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BackgroundMask mandates for children during the COVID-19 pandemic varied in different locations. A risk-benefit analysis of this intervention has not yet been performed. In this study, we performed a systematic review to assess research on the effectiveness of mask wearing in children.MethodsWe performed database searches up to February 2023. The studies were screened by title and abstract, and included studies were further screened as full-text references. A risk-of-bias analysis was performed by two independent reviewers and adjudicated by a third reviewer.ResultsWe screened 597 studies and included 22 in the final analysis. There were no randomised controlled trials in children assessing the benefits of mask wearing to reduce SARS-CoV-2 infection or transmission. The six observational studies reporting an association between child masking and lower infection rate or antibody seropositivity had critical (n=5) or serious (n=1) risk of bias; all six were potentially confounded by important differences between masked and unmasked groups and two were shown to have non-significant results when reanalysed. Sixteen other observational studies found no association between mask wearing and infection or transmission.ConclusionsReal-world effectiveness of child mask mandates against SARS-CoV-2 transmission or infection has not been demonstrated with high-quality evidence. The current body of scientific data does not support masking children for protection against COVID-19.

Background Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections. Methods This was a retrospective cohort of all patients with an ID consult within an academic health system from 1 January 2014 through 31 December 2023, including community, general, and transplant ID consult services. Results There were 60 820 inpatient ID consults (17 235 community, 29 999 general, and 13 586 transplant) involving 37 848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (P <.001). In total, 7.5% of patients receiving an ID consult died during admission and 1006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (P <.001). Six-month mortality was 9% for all nonobstetric admissions versus 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID. In total 2866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. A total of 16.3% of patients had a do-not-resuscitate order during the index hospitalization; 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult. Conclusions Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care. [ABSTRACT FROM AUTHOR]

The progressive increase in HIV infection among older adults requires constant research and monitoring, given that geriatric syndromes associated with HIV comorbidities have become an important public health problem. We reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and it has a central question: Is the incidence of cognitive impairment higher in older patients living with HIV than in their seronegative peers? The following databases were searched for this review: MEDLINE/PubMed, EMBASE, LILACS, Web of Science, and Scopus. The inclusion criteria were studies whose samples were ≥ 50% patients aged ≥ 50 years, with and without HIV, and a main outcome related to the incidence of cognitive impairment. Only cohort studies with follow-up lasting ≥ 24 months were considered. Three reviewers independently screened the documents for eligibility criteria, extracted the data, assessed the risk of bias (Newcastle-Ottawa Scale), and evaluated the quality of evidence. A narrative synthesis was prepared. In total, 10 798 trials were screened, 8884 were excluded, 14 were analyzed, and 5 were included in this review. Only 1 applied cognitive assessment tests; the rest used secondary data from the medical records. Most found that the incidence of cognitive disorders was higher among older people living with HIV, which highlights the need for public policies aimed at primary and secondary prevention strategies. Further research from other countries is still required. PROSPERO register (CRD42022321914).

Introduction: HIV (Human Immunodeficiency Virus) continues to be a major global public health issue with no cure. Vitamin D is a fat-soluble hormone that is majorly involved in the classical function of calcium and phosphorus hemostasis and bone mineralization as well as non-classical functions of immune modulation in various viral and autoimmune diseases. A combination of both traditional risk factors, HIV- specific and antiretroviral therapy (ART)-specific contributors leave HIV-infected persons (PLHIV) at a greater risk for low 25-OH-Vitamin D levels and frank vitamin D deficiency. Aims and Setting: The current study was conducted to assess and characterize the prevalence of Vitamin D deficiency in PLHIV-on-ART attending a tertiary care hospital and assess the factors that may be affecting it. Methods: 95 PLHIV registered at an ART center were selected over a period of 6 months based on Inclusion and Exclusion criteria. Flow cytometry estimation of CD4 count and ELISA based quantitative assessment of serum 25-OH Vitamin D3 were done along with detailed clinical examination. P

Copyright of Arquivos de Ciências da Saúde da UNIPAR is the property of Associacao Paranaense de Ensino e Cultura and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To determine the prevalence, epidemiological profile, and clinical characteristics of Oral or Oropharyngeal Mucosal Lesions (OOPML) in patients attended at the Otorhinolaryngology Service of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ) from 2005 to 2017. Methods: Statistical analysis of descriptive data from medical records (gender, age, education level, skin color, origin, smoking, alcoholism, HIV co-infection, time of disease evolution, first symptom, and OOPML location) was performed. Results: Of 7551 patients attended at the service, 620 (8.2%) were included in the study. OOPML were classified into developmental anomalies (n = 3), infectious diseases (non-granulomatous n = 220; granulomatous n = 155), autoimmune diseases (n = 24), neoplasms (benign n = 13; malignant, n = 103), and unclassified epithelial/soft tissue diseases (n = 102). OOPML of infectious diseases (60.5%) and neoplasms (18.7%) were the most frequent. The predominant demographics of patients with OOPML were: males (63.5%), white (53.5%), and those in the fifth to sixth decades of life (43.3%). Local pain (18.1%) and odynophagia (15%) were the most reported first symptoms, and the most frequent OOPML sites were the palatine tonsil (28.5%), hard palate (22.7%), and tongue (20.3%). The median evolution time was three months. Conclusions: Infectious OOPML were the most frequent, as expected in a reference center for infectious diseases, and thus, they are likely to be less frequent in general care and/or dental services. Underreporting of OOPML is possible, as oral/oropharyngeal examination is often not included in the routine medical examination. Oral cavity/oropharynx examination should be performed by specialists, such as dentists and otorhinolaryngologists, who have the expertise in identifying OOPML, even in incipient/asymptomatic cases. Given the numerous diseases in which OOPML can present, diagnosis could be facilitated by multidisciplinary teams, potentially enabling the early treatment of diseases, and thus, reduce morbidity and improve prognosis. The use of standardized medical records for oral/oropharyngeal systematic examination could provide relevant tools for differential diagnoses and information for new clinical-epidemiological studies. Level of evidence: Level 3.

Cryptococcus neoformans is a global invasive mycosis that is known to cause significant morbidity and mortality. It is commonly observed that individuals with compromised immune systems are more prone to developing cryptococcal meningitis. Although ocular involvement is rare, previous studies have indicated that ocular lesions precede symptomatic meningitis in only 27 % of patients with central nervous system involvement. Intraocular infections typically manifest as chorioretinopathy and vitreous inflammation, often leading to severe vision loss. In this case, we present the clinical details of a 57-year-old immunocompetent woman who visited the ophthalmology department of West China Hospital of Sichuan University with a progressive loss of vision in her right eye. After a thorough evaluation, she was diagnosed with fungal endophthalmitis, and subsequently initiated on appropriate induction anti-fungal therapy for cryptococcal meningoencephalitis. This case highlights the importance of early recognition and treatment, which can potentially improve the prognosis for patients.

Objective: A new monthly virtual education curriculum on sexual healthcare was launched in 2021. This is an analysis of the pilot education series designed to increase primary care providers' knowledge of sexual health best practices including taking thorough sexual histories, STI screening and treatment, and PrEP prescribing. Methods: A Sexual Health Curriculum Series was developed as part of a quality improvement initiative at a large urban safety-net hospital in Dallas County, Texas. Didactic sessions were administered to primary care providers and staff via a virtual meeting platform once a month from May 2021 to April 2022. Results: A total of 52 participants completed the pre-series survey, and 21 participants filled out the final post-series survey. 70% of respondents who completed the post-series survey reported that they learned new information that was incorporated into their practice. The average percentage correct on individual pre-session surveys was 60% compared to 63% on individual post-session surveys (p = 0.03). Conclusion: Sexual health education is an important tool to help primary care providers adhere to sexual health best practices. There is a need for ongoing implementation of innovative strategies to improve knowledge and adherence to sexual health best practices. A sexual health curriculum may be effective in helping primary providers recognize patients at increased risk and apply evidence-based guidelines to their practices. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence and type of medication discrepancies and factors associated with unintentional discrepancies and identify the rate of hospital readmission and emergency service visit within 30 days after discharge among hospitalized patients with infectious diseases and receiving clinical pharmacist-led medication reconciliation during the coronavirus disease-2019 (COVID-19) pandemic. Materials and Methods: This observational study was conducted in the internal medicine and infectious diseases wards of a tertiary university hospital between July 2020 and February 2021 among hospitalized adult patients with infectious diseases. Medication reconciliation service (including patient counseling) was provided in person or by telephone. The number and type of medication discrepancies detected during the medication reconciliation services, the acceptance rate of pharmacists' recommendation, and factors associated with having at least one unintentional medication discrepancy at admission were evaluated. At follow-up, hospital readmission and emergency service visit within 30 days after discharge were assessed by telephone. Results: Among 146 patients, 84 (57.5%) had at least one unintentional discrepancy at admission. Only three unintentional discrepancies were determined in three patients at hospital discharge. All the pharmacists' recommendations for medication discrepancies were accepted by the physicians. Having COVID-19 [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.15-4.40; p<0.05], being at a high risk for medication error (OR: 2.01, 95% CI: 1.03-3.92; p<0.05), and higher number of medications used at home (OR: 1.41, 95% CI: 1.23-1.61; p<0.001) were associated with having at least one unintentional discrepancy at admission. The rates of 30 day hospital readmission and admission to the emergency medical service were 12.3% and 15.8%, respectively. Conclusion: Medication reconciliation service provided by in-person or by telephone was useful for detecting and solving unintentional medication discrepancies during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants. [ABSTRACT FROM AUTHOR]

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased 2–4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Lyme disease is a common tickborne disease with a common presentation. Untreated Lyme disease can affect other organs. This can lead to anion gap metabolic acidosis through severe renal failure. Unlike anion gap metabolic acidosis, osmolar gap can be caused by ingestion of ethanol, toxic alcohols, solvents, and salicylates. Therefore, a presentation with osmolar gap and anion gap metabolic acidosis yields a variety of differential diagnoses. Case Report: A 72-year-old man presented after being found down. There were few historical cues, and workup was negative for seizures or any acute cerebrovascular incident. Laboratory results were revealing of severe anion gap acidosis with osmolar gap. During clinical decision making and diagnostic dilemma, toxidrome syndromes for potential ingestions and inhalations were sought in addition to thorough workup, which expanded to include infectious etiologies. This patient's presentation was unique: Lyme disease in the setting of severe anion gap metabolic acidosis with an osmolar gap. Conclusions: The outcome of critically ill patients can be determined by the clinician's method to address the diagnostic dilemma and quality of supportive care. Critically ill patient outcomes can be subject to the clinician's method to address a diagnostic quandary. This unique case poses an important reminder for clinicians to maintain their standard methodologies of critical thinking amidst the noise of distracting medical information. [ABSTRACT FROM AUTHOR]

Data on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population. We conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals. We included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021–12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8–58.9 %), 83.0 % (75.4–88.3 %), and 87.1 % (30.6–97.6 %), respectively. Three doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations. [ABSTRACT FROM AUTHOR]

Infectious disease management of Staphylococcus aureus bacteremia (SAB) was surveyed through the Emerging Infections Network. Although there were areas of consensus, we found substantial practice variation in diagnostic evaluation and management of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices.

Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.

Clinical expertise in infectious diseases is crucial in treating patients with infectious complications. The new board certification in infectious diseases will establish this expertise in Germany. The role of the specialty of infectious diseases in German hospitals and the definition for clinical services in hospitals (levels 2 and 3) are outlined here.

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BackgroundTuberculosis (TB) is the leading cause of infectious disease deaths worldwide and is the leading cause of death among people with HIV. The World Health Organization (WHO) has called for collaboration between public and private healthcare providers to maximize integration of TB/HIV services and minimize costs. We systematically reviewed published models of public-private sector diagnostic and referral services for TB/HIV co-infected patients.MethodsWe searched PubMed, the Cochrane Central Register of Controlled Trials, Google Scholar, Science Direct, CINAHL and Web of Science. We included studies that discussed programs that linked private and public providers for TB/HIV concurrent diagnostic and referral services and used Review Manager (Version 5.3, 2015) for meta-analysis.ResultsWe found 1,218 unduplicated potentially relevant articles and abstracts; three met our eligibility criteria. All three described public-private TB/HIV diagnostic/referral services with varying degrees of integration. In Kenya private practitioners were able to test for both TB and HIV and offer state-subsidized TB medication, but they could not provide state-subsidized antiretroviral therapy (ART) to co-infected patients. In India private practitioners not contractually engaged with the public sector offered TB/HIV services inconsistently and on a subjective basis. Those partnered with the state, however, could test for both TB and HIV and offer state-subsidized medications. In Nigeria some private providers had access to both state-subsidized medications and diagnostic tests; others required patients to pay out-of-pocket for testing and/or treatment. In a meta-analysis of the two quantitative reports, TB patients who sought care in the public sector were almost twice as likely to have been tested for HIV than TB patients who sought care in the private sector (risk ratio [RR] 1.98, 95% confidence interval [CI] 1.88-2.08). However, HIV-infected TB patients who sought care in the public sector were marginally less likely to initiate ART than TB patients who sought care from private providers (RR 0.89, 95% CI 0.78-1.03).ConclusionThese three studies are examples of public-private TB/HIV service delivery and can potentially serve as models for integrated TB/HIV care systems. Successful public-private diagnostic and treatment services can both improve outcomes and decrease costs for patients co-infected with HIV and TB.

Objective: To report the diagnostic test accuracy of dipstick urinalysis for the detection of urinary tract infections (UTIs) in febrile infants aged 90 days or less attending the emergency department (ED).Design: Retrospective cohort study.Patients: Febrile infants aged 90 days or less attending between 31 August 2018 and 1 September 2019.Main Outcome Measures: The sensitivity, specificity and predictive values of dipstick urinalysis in detecting UTIs defined as growth of ≥100 000 cfu/mL of a single organism and the presence of pyuria (>5 white blood cells per high-power field).Setting: Eight paediatric EDs in the UK/Ireland.Results: A total of 275 were included in the final analysis. There were 252 (92%) clean-catch urine samples and 23 (8%) were transurethral bladder catheter samples. The median age was 51 days (IQR 35-68.5, range 1-90), and there were 151/275 male participants (54.9%). In total, 38 (13.8%) participants had a confirmed UTI. The most sensitive individual dipstick test for UTI was the presence of leucocytes. Including 'trace' as positive resulted in a sensitivity of 0.87 (95% CI 0.69 to 0.94) and a specificity of 0.73 (95% CI 0.67 to 0.79). The most specific individual dipstick test for UTI was the presence of nitrites. Including trace as positive resulted in a specificity of 0.91 (95% CI 0.86 to 0.94) and a sensitivity of 0.42 (95% CI 0.26 to 0.59).Conclusion: Point-of-care urinalysis is moderately sensitive and highly specific for diagnosing UTI in febrile infants. The optimum cut-point to for excluding UTI was leucocytes (1+), and the optimum cut-point for confirming UTI was nitrites (trace).Trial Registration Number: NCT04196192. [ABSTRACT FROM AUTHOR]

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Hepatitis C viral infection is a major public health concern and leading cause of chronic liver disease in the United States. Hepatitis C is primarily transmitted through blood exchange and is highly prevalent among people who inject drugs. Despite the availability of direct-acting antiviral (DAA) treatment, cost and barriers to access remain prohibitive for many patients., Summary: In 2018, University of Kentucky HealthCare (UKHC) began a screening program for patients admitted to its emergency department (ED). Despite identifying hepatitis C RNA-positive patients, connection to care proved challenging due to unavailability of follow-up clinic appointments, communication barriers, and lack of insurance coverage. In 2023, UKHC implemented a pharmacist-led hepatitis C screening, assessment, and treatment initiative in the ED following American Association for the Study of Liver Diseases (AASLD) simplified treatment guidelines. Pharmacists order needed laboratory assessments and complete imaging for liver fibrosis in eligible patients. Patients diagnosed with hepatitis C who meet simplified treatment criteria are prescribed DAA therapy by a hepatitis C advanced practice provider employed by the program. The UKHC specialty pharmacy then follows up with dispensing of DAA therapy and proactive refill management for subsequent fills., Conclusion: This holistic, interdisciplinary treatment model has allowed UKHC to increase treatment attachment rates for hepatitis C diagnoses in the ED from approximately 10% to 54%. This program has also reduced the median time to treatment of hepatitis C-infected individuals encountered in the ED from approximately 420 days to 17 days., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Competing interests: None declared.

Objective: To describe the association of respiratory viral test results and the risk of invasive bacterial infection (IBI) for febrile young infants presenting to emergency care., Design: A planned secondary analysis within the Febrile Infants Diagnostic assessment and Outcome (FIDO) study, a prospective multicentre observational cohort study conducted across the UK and Ireland., Setting: 35 paediatric emergency departments and assessment units across the UK and Ireland between 6 July 2022 and 31 August 2023., Patients: Febrile infants aged 90 days and under presenting to emergency care., Main Outcome Measures: IBI (meningitis or bacteraemia) among febrile infants, undergoing respiratory viral testing for respiratory syncytial virus (RSV), influenza and SARS-CoV-2., Results: 1395 out of 1821 participants underwent respiratory viral testing, of those tested 339 (24.5%) tested positive for at least one of, SARS-CoV-2, RSV or influenza. A total of 45 infants (3.2%) were diagnosed with IBI. Of these, IBI occurred in 40 out of 1056 (3.8%) participants with a negative viral test and 5 out of 339 (1.5%) occurred in participants with a positive viral respiratory test (p=0.034). Infants aged 29 days and older with a positive respiratory viral test had a significantly lower rate of IBI (0.7%) compared with those with a negative test (3.2%) (p=0.015)., Conclusions: Young febrile infants with a positive respiratory viral test for SARS-CoV-2, RSV or influenza are at lower risk of IBI. Infants over 28 days of age with a positive viral test represent the lowest risk cohort., Trial Registration Number: NCT05259683., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The gold standard for diagnosis of meningitis is the isolation of a pathogen from cerebrospinal fluid (CSF) by culture or PCR. However, treatment is routinely commenced based on CSF findings prior to microbiological results. This study determined the predictive value of CSF parameters for diagnosing bacterial and viral meningitis in young infants., Methods: Multicentre retrospective (2010-2020) cohort study of 1088 CSF results from infants aged 0-90 days. The predictive value of CSF parameters (white blood cell count (WCC), neutrophil, protein, glucose) was evaluated in 538 meningitis cases (39 bacterial, 499 viral) compared with controls with negative CSF microbiological testing and no prior antibiotics., Results: For bacterial meningitis, the sensitivity of the commonly used CSF WCC cut-off of 20×10 6 /L for neonates, 15×10 6 /L for infants 1-2 months old and 5×10 6 /L for infants 2-3 months old was 89%, 91% and 86% and the specificity was 78%, 77% and 61%, respectively. CSF protein levels ≥1 g/L in neonates and ≥0.8 g/L in infants aged 1-3 month, or CSF neutrophils ≥2×10 6 /L, independently increased the likelihood of bacterial meningitis (positive likelihood ratios ≥5 and ≥3, respectively). 3 of 39 cases of bacterial meningitis would have been missed using the commonly used WCC cut-offs alone. However, two would have been identified using CSF protein and neutrophil thresholds. All CSF parameters were poor at identifying viral meningitis., Conclusion: A single CSF parameter cannot reliably diagnose bacterial meningitis. For identification of bacterial meningitis, elevation of CSF WCC, neutrophil count or protein levels above threshold values improves accuracy of diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines., Design: An open-label, phase IV randomised study conducted across six UK sites., Setting: Neonatal units, postnatal wards, community recruitment following discharge., Participants: 129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups)., Interventions: Infants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines., Main Outcome Measures: Serum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups., Results: There were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02)., Conclusions: Both schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference., Trial Registration Number: NCT03125616., Competing Interests: Competing interests: JL and RB perform contract research on behalf of UKHSA for GlaxoSmithKline (GSK), Pfizer and Sanofi. JC works for an institution which conducts meningococcal vaccine research on behalf of GSK; he receives no personal payment or inducement of any kind. MS was an employee of the University of Oxford and Oxford University Hospitals Foundation NHS trust up until September 2022, and in this role acted as an investigator for clinical research studies funded or otherwise supported by the vaccine manufacturers GSK, Janssen, AstraZeneca, Pfizer, Novavax and MCM vaccines. He received no personal financial benefit for this work. As of September 2022, MS has been an employee of Moderna UK and holds equity in this company; however, all study activities and data analysis were completed before this date., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections., Design: Multi-centre observational cohort study using data from 2009 to 2018 clinical records., Setting: Canadian children's hospitals (7) and community hospitals (3)., Patients: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections., Interventions: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation., Main Outcome Measures: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates., Results: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018., Conclusions: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes., Competing Interests: Competing interests: PJG has received grants from the Canadian Institutes of Health Research (CIHR), the PSI Foundation and The Hospital for Sick Children. He has received non-financial support from the EBMLive Steering Committee (expenses reimbursed to attend conferences) and the CIHR Institute of Human Development, Child and Youth Health (as a member of the institute advisory board, expenses reimbursed to attend meetings), is a member of the CMAJ Open and BMJ Evidence-Based Medicine Editorial Board. OD was supported by a Chercheur Boursier Clinicien Award, from the Fonds de recherche du Québec – Santé. PP has received grants from the Hospital for Sick Children Foundation and CIHR. The other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: JEGC is a sub-investigator on the Merck Sharp & Dohme (MSD, a subsidiary of Merck) sponsored MK-1654-004 and MK-1654-007 studies of clesrovimab, an investigational extended half-life monoclonal antibody towards RSV fusion protein. He has not nor has ever been employed or funded by Merck.

Background: The widespread use of pneumococcal conjugate vaccines (PCV) has changed the epidemiology of invasive pneumococcal disease (IPD) in children globally., Methods: Multicentre prospective audit of IPD episodes from five paediatric hospitals in Australia over 5.5 years between 2016 and June 2021. Children (<18 years) with Streptococcus pneumoniae isolated from a sterile site were included., Results: There were 377 IPD episodes in 375 children: 338 (90%) had received ≥3 PCV doses; 42 (11%) had IPD risk factors. The most common presentations were complicated pneumonia (254, 67%), bacteraemia (65, 17%) and meningitis (29, 8%). Five (1%) children died.Serotype information was available for 230 (61%) episodes; 140 (61%) were 13vPCV vaccine serotypes (VTs). The majority (85%) of episodes of complicated pneumonia were due to a VT; predominantly 3, 19A, 19F. Children with risk factors were more likely to present with bacteraemia ± sepsis (42% vs 12%) and to have a non-vaccine serotype (NVT) (74% vs 32%). Resistance to ceftriaxone (meningitis cut-off) occurred in 17% of 23B isolates (n=12) and accounted for 22% (5/23) of meningitis cases., Conclusions: Complicated pneumonia is the most common IPD presentation. NVTs account for the majority of bacteraemia and meningitis episodes. High rates of ceftriaxone resistance for NVT 23B support the addition of vancomycin for empiric treatment of suspected meningitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: SBD has previously received honoraria from Sanofi for taking part in RSV advisory boards and has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD and Sanofi with fees paid to his institution. SBD is a member of the UK Department of Health and Social Care (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and Medicines and Healthcare products Regulatory Agency (MHRA) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA or PMEAG.

Concurrent tubercular involvement of two or more non-contiguous organs is termed disseminated tuberculosis (TB) and is rare in immunocompetent patients. We describe the case of a young immunocompetent woman with disseminated TB who presented with primary complaints of amenorrhea and dysuria. Abdominal ultrasound showed a uterine cervical mass, which on histopathological evaluation revealed epithelioid granulomata with Langhans giant cells and acid-fast bacilli (AFB). Her chest radiograph showed scattered air space opacities bilaterally, and contrast-enhanced computed tomography of the abdomen revealed the involvement of bilateral kidneys, para-aortic lymph nodes, adrenals, sacroiliac regions, and the gastrointestinal tract. A colonoscopy picked up an ulcer in the terminal ileum, which on histopathology was positive for AFB. The patient was started on anti-tubercular treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Varma et al.)

Background : Evaluating patients with ascending sensorimotor deficits has a broad differential diagnosis at initial presentation which can be further narrowed upon neurologic examination but may represent a diagnostic and therapeutic dilemma in light of findings raising suspicion for multiple possible etiologies. Data Collection : In this case, a 29-year-old patient presented with ascending bilateral lower extremity sensory loss, paresthesias, and weakness which progressed to the inability to ambulate. Conclusions : This case highlights the diagnostic approach to patients with bilateral lower extremity sensorimotor deficits, discusses the development of a comprehensive differential diagnosis, and further evaluates the most likely etiologies. Furthermore, this case reviews complexities related to clinical reasoning in the setting of diagnostic uncertainty, particularly when the neurologic structures affected portend high risk for severe disability and early treatment may improve outcome., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The following case describes a constellation of progressive cognitive and motor deficits in a 73-year-old man with cirrhosis and history of early-stage hepatocellular carcinoma confined to his liver. He had deficits in calculation, language, and writing, as well as subtle right-sided weakness. Magnetic resonance imaging (MRI) of the brain demonstrated non-enhancing white matter lesions without mass effect in the bilateral parietal and left occipitotemporal regions, correlating with neurologic exam findings. The patient's basic blood and cerebrospinal fluid (CSF) studies were within normal limits. Our differential included inflammatory and demyelinating conditions, hepatic encephalopathy, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy (PML), and central nervous system (CNS) tumors. He did not improve with an empiric course of high-dose steroids or adequate hepatic encephalopathy treatment. A repeat lumbar puncture sent for additional CSF studies revealed a positive John Cunningham (JC) virus PCR test, confirming diagnosis of PML. Although the patient did not have any known overt immunosuppressive condition or treatment, the patient's cirrhosis and age placed him at higher risk for developing JC virus CNS reactivation. In a published case series of patients with PML and no classic immunosuppressive condition that includes several patients with concomitant cirrhosis, prognosis is much worse compared to those with known, reversible causes of immunosuppression., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: To determine whether culture yield and time to positivity (TTP) differ between peripheral and central vascular catheter-derived blood cultures (BCx) in neonatal intensive care unit (NICU) patients evaluated for late-onset sepsis.Design: Single-centre, retrospective, observational study.Setting: Level IV NICU.Participants: The study included infants >72 hours old admitted to NICU in 2007-2019 with culture-confirmed bacteraemia. All episodes had simultaneous BCx drawn from a peripheral site and a vascular catheter ('catheter culture').Main Outcome Measures: Dual-site culture yield and TTP.Results: Among 179 episodes of late-onset bacteraemia (among 167 infants) with concurrently drawn peripheral and catheter BCx, the majority (67%, 120 of 179) were positive from both sites, compared with 17% (30 of 179) with positive catheter cultures only and 16% (29 of 179) with positive peripheral cultures only. 66% (19 of 29) of episodes with only positive peripheral BCx grew coagulase-negative Staphylococcus, while 34% (10 of 29) were recognised bacterial pathogens. Among 120 episodes with both peripheral and catheter BCx growth, catheter cultures demonstrated bacterial growth prior to paired peripheral cultures in 78% of episodes (93 of 120, p<0.001). The median TTP was significantly shorter in catheter compared with peripheral cultures (15.0 hours vs 16.8 hours, p<0.001). The median elapsed time between paired catheter and peripheral culture growth was 1.3 hours.Conclusion: Concurrently drawn peripheral and catheter BCx had similar yield. While a majority of episodes demonstrated dual-site BCx growth, a small but important minority of episodes grew virulent pathogens from either culture site alone. While dual-site culture practices may be useful, clinicians should balance the gain in sensitivity of bacteraemia detection against additive contamination risk. [ABSTRACT FROM AUTHOR]

Background: The composition of the infant gastrointestinal (GI) microbiome has been linked to adverse long-term health outcomes and neonatal sepsis. Several factors are known to impact the composition of the microbiome, including mode of delivery, gestational age, feeding method and exposure to antibiotics. The impact of intrapartum antibiotics (IPAs) on the infant microbiome requires further research.Objective: We aimed to evaluate the impact of IPAs on the infant GI microbiome.Methods: We searched Ovid MEDLINE and Embase Classic+Embase for articles in English reporting on the microbiome of infants exposed to IPAs from the date of inception to 3 January 2021. Primary outcomes included abundance and colonisation of Bifidobacterium and Lactobacillus, as well as alpha and beta diversity.Results: 30 papers were included in this review. In the first year of life, following exposure to IPAs, 30% (6/20) of infant cohorts displayed significantly reduced Bifidobacterium, 89% (17/19) did not display any significant differences in Lactobacillus colonisation, 21% (7/34) displayed significantly reduced alpha diversity and 35% (12/34) displayed alterations in beta diversity. Results were further stratified by delivery, gestational age (preterm or full term) and feeding method.Conclusions: IPAs impact the composition of the infant GI microbiome, resulting in possible reductions Bifidobacterium and alpha diversity, and possible alterations in beta diversity. Our findings may have implications for maternal and neonatal health, including interventions to prevent reductions in health-promoting bacteria (eg, probiotics) and IPA class selection. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: Syphilis is a major public health issue worldwide. In people living with human immunodeficiency virus (PLHIV), there are higher incidences of both syphilis and neurosyphilis. The criteria for referring PLHIV with syphilis for lumbar puncture is controversial, and the diagnosis of neurosyphilis is challenging. OBJECTIVE: To describe the knowledge, attitudes, and practices of infectious disease specialists and residents in the context of care for asymptomatic HIV-syphilis coinfection using close-ended questions and case vignettes. DESIGN AND SETTING: Cross-sectional study conducted in three public health institutions in São Paulo (SP), Brazil. METHODS: In this cross-sectional study, we invited infectious disease specialists and residents at three academic healthcare institutions to answer a self-completion questionnaire available online or in paper form. RESULTS: Of 98 participants, only 23.5% provided answers that were in line with the current Brazilian recommendation. Most participants believed that the criteria for lumbar puncture should be extended for people living with HIV with low CD4+ cell counts (52.0%); in addition, participants also believed that late latent syphilis (29.6%) and Venereal Disease Research Laboratory (VDRL) titers ≥ 1:32 (22.4%) should be conditions for lumbar puncture in PLHIV with no neurologic symptoms. CONCLUSION: This study highlights heterogeneities in the clinical management of HIV-syphilis coinfection. Most infectious disease specialists still consider syphilis stage, VDRL titers and CD4+ cell counts as important parameters when deciding which patients need lumbar puncture for investigating neurosyphilis.

Abstract Background To retrospectively analyze CT appearances and progression pattern of COVID-19 during hospitalization, and analyze imaging findings of follow-up on thin-section CT. Methods CT findings of 69 patients with COVID-19 were evaluated on initial CT, peak CT, and pre-discharge CT. CT pattern were divided into four types on CT progression. Lesion percentage of pulmonary lobe (lobe score) was graded. Correlation analysis was made between scores and intervals. 53 patients were followed up by CT. Results Among 69 patients, 33.3% exhibited improvement pattern, 65.2% peak pattern, 1.5% deterioration pattern, and 0% fluctuation pattern. The lobe scores were positively correlated with most of intervals. It was more common to observe consolidation, pleural thickening and pleural effusion on the peak CT, and irregular line and reticulation on pre-discharge CT. The peak-initial interval were shortened when the initial CT with consolidation and pleural thickening. The intervals were extended when the irregular lines appeared on peak CT and reticulation on pre-discharge CT. Among 53 follow-up patients, 37.7% showed normal chest CT, and 62.3% showed viral pneumonia remained that mainly included GGO (100.0%) and irregular lines (33.3%). Conclusions COVID-19 displayed different appearances on CT as progressing. The peak pattern was the most common progression pattern. The CT appearances showed closely related to the intervals. The COVID-19 pneumonia can be remained or completely absorbed on CT with follow-up.

Objective: To analyze the antibiotic prescription rate in low-risk patients evaluated at a telemedicine program that adopts antibiotic stewardship protocols. Methods: Adult patients who accessed a single direct-to-consumer telemedicine center (Jan/2019–Feb/2020) were retrospectively enrolled. Diseases amenable to antimicrobial treatment were classified under five diagnostic groups: upper respiratory tract infection (URI), acute pharyngotonsillitis (PT), acute sinusitis (AS), urinary tract infection (UTI), and acute diarrhea (AD). Physicians were trained on and advised to strictly follow the current guideline recommendations supported by institutional antibiotic stewardship protocols, readily available online during consultations. We analyzed the antibiotic prescription rate among patients, referral rate, and antibiotic class through descriptive statistics. Results: A total of 2328 patients were included in the study. A total of 2085 (89·6%) patients were discharged with usual recommendations, medication (if needed), and instructions about red flags, while 243 (10·4%) were referred to a face-to-face consultation. Among the discharged patients, the antibiotic prescription rates by the diagnostic group were URI — 2·5%, PT — 35·0%, AS — 51·8%, UTI — 91.6%, and AD — 1·6%. In most cases, prescribed antibiotics were in line with institutional stewardship protocols. Conclusions: Low prescription rate of antibiotics can be achieved using antibiotic stewardship protocols at direct-to-consumer telemedicine consultations, showing high adherence to international guidelines. These results reinforce telemedicine as a cost-effective and safe strategy for the initial assessment of acute non-urgent symptoms.

Objectives: Multiplex gastrointestinal PCR (GI-PCR) allows fast and simultaneous detection of 22 enteric pathogens (including Campylobacter, Salmonella, Shigella/enteroinvasive Escherichia coli (EIEC), among other bacteria, parasites and viruses). However, its impact on the management of children with infectious diarrhoea remains unknown.Patients/design: All children eligible for stool culture from May to October 2018 were prospectively included in a monocentric study at Robert-Debré University-Hospital.Intervention: A GI-PCR (BioFire FilmArray) was performed on each stool sample.Main Measures: Data on the children's healthcare management before and after GI-PCR results were collected. Stool culture results were also reported.Results: 172 children were included. The main criteria for performing stool analysis were mucous/bloody diarrhoea and/or traveller's diarrhoea (n=130). GI-PCR's were positive for 120 patients (70%). The main pathogens were enteroaggregative E. coli (n=39; 23%), enteropathogenic E. coli (n=34; 20%), Shigella/EIEC (n=27; 16%) and Campylobacter (n=21; 12%). Compared with stool cultures, GI-PCR enabled the detection of 21 vs 19 Campylobacter, 12 vs 10 Salmonella, 27 Shigella/EIEC vs 13 Shigella, 2 vs 2 Yersinia enterocolitica, 1 vs 1 Plesiomonas shigelloides, respectively. Considering the GI-PCR results and before stool culture results, the medical management was revised for 40 patients (23%): 28 initiations, 2 changes and 1 discontinuation of antibiotics, 1 hospitalisation, 2 specific room isolations related to Clostridioides difficile infections, 4 additional test prescriptions and 2 test cancellations.Conclusion: The GI-PCR's results impacted the medical management of gastroenteritis for almostone-fourth of the children, and especially the prescription of appropriate antibiotic treatment before stool culture results. [ABSTRACT FROM AUTHOR]

Objective: Determine non-invasive ventilation with continuous positive airway pressure (CPAP) outcomes for paediatric respiratory distress in low-income and middle-income countries (LMICs).Design: Systematic review and meta-analysis.Setting: LMIC hospitals.Patients: One month to 15 year olds with respiratory distress.Interventions: We searched Medline, Embase, LILACS, Web of Science and Scopus on 7 April 2020. Included studies assessed CPAP safety, efficacy or effectiveness. All study types were included; neonatal only studies were excluded. Data were extracted by two reviewers and bias was assessed. Certainty of evidence was evaluated, and risk ratios (RR) were produced for meta-analyses. (PROSPERO protocol CRD42018084278).Results: 2174 papers were screened, 20 were included in the systematic review and 3 were included in two separate meta-analyses of mortality and adverse events. Studies suitable for meta-analysis were randomised controlled trials (RCTs) from Bangladesh, Ghana and Malawi. For meta-analyses comparing death or adverse events between CPAP and low-flow oxygen recipients, we found no clear CPAP effect on mortality (RR 0.75, 95% CI 0.33 to 1.72) or adverse events (RR 1.52, CI 0.71 to 3.26). We downgraded the certainty of evidence for both death and adverse events outcomes to 'low' due to design issues and results discrepancies across RCTs.Conclusions: Evidence for CPAP efficacy against mortality and adverse events has low certainty and is context dependent. Hospitals introducing CPAP need to have mechanisms in place to optimise safety in the context it is being used; this includes the location (a high dependency or intensive care area), adequate numbers of staff trained in CPAP use, close monitoring and mechanisms for escalation, daily direct physician supervision, equipment that is age appropriate and user-friendly and continuous monitoring of outcomes and quality of care. [ABSTRACT FROM AUTHOR]

As the curve continues to flatten during the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic, and more physicians resume outpatient clinical work, the question arises of how to ensure the safety of the patients and staff while performing cases. Many institutions and health-care offices have turned to screening questionnaires to determine the likelihood of coronavirus disease 2019 (COVID-19) positivity. However, screening questionnaires are woefully inadequate as studies have shown that roughly 6.4% to 50% of patients may spread this virus without any symptoms. In this study, we have outlined a proposal to restart elective procedures after the curve has flattened in a certain locale, particularly for ambulatory surgery centers (ASCs). Until additional data are collected for specific sensitivity and specificity values for PCR testing, we recommend performing 2 consecutive polymerase chain reaction (PCR) tests to minimize false negative rates. The algorithm described in this study can help ASCs begin their practices and provide local public health officials with valuable data that can help establish true sensitivity and specificity rates for these tests. [ABSTRACT FROM AUTHOR]

Meningitis is a serious clinical health issue in most developing countries. Late diagnosis and treatment result in significant morbidity and mortality. This research aims to study the utility of CSF lactate, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) as diagnostic markers in acute meningitis, and to differentiate among varied aetiologies of acute meningitis and their outcomes. A cross-sectional observational case–control study was conducted in 30 patients of suspected meningitis of varied aetiologies and 30 controls without any pre-existing neurological disorder and who underwent lumbar puncture during spinal anesthesia. A fresh CSF sample was collected in a heparinized vial following an aseptic lumbar puncture. The levels of lactate, LDH and ADA were estimated and recorded. CSF lactate was significantly elevated in bacterial meningitis (BM) and cryptococcal meningitis, with 100% sensitivity when compared to controls. Elevated LDH was found only in BM, hence elevated LDH levels may strongly signify bacterial etiology. Significantly elevated ADA levels were noted in tuberculous meningitis. Significantly elevated levels of lactate and ADA were suggestive of slower clinical recovery and a prolonged hospital stay (p < 0.001). Estimation of CSF lactate, LDH, and ADA levels is a rapid, inexpensive and simple procedure and can play a major role in the early differentiation of bacterial, viral, tuberculous, and fungal meningitis. This would facilitate the initiation of appropriate treatment as early as possible, thereby decreasing mortality and complications. [ABSTRACT FROM AUTHOR]

Introduction: Fluconazole is an important antifungal in the prevention and treatment of invasive Candida infections in neonates, even though its use in preterm infants is still off-label. Here, we performed a population pharmacokinetic study on fluconazole in preterm neonates in order to optimise dosing through the identified predictive patient characteristics.Methods: Fluconazole concentrations obtained from preterm infants from two studies were pooled and analysed using NONMEM V.7.3. The developed model was used to evaluate current dosing practice. A therapeutic dosing strategy aiming to reach a minimum target exposure of 400 and 200 mg×hour/L per 24 hours for fluconazole-susceptible C. albicans meningitis and other systemic infections, respectively, was developed.Results: In 41 preterm neonates with median (range) gestational age 25.3 (24.0-35.1) weeks and median postnatal age (PNA) at treatment initiation 1.4 (0.2-32.5) days, 146 plasma samples were collected. A one-compartment model described the data best, with an estimated clearance of 0.0147 L/hour for a typical infant of 0.87 kg with a serum creatinine concentration of 60 µmol/L and volume of distribution of 0.844 L. Clearance was found to increase with 16% per 100 g increase in actual body weight, and to decrease with 12% per 10 µmol/L increase in creatinine concentration once PNA was above 1 week. Dose adjustments based on serum creatinine and daily dosing are required for therapeutic target attainment.Conclusion: In preterm neonates, fluconazole clearance is best predicted by actual body weight and serum creatinine concentration. Therefore, fluconazole dosing should not only be based on body weight but also on creatinine concentration to achieve optimal exposure in all infants.Ethics Statement: The Erasmus MC ethics review board approved the protocol of the DINO Study (MEC-2014-067) and the Radboud UMC ethics review board waived the need for informed consent for cohort 2 (CMO-2021-8302). Written informed consent from parents/legal guardians was obtained prior to study initiation. [ABSTRACT FROM AUTHOR]

Background: Early recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with severe disease among young children hospitalised with RSV infection.Methods: We conducted a retrospective cohort study of all children <2 years of age hospitalised for RSV lower respiratory tract infection at a single tertiary paediatric hospital over three RSV seasons (January 2017-December 2019). We classified children as having 'moderate' or 'severe' disease based on the level of respiratory intervention and used univariable and multivariable regression models to determine factors associated with severe disease.Results: Of 970 hospitalised children, 386 (40%) were classified as having 'severe' and 584 (60%) as having 'moderate' RSV disease. On multivariable analyses, age <2 months (OR: 2.3, 95% CI 1.6 to 3.3, p<0.0001), prematurity (OR: 1.6, 95% CI 1.1 to 2.4, p=0.02) and RSV-parainfluenza virus type 3 (PIV3) codetection (OR: 2.6, 95% CI 1.05 to 6.5, p=0.04) were independently associated with severe disease.Conclusion: Younger age, prematurity and PIV3 codetection were associated with severe RSV disease in children <2 years of age hospitalised with RSV infection. The association between PIV3 and severe RSV disease is a novel finding and warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: To report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC).Design: Retrospective multicentre cohort study.Patients: Febrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019.Main Outcome Measures: The sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI.Setting: Six paediatric Emergency Departments in the UK/Ireland.Results: 555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001).Conclusion: None of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making.Trial Registration Number: NCT04196192. [ABSTRACT FROM AUTHOR]

Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among its wildlife hosts in endemic areas. Investigations undertaken in colonial India after the introduction of plague in 1896 suggest that, only a decade after plague arrived, a heritable, plague-resistant phenotype had become prevalent among commensal rats of cities undergoing severe plague epidemics. To understand the possible evolutionary basis of these observations, we developed a mathematical model coupling environmentally forced plague dynamics with evolutionary selection of rats, capitalizing on extensive archival data from Indian Plague Commission investigations. Incorporating increased plague resistance among rats as a consequence of intense natural selection permits the model to reproduce observed changes in seasonal epidemic patterns in several cities and capture experimentally observed associations between climate and flea population dynamics in India. Our model results substantiate Victorian era claims of host evolution based on experimental observations of plague resistance and reveal the buffering effect of such evolution against environmental drivers of transmission. Our analysis shows that historical datasets can yield powerful insights into the transmission dynamics of reemerging disease agents with which we have limited contemporary experience to guide quantitative modeling and inference.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.