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Background: Lower respiratory tract infection (LRTI) is the most common infection causing significant mortality with a 3-5% death rate in adults. The emerging nature of antimicrobial resistance to pathogens makes its treatment more challenging and complicated for physicians. Aims and Objectives: The study was designed to obtain a comprehensive insight into the microbial profile and resistance patterns of the isolated pathogens in LRTI in a tertiary care hospital in Kolkata. Materials and Methods: The cross-sectional observational study was carried out in the Microbiology Department of N.R.S Medical College from January to December 2021. Specimens collected from 782 clinically suspected LRTI cases were processed as per standard laboratory protocol following clinical and laboratory standard Institute guidelines. Results: Out of 782 respiratory samples, 47.83% showed significant bacterial growth. The major risk factor was found to be type II diabetes mellitus (47.44%) followed by chronic obstructive pulmonary disease (36.57%) and smoking (21.35%). 85.56% growth was monomicrobial and Gram-negative organisms (88.50%) predominated. Klebsiella pneumoniae (36.90%) was the most predominant Gram-negative bacilli followed by Pseudomonas aeruginosa (17.11%) and Acinetobacter species (13.90%). Staphylococcus aureus was the predominant Gram-positive isolate (7.49%). Gram-negative organisms showed the highest resistance to penicillin and cephalosporins, whereas the lowest resistance in carbapenems. Piperacillin/tazobactam and levofloxacin showed good susceptibility. Linezolid was the most susceptible antimicrobial followed by vancomycin in the case of Gram-positive organisms. Extended-spectrum β-lactamase was detected as the mechanism of resistance in 31.12% of cases and carbapenemase was detected in 19.64% of cases. Conclusion: Increasing antimicrobial resistance and varied bacterial etiology make it necessary to develop appropriate antibiotic policy and implement antimicrobial stewardship for effective and prompt therapy. [ABSTRACT FROM AUTHOR]

Background: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. Methods: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. Results: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. Conclusions: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsAccurate and rapid identification of causative pathogens is essential to guide the clinical management of lower respiratory tract infections (LRTIs). Here we conducted a single-centre prospective study in 284 patients suspected of lower respiratory tract infections to evaluate the utility of a nucleic acid test based on highly multiplexed polymerase chain reaction (PCR) and CRISPR-Cas12a.We determined the analytical and diagnostic performance of the CRISPR assay using a combination of reference standards, including conventional microbiological tests (CMTs), metagenomic Next-Generation Sequencing (mNGS), and clinical adjudication by a panel of experts on infectious diseases and microbiology.The CRISPR assay showed a higher detection rate (63.0%) than conventional microbiological tests (38.4%) and was lower than metagenomic Next-Generation Sequencing (72.9%). In detecting polymicrobial infections, the positivity rate of the CRISPR assay (19.4%) was higher than conventional microbiological tests (3.5%) and lower than metagenomic Next-Generation Sequencing (28.9%). The overall diagnostic sensitivity of the CRISPR assay (67.8%) was higher than conventional microbiological tests (41.8%), and lower than metagenomic Next-Generation Sequencing (93.2%).Considering the low cost, ease of operation, short turnaround time, and broad range of pathogens detected in a single test, the CRISPR assay has the potential to be implemented as a screening tool for the aetiological diagnosis of lower respiratory tract infections patients, especially in cases where atypical bacteria or coinfections are suspected. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infection (LRTI) is the most common infection causing significant mortality with a 3–5% death rate in adults. The emerging nature of antimicrobial resistance to pathogens makes its treatment more challenging and complicated for physicians. Aims and Objectives: The study was designed to obtain a comprehensive insight into the microbial profile and resistance patterns of the isolated pathogens in LRTI in a tertiary care hospital in Kolkata. Materials and Methods: The cross-sectional observational study was carried out in the Microbiology Department of N.R.S Medical College from January to December 2021. Specimens collected from 782 clinically suspected LRTI cases were processed as per standard laboratory protocol following clinical and laboratory standard Institute guidelines. Results: Out of 782 respiratory samples, 47.83% showed significant bacterial growth. The major risk factor was found to be type II diabetes mellitus (47.44%) followed by chronic obstructive pulmonary disease (36.57%) and smoking (21.35%). 85.56% growth was monomicrobial and Gram-negative organisms (88.50%) predominated. Klebsiella pneumoniae (36.90%) was the most predominant Gram-negative bacilli followed by Pseudomonas aeruginosa (17.11%) and Acinetobacter species (13.90%). Staphylococcus aureus was the predominant Gram-positive isolate (7.49%). Gram-negative organisms showed the highest resistance to penicillin and cephalosporins, whereas the lowest resistance in carbapenems. Piperacillin/tazobactam and levofloxacin showed good susceptibility. Linezolid was the most susceptible antimicrobial followed by vancomycin in the case of Gram-positive organisms. Extended-spectrum β-lactamase was detected as the mechanism of resistance in 31.12% of cases and carbapenemase was detected in 19.64% of cases. Conclusion: Increasing antimicrobial resistance and varied bacterial etiology make it necessary to develop appropriate antibiotic policy and implement antimicrobial stewardship for effective and prompt therapy.

Abstract Background Lower respiratory tract infections (LRTIs) are a major global health concern, particularly among older adults, who have an increased risk of poorer health outcomes that persist beyond the acute infectious episode. We aimed to investigate the mid-term (up to 7 years) and long-term (up to 12 years) effects of LRTIs on the objective health status trajectories of older adults, while also considering potential sex differences. Methods Cohort data of adults aged ≥ 60 years from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) collected between 2001 and 2016 was analyzed. Information on LRTIs was obtained from the Swedish National Patient Register, and objective health status was assessed using the Health Assessment Tool (HAT) which incorporates indicators of mild and severe disability, cognitive and physical functioning, and multimorbidity. The LRTI-exposed and -unexposed participants were matched using propensity score matching based on an expansive list of potential confounders. Mixed linear models were used to analyze the association between LRTIs and changes in HAT scores. Results The study included 2796 participants, 567 of whom were diagnosed with a LRTI. LRTIs were independently associated with an excess annual decline of 0.060 (95% CI: -0.107, -0.013) in the HAT score over a 7-year period. The associations were stronger among males, who experienced an excess annual decline of 0.108 (95% CI: -0.177, -0.039) in up to 7-years follow-up, and 0.097 (95% CI: -0.173, -0.021) in up to 12-years follow-up. The associations were not statistically significant among females in either follow-up period. Conclusion LRTIs, even years after the acute infectious period, seem to have a prolonged negative effect on the health of older adults, particularly among males. Preventative public health measures aimed at decreasing LRTI cases among older adults could help in preserving good health and functioning in old age.

INTRODUCTION. Respiratory syncytial virus (RSV) is one of the most widespread pathogens that typically cause acute upper and lower respiratory tract infections in children and adults. Monoclonal antibody products have long been used for passive immunoprophylaxis in premature infants with bronchopulmonary dysplasia. However, vaccines have recently been licensed for the prophylactic immunisation of older adults with various risk factors for severe RSV infection (primarily, chronic cardiovascular and respiratory diseases and diabetes mellitus).AIM. This study aimed to review the current status of the development of vaccines for active immunisation against RSV infection, including the epidemiological rationale for their development, clinical trial results for licensed vaccines, recommendations for vaccination, and promising pipeline vaccines for RSV prevention.DISCUSSION. Initially hindered by the unique immunopathogenesis of RSV infection and the genetic hypervariability of RSV for a long time, attempts to develop an RSV vaccine succeeded when international researchers managed to identify a conservative neutralising antibody target capable of inducing specific immunity against RSV. This target, the RSV capsid protein stabilised in its prefusion (pre-F) conformation, can mediate viral entry into the cell following a conformational change. Several subunit vaccines based on recombinant pre-F proteins have successfully passed clinical trials and have been approved for the immunisation of older adults. In addition, one of these vaccines has been recommended for use during pregnancy to prevent RSV infection in newborns and infants. Currently, programmes are being implemented to develop novel RSV vaccines based on messenger RNA (mRNA) and non-replicating attenuated influenza vectors. This article examines and summarises the efficacy and safety parameters of two RSV vaccines approved in multiple countries around the world. Both vaccines have satisfactory safety profiles and comparable prophylactic efficacy parameters.CONCLUSIONS. Prelicensure clinical trials of novel RSV vaccines, including those being developed in the Russian Federation, should include prophylactic efficacy assessments in target patient populations. For vaccines approved by leading international regulators, clinical trials required for approval in the Russian Federation will be limited to bridging studies confirming the immunogenicity and safety of the vaccines.

The value of C-reactive protein point-of-care testing (CRP POCT) to guide antibiotic prescriptions in adults has previously been emphasized. The aim of this study was to assess the impact of CRP POCT on antibiotic prescriptions by general practitioners (GPs) for suspected lower respiratory tract infections in children ≥3 years old and in adults. This was an open-label randomized trial (NCT03540706) conducted in 26 GPs in France between October 2019 and March 2023. Of the 404 participating patients, 207 (51.2%) were randomized to the CRP POCT group and 197 (48.8%) to the control group (i.e. no CRP POCT). During consultations, GPs measured CRP levels in patients randomized to the CRP POCT group. The primary endpoint was the proportion of patients in each group who were prescribed antibiotics by their GP during the consultation. Z-tests were used for comparisons. The overall proportion of patients treated with antibiotics was similar in the CRP POCT (n = 89/207, 43% CI: 36.2, 50.0) and in the control group (n = 94/197, 47.7% CI: 40.6, 54.9), difference: −4.7 CI: −14.4, 5.0; p 0.3. Overall, 75% of the GPs followed CRP-based antibiotic prescription recommendations in the CRP POCT group. CRP POCT did not reduce antibiotic prescriptions in this trial. [ABSTRACT FROM AUTHOR]

Abstract Background In this study, we aimed to evaluate the clinical utility of Metagenomic Next-Generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) in diagnosis of Lower Respiratory Tract Infections (LRTIs). Methods In this study, we retrospectively analyzed 186 hospitalized patients who were suspected with LRTIs and performed mNGS (DNA) test of BALF simultaneously at The Fifth Affiliated Hospital of Sun Yat-Sen University from March 2023 to August 2023. Suspected LRTI was based on LRTI related clinical manifestations or imaging examination. Among them, 155 patients had undergone conventional culture and mNGS (DNA) testing simultaneously. Finally, 138 cases (89.03%,138/155) were diagnosed as LRTI and 17 cases (10.97%,17/155) were diagnosed as non-LRTI. Both detecting rate and diagnostic efficacy of mNGS and conventional culture were compared. Results The positive detection rates of pathogens between mNGS and conventional culture were significant different (81.29% VS 39.35%, P 0.05). Furthermore, 77.54% and 35.51% of LRTI cases were being etiologically diagnosed by mNGS and culture respectively. Importantly, mNGS directly led to a change of treatment regimen in 58 (37.42%) cases, including antibiotic adjustment (29.68%) and ruling out active infection (7.74%). Moreover, treatment regimen remained unchanged in 97 (62.58%) cases, considering the current antibiotic therapy already covered the detected pathogens (36.13%) or empirical treatment was effective (11.61%). Conclusions mNGS can identify a wide range of pathogens in LRTIs, with improved sensitivity and being more superior at diagnosing LRTIs etiologically. mNGS has the potential to enhance clinical outcomes by optimizing the treatment regimens.

Background: In this study, we aimed to evaluate the clinical utility of Metagenomic Next-Generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) in diagnosis of Lower Respiratory Tract Infections (LRTIs). Methods: In this study, we retrospectively analyzed 186 hospitalized patients who were suspected with LRTIs and performed mNGS (DNA) test of BALF simultaneously at The Fifth Affiliated Hospital of Sun Yat-Sen University from March 2023 to August 2023. Suspected LRTI was based on LRTI related clinical manifestations or imaging examination. Among them, 155 patients had undergone conventional culture and mNGS (DNA) testing simultaneously. Finally, 138 cases (89.03%,138/155) were diagnosed as LRTI and 17 cases (10.97%,17/155) were diagnosed as non-LRTI. Both detecting rate and diagnostic efficacy of mNGS and conventional culture were compared. Results: The positive detection rates of pathogens between mNGS and conventional culture were significant different (81.29% VS 39.35%, P < 0.05). Compared with paired conventional culture result, the sensitivity of mNGS in diagnosis of LRTIs was more superior (88.41% VS 43.48%; P < 0.05), the specificity was opposite (76.47% VS 94.12%; P > 0.05). Furthermore, 77.54% and 35.51% of LRTI cases were being etiologically diagnosed by mNGS and culture respectively. Importantly, mNGS directly led to a change of treatment regimen in 58 (37.42%) cases, including antibiotic adjustment (29.68%) and ruling out active infection (7.74%). Moreover, treatment regimen remained unchanged in 97 (62.58%) cases, considering the current antibiotic therapy already covered the detected pathogens (36.13%) or empirical treatment was effective (11.61%). Conclusions: mNGS can identify a wide range of pathogens in LRTIs, with improved sensitivity and being more superior at diagnosing LRTIs etiologically. mNGS has the potential to enhance clinical outcomes by optimizing the treatment regimens. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections (LRTIs) have an immediate significant impact on morbidity and mortality among older adults. However, the impact following the infectious period of LRTI remains understudied. We aimed to assess the short- to long-term impact of LRTIs on hospitalization, mortality, and healthcare utilization in older adults. Methods: Data from the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K) was analyzed, with data from 2001 to 2019 for mortality and 2001–2016 for healthcare utilization. LRTI-exposed participants were identified and matched with LRTI-nonexposed based on sociodemographics, lifestyle factors, and functional and clinical characteristics. Statistical models evaluated post-LRTI hospitalization risk, days of inpatient hospital admissions, healthcare visits, and mortality. Results: 567 LRTIs-exposed participants during the study period and were matched with 1.701 unexposed individuals. LRTI-exposed individuals exhibited increased risk of hospitalization at 1-year (HR 2.14, CI 1.74, 2.63), 3-years (HR 1.74, CI 1.46, 2.07), and 5-years (HR 1.59, CI 1.33, 1.89). They also experienced longer post-LRTI hospital stays (IRR 1.40, CI 1.18, 1.66), more healthcare visits (IRR 1.47, CI 1.26, 1.71), specialist-care visits (IRR 1.46, CI 1.24, 1.73), and hospital admissions (IRR 1.57, CI 1.34, 1.83) compared to nonexposed participants over 16-years of potential follow-up. Additionally, the 19-year risk of mortality was higher among LRTI-exposed participants (HR 1.45, CI 1.24, 1.70). Men exhibited stronger associations with these risks compared to women. Conclusions: LRTIs pose both short- and long-term risks for older adults, including increased risks of mortality, hospitalization, and healthcare visits that transpire beyond the acute infection period, although these effects diminish over time. Men exhibit higher risks across these outcomes compared to women. Given the potential preventability of LRTIs, further public health measures to mitigate infection risk are warranted. [ABSTRACT FROM AUTHOR]

Objective: Acute bronchiolitis and/or pneumonia are generally referred to as lower respiratory tract infections (LRTI). It was aimed to investigate the agents in LRTI, which is one of the most important causes of childhood deaths, by real-time polymerase chain reaction (PCR) method from the nasopharyngeal aspirate. Material and Methods: In our study, chest radiographs, clinical, demographic, laboratory characteristics, and disease agents obtained by real-time PCR were examined in patients aged 1 month to 18 years who were hospitalized with a prediagnosis of LRTI in the pediatric service during the year 2019. Results: The patients’ mean age was 25.89±36.72 months, and 57.05% (n=279) of the study group were male. Patients are grouped monthly; of the study group, 69.3% were between the ages of one and 24 months, and 16.0% were between the ages of 24 and 60 months. In the study group, 38% (n=186) of 489 patients had a fever. In 93.9% of cases, a cough was present. Of the 489 patients in the study group, 175 (35.7%) had no detectable causative agent, while 314 (64.3%) had one or more. After analyzing individual factors, 28.34% of the study group had Rhinovirus as the causative agent. Conclusion: The most frequent cause of LRTI was determined to be Rhinovirus in our investigation, in contrast to the general literature in our nation. Other data appear to be generally compatible with national and international literature. [ABSTRACT FROM AUTHOR]

Introduction FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10–12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT). Methods Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires. Results From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5–14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians' stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed 'good' user-friendliness. Conclusions Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety. [ABSTRACT FROM AUTHOR]

BackgroundWe evaluated published evidence (2012–2022) on pediatric RSV burden in 149 countries within World Health Organization (WHO) regions of Africa (AFRO), Americas (AMRO, excluding Canada and the USA), Eastern Mediterranean (EMRO), Europe (EURO, excluding European Union countries and the UK), Southeast Asia (SEARO), and Western Pacific (WPRO, excluding Australia, China, Japan, New Zealand, and South Korea).MethodsGap analysis on RSV-associated disease (hospitalizations, hospital course, mortality or case fatality, detection, and incidence) in children ≤2 years old, where hospitalization rates, hospital course, mortality rate, case fatality rate (CFR), and postmortem detection rates were summarized, by region, for each country.ResultsForty-two publications were identified covering 19% of included countries in AFRO, 18% in AMRO, 14% in EMRO, 15% in EURO, 18% in SEARO, and 13% in WPRO. Methods, case definitions, and age groups varied widely across studies. Of these 42 publications, 25 countries reported hospitalization rate, hospital course, mortality rate, CFR, and/or postmortem detection rate. RSV hospitalization rate (per 1,000 children per year/child-years) was higher among ≤3-month-olds (range, 38 in Nicaragua to 138 in the Philippines) and ≤6-month-olds (range, 2.6 in Singapore to 70 in South Africa) than in 1–2-year-olds (from 0.7 in Guatemala to 19 in Nicaragua). Based on 11 studies, in AFRO (South Africa), AMRO (Chile and Mexico), EMRO (Lebanon and Jordan), EURO (Israel and Turkey), and SEARO (India), hospitalized children ≤2 years old remained hospitalized for 3–8 days, with 9%–30% requiring intensive care and 4%–26% needing mechanical ventilation. Based on a study in India, community-based CFR was considerably higher than that in the hospital (9.1% vs. 0% in ≤3-month-olds; 7.1% vs. 2.8% in ≤6-month-olds).ConclusionsNational and regional heterogeneity of evidence limits estimates of RSV burden in ≤2-year-olds in many WHO region countries, where further country-specific epidemiology is needed to guide prioritization, implementation, and impact assessment of RSV prevention strategies.

Abstract Background Pneumonia is a leading cause of childhood morbidity and mortality. Hospital re-admission may signify missed opportunities for care or undiagnosed comorbidities. Methods We conducted a retrospective cohort study including children aged $$\ge$$ ≥ 2 months-14 years hospitalised with severe pneumonia between 2013 and 2021 in a network of 20 primary referral hospitals in Kenya. Severe pneumonia was defined using the 2013 World Health Organization criteria, and re-admission was based on clinical documentation from individual patient case notes. We estimated the prevalence of re-admission, described clinical management practices, and modelled risk factors for re-admission and inpatient mortality. Results Among 20,603 children diagnosed with severe pneumonia, 2,274 (11.0%, 95% CI 10.6–11.5) were readmitted. Re-admission was independently associated with age (12–59 months vs. 2–11 months: adjusted odds ratio (aOR) 1.70, 1.54–1.87; >5 years vs. 2–11 months: aOR 1.85, 1.55–2.22), malnutrition (weight-for-age-z-score (WAZ) -2SD: aOR 2.05, 1.84–2.29); WAZ − 2 to -3 SD vs. WAZ> -2SD: aOR 1.37, 1.20–1.57), wheeze (aOR 1.17, 1.03–1.33) and presence of a concurrent neurological disorder (aOR 4.42, 1.70-11.48). Chest radiography was ordered more frequently among those readmitted (540/2,274 [23.7%] vs. 3,102/18,329 [16.9%], p -2SD: aHR 1.87, 1.71–2.05); WAZ − 2 to -3 SD vs. WAZ >-2SD: aHR 1.46, 1.31–1.63), complete vaccination (aHR 0.74, 0.60–0.91), wheeze (aHR 0.87, 0.78–0.98) and anaemia (aHR 2.14, 1.89–2.43) were independently associated with mortality. Conclusions Children readmitted with severe pneumonia account for a substantial proportion of pneumonia hospitalisations and deaths. Further research is required to develop evidence-based approaches to screening, case management, and follow-up of children with severe pneumonia, prioritising those with underlying risk factors for readmission and mortality.

Lower respiratory tract infections (LRTIs) are one of the most common causes of hospitalization among children in the early childhood period. Knowing the pathogens that cause pneumonia, its management will be more exact and effective. In this study, we aimed to investigate the frequency of pathogens causing LRTIs in children at the end of the COVID-19 pandemic by performing a real-time multiplex polymerase chain reaction (RT-MPCR) test within our hospital. We included two hundred forty-seven children, aged between 1 month and 18 years, diagnosed with LRTIs, and hospitalized between May 2021 and April 2022. Demographic characteristics and clinical and laboratory findings were retrospectively collected from patients’ hospital records. Of the 247 children diagnosed with LRTIs, 153 (61.9%) were female. At least one pathogen was identified in the nasopharyngeal swap specimens of 218 (88.3%) patients, and 74.9% (n=185) of them were viruses. The most common identified pathogens were respiratory syncytial virus (24.7%), human bocavirus (21.1%), and severe acute respiratory syndrome coronavirus 2 (15.4%). 7.7% of identified pathogens were bacteria. Haemophilus influenzae was the most commonly detected bacteria. Despite a lengthy period of isolating the community causative agents of pneumonia, their frequency remains unchanged from before the isolation time. RT-MPCR is beneficial for the early detection of pathogens and in the prevention of unnecessary antibiotic usage.

Abstract Background Lower respiratory tract infections (LRTIs) in children are a major concern in Indonesia as it is the leading cause of morbidity and mortality. Therefore, research on LRTIs is crucial to improve children’s health. However, clinical research in children is challenging due to parental concerns. This study aims to understand parental considerations for taking part in clinical studies on LRTI in the Indonesian context. Methods A cross-sectional study using a validated online questionnaire was conducted from November 2021 to March 2022. This study included parents from two public elementary schools and two private primary schools in Semarang, Indonesia. A total of 1236 responses were analysed. Results There was a significant association between educational attainment and willingness to participate in general health and LRTI-related research requiring specimen collection; respondents with an advanced educational level were more likely to refuse participation in research. A similar pattern was observed among respondents with smaller families and younger children against participation in LRTI research. Most respondents who indicated not to participate explained that they did not perceive the necessity to take part and expressed their concerns about endangering their child’s health as a consequence of the specimen collection. Most respondents expected a personal benefit and prioritized access to the study results for their child. Conclusion Parents’ educational background and family composition are important determinants of parental engagement in research on LRTI in Indonesia. Notably, parents with a lower educational level, having large families, and older children were more inclined to participate. The emphasis on concerns about potential harm and personal benefit underscores the need for a targeted communication strategy.

This Systematic Review assesses the economic impact of Respiratory Syncytial Virus (RSV) in Latin America and the Caribbean (LAC) in relation to healthcare resource utilization and associated costs. We searched online databases from January 2012 to November 2022 to identify eligible publications. We identified 12 publications that reported direct costs, indirect costs, and resources associated with RSV and its complications. The primary direct medical resources reported were medical services, diagnostics tests and procedures, and length of stay (LOS). Direct total costs per patient ranged widely from $563 to $19,076. Direct costs are, on average, 98% higher than indirect costs. Brazil reported a higher total cost per patient than Colombia, El Salvador, México, Panamá, and Puerto Rico, while for indirect costs per patient, El Salvador and Panamá had higher costs than Brazil, Colombia, and Mexico. The mean LOS in the general ward due to RSV was 6.9 days (range 4 to 20 days) and the mean Intensive Care Unit LOS was 9.1 days (range 4 to 16 days). In many countries of the LAC region, RSV represents a considerable economic burden on health systems, but significant evidence gaps were identified in the region. More rigorous health economic studies are essential to better understand this burden and to promote effective healthcare through an informed decision-making process. Vaccination against RSV plays a critical role in mitigating this burden and should be a priority in public health strategies.

Background: Pneumonia is a leading cause of childhood morbidity and mortality. Hospital re-admission may signify missed opportunities for care or undiagnosed comorbidities. Methods: We conducted a retrospective cohort study including children aged ≥ 2 months-14 years hospitalised with severe pneumonia between 2013 and 2021 in a network of 20 primary referral hospitals in Kenya. Severe pneumonia was defined using the 2013 World Health Organization criteria, and re-admission was based on clinical documentation from individual patient case notes. We estimated the prevalence of re-admission, described clinical management practices, and modelled risk factors for re-admission and inpatient mortality. Results: Among 20,603 children diagnosed with severe pneumonia, 2,274 (11.0%, 95% CI 10.6–11.5) were readmitted. Re-admission was independently associated with age (12–59 months vs. 2–11 months: adjusted odds ratio (aOR) 1.70, 1.54–1.87; >5 years vs. 2–11 months: aOR 1.85, 1.55–2.22), malnutrition (weight-for-age-z-score (WAZ) <-3SD vs. WAZ> -2SD: aOR 2.05, 1.84–2.29); WAZ − 2 to -3 SD vs. WAZ> -2SD: aOR 1.37, 1.20–1.57), wheeze (aOR 1.17, 1.03–1.33) and presence of a concurrent neurological disorder (aOR 4.42, 1.70-11.48). Chest radiography was ordered more frequently among those readmitted (540/2,274 [23.7%] vs. 3,102/18,329 [16.9%], p < 0.001). Readmitted patients more frequently received second-line antibiotics (808/2,256 [35.8%] vs. 5,538/18,173 [30.5%], p < 0.001), TB medication (69/2,256 [3.1%] vs. 298/18,173 [1.6%], p < 0.001), salbutamol (530/2,256 [23.5%] vs. 3,707/18,173 [20.4%], p = 0.003), and prednisolone (157/2,256 [7.0%] vs. 764/18,173 [4.2%], p < 0.001). Inpatient mortality was 2,354/18,329 (12.8%) among children admitted with a first episode of severe pneumonia and 269/2,274 (11.8%) among those who were readmitted (adjusted hazard ratio (aHR) 0.93, 95% CI 0.82–1.07). Age (12–59 months vs. 2–11 months: aHR 0.62, 0.57–0.67), male sex (aHR 0.81, 0.75–0.88), malnutrition (WAZ <-3SD vs. WAZ >-2SD: aHR 1.87, 1.71–2.05); WAZ − 2 to -3 SD vs. WAZ >-2SD: aHR 1.46, 1.31–1.63), complete vaccination (aHR 0.74, 0.60–0.91), wheeze (aHR 0.87, 0.78–0.98) and anaemia (aHR 2.14, 1.89–2.43) were independently associated with mortality. Conclusions: Children readmitted with severe pneumonia account for a substantial proportion of pneumonia hospitalisations and deaths. Further research is required to develop evidence-based approaches to screening, case management, and follow-up of children with severe pneumonia, prioritising those with underlying risk factors for readmission and mortality. [ABSTRACT FROM AUTHOR]

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives. [ABSTRACT FROM AUTHOR]

Background: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. Methods: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT‐PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. Results: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2–6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p‐value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. Conclusion: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity. [ABSTRACT FROM AUTHOR]

Background: Western Montana, USA, experiences complex air pollution patterns with predominant exposure sources from summer wildfire smoke and winter wood smoke. In addition, climate change related temperatures events are becoming more extreme and expected to contribute to increases in hospital admissions for a range of health outcomes. Evaluating while accounting for these exposures (air pollution and temperature) that often occur simultaneously and may act synergistically on health is becoming more important. Methods: We explored short-term exposure to air pollution on children's respiratory health outcomes and how extreme temperature or seasonal period modify the risk of air pollution-associated healthcare events. The main outcome measure included individual-based address located respiratory-related healthcare visits for three categories: asthma, lower respiratory tract infections (LRTI), and upper respiratory tract infections (URTI) across western Montana for ages 0–17 from 2017–2020. We used a time-stratified, case-crossover analysis with distributed lag models to identify sensitive exposure windows of fine particulate matter (PM2.5) lagged from 0 (same-day) to 14 prior-days modified by temperature or season. Results: For asthma, increases of 1 µg/m3 in PM2.5 exposure 7–13 days prior a healthcare visit date was associated with increased odds that were magnified during median to colder temperatures and winter periods. For LRTIs, 1 µg/m3 increases during 12 days of cumulative PM2.5 with peak exposure periods between 6–12 days before healthcare visit date was associated with elevated LRTI events, also heightened in median to colder temperatures but no seasonal effect was observed. For URTIs, 1 unit increases during 13 days of cumulative PM2.5 with peak exposure periods between 4–10 days prior event date was associated with greater risk for URTIs visits that were intensified during median to hotter temperatures and spring to summer periods. Conclusions: Delayed, short-term exposure increases of PM2.5 were associated with elevated odds of all three pediatric respiratory healthcare visit categories in a sparsely population area of the inter-Rocky Mountains, USA. PM2.5 in colder temperatures tended to increase instances of asthma and LRTIs, while PM2.5 during hotter periods increased URTIs. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections (LRTIs) in children are a major concern in Indonesia as it is the leading cause of morbidity and mortality. Therefore, research on LRTIs is crucial to improve children's health. However, clinical research in children is challenging due to parental concerns. This study aims to understand parental considerations for taking part in clinical studies on LRTI in the Indonesian context. Methods: A cross-sectional study using a validated online questionnaire was conducted from November 2021 to March 2022. This study included parents from two public elementary schools and two private primary schools in Semarang, Indonesia. A total of 1236 responses were analysed. Results: There was a significant association between educational attainment and willingness to participate in general health and LRTI-related research requiring specimen collection; respondents with an advanced educational level were more likely to refuse participation in research. A similar pattern was observed among respondents with smaller families and younger children against participation in LRTI research. Most respondents who indicated not to participate explained that they did not perceive the necessity to take part and expressed their concerns about endangering their child's health as a consequence of the specimen collection. Most respondents expected a personal benefit and prioritized access to the study results for their child. Conclusion: Parents' educational background and family composition are important determinants of parental engagement in research on LRTI in Indonesia. Notably, parents with a lower educational level, having large families, and older children were more inclined to participate. The emphasis on concerns about potential harm and personal benefit underscores the need for a targeted communication strategy. [ABSTRACT FROM AUTHOR]

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (RSV) is an RNA virus of the family Pneumoviridae and is a common causative agent of acute respiratory infections. Infection with this virus is often severe and can result in fatalities and chronic complications, particularly in high-risk groups such as children under the age of 5 and elderly individuals over 65 years old. This review presents the latest data on the taxonomy, virion structure, and genome map of RSV, as well as its role in the etiology of acute respiratory diseases. We have analyzed over 100 publications on RSV genotyping in different parts of the world including Russia published between 2015 and 2023. The genetic composition of RSV isolates in Russia is similar to that in other regions of the world, which are predominantly represented by genotypes ON1 and BA9. The development of effective vaccines is crucial for successful disease control. The review summarizes global advances in the development of interventions against RSV, emphasizing promising treatments currently undergoing clinical trials and the ones that have recently been approved. Similar interventions (vaccines) are yet to be developed in Russia, but the similarities in genetic composition of RSV in Russia and worldwide offer hope for the rapid development of domestic vaccines against this infection. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. Methods: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analysed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. Results: Of the 3238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. Conclusions: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard-of-care diagnostics alone.

Abstract Background Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. Methods Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. Results The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. Conclusions Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.

Abstract A comprehensive understanding of the dynamics of Streptococcus pneumoniae colonization in conjunction with respiratory virus infections is essential for enhancing our knowledge of the pathogenesis and advancing the development of effective preventive strategies. Therefore, a case–control study was carried out in Addis Ababa, Ethiopia to investigate the colonization rate of S. pneumoniae and its coinfection dynamics with respiratory viruses among children under the age of 5 years. Samples from the nasopharyngeal and/or oropharyngeal, along with socio-demographic and clinical information, were collected from 420 children under 5 years old (210 cases with lower respiratory tract infections and 210 controls with conditions other than respiratory infections.). A one-step Multiplex real-time PCR using the Allplex Respiratory Panel Assays 1–4 was performed to identify respiratory viruses and bacteria. Data analysis was conducted using STATA software version 17. The overall colonization rate of S. pneumoniae in children aged less than 5 years was 51.2% (215/420). The colonization rates in cases and controls were 54.8% (115/210) and 47.6% (100/210), respectively (p = 0.14). Colonization rates were observed to commence at an early age in children, with a colonization rate of 48.9% and 52.7% among infants younger than 6 months controls and cases, respectively. The prevalence of AdV (OR, 3.11; 95% CI [1.31–8.19]), RSV B (OR, 2.53; 95% CI [1.01–6.78]) and HRV (OR, 1.7; 95% CI [1.04–2.78]) tends to be higher in children who tested positive for S. pneumoniae compared to those who tested negative for S. pneumoniae. Further longitudinal research is needed to understand and determine interaction mechanisms between pneumococci and viral pathogens and the clinical implications of this coinfection dynamics.

Abstract Objective To evaluate the dynamics of basic activity of daily living (BADL) in older patients with acute lower respiratory tract infections (LRTIs) during acute phase and to investigate risk factors associated with decreased physical function at discharge. Methods We conducted a prospective cohort study of patients aged 65 years and older who were hospitalized for acute LRTIs between April 15, 2020 and January 15, 2023. All patients received geriatric assessment at admission, including emotion, cognition, frailty, physical function status and so on. The BADL was also evaluated by the Barthel Index (BI) at two weeks before admission by recall (baseline status), at admission and at discharge. Based on the BI grades at baseline and at discharge, patients were classified into two groups: ADL decline and no ADL decline. Multivariable adjusted logistic regression models were used to evaluate the risk factors of decreased physical function. Results A total of 364 older survivors with LRTIs were included in the analysis. The median age was 74 years (IQR 61.0–82.0), 231 (62.6%) were male, the median length of stay was 10 days. In the geriatric assessment, 139 patients (38.2%) were classified as frailty, 137 patients (37.6%) experienced insomnia, 60 patients (16.5%) exhibited cognitive impairments, and 37 patients (10.2%) were defined as malnutrition. Additionally, 30 patients (8.2%) dealt with emotional disorders. On average, patients were taking 3 medications, and Charlson Comorbidity Index score was 4. 72 patients (19.8%) had function decline at discharge. In the multivariable analysis, frailty status had an odds ratio of 4.25 (95% CI 1.31–19.26) for decreased physical function and cognitive impairment had an odds ratio of 2.58 (95% CI 1.27–5.19). Conclusions About 20% older patients with LRTIs experienced functional decline at discharge. Compared to age, severity of diseases and length of stay, frailty and cognitive impairment performed better at predicting the function decline. The apply of geriatric assessment may contribute to enhance the quality of management and treatment for patients with the older with LRTIs.

Abstract Background Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). Methods This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. Results From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. Conclusions In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. Trial registration This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Objective: To evaluate the dynamics of basic activity of daily living (BADL) in older patients with acute lower respiratory tract infections (LRTIs) during acute phase and to investigate risk factors associated with decreased physical function at discharge. Methods: We conducted a prospective cohort study of patients aged 65 years and older who were hospitalized for acute LRTIs between April 15, 2020 and January 15, 2023. All patients received geriatric assessment at admission, including emotion, cognition, frailty, physical function status and so on. The BADL was also evaluated by the Barthel Index (BI) at two weeks before admission by recall (baseline status), at admission and at discharge. Based on the BI grades at baseline and at discharge, patients were classified into two groups: ADL decline and no ADL decline. Multivariable adjusted logistic regression models were used to evaluate the risk factors of decreased physical function. Results: A total of 364 older survivors with LRTIs were included in the analysis. The median age was 74 years (IQR 61.0–82.0), 231 (62.6%) were male, the median length of stay was 10 days. In the geriatric assessment, 139 patients (38.2%) were classified as frailty, 137 patients (37.6%) experienced insomnia, 60 patients (16.5%) exhibited cognitive impairments, and 37 patients (10.2%) were defined as malnutrition. Additionally, 30 patients (8.2%) dealt with emotional disorders. On average, patients were taking 3 medications, and Charlson Comorbidity Index score was 4. 72 patients (19.8%) had function decline at discharge. In the multivariable analysis, frailty status had an odds ratio of 4.25 (95% CI 1.31–19.26) for decreased physical function and cognitive impairment had an odds ratio of 2.58 (95% CI 1.27–5.19). Conclusions: About 20% older patients with LRTIs experienced functional decline at discharge. Compared to age, severity of diseases and length of stay, frailty and cognitive impairment performed better at predicting the function decline. The apply of geriatric assessment may contribute to enhance the quality of management and treatment for patients with the older with LRTIs. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of the dynamics of Streptococcus pneumoniae colonization in conjunction with respiratory virus infections is essential for enhancing our knowledge of the pathogenesis and advancing the development of effective preventive strategies. Therefore, a case–control study was carried out in Addis Ababa, Ethiopia to investigate the colonization rate of S. pneumoniae and its coinfection dynamics with respiratory viruses among children under the age of 5 years. Samples from the nasopharyngeal and/or oropharyngeal, along with socio-demographic and clinical information, were collected from 420 children under 5 years old (210 cases with lower respiratory tract infections and 210 controls with conditions other than respiratory infections.). A one-step Multiplex real-time PCR using the Allplex Respiratory Panel Assays 1–4 was performed to identify respiratory viruses and bacteria. Data analysis was conducted using STATA software version 17. The overall colonization rate of S. pneumoniae in children aged less than 5 years was 51.2% (215/420). The colonization rates in cases and controls were 54.8% (115/210) and 47.6% (100/210), respectively (p = 0.14). Colonization rates were observed to commence at an early age in children, with a colonization rate of 48.9% and 52.7% among infants younger than 6 months controls and cases, respectively. The prevalence of AdV (OR, 3.11; 95% CI [1.31–8.19]), RSV B (OR, 2.53; 95% CI [1.01–6.78]) and HRV (OR, 1.7; 95% CI [1.04–2.78]) tends to be higher in children who tested positive for S. pneumoniae compared to those who tested negative for S. pneumoniae. Further longitudinal research is needed to understand and determine interaction mechanisms between pneumococci and viral pathogens and the clinical implications of this coinfection dynamics. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. Methods: Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. Results: The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. Conclusions: Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility. [ABSTRACT FROM AUTHOR]

To characterize nirsevimab in the prevention of RSV, children from the Phase 3 MELODY trial were followed through their second RSV season. No increase in medically attended RSV lower respiratory tract infections or evidence of antibody-dependent enhancement of infection or disease severity was found for nirsevimab vs placebo recipients. Clinical Trial Registration: Clinicaltrials.gov, NCT03979313, https://clinicaltrials.gov/ct2/show/NCT03979313. [ABSTRACT FROM AUTHOR]

With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV‐neutralizing antibody, 2023 has been perceived as a game‐changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low‐to‐middle‐income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti‐RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower‐income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden. [ABSTRACT FROM AUTHOR]

Respiratory tract infections (RTIs) are among the most common and important problems in clinical medicine, making antibiotics the gold standard therapeutic option regardless of their frequent viral etiology. Their excessive and inappropriate use contributes to the rapid rise of antibiotic resistance and underscores the need for alternative strategies, especially when dealing with recurrent RTIs. Prevention is the ideal alternative, but specific vaccines targeting a wide range of respiratory pathogens are scarce. MV130 is a sublingual bacterial vaccine that induces trained immunity and provides non-specific protection against respiratory pathogens in various clinical settings according to the concept of TIbV (Trained Immunity-based Vaccine). A retrospective real-world study (RWS) was conducted to evaluate the annual incidence of RTIs and the consumption of antibiotics before and after the administration of MV130, using data sourced from the medical records of 599 patients (186 children and 413 adults) who suffered from recurrent RTIs. The median number of infectious episodes in children was significantly reduced by more than 70% from 5 episodes (interquartile range (IQR) 4.0–6.0) to 1 (IQR, 0.0–2.0) (p < 0.001) after MV130. Similarly, in adults, the median number of episodes before MV130 immunization was 5 (IQR, 4.0–6.0), which dropped by more than 80% to 1 (IQR, 0.0–1.0) during the year following MV130 immunization (p < 0.001). The median number of antibiotic courses also significantly decreased for both children and adults by over 80% (p < 0.001). This RWS showed that MV130 is an effective strategy for the prevention of respiratory infections and the reduction of associated antibiotic consumption. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections (LRTIs) are associated with significant morbidity and mortality in all age groups, especially young children and the elderly population. Various gram-positive and gram-negative organisms such as Streptococcus spp., Pseudomonas spp., and Klebsiella spp. have been implicated as a pathogen in bronchoalveolar lavage (BAL) specimens collected from such patients. Aims and Rationale of the Study: The present study is aimed at assessing the spectrum of the bacterial isolates and determining the antimicrobial resistance obtained from the BAL fluid from admitted patients at various wards and intensive care units (ICUs) of a tertiary care hospital in Dehradun.This will be the stepping stone in our efforts toward becoming a future antimicrobial steward and framing local antibiograms based on such data. Material and Methods: Two hundred BAL specimens were collected from patients admitted to various wards and ICUs of the hospital who were suffering from LRTI. The BAL specimens were subjected to direct microscopy and culture. Identification and susceptibility testing were performed. Results: The most predominant isolates were Pseudomonas aeruginosa (16/39 (41.02%)) followed by Klebsiella pneumoniae (7/39 (17.94%)) and Acinetobacter spp. (6/39 (15.38%)). Sixty-five percentage of Pseudomonas aeruginosa, 71% of Klebsiella pneumoniae, and 83% of Acinetobacter spp. showed intermediate results with colistin. Conclusion: Nonfermenters constitute a significant group of organisms isolated from bronchoalveolar lavage (BAL) specimens in patients with lower respiratory tract infections (LRTIs). Hence, it is extremely important to correctly identify and determine the resistance pattern of such isolates so that appropriate empirical therapy can be initiated for the benefit of the patient. [ABSTRACT FROM AUTHOR]

Background Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT. Methods Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months. Results 227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count. Conclusions HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background The mortality and morbidity rates in children with lower respiratory tract infection (LRTI) remain high. Objective To describe the number of bacteria that is associated with leukocytes in differential diagnosis of bacterial, mycoplasma, and viral LRTI in children. Methods Sputum smears were Gram stained for counting single-morphology bacteria associated with leukocytes. The differential diagnostic values of bacterial number were assessed in children with LRTI. Results The area under the receiver operating characteristic (ROC) curve was 0.95 for bacterial number in the differential diagnosis of bacterial infection from mycoplasma and viral infections. The area under the ROC curve was 0.62 for procalcitonin and 0.94 for bacterial number in the differential diagnosis of bacterial infection from mycoplasma infection. Conclusion The number of bacteria associated with leukocytes in sputum was valuable and rapid in differential diagnosis of bacterial infection in children with suspected bacterial, mycoplasma, and viral LRTI. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections (LRTIs) are one of the most common causes of hospitalization among children in the early childhood period. Knowing the pathogens that cause pneumonia, its management will be more exact and effective. In this study, we aimed to investigate the frequency of pathogens causing LRTIs in children at the end of the COVID-19 pandemic by performing a real-time multiplex polymerase chain reaction (RT-MPCR) test within our hospital. We included two hundred forty-seven children, aged between 1 month and 18 years, diagnosed with LRTIs, and hospitalized between May 2021 and April 2022. Demographic characteristics and clinical and laboratory findings were retrospectively collected from patients' hospital records. Of the 247 children diagnosed with LRTIs, 153 (61.9%) were female. At least one pathogen was identified in the nasopharyngeal swap specimens of 218 (88.3%) patients, and 74.9% (n=185) of them were viruses. The most common identified pathogens were respiratory syncytial virus (24.7%), human bocavirus (21.1%), and severe acute respiratory syndrome coronavirus 2 (15.4%). 7.7% of identified pathogens were bacteria. Haemophilus influenzae was the most commonly detected bacteria. Despite a lengthy period of isolating the community causative agents of pneumonia, their frequency remains unchanged from before the isolation time. RT-MPCR is beneficial for the early detection of pathogens and in the prevention of unnecessary antibiotic usage. [ABSTRACT FROM AUTHOR]

Background: Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). Methods: This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. Results: From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. Conclusions: In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. Trial registration: This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have reported the association between gut microbiota and the risk of lower respiratory tract infections (LRTIs). However, whether the association reflects a causal relationship remains obscure. Methods: A bidirectional twosample Mendelian randomization (MR) analysis was conducted by assessing genome-wide association study (GWAS) summary statistics for gut microbiota taxa and five common LRTIs. MR methods including inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode were used to analyze the causality. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. Cochran’s Q test was used to check for heterogeneity. Leave-one-out analysis was used to assess the stability of effect sizes. Detected significant associations were validated by using an independent LRTI GWAS summary statistics dataset. An optional MR method of causal analysis using summary effect estimates (CAUSE) was further performed as a validation to avoid potential false-positive results. Results: According to the MR-Egger estimates in forward MR analysis, a causal effect of gut Blautia on increased odds of bronchiectasis and pneumonia was suggested. MR-Egger regression pleiotropy intercept methods detected no significant horizontal pleiotropy between the instrumental variables of these associations. MR-PRESSO global test examined no potential horizontal pleiotropy. Cochran’s Q test showed that no heterogeneity biased the results. The leaveone-out sensitivity analyses suggested robust causality results. These associations with consistent effect direction were successfully replicated in IVW analysis by using the validation GWAS dataset. However, these evidence of causality did not survive after applying strict Bonferroni correction or CAUSE analysis. The reverse MR analysis failed to achieve consistent results in the effect of LRTIs on gut microbiota through comprehensive discovery and validation processes. Discussion: This study established no strong causality between genetically predicted gut microbiome and the risk of lower respiratory tract infections. However, specific subtypes of microbial genera, such as Blautia, were identified as potential influencers and require further investigation, particularly at the species or strain levels. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections (LRTIs) represent some of the most globally prevalent and detrimental diseases. Metagenomic next-generation sequencing (mNGS) technology has effectively addressed the requirement for the diagnosis of clinical infectious diseases. This study aimed at identifying and classifying opportunistic pathogens from the respiratory tract-colonizing microflora in LRTI patients using data acquired from mNGS analyses. A retrospective study was performed employing the mNGS data pertaining to the respiratory samples derived from 394 LRTIs patients. Linear discriminant analysis effect size (LEfSe) analysis was conducted to discern the discriminant bacteria. Receiver operating characteristic curves (ROC) were established to demonstrate discriminant bacterial behavior to distinguish colonization from infection. A total of 443 discriminant bacteria were identified and segregated into three cohorts contingent upon their correlation profiles, detection frequency, and relative abundance in order to distinguish pathogens from colonizing microflora. Among them, 119 emerging opportunistic pathogens (cohort 2) occupied an average area under the curve (AUC) of 0.976 for exhibiting the most prominent predictability in distinguishing colonization from infection, 39 were colonizing bacteria (cohort 1, 0.961), and 285 were rare opportunistic pathogens (cohort 3, 0.887). The LTRIs patients appeared modular in the form of cohorts depicting complex microbial co-occurrence networks, reduced diversity, and a high degree of antagonistic interactions in the respiratory tract microbiome. The study findings indicate that therapeutic interventions should target interaction networks rather than individual microbes, providing an innovative perspective for comprehending and combating respiratory infections. Conclusively, this study reports a profile of LRTIs-associated bacterial colonization and opportunistic pathogens in a relatively large-scale cohort, which might serve as a reference panel for the interpretation of mNGS results in clinical practice.

Objective: This study investigated the microbiological characteristics of severe lower respiratory tract infection patients not respond to initial treatment, and were transferred to a tertiary-level hospital. Material and Methods: This was a multicenter, prospective study conducted across four hospitals: Cho Ray, Pham Ngoc Thach, Gia Dinh People’s Hospital, and Can Tho Central General Hospital. Sputum specimens were collected shortly after admission and subjected to culture and real-time PCR testing. Results: Out of the 252 patients, 170 (67.4%) met the criteria for analysis and identification of pathogenic microorganisms. The most frequently isolated pathogens were Streptococcus pneumoniae (S. pneumonia) and Haemophilus influenzae (H. influenzae), comprising of 27.0% and 13.1%, respectively. Antibiotic susceptibility testing was conducted on 55 patients (32.3%). Among these cases, there were 16 instances of S. pneumoniae, 10 cases of Staphylococcus aureus (S. aureus), 10 cases of Pseudomonas aeruginosa (P. aeruginosa), 14 cases of gram-negative enteric bacteria, 2 cases of H. influenzae, 1 case of Moraxella catarrhalis (M. catarrhalis), 1 case of Enterococcus faecium, and 1 case of M. pneumoniae. The antibiogram results revealed significant findings; including a 70% prevalence of extended-spectrum beta-lactamase and 90% occurrence of Methicillin-Resistant Staphylococcus aureus. The data also indicated high resistance rates; such as 90% resistance to erythromycin, 40-80% to ciprofloxacin, 30-80% to ceftazidime, and 30-40% to imipenem. Conclusion: Pathogens associated with LRTIs referred from primary care hospitals encompass S. pneumonia, H. influenza, and S. aureus. At our facility, piperacillin, imipenem, amikacin, vancomycin, and linezolid emerged as the most effective antibiotics for addressing these LRTIs.

Background. The COVID‐19 pandemic resulted in the implementation of strict public health and social measures (PHSMs) (including mobility restrictions, social distancing, mask‐wearing and hand hygiene), limitations on non‐essential healthcare services, and public fear of COVID‐19 infection, all of which potentially affected transmission and healthcare use for other diseases such as lower respiratory tract infections (LRTIs). Objective. To determine changes in LRTI hospital admissions and in‐facility mortality in children aged

Background. Globally, pneumonia is one of the major cause of mortality and morbidity in children aged below 5 years. Lung ultrasonography (LUS) may become the next line investigation of choice before CXR and CT. Researchers have investigated the idea of employing LUS to diagnose pneumonia. Aim. To evaluate the findings of LUS in children with pneumonia and to correlate LUS findings with clinical and etiological findings in children. Methods. Study conducted in 100 children with chronic cough and fast breathing. All children undergone LUS within 24 hrs, and the data was correlated between clinical indicators and ultrasound proven pneumonia. The ROC (receiver operating characteristic curve) was drafted to estimate the cut-off values for respiratory, and laboratory variables. Results. 44% had positive LUS results. The presence of sensitivity with 88.5%, 77.45%, 95.4%, 81.6%, 79.4%, 70.45%, 84.25%, and 86.25% for the presence of fever, refusal of feeds/fluids, temperature 380C, oxygen saturation 95%, nasal flaring, grunting, chest retractions, and crepitation in children to predict the pneumonia. Leukocytosis appeared in 60% and CRP positive in 24% children. Grunting had the highest specificity of 94.66%. Chest x-ray identified 40% of pneumonia cases, while LUS identified 44% pneumonia cases. LUS had a sensitivity of 0.895 and a specificity of 0.66, and CXR had a sensitivity of 0.855 and a specificity of 0.60 to detect pneumonia. Conclusions. LUS cannot be used a sole diagnostic tool in childhood pneumonia, but it has role in the detection of complications. LUS has higher diagnostic accuracy than CXR for pneumonia diagnosis.

Cefodizime is a third–generation cephalosporin for parenteral use that has become available for the first time in the Russia. This paper reviews the use of this antibiotic in clinical practice based on the current data on antimicrobial resistance in pathogens causing lower respiratory tract infections and the results of completed clinical studies of its efficacy and safety.

Abstract Background Sleep apnea is associated with chronic comorbidities and acute complications. Existing data suggest that sleep apnea may predispose to an increased risk and severity of respiratory tract infections. Methods We investigated the incidence of lower respiratory tract infections in the first and second year before and after diagnosis of sleep apnea in a Finnish nationwide, population-based, retrospective case–control study based on linking data from the national health care registers for primary and secondary care from 2015–2019. Controls were matched for age, sex, hospital district, and multimorbidity status. We furthermore analysed the independent effect of comorbidities and other patient characteristics on the risk of lower respiratory tract infections, and their recurrence. Results Sleep apnea patients had a higher incidence of lower respiratory tract infections than their matched controls within one year before (hazard ratio 1.35, 95% confidence interval 1.16–1.57) and one year after (hazard ratio1.39, 95% confidence interval1.22–1.58) diagnosis of sleep apnea. However, we found no difference in the incidence of lower respiratory tract infections within the second year before or after diagnosis of sleep apnea in comparison with matched controls. In sleep apnea, history of lower respiratory tract infection prior to sleep apnea, multimorbidity, COPD, asthma, and age greater than 65 years increased the risk of incident and recurrent lower respiratory tract infections. Conclusions Sleep apnea patients are at increased risk of being diagnosed with a lower respiratory tract infection within but not beyond one year before and after diagnosis of sleep apnea. Among sleep apnea patients, chronic comorbidities had a significant impact on the risk of lower respiratory tract infections and their recurrence.

Community-acquired pneumonia is among the most common lower respiratory infections. The main etiological factors of lower respiratory infections are bacteria, viruses, and combinations. Pediatricians are increasingly faced with the problem of treating patients with infections caused by multidrug-resistant bacteria and viral lung infections; therefore, differential diagnosis of viral and bacterial lung infections in children is relevant. Significant progress has been made in diagnosing, treating, and preventing pneumonia in children; however, some issues require improvement in approaches to the differential diagnosis of lung infections in children. The paper aims to familiarize healthcare providers with modern principles of differential diagnosis and treatment of lung infections in children.

Abstract Background Lower respiratory tract infections (LRTIs) are a major cause of morbidity and mortality in children worldwide and disproportionally affect Sub-Saharan Africa. Despite the heaviest burden of LRIs in Ethiopia, to date, no published studies have reported a comprehensive viral etiology of LRTIs among children in Ethiopia. The objective of this study was to determine and estimate the etiological contribution of respiratory viruses to LRTIs in