Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.

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: Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD). METHODS: This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens. RESULTS: Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively). CONCLUSION: After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.

Prevalence and Clinical Characteristics of Pediatric Lower Airway Malacia: Case Series from a Tertiary Center in Turkey.

Introduction: Lower airway malacia (LAM) is characterized by a reduction in the cross-sectional luminal area during quiet respiration. There is no gold standard diagnostic test; however, flexible fiberoptic bronchoscopy (FFB) is most frequently utilized. The exact prevalence and incidence of LAM are unknown. This study aimed to determine the prevalence rates of pediatric patients diagnosed with LAM, offer a detailed understanding of their demographic and clinical characteristics, and investigate distinctions between two specific types of LAM, namely, tracheomalacia (TM) and bronchomalacia (BM). Materials and Methods: Patients younger than 18 years diagnosed with LAM using FFB were included in this retrospective case series. Demographic and clinical characteristics and comorbid disorders were compared between patients with isolated BM and those with isolated TM or tracheobronchomalacia (TM/TBM). Results: Among 390 patients who underwent FFB, 65 (16.6%) were diagnosed with LAM, 16 (24.6%) with TM, and 56 (86.2%) with BM. The median age at diagnosis was 15 months. Among them, 59 (90.8%) had other comorbidities; gastrointestinal (GI) disorders were the most common (38.5%). The most common indications for bronchoscopy were recurrent/prolonged lower respiratory tract infections (LRTI) or wheezing (43.1%), while the most frequently observed respiratory physical examination finding was stridor (35.4%). Patients with TM/TBM had significantly higher frequencies of premature births, stridor, retraction, and GI disorders. Conclusion: Patients with stridor without typical laryngomalacia features or recurrent or prolonged LRTI should undergo prompt evaluation for LAM. The potential coexistence of GI disorders such as gastroesophageal reflux disease and swallowing dysfunction should also be considered.

Mycoplasma pneumoniae detections in children with lower respiratory infection before and during the COVID-19 pandemic: a large sample study in China from 2019 to 2022.

BACKGROUND: Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China's NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. METHODS: Children hospitalised for LRTI at the Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. RESULTS: Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p <0.001). The median age of these children was preschool age (3-6 years), except for 2022, when they were school age (7-12 years), with statistical differences. Comparing the positive rates of different age groups, the school-age children (7-12 years) had the highest positive rate, followed by the preschoolers (3-6 years) in each of the 4 years. Compared among different seasons, the positive rate of MP in children with LRTI was higher in summer and autumn, whereas in 2020, it was highest in spring. The monthly positive rate peaked in July 2019, remained low from 2020 to 2021, and rebounded until 2022. Regarding the disease spectrum, severe pneumonia accounted for the highest proportion (46.3%) pre-pandemic and lowest (0%) in 2020. CONCLUSION: Trends in MP detection in children with LRTIs suggest a possible correlation between COVID-19 NPIs and significantly reduced detection rates. The positivity rate of MP gradually rose after 2 years. The epidemic season showed some differences, but school-age children were more susceptible to MP before and during the COVID-19 pandemic.

Pathogenic Role of Human Rhinovirus Mono-Infection in Pediatric Lower Respiratory Tract Infection.

Background and objective Human rhinovirus (HRV) is one of the leading causes of pediatric respiratory tract infection with a prevalence rate of 30-50%, mostly affecting children below five years of age and causing a substantial amount of economic loss. In children, it can alone or as a co-infection, cause a wide range of symptoms from mild to life-threatening ones. With the above background, the current study was carried out to emphasize the role of HRV mono-infection in pediatric acute respiratory tract infections by correlating clinical and molecular laboratory findings. Methods This study was carried out in a tertiary care teaching hospital over a duration of four years (March 2019-October 2023). Children up to 14 years of age visiting the outpatient department or admitted to the ward with diagnoses of acute respiratory tract infections (ARTIs) were included. The clinical and laboratory data were retrieved and analyzed. A nasopharyngeal swab (NPS) or throat swab (TS) was collected and sent to the Microbiology laboratory maintaining the cold chain. Nucleic acid was extracted and subjected to multiplex real-time polymerase chain reaction (RT-PCR). Result Of the 245 samples tested for the respiratory viral pathogen, 52 samples tested positive for HRV, of which 27 had HRV mono-infection. The clinico-demographic details of these 27 patients were studied in detail. The majority of the cases (24/27; 88.8%) were less than five years of age. Fever and shortness of breath were the most consistent symptoms in all. Nineteen (19/27; 62.9%) HRV mono-infection cases had underlying co-morbidities, all requiring respiratory support. The HRV mono-infection cases either developed bronchiolitis, lower respiratory tract infection, or pneumonia. All mono-infection cases had cycle threshold value (Ct) < 25, while the Ct value of HRV was > 30 in co-infection with other viruses. Conclusion Mono-infection of HRV in under-five children with underlying comorbidities and a lesser Ct value indicates severe disease manifestation and should be dealt with more cautiously.

Deciphering the microbial landscape of lower respiratory tract infections: insights from metagenomics and machine learning.

Background: Lower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types. Method: We collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria. Result: We observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time. Conclusion: Our study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Analysis of the prevalence and clinical features of respiratory syncytial virus infection in a pediatric hospital in Zhejiang Province from 2019 to 2023.

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.

Clinical Profiles, Laboratory Biomarkers, and Mortality in Cancer Patients with Lower Respiratory Tract Infections: A Prospective Cohort Study.

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission.

Risk Analysis of Respiratory Syncytial Virus Among Infants in the United States by Birth Month.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among US infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life (FYOL). METHODS: We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by the highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis, we focused on infants' first RSV season. In our secondary analysis, we compared the risk of MA RSV LRTI during infants' first RSV season to that of their FYOL. RESULTS: Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6-10% under the specific RSV index diagnosis definition and 16-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9% to 54% (specific) and 5% to 33% (sensitive) across birth month and comorbidity group. Through the FYOL, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6-11% under the specific definition, 17-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings. CONCLUSIONS: Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient- and ED-related events.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Clinical characteristics and outcomes of respiratory syncytial virus-associated ARF in immunocompetent patients: A seven-year experience at a tertiary hospital in France.

BACKGROUND: Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection. METHODS: This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48 h. RESULTS: One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one-month mortality were age and maximum oxygen flow during hospitalization. CONCLUSION: RSV-associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate.

Evaluation of Etiological Causes and Factors Affect Length of Hospitalization in Neonates Hospitalized with Lower Respiratory Tract Infection.

Objectives: This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to lower respiratory tract infection (LRTI), to determine the factors that affect the duration of hospitalization, and to determine the underlying microbial factors and evaluate them in the light of the literature. Methods: This study evaluated the data of newborns hospitalized with LTRI between 01 October 2022 and 31 March 2023. Demographic characteristics of the patients detected viral agents, duration of hospitalization and risk factors were recorded in the study form. Babies divided viral LRTI and non-viral LRTI, and then compared with each other. Additionally, the facts that might affect the duration of hospitalization were investigated. Results: The study included 57 babies. Viral agent was detected in 50.9% of the babies, the most frequently viral agent was respiratory syncytial virus (RSV) (48.2%). Other viral factors, in order of frequency; Adenovirus, SARS-CoV-2, Influenza A and B. There is no demographic difference between the viral agent positive and negative groups. The patients were evaluated according to length of hospitalization, it was seen that the hospital stay was longer in babies who were found to be viral positive and needed oxygen therapy (p=0.02, p=0.03, respectively). The male gender ratio was higher in the group with longer hospital stays, but this difference was not statistically significant. Although the rate of exclusive breastfeeding was higher in the group with a short hospitalization period, this difference was not statistically significant (p>0.05). Conclusion: RSV is currently the most frequently detected viral agent in lower respiratory tract infections in newborns. The hospital stay of babies diagnosed with RSV is longer than those with non-RSV viral agents. So struggling with RSV is important in preventing lower respiratory tract infections in newborns. It is necessary to develop a vaccine or immunoglobulin application against RSV infection not only for preterm babies but also for all newborn babies.

Scutellaria baicalensis water decoction ameliorates lower respiratory tract infection by modulating respiratory microbiota.

BACKGROUND: The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis, a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. PURPOSE: To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. METHODS: A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae. Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. High-performance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were determined by hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRT-PCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. RESULTS: Seven main components, including scutellarin, baicalin, oroxylin A-7-O-ß-d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae-induced LRTI mice, as evidenced by the dose-dependent reductions in the levels of serum inflammatory cytokines, IL-6 and TNF-α. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL-17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae, and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae-induced LRTI mice. CONCLUSION: SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Perinatal exposure to traffic related air pollutants and the risk of infection in the first six months of life: a cohort study from a low-middle income country.

OBJECTIVE: There is limited study from low-and-middle income countries on the effect of perinatal exposure to air pollution and the risk of infection in infant. We assessed the association between perinatal exposure to traffic related air pollution and the risk of infection in infant during their first six months of life. METHODS: A prospective cohort study was performed in Jakarta, March 2016-September 2020 among 298 mother-infant pairs. PM2.5, soot, NOx, and NO2 concentrations were assessed using land use regression models (LUR) at individual level. Repeated interviewer-administered questionnaires were used to obtain data on infection at 1, 2, 4 and 6 months of age. The infections were categorized as upper respiratory tract (runny nose, cough, wheezing or shortness of breath), lower respiratory tract (pneumonia, bronchiolitis) or gastrointestinal tract infection. Logistic regression models adjusted for covariates were used to assess the association between perinatal exposure to air pollution and the risk of infection in the first six months of life. RESULTS: The average concentrations of PM2.5 and NO2 were much higher than the WHO recommended levels. Upper respiratory tract infections (URTI) were much more common in the first six months of life than diagnosed lower respiratory tract or gastro-intestinal infections (35.6%, 3.5% and 5.8% respectively). Perinatal exposure to PM2.5 and soot suggested increase cumulative risk of upper respiratory tract infection (URTI) in the first 6 months of life per IQR increase with adjusted OR of 1.50 (95% CI 0.91; 2.47) and 1.14 (95% CI 0.79; 1.64), respectively. Soot was significantly associated with the risk of URTI at 4-6 months age interval (aOR of 1.45, 95%CI 1.02; 2.09). All air pollutants were also positively associated with lower respiratory tract infection, but all CIs include unity because of relatively small samples. Adjusted odds ratios for gastrointestinal infections were close to unity. CONCLUSION: Our study adds to the evidence that perinatal exposure to fine particles is associated with respiratory tract infection in infants in a low-middle income country.

Illumina and Nanopore sequencing in culture-negative samples from suspected lower respiratory tract infection patients.

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

A Retrospective Public Health Assessment and Management in Terms of the Social and Clinical Risk Factors of Respiratory Syncytial Virus Infection in Northern Canada.

Background The predominant source of respiratory infections in Northern Canada stems from RSV, leading to potentially life-threatening lower respiratory tract infections in children below the age of 2. Typically, RSV begins to appear in November or December and persists until April or May. Synagis® (Palivizumab), a monoclonal antibody, is employed to mitigate or reduce the effects of RSV. Past research indicated a reduction in hospitalizations with the use of Synagis®. Aim The aim is to estimate the cost-benefit analysis by comparing the health services cost with Synagis® program cost. Also evaluate the association of identified risk factors with the severity of RSV infection. Material and methods The dependent variable is categorized as: "Mild-Medium" cases that didn't undergo intubation or require medical evacuation; "Severe" cases that underwent intubation, required medical evacuation, and intensive care unit facilities. We also calculate the cost of health services and Synagis® of each year. Results It has been found that babies who exclusively breastfed and regularly took vitamin D did not develop severe forms of infection. Prenatal smoking and shared and crowded accommodations contribute to the spreading of RSV. The average cost of health services per participant was higher than that of the Synagis program. Conclusion They are promoting the Synagis® program during the season. Standardize the regulations prohibiting smoking around small children since they are more vulnerable to infection. Practice breastfeeding up to 24-month-old babies.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

Best Practices for Identifying Hospitalized Lower Respiratory Tract Infections Using Administrative Data: A Systematic Literature Review of Validation Studies.

INTRODUCTION: Estimating the burden of lower respiratory tract infections (LRTIs) increasingly relies on administrative databases using International Classification of Diseases (ICD) codes, but no standard methodology exists. We defined best practices for ICD-based algorithms that estimate LRTI incidence in adults. METHODS: We conducted a systematic review of validation studies assessing the use of ICD code-based algorithms to identify hospitalized LRTIs in adults, published in Medline, EMBASE, and LILACS between January 1996 and January 2022, according to PRISMA guidelines. We assessed sensitivity, specificity, and other accuracy measures of different algorithms. RESULTS: We included 26 publications that used a variety of ICD code-based algorithms and gold standard criteria, and 18 reported sensitivity and/or specificity. Sensitivity was below 80% in 72% (38/53) of algorithms and specificity exceeded 90% in 77% (37/48). Algorithms for all-cause LRTI (n = 18) that included only pneumonia codes in primary position (n = 3) had specificity greater than 90% but low sensitivity (55-72%). Sensitivity increased by 5-15%, with minimal loss in specificity, with the addition of primary codes for severe pneumonia (e.g. sepsis) while pneumonia codes were in secondary position, and by 13% with codes from LRTI-related infections (e.g. viral) or other respiratory diseases (e.g. empyema). Sensitivity increased by 8% when pneumonia codes were in any position, but specificity was not reported. In hospital-acquired pneumonia and pneumococcal-specific pneumonia, algorithms containing only nosocomial- or pathogen-specific ICD codes had poor sensitivity, which improved when broader pneumonia codes were added, in particular codes for unspecified organisms. CONCLUSION: Our systematic review highlights that most ICD code-based algorithms are relatively specific, but miss a substantial number of hospitalized LRTI adult cases. Best practices to estimate LRTI incidence in this population include the use of all pneumonia ICD codes for any LRTI outcome and, to a lesser extent, those for other LRTI-related infections or respiratory diseases.

Determinants of radiological patterns and severity in immunocompromised adults with Metapneumovirus infection.

BACKGROUND: Human Metapneumovirus (HMPV) belongs to the Pneumoviridae family and is responsible for respiratory infections. Mild infections are well-recognized in children, while its precise impact in various categories of immunocompromised adults has not been well addressed. RESEARCH QUESTION: We retrospectively studied HMPV infections in immunocompromised adults followed in two large French university medical centers. STUDY DESIGN AND METHODS: We identified immunocompromised adults with positive HMPV Polymerase Chain Reaction (PCR) for 36 months and reviewed their medical charts. For lung transplant recipients (LTR), FEV1 was collected at baseline, during and after infection. Imaging was centralized and chest involvement was categorized by dominant CT patterns. We compared severe patients (requiring oxygen or ventilation) and non hypoxemic patients. RESULTS: Seventy-two patients were included, 27 were LTR, 25 had a hematological malignancy or were hematopoietic stem cell recipients, 20 had another immunocompromised status. Twenty patients (28%) presented a hypoxemic infection, requiring hospitalization and intensive care units transfers in 50/72 (69.4%) and 9/72 (12.5%) respectively, with only one death. Hypoxemia was less pronounced in LTRs (p = 0.014). Finally, age and dyspnea remained independent factors associated with hypoxemia (p < 0.005). The most frequent radiological patterns were bronchopneumonia (34.2%) and bronchiolitis (39.5% and 64.3% in the overall population and in LTRs respectively, p = 0.045). FEV1 improved in LTRs at one month and 85% had recovered their baseline FEV1 within 6 months. INTERPRETATIONS: In immunocompromised adults, HMPV infections required frequent hospitalizations and ICU transfers, while mortality is low. In LTRs, bronchiolitis pattern was predominant with short and long-term favorable outcome.

Empagliflozin and risk of lower respiratory tract infection in heart failure with mildly reduced and preserved ejection fraction: An EMPEROR-Preserved analysis.

AIMS: Lower respiratory tract infections (LRTI) are common worldwide. Patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high risk of developing LRTI. Prior studies were able to show that sodium-glucose cotransporter 2 inhibitors may reduce the incidence of LRTI in patients with type 2 diabetes. The aim of this study was to evaluate patient characteristics and prognosis according to LRTI status and to assess the effect of empagliflozin on LRTI in 5988 patients with HFmrEF/HFpEF enrolled in the EMPEROR-Preserved trial randomized to either empagliflozin or placebo over a median follow-up of 26 months. METHODS AND RESULTS: Time-updated models were used to study the mortality risk after a LRTI. Cox regression was used to study the effect of empagliflozin on incident LRTI. Throughout the follow-up, 699 of 5988 (11.7%) patients developed LRTI: these were older, were more frequently hospitalized within the previous year, had type 2 diabetes, chronic kidney disease, and had higher N-terminal pro-B-type natriuretic peptide levels than patients without incident LRTI. Patients who developed LRTI had a 2.7-fold higher risk of subsequent mortality compared to patients without LRTI. The incidence of LRTI was 5.2 (95% confidence interval [CI] 4.6-5.8) events per 100 person-years in the empagliflozin group and 6.2 (95% CI 5.6-6.9) events per 100 person-years in the placebo group (hazard ratio 0.83, 95% CI 0.71-0.96, p = 0.014). The total number of LRTI events was reduced in the empagliflozin group (incidence rate ratio 0.80, 95% CI 0.68-0.94, p = 0.008). No effect of empagliflozin was observed on COVID-19 incidence. CONCLUSION: In EMPEROR-Preserved, LRTI was frequent and associated with a poor prognosis. Empagliflozin was associated with a reduced risk of LRTI compared to placebo.