ABSTRACT
This study presents the perspective of an international group of experts, providing an overview of existing models and policies and guidance to facilitate a proper and sustainable implementation of C-reactive protein point-of-care testing (CRP POCT) to support antibiotic prescribing decisions for respiratory tract infections (RTIs) with the aim to tackle antimicrobial resistance (AMR). AMR threatens to render life-saving antibiotics ineffective and is already costing millions of lives and billions of Euros worldwide. AMR is strongly correlated with the volume of antibiotics used. Most antibiotics are prescribed in primary care, mostly for RTIs, and are often unnecessary. CRP POCT is an available tool and has been proven to safely and cost-effectively reduce antibiotic prescribing for RTIs in primary care. Though established in a few European countries during several years, it has still not been implemented in many European countries. Due to the complexity of inappropriate antibiotic prescribing behavior, a multifaceted approach is necessary to enable sustainable change. The effect is maximized with clear guidance, advanced communication training for primary care physicians, and delayed antibiotic prescribing strategies. CRP POCT should be included in professional guidelines and implemented together with complementary strategies. Adequate reimbursement needs to be provided, and high-quality, and primary care-friendly POCT organization and performance must be enabled. Data gathering, sharing, and discussion as incentivization for proper behaviors should be enabled. Public awareness should be increased, and healthcare professionals' awareness and understanding should be ensured. Impactful use is achieved when all stakeholders join forces to facilitate proper implementation.
Subject(s)
Anti-Bacterial Agents , C-Reactive Protein , Point-of-Care Testing , Primary Health Care , Respiratory Tract Infections , Humans , C-Reactive Protein/analysis , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/diagnosis , Europe , Practice Patterns, Physicians'/statistics & numerical dataABSTRACT
AIM: To study the efficacy and safety of Eladis® in comparison with placebo in patients with non-productive cough. MATERIALS AND METHODS: A phase III clinical trial enrolled 250 patients aged 18-65 years with acute respiratory viral infection with upper respiratory tract involvement or acute bronchitis. Patients were randomized into 2 groups of 125 subjects: group 1 received Eladis® (40 mg tablets), group 2 received a matching placebo. The patients received the study drugs 1 tablet BID for 7-14 days. After the treatment, patients were followed up (day 7±2) to assess the effect of therapy on the frequency of coughing attacks, the frequency and severity of daytime and nocturnal cough, the severity of cough, the duration of clinical cough cure, and the effect on the severity of the main acute respiratory viral infection symptoms. RESULTS AND CONCLUSION: The results of the study demonstrate the overall efficacy and statistically significant superiority of Eladis® over placebo: there were significant differences between the study groups in the proportion of patients who decreased the coughing attack frequency by ≥50% by day 5 (p<0.0001). In addition, the clinical cure of cough in the Eladis® group occurred 2 days earlier: the median time was 6 days, vs 8 days in placebo group. There was a decrease in the frequency of cough attacks and a decrease in its severity by more than 3.5 points by day 5 of treatment. All the effects were associated with high safety of the drug.
Subject(s)
Cough , Respiratory Tract Infections , Humans , Cough/drug therapy , Cough/etiology , Male , Adult , Female , Middle Aged , Double-Blind Method , Respiratory Tract Infections/drug therapy , Treatment Outcome , Young Adult , Antitussive Agents/administration & dosage , Antitussive Agents/therapeutic use , Adolescent , Virus Diseases/drug therapy , AgedABSTRACT
IMPORTANCE: Despite evidence that most upper respiratory infections (URIs) are due to viruses, antibiotics are frequently prescribed for this indication in the outpatient setting. Antibiotic stewardship strategies are needed to reduce adverse patient outcomes and staggering healthcare costs due to resistant infections that ensue from inappropriate prescriptions. OBJECTIVE: To determine if individual provider scorecards detailing antibiotic prescribing rates paired with educational resources reduce inappropriate antibiotic use for URIs in the outpatient primary care setting. DESIGN, SETTING AND PARTICIPANTS: This quality improvement project investigated the number of URI-coded office visits in the primary care setting over three consecutive influenza seasons, which resulted in an antibiotic prescription in Cooper University Healthcare's 14 primary care offices. We compared provider's individual prescribing patterns to their peers' average and created a scorecard that was shared with each provider over a series of intervention phases. Data were collected from a preintervention period (November 2017-February 2018), and two postintervention phases, phase I (November 2018-February 2019) and phase II (November 2019-February 2020). INTERVENTION: A personalised, digital scorecard containing antibiotic-prescribing data for URI-coded visits from the prior influenza season was emailed to each primary care provider. Prior to the subsequent influenza season, prescribers received their updated prescribing rates as well as peer-to-peer comparisons. In both phases, the scorecard was attached to an email with antimicrobial stewardship educational materials. MAIN OUTCOMES AND MEASURES: The primary outcome was a reduction in the number of inappropriate antibiotic prescriptions for URI-related diagnoses. The diagnoses were organised into five broad coding categories, including bronchitis, sinusitis, sore throat excluding strep, influenza and tonsillitis excluding strep.
Subject(s)
Anti-Bacterial Agents , Primary Health Care , Quality Improvement , Respiratory Tract Infections , Humans , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Primary Health Care/statistics & numerical data , Primary Health Care/standards , Adult , Practice Patterns, Physicians'/statistics & numerical data , Practice Patterns, Physicians'/standards , Female , Antimicrobial Stewardship/methods , Antimicrobial Stewardship/statistics & numerical data , Male , Inappropriate Prescribing/statistics & numerical data , Inappropriate Prescribing/prevention & control , Middle AgedABSTRACT
Respiratory viral infections (VRTIs) rank among the leading causes of global morbidity and mortality, affecting millions of individuals each year across all age groups. These infections are caused by various pathogens, including rhinoviruses (RVs), adenoviruses (AdVs), and coronaviruses (CoVs), which are particularly prevalent during colder seasons. Although many VRTIs are self-limiting, their frequent recurrence and potential for severe health complications highlight the critical need for effective therapeutic strategies. Viral proteases are crucial for the maturation and replication of viruses, making them promising therapeutic targets. This review explores the pivotal role of viral proteases in the lifecycle of respiratory viruses and the development of protease inhibitors as a strategic response to these infections. Recent advances in antiviral therapy have highlighted the effectiveness of protease inhibitors in curtailing the spread and severity of viral diseases, especially during the ongoing COVID-19 pandemic. It also assesses the current efforts aimed at identifying and developing inhibitors targeting key proteases from major respiratory viruses, including human RVs, AdVs, and (severe acute respiratory syndrome coronavirus-2) SARS-CoV-2. Despite the recent identification of SARS-CoV-2, within the last five years, the scientific community has devoted considerable time and resources to investigate existing drugs and develop new inhibitors targeting the virus's main protease. However, research efforts in identifying inhibitors of the proteases of RVs and AdVs are limited. Therefore, herein, it is proposed to utilize this knowledge to develop new inhibitors for the proteases of other viruses affecting the respiratory tract or to develop dual inhibitors. Finally, by detailing the mechanisms of action and therapeutic potentials of these inhibitors, this review aims to demonstrate their significant role in transforming the management of respiratory viral diseases and to offer insights into future research directions.
Subject(s)
Antiviral Agents , Protease Inhibitors , Respiratory Tract Infections , SARS-CoV-2 , Humans , SARS-CoV-2/drug effects , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Protease Inhibitors/therapeutic use , Protease Inhibitors/pharmacology , COVID-19 Drug Treatment , Viral Proteases/metabolism , COVID-19/virology , Rhinovirus/drug effects , Rhinovirus/enzymologyABSTRACT
BACKGROUND: Misuse and overuse of antibiotics comprise leading causes of antimicrobial resistance. The study aims to assess the pattern of antibiotic prescription among primary healthcare general practitioners in the South Batinah Governorate of Oman. METHOD: A cross-sectional study of 600 antibiotic prescriptions issued in the South Batinah Governorate in 2019 was conducted to verify the triggering diagnoses and determine the appropriateness of the prescribed antibiotic. Logistic regression analysis was used to determine the association between predictors and inappropriate use. RESULTS: Respiratory infections accounted for 62% of antibiotic prescriptions, of which 92.2% were inappropriately prescribed. Extended-spectrum antibiotics were inappropriately prescribed in 33.3% of cystitis cases, while 14.3% of gastroenteritis received incorrect spectrum of antibiotics. Amoxicillin represented 46.2% of antibiotic prescriptions, of which 84.4% were unnecessarily prescribed. Lower inappropriate antibiotic prescribing rate was linked to patients ≥ 18 years (OR = 0.46, 95% CI: [0.26, 0.82]), those who underwent laboratory tests (OR = 0.22, 95% CI: [0.12, 0.39]), and consultations at health centers (OR = 0.44, 95% CI: [0.24, 0.79]). Arabic-speaking physicians were more likely to prescribe antibiotics inappropriately. CONCLUSION: Inappropriate antibiotic prescription was frequently observed in mild respiratory infections and associated with specific patient and physician characteristics. Appropriateness of antibiotic prescriptions issued can be improved through enhanced testing capacities as well as implementation of physician and community awareness campaigns.
Subject(s)
Anti-Bacterial Agents , General Practitioners , Inappropriate Prescribing , Practice Patterns, Physicians' , Primary Health Care , Humans , Oman/epidemiology , Cross-Sectional Studies , Anti-Bacterial Agents/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Inappropriate Prescribing/statistics & numerical data , Male , Female , Primary Health Care/statistics & numerical data , Adult , Middle Aged , General Practitioners/statistics & numerical data , Respiratory Tract Infections/drug therapy , Young Adult , Adolescent , Drug Prescriptions/statistics & numerical dataABSTRACT
Despite the need for effective treatments against chronic respiratory infections (often caused by pathogenic biofilms), only a few new antimicrobials have been introduced to the market in recent decades. Although different factors impede the successful advancement of antimicrobial candidates from the bench to the clinic, a major driver is the use of poorly predictive model systems in preclinical research. To bridge this translational gap, significant efforts have been made to develop physiologically relevant models capable of recapitulating the key aspects of the airway microenvironment that are known to influence infection dynamics and antimicrobial activity in vivo In this review, we provide an overview of state-of-the-art cell culture platforms and ex vivo models that have been used to model chronic (biofilm-associated) airway infections, including air-liquid interfaces, three-dimensional cultures obtained with rotating-wall vessel bioreactors, lung-on-a-chips and ex vivo pig lungs. Our focus is on highlighting the advantages of these infection models over standard (abiotic) biofilm methods by describing studies that have benefited from these platforms to investigate chronic bacterial infections and explore novel antibiofilm strategies. Furthermore, we discuss the challenges that still need to be overcome to ensure the widespread application of in vivo-like infection models in antimicrobial drug development, suggesting possible directions for future research. Bearing in mind that no single model is able to faithfully capture the full complexity of the (infected) airways, we emphasise the importance of informed model selection in order to generate clinically relevant experimental data.
Subject(s)
Anti-Bacterial Agents , Biofilms , Respiratory Tract Infections , Animals , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/drug therapy , Humans , Biofilms/drug effects , Chronic Disease , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Host-Pathogen Interactions , Bacteria/drug effects , Bacteria/growth & development , Models, Biological , Disease Models, Animal , Cell Culture TechniquesABSTRACT
BACKGROUND: Inappropriate or overuse of antibiotic prescribing in primary care highlights an opportunity for antimicrobial stewardship (AMS) programs aimed at reducing unnecessary use of antimicrobials through education, policies and practice audits that optimize antibiotic prescribing. Evidence from the early part of the pandemic indicates a high rate of prescribing of antibiotics for patients with COVID-19. It is crucial to surveil antibiotic prescribing by primary care providers from the start of the pandemic and into its endemic stage to understand the effects of the pandemic and better target effective AMS programs. METHODS: This was a matched pair population-based cohort study that used electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Participants included all patients that visited their primary care provider and met the inclusion criteria for COVID-19, respiratory tract infection (RTI), or non-respiratory or influenza-like-illness (negative). Four outcomes were evaluated (a) receipt of an antibiotic prescription; (b) receipt of a non-antibiotic prescription; (c) a subsequent primary care visit (for any reason); and (d) a subsequent primary care visit with a bacterial infection diagnosis. Conditional logistic regression was used to evaluate the association between COVID-19 and each of the four outcomes. Each model was adjusted for location (rural or urban), material and social deprivation, smoking status, alcohol use, obesity, pregnancy, HIV, cancer and number of chronic conditions. RESULTS: The odds of a COVID-19 patient receiving an antibiotic within 30 days of their visit is much lower than for patients visiting for RTI or for a non-respiratory or influenza-like-illnesses (AOR = 0.08, 95% CI[0.07, 0.09] compared to RTI, and AOR = 0.43, 95% CI[0.38, 0.48] compared to negatives). It was found that a patient visit for COVID-19 was much less likely to have a subsequent visit for a bacterial infection at all time points. CONCLUSIONS: Encouragingly, COVID-19 patients were much less likely to receive an antibiotic prescription than patients with an RTI. However, this highlights an opportunity to leverage the education and attitude change brought about by the public health messaging during the COVID-19 pandemic (that antibiotics cannot treat a viral infection), to reduce the prescribing of antibiotics for other viral RTIs and improve antibiotic stewardship.
Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , COVID-19 , Electronic Health Records , Primary Health Care , Humans , COVID-19/epidemiology , Anti-Bacterial Agents/therapeutic use , Female , Male , Middle Aged , Canada/epidemiology , Adult , Cohort Studies , Aged , Young Adult , Adolescent , SARS-CoV-2 , Inappropriate Prescribing/statistics & numerical data , Child , Respiratory Tract Infections/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Child, Preschool , Pandemics , InfantABSTRACT
BACKGROUND: Antibiotics are globally overprescribed for the treatment of upper respiratory tract infections (URTI), especially in persons living with HIV. However, most URTIs are caused by viruses, and antibiotics are not indicated. De-implementation is perceived as an important area of research that can lead to reductions in unnecessary, wasteful, or harmful practices, such as excessive or inappropriate antibiotic use for URTI, through the employment of evidence-based interventions to reduce these practices. Research into strategies that lead to successful de-implementation of unnecessary antibiotic prescriptions within the primary health care setting is limited in Mozambique. In this study, we propose a protocol designed to evaluate the use of a clinical decision support algorithm (CDSA) for promoting the de-implementation of unnecessary antibiotic prescriptions for URTI among ambulatory HIV-infected adult patients in primary healthcare settings. METHODS: This study is a multicenter, two-arm, cluster randomized controlled trial, involving six primary health care facilities in Maputo and Matola municipalities in Mozambique, guided by an innovative implementation science framework, the Dynamic Adaption Process. In total, 380 HIV-infected patients with URTI symptoms will be enrolled, with 190 patients assigned to both the intervention and control arms. For intervention sites, the CDSAs will be posted on either the exam room wall or on the clinician´s exam room desk for ease of reference during clinical visits. Our sample size is powered to detect a reduction in antibiotic use by 15%. We will evaluate the effectiveness and implementation outcomes and examine the effect of multi-level (sites and patients) factors in promoting the de-implementation of unnecessary antibiotic prescriptions. The effectiveness and implementation of our antibiotic de-implementation strategy are the primary outcomes, whereas the clinical endpoints are the secondary outcomes. DISCUSSION: This research will provide evidence on the effectiveness of the use of the CDSA in promoting the de-implementation of unnecessary antibiotic prescribing in treating acute URTI, among ambulatory HIV-infected patients. Findings will bring evidence for the need to scale up strategies for the de-implementation of unnecessary antibiotic prescription practices in additional healthcare sites within the country. TRIAL REGISTRATION: ISRCTN, ISRCTN88272350. Registered 16 May 2024, https://www.isrctn.com/ISRCTN88272350.
Subject(s)
Anti-Bacterial Agents , HIV Infections , Implementation Science , Inappropriate Prescribing , Primary Health Care , Respiratory Tract Infections , Adult , Female , Humans , Male , Ambulatory Care/organization & administration , Ambulatory Care/methods , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Decision Support Systems, Clinical , HIV Infections/drug therapy , Inappropriate Prescribing/prevention & control , Inappropriate Prescribing/statistics & numerical data , Mozambique , Practice Patterns, Physicians'/statistics & numerical data , Primary Health Care/organization & administration , Respiratory Tract Infections/drug therapy , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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 riskâ =â 1.19, 95% credible interval: 1.16-1.22, Pâ <â .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 riskâ =â -1.36, 95% credible interval: -1.55 to -1.17, Pâ <â .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. CONCLUSION: 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.
Subject(s)
Drugs, Chinese Herbal , Randomized Controlled Trials as Topic , Respiratory Tract Infections , Humans , Respiratory Tract Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Knowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians' and patients' expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections. METHODS: We searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points). RESULTS: We identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas. CONCLUSIONS: Our review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.
Subject(s)
Anti-Bacterial Agents , Primary Health Care , Humans , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Acute Disease , Soft Tissue Infections/drug therapy , Urinary Tract Infections/drug therapyABSTRACT
Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice. This study showed that ≥0.5 µM probenecid significantly inhibited HMPV replication in vitro, and 2-200 mg/kg probenecid prophylaxis or treatment reduced HMPV replication in BALB/c mice.
Subject(s)
Antiviral Agents , Metapneumovirus , Mice, Inbred BALB C , Paramyxoviridae Infections , Probenecid , Virus Replication , Animals , Metapneumovirus/drug effects , Metapneumovirus/physiology , Virus Replication/drug effects , Mice , Probenecid/pharmacology , Paramyxoviridae Infections/drug therapy , Paramyxoviridae Infections/virology , Antiviral Agents/pharmacology , Cell Line , Lung/virology , Humans , Respiratory Tract Infections/virology , Respiratory Tract Infections/drug therapy , FemaleABSTRACT
Upper respiratory tract infections (URTI) account for more than 80% of wheezing episodes in children with a high incidence of hospitalization in preschool age. Most children with symptoms of wheezing during an URTI are usually non-atopic. As the majority of wheezing episodes resulting from URTI are attributed to viral triggers, several studies have suggested the potential anti-inflammatory and antiviral properties of resveratrol. This study aims to identify the effect of resveratrol for pediatric non-atopic patients with recurrent wheezing triggered by URTIs. We conducted a prospective single-blind study to assess the effectiveness of a short course of nasal solutions incorporating resveratrol and carboxymethyl-ß-glucan, administered for 7 days at the onset of URTIs, compared to standard nasal lavage with 0.9% saline solution. A total of 19 patients entered the active group, 20 patients were assigned to the placebo group. The comparison of overall wheezing days (p < 0.001), mean wheezing days per month (p < 0.01), and wheezing episodes per patient (p < 0.001) in the two groups showed a significant reduction in the group receiving resveratrol compared with the placebo group, with less hospital access (p < 0.001) and oral corticosteroid administration (p < 0.01). Our findings seem to suggest that, in non-atopic children with recurrent wheezing secondary to URTIs, nasal resveratrol could be effective to prevent or reduce the occurrence of wheezing, when started from the onset of upper airway symptoms.
Subject(s)
Respiratory Sounds , Respiratory Tract Infections , Resveratrol , beta-Glucans , Humans , Resveratrol/administration & dosage , Resveratrol/pharmacology , Child, Preschool , Female , Male , Respiratory Sounds/drug effects , beta-Glucans/administration & dosage , beta-Glucans/therapeutic use , Single-Blind Method , Prospective Studies , Respiratory Tract Infections/drug therapy , Administration, Intranasal , Nasal Lavage , Treatment OutcomeABSTRACT
Respiratory virus infections remain a significant challenge to human health and the social economy. The symptoms range from mild rhinitis and nasal congestion to severe lower respiratory tract dysfunction and even mortality. The efficacy of therapeutic drugs targeting respiratory viruses varies, depending upon infection time and the drug resistance engendered by a high frequency of viral genome mutations, necessitating the development of new strategies. The MAPK/ERK pathway that was well delineated in the 1980s represents a classical signaling cascade, essential for cell proliferation, survival, and differentiation. Since this pathway is constitutively activated in many cancers by oncogenes, several drugs inhibiting Raf/MEK/ERK have been developed and currently used in anticancer treatment. Two decades ago, it was reported that viruses such as HIV and influenza viruses could exploit the host cellular MAPK/ERK pathway for their replication. Thus, it would be feasible to repurpose this category of the pathway inhibitors for the treatment of respiratory viral infections. The advantage is that the host genes are not easy to mutate such that the drug resistance rarely occurs during short-period treatment of viruses. Therefore, in this review we will summarize the research progress on the role of the MAPK/ERK pathway in respiratory virus amplification and discuss the potential of the pathway inhibitors (MEK inhibitors) in the treatment of respiratory viral infections.
Subject(s)
Drug Repositioning , MAP Kinase Signaling System , Respiratory Tract Infections , Humans , MAP Kinase Signaling System/drug effects , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Animals , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacologyABSTRACT
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. We aimed to investigate the associations between toll-like receptors 2 and 4 (TLR-2 and TLR-4) and ß-lactam antibiotics in COPD patients complicated with pulmonary infections. METHODOLOGY: A total of 156 COPD patients complicated with pulmonary infections were included. Their blood gas, airway resistance, health status, expression levels of TLR-2 and TLR-4, and pulmonary function were analyzed after treatment with ß-lactam antibiotics. RESULTS: Blood gas indices oxygen saturation, partial pressure of oxygen, and partial pressure of carbon dioxide at one day before treatment, on the fifteenth day of treatment, and on the first day after the end of treatment showed significant differences (p < 0.01). Significant differences were also detected in airway resistance indices (p < 0.01). The differences in the mRNA expression levels of TLR-2 and TLR-4 were significant (p < 0.05). Downward trends were observed in the clinical pulmonary infection score and acute physiology and chronic health evaluation II score, which indicated alleviation of the disease. Pulmonary function indices recorded vital capacity (VC)/predicted VC (%), recorded forced vital capacity at 1 s (FEV1)/predicted FEV1 (%), and residual volume/total lung capacity were significantly different (p < 0.05). CONCLUSIONS: ß-Lactam antibiotics had obvious therapeutic effects on COPD patients complicated with pulmonary infections, probably by suppressing or attenuating TLR-2- and TLR-4-mediated inflammatory responses. It is necessary to comprehensively evaluate and choose appropriate antibiotics, aiming for maximum relief of the pain to help patients recover quickly.
Subject(s)
Anti-Bacterial Agents , Pulmonary Disease, Chronic Obstructive , Toll-Like Receptor 2 , Toll-Like Receptor 4 , beta Lactam Antibiotics , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , beta Lactam Antibiotics/therapeutic use , Blood Gas Analysis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/complications , Respiratory Function Tests , Respiratory Tract Infections/drug therapy , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/geneticsSubject(s)
Inappropriate Prescribing , Respiratory Tract Infections , Humans , Respiratory Tract Infections/drug therapy , Inappropriate Prescribing/statistics & numerical data , Inappropriate Prescribing/prevention & control , Family Practice/methods , Family Practice/statistics & numerical data , Family Practice/standards , Practice Patterns, Physicians'/statistics & numerical data , Practice Patterns, Physicians'/standards , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic useABSTRACT
OBJECTIVES: Antimicrobial stewardship is little studied in pediatric long-term care facilities. We sought to determine whether empirical ciprofloxacin for febrile respiratory illnesses could be safely reduced in our pediatric long-term care facility. METHODS: All patients living in the 45-bed facility were included. A 1-year educational intervention for antimicrobial stewardship was implemented. Days of ciprofloxacin therapy, infections, microbiology, hospitalizations, other antibiotic use, methicillin-resistant Staphylococcus aureus and Clostridioides difficile infections, and mortality were recorded at regular intervals retrospectively from 5 years before intervention and prospectively for 8 years after intervention. Data were analyzed using statistical process control charts. RESULTS: A majority of patients had tracheostomy tubes (96%) and ventilator dependence (58%). Ciprofloxacin use declined by 76% (17 to 4 days/1000 facility patient days). Antibiotic prescriptions for bacterial tracheitis decreased by 89% (38 to 4 courses per 6-month period). No increases in positive blood or urine cultures, hospitalizations, or need for hospital antibiotics were observed. CONCLUSIONS: An antimicrobial stewardship intervention in a pediatric long-term care facility led to decreases in ciprofloxacin use, bacterial tracheitis diagnoses, and overall antibiotic use without increasing negative outcomes.
Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Ciprofloxacin , Long-Term Care , Humans , Female , Ciprofloxacin/therapeutic use , Male , Anti-Bacterial Agents/therapeutic use , Child , Retrospective Studies , Child, Preschool , Infant , Respiratory Tract Infections/drug therapy , Prospective StudiesABSTRACT
Background: Young farm animals are susceptible to opportunistic infections which may cause economic losses due to mortality and poor weight gain. The development of antimicrobial resistance and the desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events. Aim: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs. Methods: The study was conducted in 65-70-day-old Yorkshire piglets with signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action, and activity spectrum. The animal's status was assessed using clinical examination, clinical blood count, and bacteriological tests. Results: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied by normalization of hematological parameters and flora composition. The bacterium associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained weight and live market quality. Conclusion: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It has also shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms.
Subject(s)
Anti-Bacterial Agents , Swine Diseases , Animals , Swine , Swine Diseases/drug therapy , Swine Diseases/microbiology , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/veterinary , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Female , Male , Tylosin/analogs & derivativesABSTRACT
Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in susceptible groups. Conventional drug development for respiratory infections faces obstacles such as extended timescales, substantial expenses, and the rise of resistance to current treatments. Drug repurposing is a potential method that has evolved to quickly find and reuse existing medications for treating respiratory infections. Drug repurposing utilizes medications previously approved for different purposes, providing a cost-effective and time-efficient method to tackle pressing medical needs. This chapter summarizes current progress and obstacles in repurposing medications for respiratory infections, focusing on notable examples of repurposed pharmaceuticals and their probable modes of action. The text also explores the significance of computational approaches, high-throughput screening, and preclinical investigations in identifying potential candidates for repurposing. The text delves into the significance of regulatory factors, clinical trial structure, and actual data in confirming the effectiveness and safety of repurposed medications for respiratory infections. Drug repurposing is a valuable technique for quickly increasing the range of treatments for respiratory infections, leading to better patient outcomes and decreasing the worldwide disease burden.