Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial.

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Monitoring of antimicrobial resistance in respiratory tract pathogens during the COVID-19 pandemic: A retrospective study.

To understand the distribution and antimicrobial resistance (AMR) of pathogens in respiratory samples in Changle District People's Hospital in Fujian Province in recent years, and provide empirical guidance for infection control and clinical treatment in the region. A retrospective analysis was conducted on 5137 isolates of pathogens from respiratory samples collected from 2019 to 2022. The AMR patterns were systematically analyzed. For research purposes, the data was accessed on October 12, 2023. A total of 3517 isolates were included in the study, including 811 (23.06%) gram-positive bacteria and 2706 (76.94%) gram-negative bacteria. The top 3 gram-positive bacteria were Staphylococcus aureus with 455 isolates (12.94%), Streptococcus pneumoniae with 99 isolates (2.81%), and Staphylococcus hemolytic with 99 isolates (2.81%). The top 3 gram-negative bacteria were Klebsiella pneumoniae with 815 isolates (23.17%), Pseudomonas aeruginosa with 589 isolates (16.75%), and Acinetobacter baumannii with 328 isolates (9.33%). The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and K pneumoniae fluctuated between 41.9% and 70.5%, and 18.6% and 20.9%, respectively. The resistance rates of E coli, K pneumoniae, P aeruginosa, and A baumannii to carbapenems were 2.36%, 8.9%, 18.5%, and 19.6%, respectively. The prevalence of methicillin-resistant S aureus (MRSA) was 48.55%, but it decreased to 38.4% by 2022. The resistance rate of Staphylococcus haemolyticus to methicillin was 100%, and 1 case of vancomycin-resistant strain was detected. K pneumoniae, P aeruginosa, A baumannii, and S aureus are the main pathogens in respiratory samples. Although the resistance rates of some multidrug-resistant strains have decreased, ESBL-producing Enterobacteriaceae, carbapenem-resistant bacteria have still increased. Therefore, it is necessary to strengthen the monitoring of pathogen resistance, promote rational use of antibiotics, and promptly report findings.

The effect of focused lung ultrasonography on antibiotic prescribing in patients with acute lower respiratory tract infections in Danish general practice: study protocol for a pragmatic randomized controlled trial (PLUS-FLUS).

BACKGROUND: The use of antibiotics is a key driver of antimicrobial resistance and is considered a major threat to global health. In Denmark, approximately 75% of antibiotic prescriptions are issued in general practice, with acute lower respiratory tract infections (LRTIs) being one of the most common indications. Adults who present to general practice with symptoms of acute LRTI often suffer from self-limiting viral infections. However, some patients have bacterial community-acquired pneumonia (CAP), a potential life-threatening infection, that requires immediate antibiotic treatment. Importantly, no single symptom or specific point-of-care test can be used to discriminate the various diagnoses, and diagnostic uncertainty often leads to (over)use of antibiotics. At present, general practitioners (GPs) lack tools to better identify those patients who will benefit from antibiotic treatment. The primary aim of the PLUS-FLUS trial is to determine whether adults who present with symptoms of an acute LRTI in general practice and who have FLUS performed in addition to usual care are treated less frequently with antibiotics than those who only receive usual care. METHODS: Adults (≥ 18 years) presenting to general practice with acute cough (< 21 days) and at least one other symptom of acute LRTI, where the GP suspects a bacterial CAP, will be invited to participate in this pragmatic randomized controlled trial. All participants will receive usual care. Subsequently, participants will be randomized to either the control group (usual care) or to an additional focused lung ultrasonography performed by the GP (+ FLUS). The primary outcome is the proportion of participants with antibiotics prescribed at the index consultation (day 0). Secondary outcomes include comparisons of the clinical course for participants in groups. DISCUSSION: We will examine whether adults who present with symptoms of acute LRTI in general practice, who have FLUS performed in addition to usual care, have antibiotics prescribed less frequently than those given usual care alone. It is highly important that a possible reduction in antibiotic prescriptions does not compromise patients' recovery or clinical course, which we will assess closely. TRIAL REGISTRATION: ClinicalTrials.gov NCT06210282. Registered on January 17, 2024.

Using targeted second-generation sequencing technique to guide clinical diagnosis and the effect of medication on the therapeutic effect and prognosis of respiratory tract infection in children: An observational study.

To explore the effect of targeted second-generation sequencing technique to guide clinical diagnosis and medication on the therapeutic effect and prognosis of respiratory tract infection (RTI) in children. During January 2021 to June 2022, 320 children with RTI cured were selected in our hospital as the object of this retrospective study. The control group accepted empirical broad-spectrum antibacterial therapy and the observation group accepted targeted second-generation sequencing technique to guide diagnosis and medication. The therapeutic effect, improvement time of clinical symptom index, laboratory-related index, level of inflammatory factors, incidence of complications, and parents' treatment satisfaction were compared. The observation group was considerably more efficacious (91.25%) versus the controlled group (72.50%). The duration of enhancement of fever, nasal congestion, tonsillar congestion, and cough symptoms was shorter in the observation group (P < .05). Serum levels of iron, IgA, IgG as well as IgM were substantially elevated in the observation group. The levels of IL-4 and IL-10 were markedly reduced in the observation group after treatment. The prevalence of complications was considerably below that of the comparison group (21.25%) in the observation group (8.75%). Parental satisfaction with therapy was markedly higher in the observation group (92.50%) than in the control group (66.25%). The application of targeted second-generation sequencing technology to guide clinical diagnosis and drug use can elevate the RTIs efficacy and prognosis in childhood. Targeted second-generation sequencing can achieve precise treatment, reduce drug resistance of drug-resistant strains, and improve the efficacy. It has high promotion and application value.

Effect of pediatric Tuina on children's recurrent acute respiratory tract infections: a retrospective cohort study in Southern China.

OBJECTIVE: To determine the effectiveness of pediatric Tuina (PT) in preventing recurrent acute respiratory tract infections (ARTIs) in children. METHODS: This is a retrospective cohort study based on the electronic medical records of children with recurrent ARTIs in 2016. Children were divided into a PT group or a non-PT group, according to whether they had received PT or not in 2016. The primary outcome was the number of ARTI episodes in 2017 and 2018. The secondary outcomes were the number of ARTIs leading to outpatient department visits and outpatient antibiotic prescriptions due to ARTIs in the same time period. Negative binomial regressions were used to detect the association between PT and the outcomes. RESULTS: A total of 2303 children were included in the analysis, including 94 in the PT group and 2209 in the non-PT group. Children who received PT six or more times in 2016 had fewer episodes of ARTIs in 2017 [incidence rate ratio (IRR): 0.59, 95% confidence interval (CI) (0.42-0.84)] and 2018 [IRR: 0.58, 95% CI (0.36-0.94)] and fewer outpatient department visits due to ARTIs in 2017 [IRR: 0.56, 95% CI (0.38-0.83)] than children who had not received PT in 2016. There was no significant difference in the number of outpatient antibiotic prescriptions between the two groups. CONCLUSIONS: Receiving PT six or more times within one year is associated with a decrease in recurrent ARTIs in children in the following two years. Randomized controlled trials are needed for effect evaluation prior to establishing PT as a method for preventing recurrent ARTIs among children.

Rapid respiratory microbiological point-of-care-testing and antibiotic prescribing in primary care: Protocol for the RAPID-TEST randomised controlled trial.

BACKGROUND: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. METHODS: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. DISCUSSION: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. TRIAL REGISTRATION: ISRCTN16039192, prospectively registered on 08/11/2022.

Vitamin D supplementation for prevention of acute respiratory infections in older adults: A systematic review and meta-analysis.

BACKGROUND: Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults. METHODS: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17. RESULTS: Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79-1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones. CONCLUSIONS: Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries. TRIAL REGISTRATION: This study was registered on PROSPERO (CRD42023451265).

Zinc for prevention and treatment of the common cold.

BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.

Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

BACKGROUND: Early diagnosis and treatment of lower respiratory tract infections is the mainstay of management of lung disease in cystic fibrosis (CF). When sputum samples are unavailable, diagnosis relies mainly on cultures from oropharyngeal specimens; however, there are concerns about whether this approach is sensitive enough to identify lower respiratory organisms. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL) are invasive but allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may increase the accuracy of diagnosis of lower respiratory tract infections and improve the selection of antimicrobials, which may lead to clinical benefits. This is an update of a previous review that was first published in 2013 and was updated in 2016 and in 2018. OBJECTIVES: To evaluate the use of bronchoscopy-guided (also known as bronchoscopy-directed) antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. The date of the most recent searches was 1 November 2023. SELECTION CRITERIA: We included randomised controlled studies involving people of any age with CF that compared the outcomes of antimicrobial therapies guided by the results of bronchoscopy (and related procedures) versus those guided by any other type of sampling (e.g. cultures from sputum, throat swab and cough swab). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information when required. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS: We included two studies in this updated review. One study enrolled 170 infants under six months of age who had been diagnosed with CF through newborn screening. Participants were followed until they were five years old, and data were available for 157 children. The study compared outcomes for pulmonary exacerbations following treatment directed by BAL versus standard treatment based on clinical features and oropharyngeal cultures. The second study enrolled 30 children with CF aged between five and 18 years and randomised participants to receive treatment based on microbiological results of BAL triggered by an increase in lung clearance index (LCI) of at least one unit above baseline or to receive standard treatment based on microbiological results of oropharyngeal samples collected when participants were symptomatic. We judged both studies to have a low risk of bias across most domains, although the risk of bias for allocation concealment and selective reporting was unclear in the smaller study. In the larger study, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was low because Pseudomonas aeruginosa isolation in BAL samples at five years of age in both groups were much lower than the expected rate that was used for the power calculation. We graded the certainty of evidence for the key outcomes as low, other than for high-resolution computed tomography scoring and cost-of-care analysis, which we graded as moderate certainty. Both studies reported similar outcomes, but meta-analysis was not possible due to different ways of measuring the outcomes and different indications for the use of BAL. Whether antimicrobial therapy is directed by the use of BAL or standard care may make little or no difference in lung function z scores after two years (n = 29) as measured by the change from baseline in LCI and forced expiratory volume in one second (FEV1) (low-certainty evidence). At five years, the larger study found little or no difference between groups in absolute FEV1 z score or forced vital capacity (FVC) (low-certainty evidence). BAL-directed therapy probably makes little or no difference to any measure of chest scores assessed by computed tomography (CT) scan at either two or five years (different measures used in the two studies; moderate-certainty evidence). BAL-directed therapy may make little or no difference in nutritional parameters or in the number of positive isolates of P aeruginosa per participant per year, but may lead to more hospitalisations per year (1 study, 157 participants; low-certainty evidence). There is probably no difference in average cost of care per participant (either for hospitalisations or total costs) at five years between BAL-directed therapy and standard care (1 study, 157 participants; moderate-certainty evidence). We found no difference in health-related quality of life between BAL-directed therapy and standard care at either two or five years, and the larger study found no difference in the number of isolates of Pseudomonas aeruginosa per child per year. The eradication rate following one or two courses of eradication treatment and the number of pulmonary exacerbations were comparable in the two groups. Mild adverse events, when reported, were generally well tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of BAL in 4.8% of procedures. AUTHORS' CONCLUSIONS: This review, limited to two well-designed randomised controlled studies, shows no evidence to support the routine use of BAL for the diagnosis and management of pulmonary infection in preschool children with CF compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence is available for adults.

Antibacterial potential of Euphorbia canariensis against Pseudomonas aeruginosa bacteria causing respiratory tract infections.

The widespread dissemination of bacterial resistance has led to great attention being paid to finding substitutes for traditionally used antibiotics. Plants are rich in various phytochemicals that could be used as antibacterial therapies. Here, we elucidate the phytochemical profile of Euphorbia canariensis ethanol extract (EMEE) and then elucidate the antibacterial potential of ECEE against Pseudomonas aeruginosa clinical isolates. ECEE showed minimum inhibitory concentrations ranging from 128 to 512 µg/mL. The impact of ECEE on the biofilm-forming ability of the tested isolates was elucidated using crystal violet assay and qRT-PCR to study its effect on the gene expression level. ECEE exhibited antibiofilm potential, which resulted in a downregulation of the expression of the biofilm genes (algD, pelF, and pslD) in 39.13% of the tested isolates. The antibacterial potential of ECEE was studied in vivo using a lung infection model in mice. A remarkable improvement was observed in the ECEE-treated group, as revealed by the histological and immunohistochemical studies. Also, ELISA showed a noticeable decrease in the oxidative stress markers (nitric oxide and malondialdehyde). The gene expression of the proinflammatory marker (interleukin-6) was downregulated, while the anti-inflammatory biomarker was upregulated (interleukin-10). Thus, clinical trials should be performed soon to explore the potential antibacterial activity of ECEE, which could help in our battle against resistant pathogenic bacteria.

Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.

Role of probiotic as adjuvant in treating various infections: a systematic review and meta-analysis.

BACKGROUND: Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This review evaluated the role of probiotics (single and multiple regimens) as an additional regimen to treat common infectious diseases, including Helicobacter. pylori, diarrheal infections, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and HIV infections. METHODS: We searched randomized controlled trials from PubMed, Scopus, Embase, and Cochrane and identified 6,950 studies. Duplicates were removed, and titles and abstracts were filtered. Bias was evaluated using the Cochrane Risk of Bias Tool for Randomized Trials (ROB 1.0 and 2.0). The certainty of the evidence was evaluated using GRADE. Data were extracted and meta-analysis was performed using RevMan. RESULTS: A total of 32 studies were included in this study (22 H. pylori studies, 2 diarrheal infection studies, 6 UTI studies, and 2 HIV infection studies). There was no study on URTI. Probiotics, in addition to primary treatment, could improve the eradication of H. pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04). For eradicating H. pylori infection, subgroup analysis based on the therapy regimen showed that standard triple therapy was slightly superior compared to quadruple therapy in eradicating H. pylori (RR: 1.14 vs. 1.01, respectively). Single strain probiotics showed a similar effect to multiple strain probiotic regimens (both had an RR of 1.09). The effect estimates of the use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI had a high certainty of evidence. Meta-analysis was not performed for infectious diarrheal because there were only two eligible studies with different probiotic supplementations and outcome parameters. Nonetheless, they showed that the diarrheal incidence was lower and complete remission of diarrheal was higher after the regimen of probiotics. Similarly, a meta-analysis was not performed for HIV infection because the two eligible studies used different designs and comparators with contradicting findings. CONCLUSION: This meta-analysis showed beneficial use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI. Probiotic supplementation might not be beneficial for patients given a quadruple therapy. Single-strain and multi-strain probiotic regimens had similar effects in increasing the eradication rate of H. pylori. Our study also suggested that the benefits of probiotics as an additional regimen in infectious diarrheal and HIV infections remain unclear; more studies are needed to confirm the benefits.

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

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

Temporal trends in antibiotic prescribing and serious and nonserious infections in children presenting to general practice: a registry-based longitudinal cohort study of 162 507 individuals.

BACKGROUND: It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care. OBJECTIVES: Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022. METHODS: In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0-1, 2-6, 7-12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses. RESULTS: From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571-597) to 484/1000PY (95% CI 478-491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1-47.6) to 23.3% (95% CI 22.9-23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly. CONCLUSIONS: Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis.

Hungarian general practice paediatricians' antibiotic prescribing behaviour for suspected respiratory tract infections: a qualitative study.

OBJECTIVES: Inappropriate antibiotic prescribing is a major cause of antimicrobial resistance (AMR). The aim of this study was to explore paediatric general practitioners' (GP Peds) antibiotic prescription practice in suspected respiratory tract infections (RTIs), using the capability-opportunity-motivation-behaviour framework. DESIGN: The design is a qualitative study based on individual, semistructured telephone or virtual interviews. SETTING: Paediatric general practice in Hungary. We applied stratified maximum variation sampling to cover the categories of age, sex and geographical location of participants. PARTICIPANTS: We interviewed 22 GP Peds. Nine were male and 13 were female: 2 of them were less than 40 years old, 14 were between 40 and 60 years, and 6 were above 60 years. 10 worked in low-antibiotic prescription areas, 5 in areas with medium levels of antibiotic prescription, 3 in high-antibiotic prescription areas, and 4 in and around the capital city. RESULTS: Study participants had varying antibiotic prescription preferences. Personal experience and physical examination play a central role in GP Peds' diagnostic and treatment practice. Participants emphasised the need to treat children in their entirety, taking their personal medical record, social background and sometimes parents' preferences into account, besides the acute clinical manifestation of RTI. Most respondents were confident they apply the most effective therapy even if, in some cases, this meant prescribing medicines with a higher chance of contributing to the development of AMR. Some participants felt antibiotic prescription frequency has decreased in recent years. CONCLUSIONS: Our findings suggest that a more prudent attitude toward antibiotic prescribing may have become more common but also highlight relevant gaps in both physicians' and public knowledge of antibiotics and AMR. To reinforce awareness and close remaining gaps, Hungary should adopt its national AMR National Action Plan and further increase its efforts towards active professional communication and feedback for primary care physicians.

Utility of a multiplex pathogen detection system directly from respiratory specimens for treatment and diagnostic stewardship.

The availability of syndrome-based panels for various ailments has widened the scope of diagnostics in many clinical settings. These panels can detect a multitude of pathogens responsible for a particular condition, which can lead to a timely diagnosis and better treatment outcomes. In contrast to traditional identification methods based on pathogen growth on culture, syndrome-based panels offer a quicker diagnosis, which can be especially beneficial in situations requiring urgent care, such as intensive care units. One such panel is the Biofire Filmarray Pneumonia plus Panel (BFP), which we have compared against microbiological culture and identification. The lower respiratory samples from patients were tested with BFP, culture, and identification with culture considered the gold standard. The phenotypic antibiotic susceptibility results (Vitek 2) were compared with the antimicrobial resistance (AMR) genes detected in BFP. Statistical analysis was carried out using GraphPad 7.0 and MS Excel (Microsoft Inc.). The results showed a positive percent agreement of 100% and a negative percent agreement of 47.8% with an overall agreement of 76.72% compared to culture. BFP was better at identifying fastidious bacteria, and the agreement with culture was higher for high bacterial identification numbers (107 and 106). There was also a correlation between the number of pathogens detected and growth in culture. Carbapenemase genes were detected in around 80% of phenotypically resistant samples and correlated with in-house PCR 60% of the time. Hence, BFP results need to be interpreted with caution especially when multiple pathogens are detected. Similarly, the presence or absence of AMR genes should be used to guide the therapy while being watchful of unusual resistance or susceptibility. The cost constraints and low throughput call for patient selection criteria and prioritization in emergency or resource-limited conditions.IMPORTANCEApplication of syndrome-based panels in clinical microbiology is of huge support in infectious conditions requiring urgent interventions, such as pneumonia. Interpreting the results requires caution; hence, we have compared the results obtained from Biofire Filmarray Pneumonia plus Panel with standard microbiological methods.

Use of the FebriDx® host-response point-of-care test may reduce antibiotic use for respiratory tract infections in primary care: a mixed-methods feasibility study.

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.

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

Impact of lumacaftor/ivacaftor on the bacterial and fungal respiratory pathogens in cystic fibrosis: a prospective multicenter cohort study in Sweden.

BACKGROUND: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden. OBJECTIVES: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden. DESIGN: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor. METHODS: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed. RESULTS: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive. CONCLUSION: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.

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

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