Treatment Of Respiratory Infections Research Articles

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

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 1helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. 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). 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.

Impact of respiratory tract infections on spinal muscular atrophy with focus on respiratory syncytial virus infections: a single-centre cohort study.

Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder leading to muscle hypotonia, weakness, and respiratory and bulbar impairment. Infants with SMA have an increased risk of respiratory tract infections (RTI) including severe respiratory syncytial virus (RSV) infections. Therefore, guidelines for the treatment of SMA recommend RSV prophylaxis with palivizumab for patients aged below two years who have compromised motor functions ("non-sitters"). Since palivizumab is not approved for RSV prophylaxis in SMA patients in Switzerland, payers usually do not grant cost approvals for this indication. Therefore, this study aimed to investigate the frequency of severe RTI among SMA patients focusing on RSV infections requiring hospital treatment and to determine the long-term impact of RSV infections on the natural history of SMA. A single-centre cohort study at the tertiary paediatric Neuromuscular Centre Zurich, Switzerland, including data of SMA patients with a genetic-based therapy initiated below two years of age between May 2019 and December 2022. All hospitalisations were analysed with a focus on severe RTI and especially RSV infections, and their impact on nutritional and respiratory function. The costs of inpatient treatment of RSV infections were determined and compared with estimated expenses for RSV prophylaxis with palivizumab. 12 SMA patients (median age at treatment initiation: 3.5 months, range: 0-17 months) were followed for a cumulative period of 25.75 years (7 SMA type 1; 5 SMA type 2 including one presymptomatic individual). With an incidence rate of 2.34 per patient-year, the risk of severe RTI was especially high in SMA type 1 (versus 0.1 in SMA type 2, p = 0.044). A total of 37 hospitalisations (279 hospital days) was necessary for the treatment of RTI in general; 9 of them were attributed to RSV infections (in 5 SMA type 1 patients; 84 hospital days). Only 3/12 SMA patients had received seasonal RSV prophylaxis with palivizumab. No RSV infections requiring hospital treatment occurred in patients while receiving seasonal RSV prophylaxis. During RTI, nutritional support had to be commonly initiated and continued after discharge. In 3/7 SMA type 1 patients, non-invasive ventilation was started during acute treatment for RTI and continued to the end of follow-up. We observed a high risk of RTI, especially RSV infections, among young SMA patients. Failure to adhere to established care protocols, for example by omitting RSV prophylaxis, may be linked to a heightened risk of morbidity in these children.

Effectiveness of Bairui granules in the treatment of respiratory tract infections: A systematic review and meta-analysis.

Respiratory tract infections (RTIs) are characterized by a high mortality rate and clinical incidence. Bairui granules (BG), which employ a method of heat elimination and detoxification, have demonstrated benefits in the treatment of infectious respiratory diseases. A computerized search of 6 databases was conducted to identify randomized controlled trials (RCTs) relevant to the treatment of RTIs with BG up to November 30, 2023. Two researchers independently conducted data extraction, risk of bias assessment, and grading analysis. To evaluate the stability of the results, trial sequential analysis was employed. This meta-analysis included 31 RCTs with a total of 4073 patients and demonstrated that the use of BG in the treatment of RTIs was associated with enhanced treatment efficacy (relative risk = 1.19, 95% credible interval: 1.16-1.22, P < .001). It also indicated a faster resolution of symptoms including pulmonary rales, cough, and fever, as well as a reduction in serological index factors, compared to the use of Western medicine treatment (WT) alone. Additionally, the duration of hospitalization for patients was significantly reduced (relative risk = -1.36, 95% credible interval: -1.55 to -1.17, P < .001). Trial sequential analysis confirmed the stability and conclusive evidence of the study results. The efficacy of treating RTIs with BG, either alone or in combination with WT, was found to be superior to WT alone. However, further high-quality RCTs are necessary to validate these outcomes. The effectiveness of treating RTIs using BG alone or in combination with WT was determined to be superior to using WT alone, with no serious adverse effects observed. However, additional RCTs are essential to further confirm the findings of this study.

Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA).

Respiratory tract infections (RTIs) are the leading cause of antibiotic prescriptions, primarily due to the risk for secondary bacterial infections. In this study, we examined whether Echinacea could reduce the need for antibiotics by preventing RTIs and their complications, and subsequently investigated its safety profile. A comprehensive search of EMBASE, PubMed, Google Scholar, Cochrane DARE and clinicaltrials.gov identified 30 clinical trials (39 comparisons) studying Echinacea for the prevention or treatment of RTIs in 5652 subjects. Echinacea significantly reduced the monthly RTI occurrence, risk ratio (RR) 0.68 (95% CI 0.61-0.77) and number of patients with ≥1 RTI, RR = 0.75 [95% CI 0.69-0.81] corresponding to an odds ratio 0.53 [95% CI 0.42-0.67]. Echinacea reduced the risk of recurrent infections (RR = 0.60; 95% CI 0.46-0.80), RTI complications (RR = 0.44; 95% CI 0.36-0.54) and the need for antibiotic therapy (RR = 0.60; 95% CI 0.39-0.93), with total antibiotic therapy days reduced by 70% (IRR = 0.29; 95% CI 0.11-0.74). Alcoholic extracts from freshly harvested Echinacea purpurea were the strongest, with an 80% reduction of antibiotic treatment days, IRR 0.21 [95% CI 0.15-0.28]. An equal number of adverse events occurred with Echinacea and control treatment. Echinacea can safely prevent RTIs and associated complications, thereby decreasing the demand for antibiotics. Relevant differences exist between Echinacea preparations.

Multitarget Mechanism of Artemisia Plants to Fight Respiratory Tract Infections Based on Network Pharmacology and Molecular Docking

Objective: To study the mechanism of Artemisia in the treatment of respiratory tract infection (RTI) by network pharmacology and molecular docking. Methods: The active constituents and targets of Artemisia were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database to obtain disease targets associated with RTI. The key targets of intersection were used to construct the protein–protein interaction (PPI) network, and the hub gene was obtained through topological analysis to construct the pharmacology regulation network of traditional Chinese medicine. The key targets were analyzed by R language enrichment, and the regulatory network diagram of the key target function/pathway was constructed. Molecular docking verifies the binding of the drug to the target predicted by network pharmacology. Results: 144 active components of Artemisia regulated 133 target proteins related to RTI, the core components were β-sitosterol, quercetin, isorhamnetin, artemisinin, etc. Gene ontology enrichment analysis showed that Artemisia regulates receptor ligand activity, cytokine activity, and other molecular functions by acting on membrane region, membrane raft and other cellular structures in the treatment of RTI, thus affecting biological processes such as the response to drugs and bacteria-derived molecules. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), tumor necrosis factor, interleukin-17 (IL-17) signaling pathway was the main pathway for RTI treatment. The molecular docking method confirmed the high affinity between the active ingredient and the RTI target. Conclusions: Artemisia species, a multitarget medication, has been shown to be a viable therapy option for RTI by network pharmacology techniques based on data mining and molecular docking approaches.

Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

Microfluidics assembly of inhalable liposomal ciprofloxacin characterised by an innovative in vitro pulmonary model

Respiratory tract infections (RTIs) are reported to be the leading cause of death worldwide. Delivery of liposomal antibiotic nano-systems via the inhalation route has drawn significant interest in RTIs treatment as it can directly target the site of infection and reduces the risk of systemic exposure and side effects. Moreover, this formulation system can improve pharmacokinetics and biodistribution and enhance the activity against intracellular pathogens. Microfluidics is an innovative manufacturing technology that can produce nanomedicines in a homogenous and scalable way. The objective of this study was to evaluate the antibiofilm efficacy of two liposomal ciprofloxacin formulations with different vesicle sizes manufactured by using a 3D-printed microfluidic chip. Each formulation was characterised in terms of size, polydispersity index, charge and encapsulation. Moreover, the aerosolisation characteristics of the liposomal formulations were investigated and compared with free ciprofloxacin solution using laser diffraction and cascade impaction methods. The in vitro drug release was tested using the dialysis bag method. Furthermore, the drug transport and drug release studies were conducted using the alveolar epithelial H441 cell line integrated next-generation impactor in vitro model. Finally, the biofilm eradication efficacy was evaluated using a dual-chamber microfluidic in vitro model. Results showed that both liposomal-loaded ciprofloxacin formulations and free ciprofloxacin solution had comparable aerosolisation characteristics and biofilm-killing efficacy. The liposomal ciprofloxacin formulation of smaller vesicle size showed significantly slower drug release in the dialysis bag technique compared to the free ciprofloxacin solution. Interestingly, liposomal ciprofloxacin formulations successfully controlled the release of the drug in the epithelial cell model and showed different drug transport profiles on H441 cell lines compared to the free ciprofloxacin solution, supporting the potential for inhaled liposomal ciprofloxacin to provide a promising treatment for respiratory infections.

Ethiopian Medicinal Plants Used for Respiratory Tract Disorders: Ethnomedicinal Review.

Respiratory tract infections (RTIs) refer to infections in any part of the respiratory tract, which are common, with most of the world's population contracting at least one infection annually. These infections are becoming important causes of death and morbidity due to the rapid development of antimicrobial resistance that has resulted in reduced efficacy of existing drugs. Different local societies residing in Ethiopia have been reported to use traditional medicinal plants to treat RTIs. Nevertheless, up-to-date summarized data on the diversity of plants used in the traditional medicine system to treat RTIs in Ethiopia are lacking. The purpose of this review was to assess plant species used in traditional medicine to treat respiratory tract infections in Ethiopia. It attempts to compile available data required for undertaking further scientific investigations. The data were collected by searching for published scientific articles and other grey literature. Following this, medicinal plant (MP) diversity, growth forms, plant parts used, modes of remedy preparation and application, sources and distributions, and frequently treated respiratory disorders were examined. An Excel spreadsheet and SigmaPlot software were used to summarize and present the data. Two hundred twenty-nine (229) plant species that have been used to treat respiratory disorders in Ethiopia were documented. Lamiaceae was the most cited family (27 species), followed by Asteraceae (23 species), and Fabaceae (18 species), whereas cough was primarily cited as being treated by MPs and scored the highest frequency of citation (FOC = 243), followed by the common cold (FOC = 151) and asthma (FOC = 63). The top-cited plant species used in the treatment of RTIs were Eucalyptus globulus (6.8%), Allium sativum (5.5%), Zingiber officinale (4.2%), Ruta chalepensis (3.8%), and Ocimum lamiifolium (2.8%). Herbs were the dominant plant growth form (46%) used to treat respiratory diseases, and the most commonly used MP parts were leaves (37%). The leading traditional method used for preparation was decoction (25.5%), and the remedies were usually administered orally (64.6%). The MP origin reported was mainly from the wild (59%). High diversity of medicinal plants was reported as being used to treat various RTIs in Ethiopia. Information obtained from this review could be used as a reference for the selection of plants for further pharmacological, phytochemical, and toxicological investigations for their possible therapeutic applications and the development of new plant-based drugs.

Phytochemical Content, Antibacterial Activity, and Antioxidant, Anti-Inflammatory, and Cytotoxic Effects of Traditional Medicinal Plants against Respiratory Tract Bacterial Pathogens.

Respiratory tract infections (RTIs) are frequent ailments among humans and are a high burden on public health. This study aimed to determine the in vitro antibacterial, anti-inflammatory, and cytotoxic effects of indigenous medicinal plants used in the treatment of RTIs, namely, Senna petersiana, Gardenia volkensii, Acacia senegal, and Clerodendrum glabrum. Dried leaves were extracted using various organic solvents. Antibacterial activity was quantified using the microbroth dilution assay. Protein denaturation assays were used to evaluate anti-inflammatory activity. The cytotoxicity of the extracts towards THP-1 macrophages was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activity was determined using free radical scavenging activity and ferric-reducing power. Total polyphenolics were quantified. Liquid chromatography mass spectrometry was used to evaluate the acetone plant extracts. Nonpolar extracts had noteworthy antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium smegmatis where MIC values ranged between 0.16 and 0.63 mg/mL. At 100 μg/mL, A. senegal, G. volkensii, and S. petersiana had a nonsignificant effect on the viability of the THP-1 macrophages. The LC-MS analysis of the leaf extracts of S. petersiana detected Columnidin, Hercynine, L-Lysine citrate, and Gamma-Linolenate. A pentacyclic triterpenoid, cochalate, was detected in G. volkensii. Two flavonoids 7-hydroxy-2-(4-methoxyphenyl)-4-oxo-chroman-5-olate and (3R)-3-(2,4-dimethoxyphenyl)-7-hydroxy-4-oxo-chroman-5-olate were detected in the C. glabrum extract. The findings from this study indicated that the leaves of the selected plant extracts possess antioxidant, anti-inflammatory, and antibacterial activity. Therefore, they may serve as good candidates for further pharmaceutical investigations.

The Relationship between Gut Microbiota and Respiratory Tract Infections in Childhood: A Narrative Review

Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the “inter-talk” between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.

Frequency, Etiology, Mortality, Cost, and Prevention of Respiratory Tract Infections-Prospective, One Center Study.

Background: Ventilator-associated pneumonia (VAP) is the most monitored form of respiratory tract infections (RTIs). A small number of epidemiological studies have monitored community-acquired pneumonia (CAP), non-ventilator hospital-acquired pneumonia (NV-HAP) and ventilator-associated tracheobronchitis (VAT) in intensive care units (ICUs). The objective of this study was to assess the frequency, etiology, mortality, and additional costs of RTIs. Methods: One-year prospective RTI surveillance at a 30-bed ICU. The study assessed the rates and microbiological profiles of CAP, VAP, NV-HAP, VAT, and VAP prevention factors, the impact of VAP and NV-HAP on the length of ICU stays, and the additional costs of RTI treatment and mortality. Results: Among 578 patients, RTIs were found in 30%. The CAP, NV-HAP, VAP, and VAT rates/100 admissions were 5.9, 9.0, 8.65, and 6.05, respectively. The VAP incidence density/1000 MV-days was 10.8. The most common pathogen of RTI was Acinetobacter baumannii MDR. ICU stays were extended by VAP and NV-HAP for 17.8 and 3.7 days, respectively, and these RTIs increased the cost of therapy by 13,029 and 2708 EUR per patient, respectively. The mortality rate was higher by 11.55% in patients with VAP than those without device-associated and healthcare-associated infections (p = 0.0861). Conclusions: RTIs are a serious epidemiological problem in patients who are admitted and treated in ICU, as they may affect one-third of patients. Hospital-acquired RTIs extend hospitalization time, increase the cost of treatment, and worsen outcomes.

Acute illness may increase bleed risk among oral anticoagulant users

In the United States, oral anticoagulant use has increased by 54% since 2012, particularly with the use of newer direct oral anticoagulants (DOACs). Unfortunately, among clinicians in certain settings knowledge gaps persist concerning the safety of these therapies, including the risk of acute infection. A new study published in the BMJ December 21, 2021, suggests that acute respiratory tract infections (RTIs) may increase the rates of major and nonmajor bleeding in patients taking oral anticoagulants. Haroon and colleagues conducted a self-controlled case series that included over 1,200 participants on oral anticoagulant therapy who were exposed to an RTI and had major or non-major bleeding events. The analysis included longitudinal general practice EHR data from the UK’s Clinical Practice Research Datalink with over 3 million validated living patients registered at over 400 practices across the UK. The authors defined a specific “excess bleed risk” time window as a general practice consultation for an RTI for which immediate antibiotics were not prescribed. They then compared bleeding event outcomes within the excess risk window to an observation period in which the patients were unexposed to an RTI, allowing the patients to act as their own controls. This methodology had the advantage of allowing for reliable control of time invariant confounders. The researchers defined the RTI risk window as 90 days from general practice consultation, which was divided into smaller chunks of 0 to 14 days, 15 to 30 days, 30 to 60 days, and 60 to 90 days. The 0- to 14-day window was selected as the primary risk period. Additionally, a “pre-risk” window of 7 days prior to the risk period was established in which bleed events could not be captured as being “unexposed.” This was to compensate for RTI symptom onset before the day of general practice consultation as to not misclassify a bleeding event. To prevent confounding from antibiotic use and subsequent drug–drug interactions with a patient’s oral anticoagulant, a patient remained inside of the 90-day risk window as long as they weren’t prescribed antibiotics. Additionally, in order to control for experienced user bias, the total observation period began on the date of the first new prescription of warfarin or a DOAC. After adjusting for time confounders (e.g., age, calendar year, and season) the authors observed a statistically significant 268% relative increase in the rates of major bleeding—defined as either a GI bleed or an intracranial hemorrhage—in the 0- to 14-day risk window after an RTI consultation compared to the rates within the unexposed period. However, no increase in major bleeding was observed in the other aforementioned risk windows. Additionally, the authors observed a statistically significant 232% increase in the relative rates of clinically relevant non-major bleeding—defined as general practice consultation or hospital admission for haemoptysis, epistaxis, or haematuria—during the 0- to 14-day risk window. Despite 67% of the patients in the analysis being on warfarin, a sensitivity analyses demonstrated that there was little modification in the incidence rates of major and non-major bleeding during the 0- to 14-day risk window when conducting a subgroup analysis based on the specific oral anticoagulant used. A major limitation of this study was the inability for the authors to control or adjust for OTC treatments for RTI. Of particular concern are NSAIDs, which would have the potential to significantly bias the results of major bleeds away from the null given that 87% of the recorded bleed events seen were GI bleeds. The authors stated that they “explored the use of prescribed NSAIDs, but were unable to account for over-the-counter drugs” when discussing the limitations of their study. They went on to say that this confound was significant given that survey data from 1,000 adults in England with a recent RTI indicated that 60% of these patients sought OTC treatments. Other observational studies have shown that acute infection may increase international normalized ratio measure in warfarin users. As it stands, Haroon and colleagues’ study is the only one in the literature that has looked at the effect of acute infection on clinical events within the oral anticoagulant population as a whole. “These findings are important and timely given the increasing rates of oral anticoagulant use and the lack of knowledge and guidance on how to manage oral anticoagulant use during acute infection,” suggested the authors in one of their concluding remarks. “There are potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness, but further work is needed before any clinical recommendations are made.”

Factors associated with C-reactive protein testing when prescribing antibiotics in general practice: a register-based study

BackgroundThe use of C-reactive protein (CRP) tests has been shown to safely reduce antibiotic prescribing for acute respiratory tract infections (RTIs). The aim of this study was to explore patient and clinical factors associated with the use of CRP testing when prescribing antibiotics recommended for RTIs.MethodsA nation-wide retrospective cross-sectional register-based study based on first redeemed antibiotic prescriptions issued to adults in Danish general practice between July 2015 and June 2017. Only antibiotics recommended for treatment of RTIs were included in the analysis (penicillin-V, amoxicillin, co-amoxicillin or roxithromycin/clarithromycin). Logistic regression models were used to estimate odds ratios for patient-related and clinical factors on performing a CRP test in relation to antibiotic prescribing.ResultsA total of 984,149 patients redeemed at least one antibiotic prescription during the two-year period. About half of these prescriptions (49.6%) had an RTI stated as the indication, and a CRP test was performed in relation to 45.2% of these scripts.Lower odds of having a CRP test performed in relation to an antibiotic prescription was found for patients aged 75 years and above (OR 0.82, 95CI 0.79–0.86), with a Charlson Comorbidity Index of more than one (OR 0.93, 95CI 0.91–0.95), unemployed or on disability pension (OR 0.84, 95CI 0.83–0.85) and immigrants (OR 0.91, 95CI 0.88–0.95) or descendants of immigrants (OR 0.90, 95CI 0.84–0.96). Living with a partner (OR 1.08, 95CI 1.07–1.10), being followed in practice for a chronic condition (OR 1.22, 95CI 1.18–1.26) and having CRP tests performed in the previous year (OR 1.78, 95CI 1.73–1.84) were associated with higher odds of CRP testing in relation to antibiotic prescribing.ConclusionsDifferences were observed in the use of CRP tests among subgroups of patients indicating that both sociodemographic factors and comorbidity influence the decision to use a CRP test in relation to antibiotic prescriptions in general practice. Potentially, this means that the use of CRP tests could be optimised to increase diagnostic certainty and further promote rational prescribing of antibiotics. The rationale behind the observed differences could be further explored in future qualitative studies.

Advances in pathogen diagnosis of respiratory infection diseases in 2021

Respiratory tract infections (RTI) are a common and highly prevalent disease in the population, which can develop into acute respiratory distress syndrome (ARDS) in severe cases.A large variety of microorganisms can cause RTI, including bacteria, respiratory viruses, and fungi. The timely and accurate detection of these pathogens is the prerequisites of effective treatment of RTI. However, more than 50% of RTI patients failed to diagnosis of causative agents due to unavailability of qualified samples, antimicrobial treatment prior to sample collection, high variety of respiratory pathogens, and influence of the normal flora in respiratory tract. In recent years, progress on molecular diagnosis, especially the novel approaches such as clinical metagenomics and CRSIPR (Clustered regularly interspaced short palindromic repeats), has not only improved our capacity for RTI pathogen detection but also brought new challenges. In this review, we summed up the advances in RTI pathogen diagnosis in 2021 and discussed the clinical benefits and challenges from novel approaches, which provided a clinical perspective on the development and application of these diagnostic tools in the real world.

78. Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Screen on Vancomycin Utilization for Respiratory Tract Infections

Background S. aureus, including MRSA, is a common colonizer of the nares. Recent data have shown that a negative MRSA nares screen by PCR has a negative predictive value of 98%. This implies that the absence of colonization can significantly reduce empiric vancomycin utilization. This study aimed to determine the utilization of MRSA nares screening on patients receiving vancomycin for respiratory tract infections (RTI) following the addition of the screen to the institutional RTI management guidelines. MethodsThis was a retrospective chart review of adult inpatients presenting to two community-teaching hospitals who were prescribed vancomycin for the treatment of RTIs. Patients were divided into pre-guideline (Jan-Feb 2019), post-guideline 1 (Jan-Feb 2020), and post-guideline 2 (Jan-Feb 2021) groups. The primary endpoint was the difference in percent of vancomycin orders discontinued within 24 hours of a negative screen. Secondary endpoints included the percent of screens ordered, re-initiation of vancomycin within seven days for RTI, and total vancomycin days of therapy (DOT) per 1000 patient days (PD). ResultsOf 493 vancomycin orders screened, 100 orders in each arm were analyzed. There was an absolute increase of 20.6% in vancomycin orders discontinued within 24 hours of a negative screen between the pre-guideline and post-guideline 2 groups (59.1% vs. 79.7%, p = 0.0177). When compared to the pre-guideline group, utilization of the screen increased by 15% in the post-guideline 1 group (48% vs. 63%, p = 0.0328) and 26% in the post-guideline 2 group (48% vs. 74%, p = 0.000164). There was no difference in re-initiation of vancomycin. A statistically significant reduction in total vancomycin DOT/1000PD from the pre-guideline to the post-guideline 1 and 2 groups (66 to 63 to 60, respectively) was also observed. ConclusionThe addition of the MRSA nares screen to the institutional RTI guidelines increased utilization of the test and demonstrated a reduction in vancomycin utilization. With an increase in education, prospective audit and feedback, and prescriber comfort with the use of the MRSA nares screen in the post-guideline 2 group, there was significant improvement in MRSA nares screen utilization, vancomycin discontinuation after a negative screen, and vancomycin utilization.Disclosures All Authors: No reported disclosures

Efficacy and safety of discontinuing antibiotic treatment for uncomplicated respiratory tract infections when deemed unnecessary. A multicentre, randomized clinical trial in primary care

ObjectivesTo determine the benefits and harms of discontinuing unnecessary antibiotic therapy for uncomplicated respiratory tract infections (RTI) when antibiotics are considered no longer necessary. MethodsMulticentre, open-label, randomized controlled clinical trial in primary care centres from 2017 to 2020 (ClinicalTrials.gov, NCT02900820). Adults with RTIs—acute rhinosinusitis, sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for less than 3 days, which physicians no longer deemed necessary were recruited. The patients were randomly assigned in a 1:1 ratio to discontinuing antibiotic therapy or the usual strategy of continuing antibiotic treatment. The primary outcome was the duration of severe symptoms (number of days scoring 5 or 6 on a six-item Likert scale). Secondary outcomes included days with symptoms, moderate symptoms (scores of 3 or 4), antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months. ResultsA total of 467 patients were randomized, out of which 409 were considered valid for the analysis. The mean (SD) duration of severe symptoms was 3.0 (1.5) days for the patients assigned to discontinuation and 2.8 (1.3) days for those allocated to the control group (mean difference 0.2 days; 95% CI –0.1 to 0.4 days). Patients randomized to the discontinuation group used fewer antibiotics after the baseline visit (52/207 (25.1%) versus 182/202 (90.1%); p 0.001). Patients assigned to antibiotic continuation presented a relative risk of adverse events of 1.47 (95% CI 0.80–2.71), but the need for further health-care contact in the following 3 months was slightly lower (RR 0.61; 95% CI 0.28–1.37). ConclusionsDiscontinuing antibiotic treatment for uncomplicated RTIs when clinicians consider it unnecessary is safe and notably reduces antibiotic consumption.

Elucidating the anti-biofilm and anti-quorum sensing potential of selenocystine against respiratory tract infections causing bacteria: in vitro and in silico studies.

Bacteria are increasingly relying on biofilms to develop resistance to antibiotics thereby resulting in their failure in treating many infections. In spite of continuous research on many synthetic and natural compounds, ideal anti-biofilm molecule is still not found thereby warranting search for new class of molecules. The current study focuses on exploring anti-biofilm potential of selenocystine against respiratory tract infection (RTI)-causing bacteria. Anti-bacterial and anti-biofilm assays demonstrated that selenocystine inhibits the growth of bacteria in their planktonic state, and formation of biofilms while eradicating preformed-biofilm effectively. Selenocystine at a MIC50 as low as 42 and 28μg/mL effectively inhibited the growth of Klebsiella pneumonia and Pseudomonas aeruginosa. The antibacterial effect is further reconfirmed by agar cup diffusion assay and growth-kill assay. Selenocystine showed 30-60% inhibition of biofilm formation in K.pneumonia, and 44-70% in P.aeruginosa respectively. It also distorted the preformed-biofilms by degrading the eDNA component of the Extracellular Polymeric Substance matrix. Molecular docking studies of selenocystine with quorum sensing specific proteins clearly showed that through the carboxylic acid moiety it interacts and inhibits the protein function, thereby confirming its anti-biofilm potential. With further validation selenocystine can be explored as a potential candidate for the treatment of RTIs.

Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives

Respiratorytract infections (RTIs) are frequent and life-threatening diseases, accounting for several millions of deaths worldwide. RTIs implicate microorganisms, including viruses (influenza virus, coronavirus, respiratory syncytial virus (RSV)), bacteria (Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus and Bacillus anthracis) and fungi (Pneumocystis spp., Aspergillus spp. and very occasionally Candida spp.). The emergence of new pathogens, like the coronavirus SARS-CoV-2, and the substantial increase in drug resistance have highlighted the critical necessity to develop novel anti-infective molecules. In this context, antibodies (Abs) are becoming increasingly important in respiratory medicine and may fulfill the unmet medical needs of RTIs. However, development of Abs for treating infectious diseases is less advanced than for cancer and inflammatory diseases. Currently, only three Abs have been marketed for RTIs, namely, against pulmonary anthrax and RSV infection, while several clinical and preclinical studies are in progress. This article gives an overview of the advances in the use of Abs for the treatment of RTIs, based on the analysis of clinical studies in this field. It describes the Ab structure, function and pharmacokinetics, and discusses the opportunities offered by the various Ab formats, Ab engineering and co-treatment strategies. Including the most recent literature, it finally highlights the strengths, weaknesses and likely future trends of a novel anti-RTI Ab armamentarium.

1478. Impact of Short versus Long Treatment Durations for Respiratory Tract Infections Caused by Non-fermenting Gram-negative Bacilli in Lung Transplant Recipients

BackgroundIn lung transplant recipients, respiratory tract infections are associated with faster progression through stages of bronchiolitis obliterans syndrome and mortality. Common causative pathogens for respiratory tract infections (RTIs) include non-fermenting gram-negative bacilli (NFGNB). Data to guide optimal treatment durations for NFGNB RTIs in this population are limited.MethodsThis was a single-center, retrospective, cohort study of adult lung transplant recipients who received systemic antibiotic treatment for RTIs caused by NFNGB and had at least 28 days of post-treatment follow-up. Analyses were conducted for each patient’s initial NFGNB RTI as well as all independent NFGNB RTIs episodes. Groups were divided into NFGNB RTIs treated for a short (≤ 10 days) versus long (> 10 days) duration of effective antibiotic therapy. The primary outcome was the incidence of recurrent NFGNB RTIs within 28 days post-treatment. Recurrence was defined as isolation of the same organism in a respiratory culture requiring treatment with systemic antibiotics as determined by the prescribing physician.ResultsWe included 207 lung transplant recipients with 334 NFGNB RTIs (n=129 short; n=205 long) from a period of January 1, 2010 to July 1, 2019. The most common causative pathogen was P. aeruginosa (77% and 82%) and most NFGNB RTIs were treated inpatient (60% and 53%) in both groups. The median duration of therapy was 10 days and 14 days for the short and long treatment durations, respectively. The primary outcome occurred in 14/129 (11%) of the NFGNB RTIs treated for ≤ 10 days and 28/205 (14%) of those treated for > 10 days. No difference in recurrence within 28 days was detected in NFGNB RTIs treated for ≤ 10 days (aOR, 0.69; 95% CI, 0.34-1.4; p=0.149). Use of adjunctive inhaled antibiotics was associated with reduced recurrence (aOR, 0.38; 95% CI, 0.16-0.92; p=0.032).ConclusionIn lung transplant recipients with NFGNB RTIs, no difference in infection recurrence was detected between treatment durations for ≤ 10 days compared to > 10 days. Further investigation analyzing treatment durations for respiratory tract infections as well as the utility of adjunctive inhaled antibiotics are warranted in this patient population.Disclosures All Authors: No reported disclosures

CAM treatments for cough and sore throat as part of an uncomplicated acute respiratory tract infection: a systematic review of prescription rates and a survey among European integrative medical practitioners

IntroductionMost Complementary & Alternative Medicine (CAM) interventions have not been tested in clinical trials and systematic reviews (SRs). It is therefore important to collect knowledge from experienced practitioners to identify (lower level) evidence to support their use and to prioritize interventions for future research. This study aimed to document the CAM treatments for cough and sore throat as part of uncomplicated, acute respiratory tract infections (RTI), most frequently recommended by experienced integrative medical practitioners; and to assess whether these approaches have been tested in clinical trials and SRs. MethodsData on treatment approaches were collected by means of (1) a SR on prescription rates of CAM treatments for RTIs in CAM practice by searching Pubmed and CINAHL databases; and (2) a survey among integrative medical doctors and TCM practitioners in five European countries. ResultsThe SR identified 336 articles. After screening five studies were included (Anthroposophic Medicine (AM): two and homeopathy (HOM): three). The survey resulted in 262 responses (including 99 AM and 95 HOM experts). Of 19 products that were described in both the SR and the survey, two (22%) AM (Hustenelixier, Echinacea) and three (30%) homeopathic products (Belladonna, Hepar sulphuris, Mercurius solubilis) had been studied in a clinical trial and one AM treatment (Echinacea) in a SR for this indication. ConclusionsCAM treatments for RTI related cough and sore throat were identified (medicinal products, syrup, external applications, tea and acupuncture). These treatments have hardly been studied in clinical trials (26%) and SRs (5%) and require further evaluation.