

Curr Opin Infect Dis 2021 Jun;34(3):238-244

Section of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1097/QCO.0000000000000723DOI Listing
June 2021

Unique Cytokine Response in West Nile Virus Patients Who Developed Chronic Kidney Disease: A Prospective Cohort Study.

Viruses 2021 02 17;13(2). Epub 2021 Feb 17.

Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

West Nile virus (WNV) is a widespread and devastating disease, especially in those who develop neuroinvasive disease. A growing body of evidence describes sequelae years after infection, including neurological complications and chronic kidney disease (CKD). Eighty-nine out of 373 WNV-positive cases were followed for approximately two years and compared to 127 WNV-negative controls with and without CKD. Adjusted risk ratios (aRRs) were calculated via a log binomial regression to determine the impact of WNV exposure and other possible confounders on the likelihood of developing CKD. Cytokine profiles of WNV patients and controls were evaluated to characterize differences and describe potential underlying pathophysiological mechanisms. The associated risk for developing CKD was significantly associated with history of WNV infection (aRR = 1.91, 95% CI 1.13-3.25). Additionally, five distinct cytokines were found to be significantly associated with WNV infection (eotaxin, IL-8, IL-12p70, IP-10, and TNFα) after the -value was adjusted to <0.0019 due to the Bonferroni correction. These data support that WNV infection is an independent risk factor for CKD, even after accounting for confounding comorbidities. WNV participants who developed CKD had high activity of proinflammatory markers, indicating underlying inflammatory disease. This study provides new insights into CKD resultant of WNV infection.
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http://dx.doi.org/10.3390/v13020311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922428PMC
February 2021

Cluster roots of Embothrium coccineum modify their metabolism and show differential gene expression in response to phosphorus supply.

Plant Physiol Biochem 2021 Apr 16;161:191-199. Epub 2021 Feb 16.

Laboratorio de Epigenética Vegetal, Departamento de Silvicultura, Facultad de Ciencias Forestales, Universidad de Concepción, Concepción, Chile; ONG Conciencia Sur, Chile. Electronic address:

Embothrium coccineum produces cluster roots (CR) to acquire sparingly soluble phosphorus (P) from the soil through the exudation of organic compounds. However, the physiological mechanisms involved in carbon drainage through its roots, as well as the gene expression involved in the biosynthesis of carboxylates and P uptake, have not been explored. In this work, we evaluated the relationship between carboxylate exudation rate and phosphoenolpyruvate carboxylase (PEPC) activity in roots of E. coccineum seedlings grown in a nutrient-poor volcanic substrate. Second, we evaluated CR formation and the expression of genes involved in the production of carboxylates (PEPC) and P uptake (PHT1) in E. coccineum seedlings grown under three different P supplies in hydroponic conditions. Our results showed that the carboxylate exudation rate was higher in CR than in non-CR, which was consistent with the higher PEPC activity in CR. We found higher CR formation in seedlings grown at 5 μM of P supply, concomitant with a higher expression of EcPEPC and EcPHT1 in CR than in non-CR. Overall, mature CR of E. coccineum seedlings growing on volcanic substrates poor in nutrients modify their metabolism compared to non-CR, enhancing carboxylate biosynthesis and subsequent carboxylate exudation. Additionally, transcriptional responses of EcPEPC and EcPHT1 were induced simultaneously when E. coccineum seedlings were grown in P-limited conditions that favored CR formation. Our results showed, for the first time, changes at the molecular level in CR of a species of the Proteaceae family, demonstrating that these root structures are highly specialized in P mobilization and uptake.
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http://dx.doi.org/10.1016/j.plaphy.2021.02.014DOI Listing
April 2021

Human herpesvirus 6 and central nervous system disease in oncology patients: A retrospective case series and literature review.

J Clin Virol 2021 Mar 28;136:104740. Epub 2021 Jan 28.

Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1460, Houston, TX, 77030, USA.

Background: Human herpesvirus 6 (HHV-6) can reactivate with immunosuppression and cause central nervous system (CNS) dysfunction. Much of the literature describes cases after hematopoietic stem cell transplantation (HSCT), ranging from encephalitis to a post-transplant acute limbic encephalitis syndrome (PALE). Outside of HSCT, studies of HHV-6 encephalitis are limited to case reports.

Objectives: This study was designed to review HHV-6 CNS infection, and evaluate all patients admitted to MD Anderson Cancer Center between March 2016 and December 2018 with detectable HHV-6 DNA in the cerebrospinal fluid (CSF).

Study Design: Patients with HHV-6 DNA detected in the CSF using the Viracor or Biofire® Meningitis Encephalitis Panel platforms and no other identified etiology were identified and demographic features, known risk factors, imaging findings, CSF analysis, treatments and patient outcomes were extracted from medical records.

Results: 725 patients underwent HHV-6 testing during the study timeframe, with 19 cases (2.6 %) of HHV-6 mediated CNS disease identified. Most patients, 13/19 (68 %), had undergone HSCT with median time to presentation of 31 days after transplant. Survival at 240 days after transplant was 62 %. CSF had lymphocyte predominance and nearly all patients had peripheral lymphopenia. Other at risk populations identified included patients who received chimeric antigen receptor (CAR) T-cell therapy and biologic immunotherapy. Notable discordance among testing platforms was found in 5/9 (55 %) instances.

Conclusions: In addition to HSCT patients, HHV-6 reactivation leading to CNS disease also occurs in settings such as following adoptive T cell therapy or biologic immunotherapy. Significant diagnostic discordance exists between testing platforms.
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http://dx.doi.org/10.1016/j.jcv.2021.104740DOI Listing
March 2021

A Clinical Pilot Study of Spaced Retrieval Practice with a Self-Generation Booster to Improve Health-Related Memory in Persons With HIV Disease.

Arch Clin Neuropsychol 2021 Jan 30. Epub 2021 Jan 30.

Department of Psychiatry, University of California, San Diego, CA 92093, USA.

Objective: Spaced retrieval practice (SRP) and self-generation are among the most replicated and effective mnemonic strategies in the cognitive psychology literature, but their benefits have not yet been realized in healthcare settings. This study used a randomized, between-subjects design to examine the hypothesis that SRP with a self-generation booster can improve memory for health-related information among clinically referred persons with HIV (PWH), who often have difficulty acquiring new health knowledge.

Method: A consecutive series of 41 PWH referred to a county-funded urban neuropsychology clinic were enrolled. Participants were randomly assigned to learn four statements about the treatment of a mock infectious disease in either a massed study control condition (n = 20) or an SRP condition (n = 21) in which they received two distributed free recall training tests supplemented with self-generation for missed items. The primary outcome was participants' free recall of the four treatment statements after a 20-minute delay filled with nonverbal tests.

Results: PWH participants in the SRP condition were four times more likely than controls to recall at least one treatment statement at the 20-minute delay. SRP was not related to post-test recognition or health-related decision-making performance but was associated with moderately better self-efficacy for decision-making.

Conclusions: Findings from this pilot study show the potential of SRP with a self-generation booster to improve learning and memory for health-related information among PWH in clinic.
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http://dx.doi.org/10.1093/arclin/acaa130DOI Listing
January 2021

Adjunctive steroids in adults with encephalitis: a propensity score analysis.

J Neurol 2021 Jun 21;268(6):2151-2160. Epub 2021 Jan 21.

Division of Infectious Diseases, UT Health Science Center At Houston, McGovern Medical School, 6431 Fannin St. MSB 2.112, Houston, TX, 77030, USA.

Objective: Adjuvant steroids have been used for the treatment of encephalitis, although there is limited data regarding its benefit. We described the use and impact of adjunctive steroids on adverse clinical outcomes (ACO) in adults with encephalitis.

Methods: Retrospective observational study of 230 adults with encephalitis at two tertiary care hospital systems in Houston, Texas, between August 2008 and September 2017. An ACO was assessed at the time of death or discharge and defined as a Glasgow Outcome Scale 1-4. A propensity score analysis was performed.

Results: Out of 230 adult encephalitis patients enrolled, 121 (52.6%) received steroids. Adjunctive steroids were given more frequently to those who had focal neurological deficits (P = 0.01), required mechanical ventilation (MV) (P = 0.01), had intensive care unit admission (P < 0.001), had white matter abnormalities (P = 0.01) or cerebral edema on magnetic resonance imaging of the brain (P = 0.003). An ACO was seen in 135 (58.7%) of patients. The use of adjunctive steroids did not impact ACOs (P = 0.52) on univariate analyses or after propensity score matching. Predictors for an ACO in logistic regression analyses included a Glasgow Coma Score (GCS) < 8, fever, MV, and cerebral edema.

Interpretation: Adjunctive steroids are used more frequently in sicker patients and are not associated with improved clinical outcomes.
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http://dx.doi.org/10.1007/s00415-021-10398-9DOI Listing
June 2021

Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies.

Authors:
Rodrigo Hasbun

Expert Rev Anti Infect Ther 2020 Dec 24:1-7. Epub 2020 Dec 24.

Professor of Medicine, McGovern Medical School UT Health, Houston, TX, USA.

: Healthcare-associated ventriculitis and meningitis occur after neurosurgical procedures, is associated with an adverse outcome in the majority of patients and represent a diagnostic challenge to clinicians. As the cerebrospinal fluid (CSF) culture is the cornerstone of diagnosis, obtaining CSF studies prior to starting antibiotic therapy is key.: This review will evaluate the incidence, risk factors, clinical presentation, diagnosis, empirical intravenous antibiotic therapy, adjunctive intrathecal therapy, microbiology, prognosis, and prevention of HCAVM. We highlight the challenges and limitations of the currently available diagnostic methods and definitions and explore novel technologies. Our review included the search for published literature until June 2020.: Despite available preventive measures, HCAVM continues to occur and to be independently associated with significant neurological morbidity and mortality in the majority of patients. The cornerstone of the diagnosis of HCAVM is a positive CSF culture but the microbiological yield is reduced to ~50% with prior antimicrobial therapy. Although the CSF profile is not affected by antibiotic therapy it has a fair diagnostic accuracy. Future research efforts should concentrate in identifying novel diagnostic tools such as polymerase chain reaction (PCR) or metagenomic sequencing.
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http://dx.doi.org/10.1080/14787210.2021.1866544DOI Listing
December 2020

The Use of Adjunctive Steroids in Central Nervous Infections.

Front Cell Infect Microbiol 2020 23;10:592017. Epub 2020 Nov 23.

Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX, United States.

Central nervous system (CNS) infections continue to be associated with significant neurological morbidity and mortality despite various existing therapies. Adjunctive steroid therapy has been employed clinically to reduce inflammation in the treatment of CNS infections across various causative pathogens. Steroid therapy can potentially improve clinical outcomes including reducing mortality rates, provide no significant benefit, or cause worsened outcomes, based on the causative agent of infection. The data on benefits or harms of adjunctive steroid therapy is not consistent in outcome or density through CNS infections, and varies based on the disease diagnosis and pathogen. We summarize the existing literature on the effects of adjunctive steroid therapy on outcome for a number of CNS infections, including bacterial meningitis, herpes simplex virus, West Nile virus, tuberculosis meningitis, cryptococcal meningitis, , neurocysticercosis, autoimmune encephalitis, toxoplasmosis, and bacterial brain abscess. We describe that while steroid therapy is beneficial and supported in pathogens such as pneumococcal meningitis and tuberculosis, for other diseases, like and they are associated with worse outcomes. We highlight areas of consistent and proven findings and those which need more evidence for supported beneficial clinical use of adjunctive steroid therapy.
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http://dx.doi.org/10.3389/fcimb.2020.592017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719626PMC
June 2021

Risk Classification for Respiratory Viral Infections in Adult Solid Organ Transplantation Recipients.

Transplant Proc 2021 Mar 4;53(2):737-742. Epub 2020 Dec 4.

Department of Internal Medicine, UT Health McGovern Medical School, Houston, Texas.

Introduction: Molecular testing such as nasopharyngeal viral polymerase chain reaction (PCR) (NVP) is available now in most hospitals and widely used to identify respiratory viral infections (RVIs) in solid organ transplantation (SOT) recipients.

Materials And Methods: A retrospective multicenter study at 8 hospitals from March 1, 2016, to April 30, 2019. We included all adult SOT recipients who were admitted to the hospitals and had their first NVP post transplantation.

Results: A total of 102 adult SOT recipients were enrolled. NVP test was positive in 33 (32.4%) SOT recipients and negative in 69 (67.6%). Median age was more than 60 years old with female predominance in both groups. The majority of patients who had positive NVP were hospitalized either in fall or winter seasons (91%). RVI symptoms were documented in about 73% of the positive NVP group. Rhinovirus was the most common identified virus (48.4%). On logistic regression analysis, clinical presentation in fall or winter seasons, presenting with upper respiratory infection (URI) symptoms and taking prednisone ≥10 mg/d were significantly associated with positive NVP. This model classified patients into 3 categories of risk for RVIs-low (none of the variables), 0%; intermediate (1 variable), 6.5%; and high (≥2 variables), 55.4% with P < .001 for all predictors.

Conclusion: SOT recipients who are taking prednisone (≥10 mg) and have URI symptoms in fall or winter seasons are more likely to have RVIs.
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http://dx.doi.org/10.1016/j.transproceed.2020.10.011DOI Listing
March 2021

Predicting Inpatient Mortality Among Encephalitis Patients: A Novel Admission Risk Score.

Open Forum Infect Dis 2020 Nov 7;7(11):ofaa471. Epub 2020 Oct 7.

Department of Internal Medicine, UT Health McGovern Medical School, Houston, Texas, USA.

Background: Identifying underlying commonalities among all-cause encephalitis cases can be extraordinarily useful in predicting meaningful risk factors associated with inpatient mortality.

Methods: A retrospective cohort of patients with encephalitis was derived from a clinical chart review of adult patients (age ≥18 years) across 16 different hospitals in Houston, Texas, between January 2005 and July 2015. Clinical features at admission were assessed for their correlation with inpatient mortality and used to derive a final risk score prediction tool.

Results: The study included a total of 273 adult patients with all-cause encephalitis, 27 (9.9%) of whom died during hospitalization. A limited number of clinical features were substantially different between patients who survived and those who died (Charlson score, Glasgow coma scale [GCS], immunosuppression, fever on admission, multiple serologic studies, and abnormal imaging). A final multivariable logistic model was derived with the following risk factors, which were transformed into a scoring system: 1 point was assigned to the presence of a Charlson score >2, thrombocytopenia, or cerebral edema, and 2 points for a GCS value <8. Patients were then classified into different risk groups for inpatient mortality: 0 points (0%), 1 point (7%), 2 points (10.9%), 3 points (36.8%), and ≥4 points (81.8%).

Conclusions: The risk score developed from this study shows a high predictive value. This can be highly beneficial in alerting care providers to key clinical risk factors associated with in-hospital mortality in adults with encephalitis.
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http://dx.doi.org/10.1093/ofid/ofaa471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651585PMC
November 2020

Management of Acute Bacterial Meningitis in Children.

Infect Drug Resist 2020 11;13:4077-4089. Epub 2020 Nov 11.

Division of Infectious Diseases, Department of Internal Medicine, UT Health, McGovern Medical School, Houston, TX, USA.

Acute community-acquired bacterial meningitis (ABM) in children continues to have high rates of neurological morbidity and mortality despite the overall declining rates of infection attributed to the use of vaccines and intrapartum Group B prophylaxis. Prompt diagnosis and early antibiotic therapy are crucial and should not be delayed to obtain cranial imaging. Differentiating bacterial from viral meningitis continues to be a clinical dilemma especially in patients with previous antibiotic exposure. Clinical models and inflammatory biomarkers can aid clinicians in their diagnostic approach. Multiplex polymerase chain reaction and metagenomic next-generation sequencing are promising tools that can help in early and accurate diagnosis. This review will present the epidemiology of ABM in children, indications of cranial imaging, role of different models and serum biomarkers in diagnosing ABM, and management including the use of adjunctive therapies and methods of prevention.
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http://dx.doi.org/10.2147/IDR.S240162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667001PMC
November 2020

Real-time intracranial pressure monitoring during high-dose methotrexate treatment for primary central nervous system lymphoma.

Cancer Treat Res Commun 2020 2;25:100234. Epub 2020 Nov 2.

Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston - McGovern Medical School, 6431 Fannin St. Houston, TX, 77030, United States; Memorial Hermann Hospital-Texas Medical Center, 6411 Fannin St. Houston, TX, 77030, United States; Center for Precision Health, School of Biomedical Informatics, the University of Texas Health Science Center at Houston - McGovern Medical School, 6431 Fannin St. Houston, TX, 77030, United States. Electronic address:

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma with exclusive central nervous system (CNS) and/or ocular involvement. Increased intracranial pressure (ICP) from cerebral edema can commonly presents secondary to the mass effect of PCNSL. Methotrexate-based induction chemotherapy is the gold standard for treatment, however, several neurotoxic complications have been associated with high-dose methotrexate (HD-MTX) treatment. Tumor lysis and other biochemical disruptions following administration of HD-MTX are postulated to increase cerebral edema and ICP in predisposed patients, therefore, in the setting of ring-enhancing lesions with significant mass effect, monitoring of ICP to prevent cerebral herniation may be necessary.

Presentation Of Case: We present the case of a patient with diffuse cerebral edema secondary to PCNSL, who was treated with methotrexate-based induction chemotherapy and underwent real-time ICP monitoring to allow for early recognition, and management with aggressive medical therapy to prevent worsening cerebral edema and potential fatal herniation.

Discussion And Conclusions: Treatment of patients with high tumor burden PCNSL can prove to be challenging, particularly at the time of initiation of methotrexate based induction chemotherapy in the setting of impending cerebral herniation, as in the case presented. Close monitoring of the patient's ICP proved advantageous in rapidly recognizing, and successfully treating elevations in ICP that could have worsened mass effect and lead to fatal herniation.
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http://dx.doi.org/10.1016/j.ctarc.2020.100234DOI Listing
November 2020

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.

BMC Infect Dis 2020 Oct 23;20(1):788. Epub 2020 Oct 23.

Department of Infectious Diseases and Clinical Microbiology, Erciyes University School of Medicine, Kayseri, Turkey.

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.
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http://dx.doi.org/10.1186/s12879-020-05502-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585215PMC
October 2020

Reply to Mathon et al.

Clin Infect Dis 2021 05;72(9):e433

Department of Internal Medicine, UT Health McGovern Medical School, Houston, Texas, USA.

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http://dx.doi.org/10.1093/cid/ciaa1094DOI Listing
May 2021

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

Epidemiol Infect 2020 07 27;148:e173. Epub 2020 Jul 27.

UT Health McGovern Medical School, Houston, TX, USA.

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.
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http://dx.doi.org/10.1017/S0950268820001648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439290PMC
July 2020

HIV Testing in Adults Presenting With Central Nervous System Infections.

Open Forum Infect Dis 2020 Jun 6;7(6):ofaa217. Epub 2020 Jun 6.

Division of Infectious Diseases, Department of Internal Medicine, University of Texas (UT Health), McGovern Medical School, Houston, Texas, USA.

Background: Universal HIV testing in adults presenting to a health care setting was recommended by the Centers for Disease Control and Prevention (CDC) in 2006, but compliance in central nervous system (CNS) infections is unknown.

Methods: A multicenter study of adults presenting with CNS infections to 18 hospitals in Houston and New Orleans between 2000 and 2015 was done to characterize HIV testing and explore factors associated with a positive HIV test.

Results: A total of 1478 patients with a diagnosis of meningitis or encephalitis were identified; 180 were excluded because of known HIV diagnosis (n = 100) or were <17 years old (n = 80). Out of 1292 patients, 642 (49.7%) had HIV testing, and testing did not differ significantly before or after the CDC recommendations in 2006 (53% vs 48%; = .068). An HIV test was more commonly done in patients who were non-Caucasian, had fever >38°C, or had seizures on presentation, and of those tested, non-Caucasian patients and those with photophobia were more likely to have a positive HIV test ( < .05). HIV testing also varied by type of CNS infection: community-acquired bacterial meningitis (98/130, 75.4%), encephalitis (174/255, 68.2%), aseptic meningitis (285/619, 46.0%), and health care-associated meningitis (85/288, 29.5%; < .001).

Conclusions: Even though HIV testing should be done in all adults presenting with a CNS infection, testing remains ~50% and did not improve after the recommendation for universal testing by the CDC in 2006.
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http://dx.doi.org/10.1093/ofid/ofaa217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320826PMC
June 2020

Interferon-γ and voriconazole combined therapy for refractory meningeal coccidioidomycosis in a patient with interferon-γ deficiency.

IDCases 2020 21;21:e00835. Epub 2020 May 21.

Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School at UT Health, Houston TX, USA.

Coccidioides meningitis (CM) is a challenging infection, given the limited penetration to the cerebrospinal fluid of conventional antifungals, resulting in a high risk of recurrence. We present the first case of a successfully treated persistent CM with voriconazole and adjuvant INF-γ 1b.
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http://dx.doi.org/10.1016/j.idcr.2020.e00835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262437PMC
May 2020

Infectious and Autoimmune Causes of Encephalitis in Children.

Pediatrics 2020 06 1;145(6). Epub 2020 May 1.

Section of Pediatric Tropical Medicine, National School of Tropical Medicine,

Background And Objectives: Encephalitis can result in neurologic morbidity and mortality in children. Newly recognized infectious and noninfectious causes of encephalitis have become increasingly important over the past decade.

Methods: We retrospectively reviewed medical records from pediatric patients in Houston diagnosed with encephalitis in both an urban and rural catchment area between 2010 and 2017. We conducted an investigation to understand the etiology, clinical characteristics, and diagnostic testing practices in this population.

Results: We evaluated 231 patients who met the case definition of encephalitis, among which 42% had no recognized etiology. Among those with an identified etiology, the most common were infectious (73; 31%), including viral ( = 51; 22%), with the most frequent being West Nile virus (WNV; = 12), and bacterial ( = 19; 8%), with the most frequent being ( = 7). Among cases of autoimmune encephalitis ( = 60; 26%), the most frequent cause was anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis ( = 31). Autoimmune causes were seen more commonly in female ( < .01) patients. Testing for herpes simplex virus and enterovirus was nearly universal; testing for anti-NMDAR encephalitis, WNV, and was less common.

Conclusions: WNV was the most common infectious cause of encephalitis in our pediatric population despite lower testing frequency for WNV than herpes simplex virus or enterovirus. Increasing testing for anti-NMDAR encephalitis resulted in frequent identification of cases. Increased awareness and testing for WNV and would likely result in more identified causes of pediatric encephalitis. Earlier etiologic diagnosis of encephalitides may lead to improve clinical outcomes.
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http://dx.doi.org/10.1542/peds.2019-2543DOI Listing
June 2020

Compliance with international guidelines in adults with encephalitis.

J Clin Virol 2020 06 14;127:104369. Epub 2020 Apr 14.

Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX, United States.

Background: Encephalitis is associated with significant neurological disability and mortality. Many guidelines are published for encephalitis management but compliance with them is unknown.

Objectives: To evaluate the appropriate management and compliance to the current guidelines in adults with encephalitis.

Study Design: A retrospective multicenter study at 17 hospitals in the Greater Houston area from August 1, 2008 through September 30, 2017. All cases met the definition for possible or probable encephalitis as per the international encephalitis consortium guidelines.

Results: A total of 241 adults (age >17 years) with encephalitis were enrolled. The most common etiologies were unknown (41.9 %), viral (27.8 %) and autoimmune (21.2 %). An adverse clinical outcome was seen in 49 % with 12.4 % in hospital mortality. A high compliance with guidelines (>90 %) was only seen in obtaining a brain computerized tomography (CT) scan, blood cultures and cerebrospinal fluid (CSF) gram stain and culture. A CSF herpes virus simplex (HSV) polymerase chain reaction (PCR) was done in 84 % and only repeated in 14.2 % of patients with an initial negative result. Furthermore, only two-thirds of patients were started empirically on intravenous acyclovir and antibiotics. Evaluation for other etiologies were not uniformly performed: arboviral serologies (57.3 %), CSF anti-N-Methyl-d-Aspartate Receptor (NMDA) receptor antibody (35.7 %), and CSF varicella zoster virus (VZV) PCR (32 %). The highest yield for the tests were arboviral serologies (42 %), anti-NMDA antibodies (41.2 %) and VZV PCR (16.4 %).

Conclusion: The management of encephalitis as per current guidelines is suboptimal leading to underutilization of currently available diagnostic tests and empirical therapy.
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http://dx.doi.org/10.1016/j.jcv.2020.104369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194944PMC
June 2020

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

Authors:
Rodrigo Hasbun

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Department of Medicine, Division of Infectious Diseases, McGovern Medical School UT Health, Houston, Texas, USA

Mizrahi and colleagues present a well-described case of the emergence of drug resistance in 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.
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http://dx.doi.org/10.1128/AAC.02251-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038279PMC
February 2020

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

J Neuroinflammation 2020 Jan 4;17(1). Epub 2020 Jan 4.

Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.

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 [C]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 [C]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.
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http://dx.doi.org/10.1186/s12974-019-1692-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942362PMC
January 2020

Prediction of unfavorable outcomes in West Nile virus neuroinvasive infection - Result of a multinational ID-IRI study.

J Clin Virol 2020 01 11;122:104213. Epub 2019 Nov 11.

ESCMID Study Group for Infectious Diseases of the Brain - ESGIB, Switzerland; ID-IRI, Ankara, Turkey.

Background: WNV causes 1.4% of all central nervous system infections and is the most common cause of epidemic neuro-invasive disease in humans.

Objectives: Our main objective was to investigate retrospectively West Nile virus neuroinvasive disease (WNND) cases hospitalized during 2010-2017 and identified factors that can influence prognosis.

Study Design: We documented the demographic, epidemiologic, clinical and laboratory data of WNND and identified factors that can influence prognosis. The data were recruited through Infectious Diseases International Research Initiative (ID-IRI), which serves as a network for clinical researches.

Results: We investigated 165 patients with WNND in 10 countries from three continents. 27 patients died and the mortality rate was 16.4%. In an univariate analysis age, congestive heart failure, neoplasm and ischemic heart disease (p < 0.001), neuropsychiatric disorders (p = 0.011), chronic hepatitis (p = 0.024) and hypertension (p = 0.043) were risk factors for death. Fatal evolution was also correlated with ICU addmission, disorientation, speech disorders, change in consciousnes, coma, a low Glasgow coma score, obtundation, confusion (p < 0.001), history of syncope (p = 0.002) and history of unconsciousness (p = 0.037). In a binomial logistic regresssion analysis only age and coma remained independent prediction factors for death. We created an equation that was calculated according to age, co-morbidities and clinical manifestations that may be used to establish the prognosis of WNND patients.

Conclusions: WNND remain an important factor for morbidity and mortality worldwide, evolution to death or survival with sequelae are not rare. Our study creates an equation that may be used in the future to establish the prognosis of WNND patients.
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http://dx.doi.org/10.1016/j.jcv.2019.104213DOI Listing
January 2020

The comparison of Gram-positive and Gram-negative healthcare-associated ventriculitis and meningitis in adults and children.

Intensive Care Med 2020 01 30;46(1):128-131. Epub 2019 Oct 30.

Infectious Disease Division, Department of Internal Medicine, McGovern Medical School at the University of Texas Health Science Center in Houston, 6431 Fannin St. 2.112 MSB, Houston, TX, 77030, USA.

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http://dx.doi.org/10.1007/s00134-019-05815-7DOI Listing
January 2020

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

Eur J Clin Microbiol Infect Dis 2020 Jan 9;39(1):45-52. Epub 2019 Sep 9.

Vall d'Hebron Institute of Research, CIBERES, Barcelona, Spain.

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.
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http://dx.doi.org/10.1007/s10096-019-03691-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222138PMC
January 2020

Seroprevalence of Strongyloides stercoralis and Evaluation of Universal Screening in Kidney Transplant Candidates: A Single-Center Experience in Houston (2012-2017).

Open Forum Infect Dis 2019 Jul;6(7)

Division of Infectious Diseases, McGovern Medical School, University of Texas Health Science Center at Houston.

Background: Disseminated strongyloidiasis in solid organ transplant recipients is a rare but devastating infection. In our center, we implemented a universal screening of all candidates for kidney transplantation. We assessed the seroprevalence and utility of universal screening for strongyloidiasis in our center.

Methods: Patients were identified from our transplant referral list (from July 2012 to June 2017). Demographics, pretransplant laboratory, and serological screenings were retrospectively collected. For Strongyloides-seropositive (SSp) patients, data on travel history, symptoms, treatment, and stool ova and parasite examinations were extracted. Logistic regression and multiple imputation for missing data were performed.

Results: A total of 1689 patients underwent serological screening, of whom 168 (9.9%) were SSp. Univariate analysis revealed that SSp patients had higher rates of eosinophilia, diabetes mellitus, latent tuberculosis and were likely to be either Hispanic or Asian (P < .05). In multivariate analysis, eosinophilia (P = .01), diabetes mellitus (P = .02), and Asian race (P = .03) were associated with being SSp, but 45 (27%) of the SSp patients did not have any of these 3 factors, and 18 SSp patients (11%) had no epidemiological risk factors. All patients received ivermectin, and none developed disseminated strongyloidiasis. Of patients who underwent serological screening on multiple occasions, 6.8% seroconverted while waiting for kidney transplantation.

Conclusions: We found a high rate of Strongyloides seropositivity among our kidney transplantation candidates. No epidemiological risk factors effectively predicted SSp status in our population, and universal screening identified a large number of patients without such factors. Serial screening should be considered when a long wait time is expected before transplantation.
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http://dx.doi.org/10.1093/ofid/ofz172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656655PMC
July 2019

Neurological and Psychiatric Adverse Effects of Antimicrobials.

CNS Drugs 2019 08;33(8):727-753

Section of Infectious Diseases, Department of Medicine, UT Health McGovern Medical School, 6431 Fannin St. MSB 2.112, Houston, TX, 77030, USA.

Antimicrobials are a widely used class of medications, but several of them are associated with neurological and psychiatric side effects. The exact incidence of neurotoxicity with anti-infectives is unknown, although it is estimated to be < 1%. Neurotoxicity occurs with all classes of antimicrobials, such as antibiotics, antimycobacterials, antivirals, antifungals and antiretrovirals, with side effects ranging from headaches, anxiety and depression to confusion, delirium, psychosis, mania and seizures, among others. It is important to consider these possible side effects to prevent misdiagnosis or delayed treatment as drug withdrawal can be associated with reversibility in most cases. This article highlights the different neurotoxic effects of a range of antimicrobials, discusses proposed mechanisms of onset and offers general management recommendations. The effects of antibiotics on the gut microbiome and how they may ultimately affect cognition is also briefly examined.
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http://dx.doi.org/10.1007/s40263-019-00649-9DOI Listing
August 2019
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