BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly termed Wegener\'s granulomatosis, is an autoimmune disease marked by necrotizing granulomatous inflammation and vasculitis affecting small-sized vessels. It commonly impacts the renal and respiratory systems.
METHODS: This retrospective case series sampling conducted in a tertiary care hospital between May 2023 and April 2024 examined six newly diagnosed GPA patients who were proteinase 3 cytoplasmic-antinuclear cytoplasmic antibody (PR3 c-ANCA) positive and had concurrent respiratory infections. None of them had any prior immunosuppressive conditions. The age range was 18-47 years with a mean of 35.0 (standard deviation: 11.83). All the patients had pneumonia (N=6, 100%). Out of all, five had bacterial pneumonia (N=5, 83.3%) and one had tuberculous pneumonia (N=1, 16.7%). A high level of PR3 c-ANCA (>150 RU/mL) was noted in four patients (N=4, 66.7%). Common symptoms included dry cough (N=5, 83.3%), loss of weight and appetite (N=2, 33.3%), and fever (N=2, 33.3%). Three patients had otitis media and/or nasal polyposis (N=3, 50%). Two patients (N=2, 33.3%) with life-threatening organ dysfunction were given concurrent antibiotics and steroids; the antibiotics were later modified based on culture and sensitivity results. One of these patients received antituberculosis therapy as Mycobacterium tuberculosis (MTB) was detected after 27 days of incubation in mycobacterial growth indicator tube broth. The remaining four patients (N=4, 66.7%) received antibiotics initially for 5-7 days until clinical resolution of pneumonia. Ultimately, they all showed clinical and radiological resolution (N=6, 100%) within 3-6 months of treatment.
RESULTS: The patients exhibited constitutional symptoms such as fever and weight loss; lower airway disease symptoms including dry cough and hemoptysis; nasal and ear disease symptoms like epistaxis, ear pain, and ear discharge; and a renal disease symptom, hematuria. Computed tomography of the thorax revealed bilateral consolidations, most of which were cavitating. Bronchoalveolar lavage cultures grew Escherichia coli, Burkholderia cepacia, Pseudomonas aeruginosa, Klebsiella pneumoniae, and MTB, whereas pus swab cultures from otitis media grew Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci.
CONCLUSIONS: This study highlights the therapeutic challenges of GPA complicated by concurrent infections. Patients exhibited typical GPA signs, confirmed by PR3 c-ANCA levels. Concurrent infections require cautious antibiotic treatment before starting immunosuppressive therapy, except in life-threatening organ dysfunction. A unique case presented with both tuberculosis and GPA. Tailored treatment regimens combining antibiotics and immunosuppressives, including corticosteroids, methotrexate, and rituximab, resulted in clinical and radiological improvement in all the patients within 3-6 months. The addition of co-trimoxazole reduced the incidence of non-severe GPA relapses.
CONCLUSIONS: Tailored treatment plans addressing both infectious and autoimmune aspects are essential for optimal care in GPA complicated by concurrent infections. This study highlights the need for a multidisciplinary approach involving pulmonologist, rheumatologist, microbiologist, and pathologist in the diagnosis and treatment of GPA, emphasizing the importance of individualized treatment plans tailored to the specific clinical scenario.

The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021-2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children.
OBJECTIVE: The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19-2019/20.The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression.The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged < 4, and cough was shown to be a reliable indicator of viral co-detection.Given the evolving epidemiological landscape following the COVID-19 pandemic, future research utilizing the methodology described here, while considering the circulation of SARS-CoV-2, could further enrich the understanding of concurrent respiratory pathogens.

Although antibiotics are most frequently prescribed for respiratory tract infections, effective interventions for their proper use by physicians have not been fully established. We assessed the impact of educational films on the rates of antibiotic prescriptions for respiratory tract infections using fictitious scenarios. In this nationwide web-based survey prospective study, a total of 1100 physicians were included. The physicians were required to view educational short films and determine the need for prescribing antibiotics in 10 fictitious scenarios involving adults diagnosed with different acute respiratory tract infectious diseases. The antibiotic prescription rates for each scenario were compared before and after viewing the educational short film. The rates of antibiotic prescription significantly decreased after viewing the educational film, especially in cases with a narrowly defined common cold (from 51% to 15%), mild pharyngolaryngitis (from 71% to 25%), and acute bronchitis without chronic respiratory underlying diseases (from 63% to 23%). Alternatively, a slight decrease in rates was observed in cases with moderate or severe rhinosinusitis (from 94% to 79%), moderate or severe acute pharyngitis (from 88% to 69%), and acute bronchitis with chronic lung disease (from 70% to 58%), for which antibiotics are recommended. Educational short films may encourage the proper use of antibiotics for respiratory tract infections; however, the possibility of undertreatment in patients requiring antibiotics must be considered.

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood-brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the \"Trojan horse\" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans.

OBJECTIVE: To assess the impact of an intervention package on the prescription of antibiotic and subsequently the rate of clinical recovery for non-severe acute febrile illnesses at primary health centers.
METHODS: Patients over 6 months of age presenting to primary health care centres with fever or history of fever within the past 7 days were randomized to receive either the intervention package constituted of point-of-care tests including COVID-19 antigen tests, a diagnostic algorithm and training and communication packages, or the standard practice. The primary outcomes were antibiotic prescriptions at Day 0 (D0) and the clinical recovery at Day 7 (D7). Secondary outcomes were non-adherence of participants and parents/caregivers to prescriptions, health workers\' non-adherence to the algorithm, and the safety of the intervention.
RESULTS: A total of 1098 patients were enrolled. 551 (50.2%) were randomized to receive the intervention versus 547 (49.8%) received standard care. 1054 (96.0%) completed follow-up and all of them recovered at D7 in both arms. The proportion of patients with antibiotic prescriptions at D0 were 33.2% (183/551) in the intervention arm versus 58.1% (318/547) under standard care, risk difference (RD) -24.9 (95% CI -30.6 to -19.2, p < 0.001), corresponding to one more antibiotic saved every four (95% CI: 3 to 5) consultations. This reduction was also statistically significant in children from 6 to 59 months (RD -34.5; 95% CI -41.7 to -27.3; p < 0.001), patients over 18 years (RD -35.9; 95%CI -58.5 to -13.4; p = 0.002), patients with negative malaria test (RD -46.9; 95% CI -53.9 to -39.8; p < 0.001), those with a respiratory diagnosis (RD -48.9; 95% CI -56.9 to -41.0, p < 0.001) and those not vaccinated against COVID-19 (-24.8% 95%CI -30.7 to -18.9, p-value: <0.001). A significant reduction in non-adherence to prescription by patients was reported (RD -7.1; 95% CI -10.9 to -3.3; p < 0.001).
CONCLUSIONS: The intervention was associated with significant reductions of antibiotic prescriptions and non-adherence, chiefly among patients with non-malaria fever, those with respiratory symptoms and children below 5 years of age. The addition of COVID-19 testing did not have a major impact on antibiotic use at primary health centers.
BACKGROUND: Clinitrial.gov; NCT04081051 registered on 06/09/2019.

We sequenced and genotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, adenovirus, and respiratory syncytial virus, among other pathogens, from residual anterior nasal swabs self-collected for rapid SARS-CoV-2 antigen testing at the US Naval Academy. This is a key proof-of-concept for an acute respiratory infection surveillance approach, which could leverage prevalent SARS-CoV-2 antigen self-testing.

BACKGROUND: Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study.
OBJECTIVE: We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment.
METHODS: A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups.
RESULTS: All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025.
CONCLUSIONS: This study will quantify immunocompromised individuals\' physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities.
UNASSIGNED: RR1-10.2196/52643.

OBJECTIVE: Understanding the seasonal behaviours of respiratory viruses is crucial for preventing infections. We evaluated the seasonality of respiratory viruses using time-series analyses.
METHODS: This study analysed prospectively collected nationwide surveillance data on eight respiratory viruses, gathered from the Korean Influenza and Respiratory Surveillance System. The data were collected on a weekly basis by 52 nationwide primary healthcare institutions between 2015 and 2019. We performed Spearman correlation analyses, similarity analyses via dynamic time warping (DTW) and seasonality analyses using seasonal autoregressive integrated moving average (SARIMA).
RESULTS: The prevalence of rhinovirus (RV, 23.6%-31.4%), adenovirus (AdV, 9.2%-16.6%), human coronavirus (HCoV, 3.0%-6.6%), respiratory syncytial virus (RSV, 11.7%-20.1%), influenza virus (IFV, 11.7%-21.5%), parainfluenza virus (PIV, 9.2%-12.6%), human metapneumovirus (HMPV, 5.6%-6.9%) and human bocavirus (HBoV, 5.0%-6.4%) were derived. Most of them exhibited a high positive correlation in Spearman analyses. In DTW analyses, all virus data from 2015 to 2019, except AdV, exhibited good alignments. In SARIMA, AdV and RV did not show seasonality. Other viruses showed 12-month seasonality. We describe the viruses as winter viruses (HCoV, RSV and IFV), spring/summer viruses (PIV, HBoV), a spring virus (HMPV) and all-year viruses with peak incidences during school periods (RV and AdV).
CONCLUSIONS: This is the first study to comprehensively analyse the seasonal behaviours of the eight most common respiratory viruses using nationwide, prospectively collected, sentinel surveillance data.

UNASSIGNED: Cefpodoxime, a third-generation cephalosporin, is a broad-spectrum antibiotic widely used to treat acute upper respiratory tract infections (RTI). This systematic review aims to present a comprehensive view of all the available pharmacokinetics (PK) data associated with the pharmacodynamics (PD) parameters of cefpodoxime in humans.
UNASSIGNED: The PubMed, Google Scholar, Cochrane Library, and Science Direct, were systematically searched to identify studies on the PK of cefpodoxime. Out of 746 papers, 26 articles meeting the eligibility criteria were included that have reported the PK data. The drug exposure for the patients undergoing hemodialysis was 50% lower than healthy participants. The renal clearance was almost 27% less in pediatric patients than in adults. The plasma concentrations of cefpodoxime exceeded the minimum inhibitory concentration (MIC) for 90% of skin pathogens, including Streptococcus species and Staphylococcus species (i.e.) < 1 μg/mL and 2-4 μg/mL respectively.
UNASSIGNED: The current study includes detailed information on clinical PK of cefpodoxime in healthy, diseased, pediatric populations as well as drug-drug interactions and drug-food interactions. Moreover, this systematic review also explicated PK/PD properties of drug with a specific impact on MIC of drug. The present review will also assist clinicians in the development of PK models for cefpodoxime.