Doxycycline with or without famciclovir for infectious ophthalmic and respiratory disease: a prospective, randomized, masked, placebo-controlled trial in 373 kittens.

OBJECTIVES: The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir. METHODS: Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation. RESULTS: For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery (P = 0.049) and clinical resolution (P = 0.030), but not ophthalmic recovery (P = 0.064) or ophthalmic resolution (P = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D (P = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D. CONCLUSIONS AND RELEVANCE: The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage.

[Comparative assessment of the clinical effectiveness of direct-acting antiviral drugs in outpatient patients with acute respiratory viral infections].

AIM: To evaluate the clinical effectiveness, safety and compare the incidence of hospitalization during treatment with antiviral drugs with a direct mechanism of action (riamilovir and umifenovir) in people with acute respiratory viral infections (ARVI) in an outpatient setting. MATERIALS AND METHODS: The study included 150 outpatients with ARVI aged 18-27 years: 50 patients received riamilovir 250 mg 3 times a day for 5 days, the second group included 50 patients who received umifenovir 200 mg 4 times a day for 5 days, 50 individuals received only pathogenetic treatment. RESULTS: The use of direct-acting antiviral drugs was characterized by the least severity of pain and aches in the body, general weakness, and in the group of patients receiving riamilovir, the lowest severity of rhinitis, cough, and the lowest morning body temperature were recorded compared to other groups. In riamilovir group reduction in the duration of the disease was observed. The lowest frequency of ARVI pathogens detection was observed on the 6th day in riamilovir group. Outpatient treatment with riamilovir was accompanied by a minimal number of cases of the disease requiring hospitalization. CONCLUSION: The use of direct antiviral drugs contributes to the rapid relief of ARVI symptoms in patients receiving medical care on an outpatient basis. The antiviral drug riamilovir showed the most pronounced effectiveness (clinical and laboratory).

The impact of a multi-faceted intervention on non-prescription dispensing of antibiotics by urban community pharmacies in Indonesia: a mixed methods evaluation.

INTRODUCTION: Non-prescription antibiotic dispensing is prevalent among community pharmacies in several low- and middle-income countries. We evaluated the impact of a multi-faceted intervention to address this challenge in urban community pharmacies in Indonesia. METHODS: A pre-post quasi-experimental study was carried out in Semarang city from January to August 2022 to evaluate a 7-month long intervention comprising: (1) online educational sessions for pharmacists; (2) awareness campaign targeting customers; (3) peer visits; and (4) pharmacy branding and pharmacist certification. All community pharmacies were invited to take part with consenting pharmacies assigned to the participating group and all remaining pharmacies to the non-participating group. The primary outcome (rate of non-prescription antibiotic dispensing) was measured by standardised patients displaying symptoms of upper respiratory tract infection, urinary tract infection (UTI) and seeking care for diarrhoea in a child. χ2 tests and multivariate random-effects logistic regression models were conducted. Thirty in-depth interviews were conducted with pharmacists, staff and owners as well as other relevant stakeholders to understand any persistent barriers to prescription-based dispensing of antibiotics. FINDINGS: Eighty pharmacies participated in the study. Postintervention, non-prescription antibiotics were dispensed in 133/240 (55.4%) consultations in the participating group compared with 469/570 (82.3%) in the non-participating group (p value <0.001). The pre-post difference in the non-prescription antibiotic dispensing rate in the participating group was 20.9% (76.3%-55.4%) compared with 2.3% (84.6%-82.3%) in the non-participating group (p value <0.001).Non-prescription antibiotics were less likely to be dispensed in the participating group (OR=0.19 (95% CI 0.09 to 0.43)) and more likely to be dispensed for the UTI scenario (OR=3.29 (95% CI 1.56 to 6.94)). Barriers to prescription-based antibiotic dispensing included fear of losing customers, customer demand, and no supervising pharmacist present. INTERPRETATION: Multifaceted interventions targeting community pharmacies can substantially reduce non-prescription antibiotic dispensing. Future studies to evaluate the implementation and sustainability of this intervention on a larger scale are needed.

Traditional Chinese Medicine in the treatment of recurrent respiratory tract infections in children: an overview of systematic reviews and Meta-analyses.

OBJECTIVE: To evaluate and summarise the evidence from published Meta-analyses/systematic reviews (MAs/SRs) of Traditional Chinese Medicine (TCM) in the treatment of recurrent respiratory tract infections (RRTIs) and to provide a scientific basis for the clinical treatment of RRTIs with TCM. METHODS: Studies were retrieved from Chinese and English databases including the China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, SinoMed, PubMed, Web of Science, the Cochrane Library and EMbase from their establishment date to March 2023. Involved studies were screened, extracted, and evaluated for quality by two researchers independently. The a measurement tool to assess systematic reviews (AMSTAR) 2 scale was used for methodological quality evaluation, as well as the preferred reporting items for systematic reviews and Meta-analyses (PRISMA) 2020 statement for report quality evaluation, the risk of bias in systematic reviews (ROBIS) tool for risk of bias, and the grading of recommendations, assessment, development and evaluation (GRADE) quality assessment tool for evidence quality. RESULTS: Twenty MAs/SRs studies were included, including analyses of 274 original studies involving 38 335 patients with RRTIs. The AMSTAR 2 scale evaluation results showed that 19 studies were of very low quality and one of moderate quality. The ROBIS evaluation results showed that 11 MAs/SRs were at high risk and nine at low risk of bias. The PRISMA 2020 report quality showed the included studies had scores between 23.5 and 35.5, among them one with high quality, 17 with moderate quality and two with low quality. The GRADE system results showed that among 126 outcome indicators, only 17 had moderate quality of evidence, 27 had low quality, 82 had very low quality, and none had high quality. CONCLUSIONS: The MAs/SRs methodological quality of using TCM for treatment RRTIs is generally poor, the quality of reports as well as of evidence is generally low, and the risk of bias is high; therefore we should treat these results with caution.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

BACKGROUND: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. METHODS: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. RESULTS: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). CONCLUSION: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Background: Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1 helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Methods: Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. Results: New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). Conclusion: OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Is There a Role for Immunostimulant Bacterial Lysates in the Management of Respiratory Tract Infection?

Bacterial Lysates are immunostimulants clinically prescribed for the prevention of respiratory tract infections (RTIs). It has been shown that Bacterial Lysates upregulate the immune system, acting both on innate and adaptive reactions. In fact, there are demonstrations of their efficacy in restoring the integrity and immune function of epithelial barriers, activating ILC3 and dendritic cells with an enhanced Th1 response, and producing serum IgG and serum and salivary IgA specific to the administered bacterial antigens. The activated immune system also protects against other bacteria and viruses due to a trained immunity effect. Most studies show that the number of RTIs and their severity decrease in Bacterial Lysates-pretreated patients, without relevant side effects. The Bacterial Lysates treatment, in addition to reducing the number of RTIs, also prevents the deterioration of the underlying disease (i.e., COPD) induced by repeated infections. Despite these positive data, the most recent meta-analyses evidence the weakness of the studies performed, which are of low quality and have an inadequate number of patients, some of which were non-randomized while others were without a control group or were performed contemporarily in different clinical conditions or with different ages. The high heterogeneity of the studies does not allow us to state Bacterial Lysates' effectiveness in preventing RTIs with sufficient certainty. To completely define their indications, double-blind, placebo-controlled, multicenter, randomized clinical trials should be performed for each product and for each indication. The study population should be adequate for each indication. For this purpose, an adequate run-in phase will be necessary.

Bacterial co-infections in cancer patients with COVID-19: predictors and antimicrobial resistance trends.

INTRODUCTION: Within the context of the coronavirus disease 2019 (COVID-19) pandemic, this study investigated the multifaceted challenges of bacterial infections in cancer patients with COVID-19. It focuses on clinical predictors, resistance patterns, and microbiological characteristics. METHODOLOGY: Over 18 months, 112 adult cancer patients with coronavirus infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) were enrolled. Bloodstream and respiratory samples were evaluated for bacterial infection using the Phoenix automation system for definitive species identification. In vitro susceptibility testing followed the Clinical Laboratory Standards Institute (CLSI) M100-Ed30 guidelines. RESULTS: Bacterial infections affected 25.0% of patients, encompassing bacteremia (21.4%) and respiratory tract infections (8.0%). Multivariable analysis identified hypertension, age < 60, and critical COVID-19 as significant predictors for bacterial infections (p-values = 0.024, 0.029, and 0.039, respectively). Most patients received antimicrobial therapy (93.8%), including last-resort carbapenems (52.7%) and colistin (8.9%). Thirty-three bacterial isolates were identified, with secondary infections doubling co-infection rates. Escherichia coli, Klebsiella species, and Staphylococcus aureus were the most common co-infecting species, while Klebsiella, Acinetobacter, and Pseudomonas species were more frequently associated with secondary infections. Alarmingly, 84.8% of isolates displayed high resistance patterns. All isolated S. aureus species were methicillin-resistant, and 62.5% of Gram-negative bacteria were exclusively sensitive to colistin. CONCLUSIONS: The dominance of highly transmissible hospital-acquired bacterial species, with increased resistance and extensive antibiotic use in COVID-19 patients, necessitates strict infection control and antimicrobial stewardship. Developing customized antimicrobial strategies for cancer patients with COVID-19 is crucial to managing bacterial infections effectively and improving patient outcomes.

[Primary ciliary dyskinesia associated with a novel DNAH11 genetic variant: a case report].

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder associated with abnormalities in ciliary structure and function. Here, we report A 22-year-old non-smoking Chinese man with recurrent episodes of respiratory tract infections and sinusitis since high school period. The diagnosis is more complicated by the atypical symptoms and the late age of onset. We summarized the clinical characteristics of this case and literature review. This report aimed to improve the clinical understanding of primary ciliary dyskinesia.

Advantages of metagenomic next-generation sequencing in the management of ANCA-associated vasculitis patients with suspected pulmonary infection as a rule-out tool.

OBJECTIVE: Pulmonary infection is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). It is sometimes difficult to differentiate pulmonary infection from pulmonary involvement of vasculitis in AAV patients. Fiberoptic bronchoscopy and bronchoalveolar lavage fluid (BALF) assays are useful diagnostic methods. In addition to conventional microbiological tests (CMTs), metagenomic next-generation sequencing (mNGS) facilitates rapid and sensitive detection of various pathogens. The current study aimed to evaluate the advantages of additional BALF mNGS in the management of pulmonary infection in AAV patients. METHODS: 27 patients with active AAV and suspected pulmonary infection whose BALF samples were tested by mNGS and CMTs and 17 active AAV patients whose BALF were tested by CMTs alone were retrospectively recruited. The results of microbiological tests, and adjustments of treatment following BALF mNGS, were described. The durations of antimicrobial treatment and in-hospital mortality in patients were compared. RESULTS: Among the 27 patients whose BALF samples were tested by mNGS, 25.9% of patients did not have evidence of pathogenic microorganism in their BALF samples, 55.6% had polymicrobial infections, including bacteria, fungi and viruses. Of these 27 patients, 40.7% did not have evidence of pathogenic microorganism in their BALF or serum samples according to CMTs. Patients in the BALF mNGS/CMT group received a significantly shorter duration of antibacterial and total antimicrobial treatment than patients in the CMT alone group (17.3 ± 14.7 vs. 27.9 ± 19.0 days, P = 0.044; 18.9 ± 15.0 vs. 29.5 ± 17.7 days, P = 0.040, respectively). Fewer patients in the BALF mNGS/CMT group died than in the CMT alone group (4/27 vs. 7/17, P = 0.049). CONCLUSION: Compared with CMT alone, additional mNGS tests may shorten the duration of antimicrobial treatment and possibly decrease death from severe infection by providing precise and quick diagnosis of infection.

Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial-viral differentiation.

Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial-viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1ß, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial-viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1ß, IL7, IP10, MIP1α, MIP1ß, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein-protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial-viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs. IMPORTANCE: Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Membranous tonsillitis: Aetiology, prevalence and prescribing patterns in patients with upper respiratory tract infection.

Background Membranous tonsillitis is one of the most common forms of acute tonsillitis in childhood. Although many different microorganisms may cause this disease, clinicians generally consider bacterial agents as a possible cause and prescribe a penicillin-group of antibiotic. This study aimed to determine the aetiology of membranous tonsillitis and prescribing errors. In addition, we investigated the effectiveness of epidemiological, clinical and laboratory parameters and their role in guiding treatment. Methods We did this retrospective study at the paediatric emergency department of a tertiary referral hospital including 423 outpatient children aged 0 to 18 years diagnosed with membranous tonsillitis. Results Group A beta-haemolytic streptococcus was found in 132 (31.2%) patients, Epstein-Barr virus (EBV) in 103 (24.3%), and other viral aetiologies in 188 (44.4%). The prescription rate of antibiotics in the EBV-positive group was 27%, and Downey cells were seen at a rate of 98% in this group. Only 7% of patients with a positive throat culture were started on appropriate antibiotics. Conclusion EBV and group A beta-haemolytic streptococcus were the most common causes of membranous tonsillitis. Throat culture and peripheral blood smears are the most useful tests for paediatric emergency clinicians; these are fast and can help ensure correct diagnosis and guide treatment in almost all patients.

Prescription patterns of antibiotics and associated factors among outpatients diagnosed with respiratory tract infections in Jinja city, Uganda, June 2022-May 2023.

BACKGROUND: Most respiratory tract infections (RTIs) are viral and do not require antibiotics, yet their inappropriate prescription is common in low-income settings due to factors like inadequate diagnostic facilities. This misuse contributes to antibiotic resistance. We determined antibiotic prescription patterns and associated factors among outpatients with RTIs in Jinja City, Uganda. METHODS: We conducted a retrospective observational study that involved data abstraction of all patient records with a diagnosis of RTIs from the outpatient registers for the period of June 1, 2022, to May 31, 2023. An interviewer-administered questionnaire capturing data on prescribing practices and factors influencing antibiotic prescription was administered to drug prescribers in the health facilities where data were abstracted and who had prescribed from June 1, 2022, to May 31, 2023. We used modified Poisson regression analysis to identify factors associated with antibiotic prescription. RESULTS: Out of 1,669 patient records reviewed, the overall antibiotic prescription rate for respiratory tract infections (RTIs) was 79.8%. For specific RTIs, rates were 71.4% for acute bronchitis, 93.3% for acute otitis media, and 74.4% for acute upper respiratory tract infections (URTIs). Factors significantly associated with antibiotic prescription included access to Uganda Clinical Guidelines (Adjusted prevalence ratio [aPR] = 0.61, 95% CI = 0.01-0.91) and Integrated Management of Childhood Illness guidelines (aPR = 0.14, 95% CI = 0.12-0.87, P = 0.002), which reduced the likelihood of prescription. Prescribers without training on antibiotic use were more likely to prescribe antibiotics (aPR = 3.55, 95% CI = 1.92-3.98). Patients with common cold (aPR = 0.06, 95% CI = 0.04-0.20) and cough (aPR = 0.11, 95% CI = 0.09-0.91) were less likely to receive antibiotics compared to those with pneumonia. CONCLUSION: The study reveals a high rate of inappropriate antibiotic prescription for RTIs, highlighting challenges in adherence to treatment guidelines. This practice not only wastes national resources but also could contribute to the growing threat of antibiotic resistance. Targeted interventions, such as enforcing adherence to prescription guidelines, could improve prescription practices and reduce antibiotic misuse in this low-income setting.

Antimicrobial prescription pattern and appropriateness for respiratory tract infection in outpatients: a systematic review and meta-analysis.

BACKGROUND: Millions of people die every year as a result of antimicrobial resistance worldwide. An inappropriate prescription of antimicrobials (e.g., overuse, inadequate use, or a choice that diverges from established guidelines) can lead to a heightened risk of antimicrobial resistance. This study aimed to determine the rate and appropriateness of antimicrobial prescriptions for respiratory tract infections. METHODS: This review was conducted in accordance with the PRISMA guidelines. Web of Science, PubMed, ProQuest Health and Medicine, and Scopus were searched between October 1, 2023, and December 15, 2023, with no time constraints. Studies were independently screened by the first author and the co-authors. We included original studies reporting antimicrobial prescription patterns and appropriateness for respiratory tract infections. The quality of included studies' was assessed via the Joanna Briggs Institute's Critical Appraisal Checklists for Cross-Sectional Studies. The assessment of publication bias was conducted using a funnel plot and Egger's regression test. A random effect model was employed to estimate the pooled antibiotic prescribing and inappropriate rates. Subgroup analysis was conducted by country, study period, data source, and age group. RESULTS: Of the total 1220 identified studies, 36 studies were included in the review. The antimicrobial prescribing rate ranged from 25% (95% CI 0.24-0.26) to 90% (95% CI 0.89-0.91). The pooled antimicrobial prescription rate was 66% (95% CI 0.57 to 0.73). Subgroup analysis by region revealed that the antimicrobial prescription rate was highest in Africa (79%, 95% CI 0.48-0.94) and lowest in Europe (47%, 95% CI 0.32-0.62). Amoxicillin and amoxicillin-clavulanate antimicrobials from the Access group, along with azithromycin and erythromycin from the Watch group, were the most frequently used antimicrobial agents. This study revealed that the major reasons for antimicrobial prescription were acute bronchitis, pharyngitis, sinusitis, and the common cold. The pooled inappropriate antimicrobial prescription rate was 45% (95% CI 0.38-0.52). Twenty-eight of the included studies reported that prescribing antimicrobials without proper indications was the main cause of inappropriate antimicrobial prescriptions. Additionally, subgroup analysis by region showed a higher inappropriate antimicrobial prescription rate in Asia at 49% (95% CI 0.38-0.60). The result of the funnel plot and Egger's tests revealed no substantial publication bias (Egger's test: p = 0.268). CONCLUSION: The prescribing rate and inappropriate use of antimicrobials remain high and vary among countries. Further studies should be conducted to generate information about factors contributing to unnecessary antimicrobial prescriptions in outpatients. SYSTEMATIC REVIEW REGISTRATION: Systematic review registration: CRD42023468353.

Nirsevimab and Acute Bronchiolitis Episodes in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVES: In the 2023-2024 respiratory syncytial virus (RSV) season, Spain became one of the first countries to introduce universal RSV prophylaxis, during which all infants born at this time were eligible to receive nirsevimab. Locally, most Spanish regions also immunized infants younger than age 6 months at the start of the season (extended catch-up). The aim of this study was to assess how RSV prophylaxis affected the number of infants presenting to pediatric emergency departments with acute respiratory infections. METHODS: A retrospective study was conducted in 15 Spanish pediatric emergency departments from 9 different regions between the 2018 and 2024 epidemic seasons (November-January). We compared the seasons occurring in 2018-2023 and the 2023-2024 season regarding the number of episodes of lower respiratory tract infection and acute bronchiolitis, acute bronchiolitis-related hospital admissions, and PICU admissions. RESULTS: A comparison with the average rates for the previous epidemic seasons revealed a 57.7% decrease in episodes of lower respiratory tract infection in 2023-2024 (95% CI, 56.5-58.8; P < .001; range among hospitals, 4.8-82.8), a 59.2% decrease in episodes of acute bronchiolitis (95% CI, 57.9-60.4; P < .001; range, 6.9-84.1), a 63.1% reduction in acute bronchiolitis-related hospital admissions (95% CI, 60.9-65.2; P < .001; range, 31.4-86.8), and a 63.1% reduction in PICU admissions (95% CI, 58.1-67.9; P < .001; range, 18.2-81.8). Hospitals in regions applying extended catch-up showed better results. CONCLUSIONS: Nirsevimab can protect a broad infant population against RSV infection with high effectiveness. Approaches including extended catch-up are the most effective, although cost- effectiveness must be considered.

A low-dose multicomponent medication as a new approach in prevention and early add-on treatment of recurrent respiratory infections in children: a Delphi Consensus.

OBJECTIVE: Recurrent respiratory infections (RRIs) represent a demanding challenge in pediatricians' clinical practice. A previous Inter-Society Consensus defined criteria for identifying children with RRIs and assessed the available treatments, considering the evidence grade. MATERIALS AND METHODS: The present Delphi consensus proposed a series of statements concerning the practical use of Citomix, a multicomponent low-dose medication. The participants should be primary care, private practice, and hospital/university pediatricians with extensive experience using this product to manage children with RRIs. One hundred twelve Italian pediatricians voted for the statements. RESULTS: The agreement grade was high for all statements (ranging from 69.6% to 99.1%). The participants expressed their satisfaction with using this medication, which may represent a valuable and safe option for preventing and adding on treating children with RRIs. These statements reflected their personal opinions based on daily clinical practice. CONCLUSIONS: The results of this Delphi consensus represented an input for further evidence-based studies highlighting the effectiveness of low-dose medications for both the prevention and treatment of RRIs.

Antibiotic prescription patterns in the emergency department of a tertiary healthcare center in Nepal: a descriptive cross-sectional study.

OBJECTIVE: To describe antibiotic prescription patterns in the emergency department (ED) of a tertiary healthcare center in Nepal. METHODS: This was a descriptive cross-sectional study of hospital records of patients who visited the ED. RESULTS: Of the 758 ED patients included in the study, 384 (50.6%) received a total of 536 antibiotic prescriptions. Common indications for antibiotic prescriptions included respiratory infection (37.5%), gastrointestinal infection (19.3%), urinary infection (10.4%), and prophylaxis (29.9%). Antibiotics listed as essential in the National List of Essential Medicines (NLEM) and generic formulations were used in 77.1% and 61.9% of the antibiotic prescriptions, respectively. Injectable antibiotics were prescribed to 54.9% of the 384 patients. Frequently prescribed antibiotics included ceftriaxone (34.1%), metronidazole (18.5%), amoxicillin + clavulanic acid (15.9%), and cefixime (14.3%). Bacterial culture testing was performed in 15.1% of the patients who received antibiotics. CONCLUSIONS: This study showed that overuse of antibiotics, prescription of branded antibiotics, prescription of antibiotics not listed in the NLEM, prophylactic use of antibiotics, and empirical treatment of suspected infections without isolation of pathogens were all prevalent. We recommend more research to determine the causes underlying these practices and develop interventions to limit such practices.

Short-Term Exposure to Ambient Air Pollution and Antimicrobial Use for Acute Respiratory Symptoms.

Importance: Ambient air pollution and antimicrobial resistance pose significant global public health challenges. It is not known whether ambient air pollution is associated with increased consumption of antimicrobials. Objective: To assess whether a short-term association exists between ambient air pollution levels and antimicrobial consumption among the general population seeking primary care consultations for acute respiratory symptoms. Design, Setting, and Participants: This 2-stage cross-sectional ecological time series analysis study using data on daily ambient air pollution and antimicrobial consumption was conducted in the 11 largest cities in Catalonia, Spain, from June 23, 2012, to December 31, 2019, among all inhabitants aged 12 years or older. Statistical analysis was performed from November 2022 to December 2023. Exposures: Daily ambient air pollution (particulate matter of 10 µg/m3 [PM10], particulate matter of 2.5 µg/m3 [PM2.5], and nitrogen dioxide [NO2]). Main Outcomes and Measures: The main outcome was antimicrobial consumption associated with primary care consultations for acute respiratory symptoms in the 30 days before and after the dispensing of the antimicrobial. Antimicrobial consumption was measured as defined daily doses (DDDs) per 1000 inhabitants per day. Results: Among 1 938 333 inhabitants (median age, 48 years [IQR, 34-65 years]; 55% female participants), there were 8 421 404 antimicrobial dispensations, with a median of 12.26 DDDs per 1000 inhabitants per day (IQR, 6.03-15.32 DDDs per 1000 inhabitants per day). The median adjusted morbidity score was 2.0 (IQR, 1.0-5.0). For the 1 924 814 antimicrobial dispensations associated with primary care consultations for acute respiratory symptoms, there was a significant correlation between increases of 10 µg/m3 in the concentration of the 3 pollutants studied and heightened antimicrobial consumption at day 0 (PM10: relative risk [RR], 1.01 [95% CI, 1.01-1.02]; PM2.5: RR, 1.03 [95% CI, 1.01-1.04]; NO2: RR, 1.04 [95% CI, 1.03-1.05]). A delayed association emerged between increases in PM2.5 concentration and antimicrobial consumption between day 7 (RR, 1.00 [95% CI, 1.00-1.01]) and day 10 (RR, 1.00 [95% CI, 1.00-1.01]) after exposure. Conclusions and Relevance: In this 2-stage cross-sectional study using ecological time series analysis, short-term exposure to air pollution was associated with increased antimicrobial use associated with primary care consultations for acute respiratory symptoms in the general population. This finding could contribute to informing policy decisions aimed at reducing air pollution and its associated risks, thereby promoting respiratory health and reducing antimicrobial use.

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. CONCLUSION: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.