Understanding patient demand for and use of antibiotics for upper respiratory tract infection: A qualitative application of the Necessity-Concerns Framework in Saudi Arabia.

Background: Reducing antimicrobial resistance (AMR) is a priority for public health. Inappropriate patient demand is an important driver of unnecessary antibiotic use. To develop an effective intervention to reduce inappropriate demand for antibiotics in upper respiratory tract infections (URTIs), it is important to identify patient perceptions that influence demand for, and appropriate use of antibiotics. Aim: To identify and describe the beliefs about antibiotics necessity and concerns that patients with URTIs have, in Riyadh, Saudi Arabia. Method: An exploratory qualitative approach was used. One-to-one, face-to-face or telephone semi-structured interviews were conducted with participants recruited using purposive sampling (based on age and gender) from primary healthcare centre in Riyadh, Saudi Arabia were conducted. Only adult patients who currently experience URTIs symptoms and agreed to participate were recruited. Recruitment for interviews continued until data saturation point was reached. The interview guide explored patients' necessity beliefs and concerns about antibiotics, AMR perceptions, and expectations from URTIs consultation. Interview transcripts were coded using QSR NVivo 12 using framework analysis informed by the Necessity-Concerns Framework to identify key motivations driving antibiotic requests and consultations. Results: the study interviewed 32 participants (44% were male, average age was 36.84). Results identified that the patients often relate their personal need for antibiotics when encountering an URTIs symptoms to the type, severity and duration of symptoms. Patients also linked antibiotics with quicker recovery, generally expressing few concerns about antibiotics mainly because of its short duration of use. However, some conveyed their concern about frequent administration of antibiotics and effect on the body's immune system function, which may make them more prone to infections in the future. Participants varied widely in their awareness of AMR; this was associated with many misconceptions, such as confusing AMR with antibiotics efficacy and tolerance. Interestingly, the interplay between necessity beliefs and concerns was observed to influence the decision to start and stop antibiotic, potentially impacting inappropriate antibiotic demand and unnecessary use. Conclusion: This study highlighted important beliefs and misconceptions about antibiotics and AMR in Saudi population which can be targeted in future interventions to reduce inappropriate demand for antibiotics and optimise appropriate usage.

Is there evidence to support probiotic use for healthy people?

Probiotics are typically marketed as foods and dietary supplements, categories for products intended to maintain health in generally healthy populations and which, unlike drugs, cannot claim to treat or cure disease. This review addresses the existing evidence that probiotics are beneficial to healthy people. Our approach was to perform a descriptive review of efficacy evidence that probiotics can prevent urinary, vaginal, gastrointestinal, and respiratory infections, and improve risk factors associated with cardiovascular health or reduce antibiotic use. Other endpoints such as mental, dental or immune health were not specifically addressed. We concluded that there is sufficient evidence of efficacy and safety for clinicians and consumers to consider using specific probiotics for some indications - such as use probiotics to support gut function during antibiotic use - for certain people. However, we did not find a high level of evidence to support recommendations for other endpoints we reviewed for healthy people. Although evidence for some indications is suggestive of preventive benefits of probiotics, additional research is needed.

A Nationwide Online Tracking System of pediatric ICU demand and capacity during a respiratory epidemic in Uruguay / Desarrollo de un Sistema Nacional de Monitoreo En Línea de Capacidad y Demanda de las Unidades de Cuidados Intensivos Pediátricas Durante Una Epidemia Respiratoria

Monitoring national capacity of pediatric intensive care (PICU) beds is important for resource allocation. We describe the development and application of an online tool for bed occupancy monitoring during the respiratory epidemic of 2023 in Uruguay. A 5-minute survey was sent out daily to each PICU designated staff utilizing an instant messaging application, throughout the 12-week of 2023 winter season. The survey gathered information on staffed bed capacity, occupancy rates, invasive mechanical ventilation (IMV) demand and number of children admitted for lower respiratory tract infections (LRTIs). Data was manually entered using the REDcap Software platform. A comparison between PICUs from the capital city Montevideo (MVD) and the inland region (INN) was performed. Participating PICUs had access to a daily dashboard with nationwide data. We collected data from 100% (n=20) of Uruguayan PICUs, 68% in MVD (2.72 PICU beds per-10,000 <18 years) and 32% in the INN (0.86 PICU beds per-10,000 <18 years). National average bed occupancy rate was 55.5%, without differences between MVD and INN. However, LRTI admissions and IMV incidence were notably higher among INN PICUs compared with MVD PICUs, 83.0% vs. 71% (P<0.01) and 19.9% vs. 14.7% (P<0.01) respectively. During one week occupancy exceeded 80% without differences between MVD and INN. The implementation of a nationwide PICU bed monitoring tool was possible. Although occupancy rates did not reach critical levels at a national grade, regional differences were found that merit further study to improve vital PICUs resource allocation.

Monitorear la capacidad nacional de camas de cuidados intensivos pediátricos (UCIP) es importante para la asignación de recursos. Describimos el desarrollo y aplicación de una herramienta online para el seguimiento de la ocupación de camas durante la epidemia respiratoria de 2023 en Uruguay. Se envió diariamente una encuesta de 5 minutos a cada personal designado de la UCIP mediante una aplicación de mensajería instantánea, durante las 12 semanas de la temporada de invierno de 2023. La encuesta recopiló información sobre la capacidad de camas con personal, las tasas de ocupación, la demanda de ventilación mecánica invasiva (IMV) y el número de niños admitidos por infecciones del tracto respiratorio inferior (LRTI). Los datos se ingresaron manualmente utilizando la plataforma del software REDcap. Se realizó una comparación entre UCIP de la capital Montevideo (MVD) y del interior (INN). Las UCIP participantes tuvieron acceso a un panel diario con datos a nivel nacional. Se recolectaron datos del 100% (n=20) de las UCIP uruguayas, el 68% en MVD (2,72 camas UCIP por 10.000 <18 años) y el 32% en el INN (0,86 camas UCIP por 10.000 <18 años). La tasa de ocupación de camas promedio nacional fue del 55,5%, sin diferencias entre MVD e INN. Sin embargo, los ingresos por LRTI y la incidencia de IMV fueron notablemente mayores entre las UCIP INN en comparación con las UCIP MVD, 83,0% frente a 71% (P<0,01) y 19,9% frente a 14,7% (P<0,01), respectivamente. Durante una semana la ocupación superó el 80% sin diferencias entre MVD y INN. Fue posible implementar una herramienta de monitoreo de camas UCIP a nivel nacional. Aunque las tasas de ocupación no alcanzaron niveles críticos a nivel nacional, se encontraron diferencias regionales que merecen más estudios para mejorar la asignación de recursos vitales de las UCIP.

The diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients with respiratory tract infections.

Metagenomic next-generation sequencing (mNGS) is an unbiased and rapid method for detecting pathogens. This study enrolled 145 suspected severe pneumonia patients who were admitted to the Affiliated Hospital of Jining Medical University. This study primarily aimed to determine the diagnostic performance of mNGS and conventional microbiological tests (CMTs) using bronchoalveolar lavage fluid samples for detecting pathogens. Our findings indicated that mNGS performed significantly higher sensitivity (97.54% vs 28.68%, P < 0.001), coincidence (90.34% vs 35.17%, P < 0.001), and negative predictive value (80.00% vs 13.21%, P < 0.001) but performed lower specificity than CMTs (52.17% vs 87.5%, P < 0.001). Streptococcus pneumoniae as the most common bacterial pathogen had the largest proportion (22.90%, 30/131) in this study. In addition to bacteria, fungi, and virus, mNGS can detect a variety of atypical pathogens such as Mycobacterium tuberculosis and non-tuberculous. Mixed infections were common in patients with severe pneumonia, and bacterial-fungal-viral-atypical pathogens were the most complicated infection. After adjustments of antibiotics based on mNGS and CMTs, the clinical manifestation improved in 139 (95.86%, 139/145) patients. Our data demonstrated that mNGS had significant advantage in diagnosing respiratory tract infections, especially atypical pathogens and fungal infections. Pathogens were detected timely and comprehensively, contributing to the adjustments of antibiotic treatments timely and accurately, improving patient prognosis and decreasing mortality potentially.IMPORTANCEMetagenomic next-generation sequencing using bronchoalveolar lavage fluid can provide more comprehensive and accurate pathogens for respiratory tract infections, especially when considering the previous usage of empirical antibiotics before admission or complicated clinical presentation. This technology is expected to play an important role in the precise application of antimicrobial drugs in the future.

Prevalence of Haemophilus influenzae in the nasopharynx of children from regions with varying incidence of invasive H. influenzae serotype a disease: Canadian Immunization Research Network (CIRN) study.

Haemophilus influenzae serotype a (Hia) has recently emerged as an important cause of invasive disease in the North American Arctic and Sub-Arctic regions, mainly affecting young Indigenous children. In this study, we addressed the question of whether the prevalence of Hia and all H. influenzae in the nasopharynx differed between paediatric populations from regions with high versus low incidence of invasive Hia disease. Nasopharyngeal specimens from children with acute respiratory tract infections (ARTI) collected for routine diagnostic detection of respiratory viruses were analysed with molecular-genetic methods to identify and serotype H. influenzae. In Nunavut, a region with a high incidence of invasive Hia disease, all H. influenzae and particularly Hia were found in the nasopharynx of 60.6% and 3.0% children. In Southern Ontario (Hamilton region), where Hia invasive disease is rare, the frequencies of all H. influenzae and Hia detection were 38.5% and 0.6%, respectively. In both cohorts, non-typeable H. influenzae was prevalent (57.0% and 37.9%, respectively). Considering that Hia is an important cause of severe invasive disease in Nunavut children, 3% prevalence of Hia among children with ARTI can reflect continuing circulation of the pathogen in the Northern communities that may result in invasive disease outbreaks.

How to protect long-term care facilities from pandemic-like events? - A systematic review on the effectiveness of non-pharmacological measures to prevent viral respiratory infections.

BACKGROUND: The SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long-term care facilities (LTCFs) are a high-risk setting with severe outbreaks and burden of disease. Non-pharmacological interventions (NPIs) constitute the primary defence mechanism when pharmacological interventions are not available. However, evidence on the effectiveness of NPIs implemented in LTCFs remains unclear. METHODS: We conducted a systematic review assessing the effectiveness of NPIs implemented in LTCFs to protect residents and staff from viral respiratory pathogens with pandemic potential. We searched Medline, Embase, CINAHL, and two COVID-19 registries in 09/2022. Screening and data extraction was conducted independently by two experienced researchers. We included randomized controlled trials and non-randomized observational studies of intervention effects. Quality appraisal was conducted using ROBINS-I and RoB2. Primary outcomes encompassed number of outbreaks, infections, hospitalizations, and deaths. We synthesized findings narratively, focusing on the direction of effect. Certainty of evidence (CoE) was assessed using GRADE. RESULTS: We analysed 13 observational studies and three (cluster) randomized controlled trials. All studies were conducted in high-income countries, all but three focused on SARS-CoV-2 with the rest focusing on influenza or upper-respiratory tract infections. The evidence indicates that a combination of different measures and hand hygiene interventions can be effective in protecting residents and staff from infection-related outcomes (moderate CoE). Self-confinement of staff with residents, compartmentalization of staff in the LTCF, and the routine testing of residents and/or staff in LTCFs, among others, may be effective (low CoE). Other measures, such as restricting shared spaces, serving meals in room, cohorting infected and non-infected residents may be effective (very low CoE). An evidence gap map highlights the lack of evidence on important interventions, encompassing visiting restrictions, pre-entry testing, and air filtration systems. CONCLUSIONS: Although CoE of interventions was low or very low for most outcomes, the implementation of NPIs identified as potentially effective in this review often constitutes the sole viable option, particularly prior to the availability of vaccinations. Our evidence-gap map underscores the imperative for further research on several interventions. These gaps need to be addressed to prepare LTCFs for future pandemics. TRIAL REGISTRATION: CRD42022344149.

Parental Concerns for Children With Cold-like Symptoms With Reduced Access to Evaluation in Primary Care Settings During the COVID-19 Pandemic: A Qualitative Study.

INTRODUCTION: We aimed to explore the concerns of parents when their children had symptoms of infection during the COVID-19 pandemic. METHOD: Two Norwegian internet forums were searched for parents' experiences when their children had upper respiratory infection symptoms in 2020-2021. A total of 197 posts were included and analyzed using thematic analysis. RESULTS: Parents described COVID-19-related and general worries regarding their children with upper respiratory infection symptoms. The first theme, "It is not 'just a cold' during the pandemic," captures how infection control measures influenced parents' concerns. The second theme, "Concerns and consequences of fever and cold symptoms," describes general parental worries. Varying levels of worries regarding health care services, limitations of family life, and concerns for relatives were highlighted. DISCUSSION: Knowledge of parents' concerns about cold symptoms may help primary health care providers target individual patient counseling and provide background information when policymakers develop information material for infection prevention and treatment.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Early family socioeconomic status and asthma-related outcomes in school-aged children: Results from seven birth cohort studies.

OBJECTIVE: To examine the associations between maternal education and household income during early childhood with asthma-related outcomes in children aged 9-12 years in the UK, the Netherlands, Sweden, Australia, the USA and Canada. METHODS: Data on 31 210 children were obtained from 7 prospective birth cohort studies across six countries. Asthma-related outcomes included ever asthma, wheezing/asthma attacks and medication control for asthma. Relative social inequalities were estimated using pooled risk ratios (RRs) adjusted for potential confounders (child age, sex, mother ethnic background and maternal age) for maternal education and household income. The Slope Index of Inequality (SII) was calculated for each cohort to evaluate absolute social inequalities. RESULTS: Ever asthma prevalence ranged from 8.3% (Netherlands) to 29.1% (Australia). Wheezing/asthma attacks prevalence ranged from 3.9% (Quebec) to 16.8% (USA). Pooled RRs for low (vs high) maternal education and low (vs high) household income were: ever asthma (education 1.24, 95% CI 1.13 to 1.37; income 1.28, 95% CI 1.15 to 1.43), wheezing/asthma attacks (education 1.14, 95% CI 0.97 to 1.35; income 1.22, 95% CI 1.03 to 1.44) and asthma with medication control (education 1.16, 95% CI 0.97 to 1.40; income 1.25, 95% CI 1.01 to 1.55). SIIs supported the lower risk for children with more highly educated mothers and those from higher-income households in most cohorts, with few exceptions. CONCLUSIONS: Social inequalities by household income on the risk of ever asthma, wheezing/asthma attacks, and medication control for asthma were evident; the associations were attenuated for maternal education. These findings support the need for prevention policies to address the relatively high risks of respiratory morbidity in children in families with low socioeconomic status.

Exploring the Impact of Antibiotics on Fever Recovery Time and Hospital Stays in Children with Viral Infections: Insights from Advanced Data Analysis.

Background: Antibiotic overuse in pediatric patients with upper respiratory tract infections (UR-TIs) raises concerns about antimicrobial resistance. This study examines the impact of antibiotics on hospital stay duration and fever resolution in pediatric patients diagnosed with viral infections via a multiplex polymerase chain reaction (PCR) respiratory panel. Methods: In the pediatric ward of Imam Abdulrahman Bin Faisal Hospital, a retrospective cohort analysis was conducted on pediatric patients with viral infections confirmed by nasopharyngeal aspirates from October 2016 to December 2021. Cohorts receiving antibiotics versus those not receiving them were balanced using the gradient boosting machine (GBM) technique for propensity score matching. Results: Among 238 patients, human rhinovirus/enterovirus (HRV/EV) was most common (44.5%), followed by respiratory syncytial virus (RSV) (18.1%). Co-infections occurred in 8.4% of cases. Antibiotic administration increased hospital length of stay (LOS) by an average of 2.19 days (p-value: 0.00). Diarrhea reduced LOS by 2.26 days, and higher albumin levels reduced LOS by 0.40 days. Fever and CRP levels had no significant effect on LOS. Time to recovery from fever showed no significant difference between antibiotic-free (Abx0) and antibiotic-received (Abx1) groups (p-value: 0.391), with a hazard ratio of 0.84 (CI: 0.57-1.2). Conclusions: Antibiotics did not expedite recovery but were associated with longer hospital stays in pediatric patients with acute viral respiratory infections. Clinicians should exercise caution in prescribing antibiotics to pediatric patients with confirmed viral infections, especially when non-critical.

Model-based disease mapping using primary care registry data.

BACKGROUND: Spatial modeling of disease risk using primary care registry data is promising for public health surveillance. However, it remains unclear to which extent challenges such as spatially disproportionate sampling and practice-specific reporting variation affect statistical inference. METHODS: Using lower respiratory tract infection data from the INTEGO registry, modeled with a logistic model incorporating patient characteristics, a spatially structured random effect at municipality level, and an unstructured random effect at practice level, we conducted a case and simulation study to assess the impact of these challenges on spatial trend estimation. RESULTS: Even with spatial imbalance and practice-specific reporting variation, the model performed well. Performance improved with increasing spatial sample balance and decreasing practice-specific variation. CONCLUSION: Our findings indicate that, with correction for reporting efforts, primary care registries are valuable for spatial trend estimation. The diversity of patient locations within practice populations plays an important role.

Syndromic case definitions for lower respiratory tract infection (LRTI) are less sensitive in older age: an analysis of symptoms among hospitalised adults.

BACKGROUND: Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (< 65y). METHODS: We included adults (≥ 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥ 65y reduced the probability of meeting syndromic LRTI case definitions, using patients' symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. RESULTS: Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. After controlling for sex, dementia and comorbidities, age ≥ 65y significantly reduced the probability of meeting the case definition (aOR = 0.67, 95% CI:0.63-0.71). Cases aged ≥ 65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥ 85y were characterised by lack of cough but frequent confusion and falls. CONCLUSIONS: LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.

Integrative analyses identify opportunistic pathogens of patients with lower respiratory tract infections based on metagenomic next-generation sequencing.

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.

An In Vitro Study on the Antibacterial Activity of Statins Against the Most Common Bacterial Pathogens Causing Respiratory Tract Infections in a Tertiary Care Hospital.

Introduction The vast pleiotropic effect of statins has intrigued many researchers to select them as potential candidates against bacterial infections. The role of statins against bacterial pathogens remains debatable. This study was undertaken to evaluate and compare the antibacterial effect of commonly available statins against the most frequently isolated bacterial pathogens causing respiratory tract infections in our tertiary care hospital using sputum as a sample. Materials and methods The study was conducted in the Microbiology Laboratory of our hospital. Drugs including atorvastatin, rosuvastatin, and simvastatin were purchased in pure form from Sigma Aldrich. Dimethylsulfoxide (DMSO) was used as a solvent for all three drugs. The positive controls used were gentamycin and amoxicillin for Gram-negative and Gram-positive bacteria, respectively. Data regarding all the culture and sensitivity results of sputum samples of patients admitted to the Respiratory Intensive Care Unit over the past 12 months were analyzed. The most common bacterial pathogens Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae isolated from sputum specimens were taken for our study. The antibacterial effect of statins was studied using two methods: the agar cup diffusion method and the broth dilution method. The zone of inhibition and minimum inhibitory concentration of the drugs were calculated and analyzed. Statistical analysis was performed using GraphPad Prism software version 10.2.0. A one-way ANOVA test was used to determine if there was any statistical difference between the different statins and antibiotic groups. An unpaired t-test was used to determine the statistical difference between the statins. Results and discussion For the agar cup diffusion method, our results displayed a lack of antibacterial activity of all three statins atorvastatin, rosuvastatin, and simvastatin against all three bacterial strains Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae after overnight incubation by agar cup method at concentrations of 3.125 µg/ml, 6.25 µg/ml, 12.5 µg/ml, 25 µg/ml and 50 µg/ml, respectively. The zone of inhibition observed was less than 4 mm (resistant) for all the serial dilutions of atorvastatin, rosuvastatin, and simvastatin. For the broth dilution method, the ANOVA test showed amoxicillin and gentamicin to have high statistically significant microbial growth inhibitory activity (p-value < 0.005) compared to atorvastatin and rosuvastatin. Statistically, though atorvastatin showed significant antimicrobial activity compared to normal saline and rosuvastatin, this was not considered clinically significant as the antimicrobial activity shown by atorvastatin was very negligible compared to the controls used and did not correspond to the serial dilutions of the drug.  Conclusion Atorvastatin, rosuvastatin, and simvastatin lacked antibacterial activity against all three bacterial strains isolated from sputum specimens: Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae. Hence, the use of statins as an antimicrobial drug for respiratory tract infections has limited applications.

At Early Rheumatoid Arthritis Stage, the Infectious Spectrum Is Driven by Non-Familial Factors and Anti-CCP Immunization.

Background/Objectives: Patients with rheumatoid arthritis (RA) are prone to develop infections. Methods: Accordingly, 195 untreated early (e)RA patients and 398 healthy controls were selected from women in Tatarstan's cohort to study infectious history in the anamnesis (four criteria) and in the previous year (16 criteria). Information about annual infections was collected face-to-face from year to year by a qualified rheumatologist/general practitioner and included the active use of information from medical records. Results: In the anamnesis, tuberculosis, and pneumonia, and in the previous year, respiratory tract infections, skin infections, and herpes simplex virus reactivation incidence were reported to be increased in eRA patients, as well as the event number and duration of acute and chronic tonsillitis. Moreover, more bacterial-suspected upper respiratory infections and urinary tract infections were retrieved in sporadic eRA patients as compared to familial eRA patients. An elevated immunization against CCP prevented respiratory tract infection in those with HSV exacerbation. Finally, associations were retrieved between infection (event number/delay) and RA indices: (i) chronic tonsillitis exacerbations with disease activity and health assessment (HAQ) in familial eRA; (ii) bacterial-suspected upper respiratory infections with the number of swollen and tender joints in sporadic eRA; and (iii) HSV exacerbation with inflammation in eRA patients with negative/low response against CCP. Here, we demonstrate the complex nature of the interplay of RA with specific infections. Conclusions: For the first time, differences in the patterns of annual trivial infections and their links with RA indices were found in cohorts of familial and sporadic cases of the disease. Additionally, for the first time, we identified a remarkable relationship between early RA and exacerbations of chronic tonsillitis, as well as tuberculosis in the patient's history. Altogether, this study supports the existence of a complex interplay between infections and RA at onset driven by familial status and the presence of anti-CCP Ab at elevated levels.

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives.

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.

Individualized Supplementation of Immunoactive Micronutrients and Severity of Upper Respiratory Infection Symptoms-A Randomized Intervention Study.

Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of individualized supplementation on the severity of upper respiratory tract infections (URIs). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin D were measured in dried blood spots from 59 healthy participants. Accordingly, a personalized supplement was provided with or without the respective micronutrients. We used WURSS-21 questionnaires to assess the disease status. The blood values converged during the intervention and micronutrients no longer differed between treated and untreated volunteers at the end of the intervention period. The incidence and severity of the illness did not significantly differ between the groups. However, when analyzing the WURSS-21 scores by the intention to treat, the initially randomized treatment arm revealed a significantly higher score than the placebo arm. Upon acute administration, individualized combinations of selenium, zinc and vitamin D do not reduce the number, or contribute to a milder course of URIs. Therefore, supplementation in acute infectious situations seems questionable. Further studies must address the habitual diet in more detail, to better understand the impact of individual micronutrient status on the prevention of URI.

Mycoplasma pneumoniae Outbreak in 2023: Post-pandemic Resurgence of an Atypical Bacterial Pathogen.

The syndromic nature of infections caused by pneumonia-causing pathogens including Mycoplasma pneumoniae necessitates detection via multiplex PCR for accurate and timely diagnosis to control the infection spread. In this study, we demonstrate an increase in the detection of M. pneumoniae in the outpatient population, during 2023, as compared to the previous two years (2021-2022). In this aggregated survey, respiratory samples collected within the continental United States were tested for the presence of M. pneumoniae and other respiratory bacterial and viral pathogens using a multiplex PCR assay. Patient data was analyzed on the basis of age, gender and geographical location. The positive detection of M. pneumoniae in 2021 and 2022 was 0.004% and 0.006%, respectively. The positivity rate of M. pneumoniae in 2023 increased to 0.21%. The highest proportion of M. pneumoniae cases were detected from Georgia with the outbreak generally concentrated in large urban settings. Median age of the patients testing positive for M. pneumoniae was 10 (interquartile range [IQR] 8-18) years with an almost equal distribution between male and female patients. Other respiratory, viral and bacterial, pathogens detected in samples positive for M. pneumoniae were similar in proportion to the M. pneumonia-negative population. A survey of the ICD-10 codes submitted in conjunction with the samples suggests that the current outbreak is mostly associated with upper respiratory tract infections. The present study is the first detailed report in the United States that shows an unprecedented increase in the detection of M. pneumoniae in the outpatient population during 2023. Our analysis suggests that this outbreak was not associated with any other bacterial or viral respiratory pathogen. The outbreak of this atypical pathogen was concentrated in the pediatric population in large urban areas. The 2023 outbreak could be a return of the cyclical M. pneumoniae outbreaks witnessed prior to the COVID-19 pandemic. Our study highlights the importance of performing continuous surveillance of respiratory pathogens, especially in the altered epidemiological landscape of the post-COVID world.

Assessment of Medical Test Overuse and Its Impact on Pediatric Emergency Department Outcomes in Upper Respiratory Tract Infections in a University Hospital in Lithuania.

Medical overuse poses potential risks to patients and contributes to increasing healthcare costs, pediatric emergency departments (PED) in particular. Often, upper respiratory tract infection (URTI) cases are viral-induced and self-limiting, and they do not require specific investigations or treatment. We conducted a retrospective study from 1 December 2021 to 31 January 2022, thereby aiming to identify the common tests and factors influencing specific diagnostic and treatment decisions for URTI in PED. In total, 307 (74.9%) URTI cases underwent complete blood count (CBC) tests, 312 (76.1%) were subjected to C-reactive protein (CRP) tests, and 110 (26.8%) received urinalysis tests. Patients with a longer duration of fever and a physician's suspicion of bacterial infection were more likely to receive CBC, CRP, and/or urinalysis tests (p < 0.05). Moreover, 75.1% of the cases were classified as viral URTIs, 9.8% were bacterial URTIs, and 15.1% were unspecified. Notably, 86 (20.1%) children received antibiotics and antibiotic prescription correlated with age, tonsillitis diagnosis, CRP values higher than 30 mg/L, and a CBC of p < 0.05. Patients triaged in the second or third categories were three times more likely to be observed for 24 h compared to patients with URTI and the fourth triage category (p < 0.05). This study highlights the need for interventions to improve the appropriateness of emergency service utilization, thereby emphasizing the importance of judicious decision making in managing pediatric URTIs.

Characteristics of children readmitted with severe pneumonia in Kenyan hospitals.

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.