Therapy Of Respiratory Infections Research Articles

Evaluating the utility of procalcitonin and a clinical decision support tool to determine duration of antimicrobial therapy for respiratory tract infections.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs). We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25ng/mL and on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs. There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001). The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle.

Раціональна антибіотикотерапія при інфекціях дихальних шляхів у дітей: сучасні рекомендації

Diseases of the respiratory tract remain relevant in pediatrics. Purpose - to provide modern recommendations for the prescription of rational antibiotic therapy for respiratory tract infections in children to improve clinical practice and preserve the effectiveness of antibacterial drugs. The principles of optimal use of antibacterial drugs in the treatment of respiratory diseases in pediatric practice are discussed. The data of the study of the pharmacological profile of azithromycin, its effectiveness and safety in the treatment of respiratory diseases are presented. A detailed analysis of the drug's spectrum of action, its pharmacokinetics, and the possibility of side effects is provided. The study includes the results of clinical trials and meta-analyses, emphasizing the importance of choosing the right dosage and duration of treatment. The presented results contribute to the understanding of optimal approaches to the use of azithromycin in the treatment of respiratory diseases in children, contributing to the improvement of clinical practice and maintaining the effectiveness of antibiotic therapy. No conflict of interests was declared by the author.

Влияние пробиотика Saccharomyces boulardii CNCM I-745 на развитие антибиотик- ассоциированного синдрома у детей, получающих системную антибактериальную терапию по поводу инфекций нижних дыхательных путей

Objective. To evaluate the effect of the Saccharomyces boulardii CNCM I-745 probiotic on the development of antibioticassociated syndrome (AAS) in children receiving systemic antibacterial therapy for respiratory tract infections. Patients and methods. We examined 80 children patients with community-acquired pneumonia aged 1 to 14 years, who received antibacterial therapy, including in combination with the Saccharomyces boulardii CNCM I-745 probiotic (38 patients). Gastrointestinal symptoms and stool characteristics according to the Bristol scale, the condition of the skin and open mucous membranes were assessed. Results. During antibacterial therapy, symptoms of AAS developed in 60% of the patients with pneumonia. Manifestations of AAS were recorded 2 times less often in children receiving «Enterol», than other children group without probiotic correction, p < 0.05. The most common manifestations of AAS were symptoms of gastrointestinal tract damage, and along with the classic manifestations – the appearance of loose, frequent stools, patients complained of abdominal pain, bloating, stool retention, up to constipation and the appearance of “sheep” stool. Exintestinal manifestations of AAS included the development of stomatitis in 23.7% of the examined groups, while in children receiving the probiotic, stomatitis developed less frequently – 7.9% versus 38.1% (p = 0.002). Moreover, 46.1% of girls receiving antibiotic therapy developed vulvovaginitis, but its frequency in the cohort of patients receiving probiotics was significantly lower – 16.7% vs 71.4% (p = 0.001). Conclusion. The use of the probiotic drug «Enterol» containing Saccharomyces boulardii CNCM I-745 in children receiving broad-spectrum antibacterial drugs prevented the development and accelerated the regression of clinical manifestations of AAS. Key words: antibiotics, antibiotic-associated diarrhea, community-acquired pneumonia, children, microbiota, probiotics, Saccharomyces boulardii CNCM I-745, enterol

155. Use of MRSA PCR and Antimicrobial Stewardship Intervention to Limit Anti-MRSA Therapy in Respiratory Tract Infections at a Community Teaching Hospital

Abstract Background Patients admitted to the hospital with respiratory tract infections (RTIs) who are at risk for MRSA are often treated empirically with anti-MRSA agents such as vancomycin or linezolid. While pre-treatment respiratory culture is recommended, it is not always feasible. An alternate, more easily obtainable test is the MRSA nasal PCR, which is used to detect nasal colonization. While a positive nasal MRSA PCR cannot determine MRSA pneumonia, a negative MRSA PCR result strongly correlates with lack of MRSA pneumonia providing a useful antimicrobial stewardship tool for de-escalation or avoidance of empiric anti-MRSA therapy. Our Antimicrobial Stewardship Program (ASP) routinely follows patients admitted with RTIs and provides recommendations for appropriate therapy based on culture and test results, including the MRSA PCR. The purpose of our quality improvement project was to assess the practice and clinical impact of reduction of specific MRSA therapy associated with a negative nasal MRSA PCR. Methods We performed a retrospective review of patients admitted to our institution with MRSA PCRs performed for the purpose of RTI workup from November-December 2022. We compared patients with negative MRSA PCRs (not detected or MSSA) with and without ASP intervention and assessed differences in patient characteristics and outcomes. If ASP intervention occurred, intervention and acceptance data was collected. Characteristics were compared using descriptive statistics. Results Shown in Table 1 and 2. There was no significant difference in age, sex, duration of MRSA therapy, SCr, length of stay, or readmission between groups. When looking at ASP intervention for 1. discontinuation of MRSA therapy or 2. ordering/collecting MRSA PCR, a total of 73 interventions occurred with a 100% acceptance rate. This encompassed 34% (52/155) of patients on MRSA therapy with a negative PCR result. Conclusion While no significant difference was found between groups in terms of duration of MRSA therapy, the slightly shorter duration in the non-ASP group was likely due to prior discontinuation of MRSA therapy thus not necessitating ASP intervention. Those with slightly longer duration received ASP intervention which led to discontinuation of unnecessary MRSA therapy. Disclosures Thomas M. File, Jr., MD, MSc, MACP, FIDSA, HealthTrackRx: Advisor/Consultant|NAbriva Therapeutics: Advisor/Consultant|ThermoFisher Scientific: Advisor/Consultant

Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial.

Echinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs). In this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1-3 and 2,240-3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan-Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10. A total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p < 0.001). Among those with an identified respiratory virus, viral clearance until day 10 based on real-time PCR from nasopharyngeal swabs was more frequent with new formulations (70 vs. 53%, p = 0.046). Tolerability and safety (adverse events: 12 vs. 6%, p = 0.19) were good and similar between formulations. There was one severe adverse event with a potential hypersensitivity reaction in a recipient of the novel spray formulation. In adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations. The study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).

BACTERIAL ISOLATES OF THE RESPIRATORY TRACT INFECTION AND THEIR CURRENT SENSITIVITY PATTERN AMONG PATIENTS ADMITTED IN TERTIARY CARE HOSPITAL.

Background &amp; Objectives: This study was aimed to observe the susceptibility pattern of bacterial isolates from respiratory tract infection (RTI). Respiratory tract infection is considered as one of the major public health problems and a leading cause of morbidity and mortality in many developing countries. Respiratory tract is the part of the human system that plays a vital role in breathing processes. In human, the respiratory system can be subdivided into an Upper respiratory tract and a Lower respiratory tract based on anatomical features. The respiratory tract is constantly exposed to microbes due to the extensive surface area. Methods: The present study was conducted retrospectively for a period of one year November 2021 to October 2022. All respiratory specimens included Sputum, BAL, throat swab; endotracheal aspirate specimens were collected aseptically from patients and cultured on the appropriate bacteriological media (Blood agar, MacConkey agar &amp; Chocolate Agar). Bacterial isolates were identified by biochemical tests and antimicrobial susceptibility performed by standard methods as per CLSI 2022. Results: 152 (72.3%) of total 210 samples were positive for bacterial culture. 126 (82.8%) were gram negative bacilli (GNB) and 26 (17.1%) were gram positive cocci (GPC). The predominant pathogen isolated was K. pneumoniae 46 (30.2%) followed by Escherichia coli 28 (18.4%).The overall susceptibility of GNB was highest towards Imipenem, Meropenem followed by Piperacillin tazobactam and Amikacin. Gram positive organisms exhibited highest susceptibility towards Vancomycin and Linezolid. Conclusion: Imipenem is the most sensitive antibiotic followed by Piperacillin tazobactam and Amikacin which can be used for empirical therapy for respiratory tract infections (RTI). The antibiotic therapy should be modified as per the culture and sensitivity report. Regular determinations of the type of bacterial pathogens and updation of antibiogram must be followed in every institution to aid in better patient management by helping the clinician in the judicious use of antibiotics.

Antibiogram Screening of Bacterial Pathogens Obtained From Respiratory ‎Manifested Patients in Great Cairo ‎

Respiratory tract infections are the most prevalent infections and implemented in hundred thousand deaths among humans globally, especially in the last years. The goal of the current investigation was to determine the prevalence and antibiotic sensitivity pattern of microorganisms isolated from respiratory samples obtained from laboratories in Great Cairo between January to June 2022. A total of 107 samples distributed as fifteen naso-oral, forty three throat and forty nine sputum were collected. Among them, 91 samples (85.04%) exhibited significant microbial growth on culture media and near equal rate in patients with male and female gender (46 and 45 respectively). The most susceptible ages were both under 12 and over 50 years. The microorganism identification and antibiotic susceptibility testing were conducted. Out of 91isolates species, 56 (61.54%) were Gram-negative bacteria, 35 (38.46%) were Gram-positive bacteria. Prime microorganisms isolated were Klebsiella pneumonia 28 (30.77%), Streptococcous pneumonia 26 (28.57%), Staphylococcous aureus 9 (9.9%), Pseudomonas aeruginosa 8 (8.79%), Escherichia coli (E. coli) 8 (8.79%), Citrobacter spp. 7 (7.69%), Proteus vulgaris 4 (4.4%) and one sample positive for non-lactose fermenting (NLF) E. coli (1.1%). In antimicrobial susceptibility assay, the isolates were mostly resistant to many antibiotics; particularly amoxicillin-clavulanic acid, ampicillin, ceftazidime, clindamycin, oxicillin and trimethoprim-sulfamethoxazole. On the other hand the isolates exposed maximum susceptibility to imipenem and piperacillin-tazobactam (100%), as well as cefoperazone-sulbactam (96.66%) and amikacin (85%).In conclusion, the precise identification of causative microorganisms and their susceptibility profiles to antibiotics is pivotal for selecting targeted and effective antibiotic therapy in respiratory tract infections, and to hinder the emergence of multidrug-resistant bacteria. Gram-negative bacteria exhibited the species most commonly obtained. A high rate of drug resistance was observed in this investigation which may be of public health significance.

Primary care experience on Stimunex® gocce in children with recurrent respiratory infections: a real-world study during the COVID-19 pandemic era.

Respiratory infections (RI) significantly burden society, mainly when there are recurrent respiratory infections (RRI). Thus, there is a need to prevent RI in clinical practice. In this regard, the modulation of the immune system and resolution of the inflammatory cascade could represent an ideal way to prevent RI. Stimunex® gocce, a multicomponent food supplement, contains Sambucus nigra extract, β-glucan, Zinc, and Vitamin D3. This study investigated its ability to prevent RRI in children using a real-world setting: the pediatric primary care. Two hundred and ninety-eight children with RRI were enrolled in the current study. The food supplement was randomly prescribed to 160 children with RRI daily for 4 months (Active group); the remaining 138 children with RRI were treated only with standard therapy for RI (Control group). The number and duration of RI, parental perception of symptom severity and treatment efficacy, use of medications, and school and working absence were evaluated. Children treated with Stimunex® gocce had significantly less RI than the Control group, both concerning upper and lower RI (p˂0.001 and 0.003, respectively) during the follow-up period. Moreover, children in the Active group experienced shorter RI duration during the treatment and follow-up phases (p˂0.001 for both). In addition, parents of treated children perceived less severe symptoms and better treatment efficacy during the first and follow-up phases (p˂0.001 for all). The food supplement was well tolerated and there was no adverse event. The current real-world study demonstrated that Stimunex® gocce supplementation in children with RRI might safely prevent RI episodes and reduce RI duration. These outcomes should be highlighted as obtained during the COVID-19 pandemic era, characterized by a dramatic reduction of RI.

Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis: A Prospective Cohort Study in Out-Of-Hours Primary Care.

Point-of-care testing (POCT) has shown promising results in the primary care setting to improve antibiotic therapy in respiratory tract infections and it might also aid general practitioners (GPs) to decide if patients should be referred to a hospital in cases of suspected sepsis. We aimed to assess whether biomarkers with possible POCT use can improve the recognition of sepsis in adults in the primary care setting. We prospectively included adult patients with suspected severe infections during out-of-hours home visits. Relevant clinical signs and symptoms were recorded, as well as the biomarkers C-reactive protein, lactate, procalcitonin, high-sensitive troponin I, N-terminal pro b-type natriuretic peptide, creatinine, urea, and pancreatic stone protein. We used a POCT device for lactate only, and the remaining biomarkers were measured in a laboratory from stored blood samples. The primary outcome was sepsis within 72 h of inclusion. The potential of biomarkers to either rule in or rule out sepsis was tested for individual biomarkers combined with a model consisting of signs and symptoms. Net reclassification indices were also calculated. In total, 336 patients, with a median age of 80 years, were included. One hundred forty-one patients (42%) were diagnosed with sepsis. The C statistic for the model with clinical symptoms and signs was 0.84 (95% CI 0.79-0.88). Both lactate and procalcitonin increased the C statistic to 0.85, but none of the biomarkers significantly changed the net reclassification index. We do not advocate the routine use of POCT in general practice for any of the tested biomarkers of suspected sepsis.

Organic Acids and Their Salts Potentiate the Activity of Selected Antibiotics against Pseudomonas aeruginosa Biofilms Grown in a Synthetic Cystic Fibrosis Sputum Medium.

The failure of antibiotic therapy in respiratory tract infections in cystic fibrosis is partly due to the high tolerance observed in Pseudomonas aeruginosa biofilms. This tolerance is mediated by changes in bacterial metabolism linked to growth in biofilms, opening up potential avenues for novel treatment approaches based on modulating metabolism. The goal of the present study was to identify carbon sources that increase the inhibiting and/or eradicating activity of tobramycin, ciprofloxacin, and ceftazidime against P. aeruginosa PAO1 biofilms grown in a synthetic cystic fibrosis sputum medium (SCFM2) and to elucidate their mode of action. After screening 69 carbon sources, several combinations of antibiotics + carbon sources that showed markedly higher anti-biofilm activity than antibiotics alone were identified. d,l-malic acid and sodium acetate could potentiate both biofilm inhibiting and eradicating activity of ciprofloxacin and ceftazidime, respectively, while citric acid could only potentiate biofilm inhibitory activity of tobramycin. The mechanisms underlying the increased biofilm eradicating activity of combinations ciprofloxacin/d,l-malic acid and ceftazidime/sodium acetate are similar but not identical. Potentiation of ceftazidime activity by sodium acetate was linked to increased metabolic activity, a functional TCA cycle, increased ROS production, and high intracellular pH, whereas the latter was not required for d,l-malic acid potentiation of ciprofloxacin. Finally, our results indicate that the potentiation of antibiotic activity by carbon sources is strain dependent.

Ингибиторозащищенный амоксициллин с повышенным содержанием амоксициллина и соотношением действующих компонентов 14:1: место в лечении внебольничных инфекций дыхательных путей и ЛОР-органов у детей. Резолюция экспертного совета

The meeting of Expert Council, which included representatives of leading Russian research and higher education medical institutions, took place in Moscow. The Council discussed approaches to therapy of respiratory tract infections and ENT infections in children considering the global increase in antimicrobial resistance of respiratory tract pathogens. Special attention was paid to the use of new dosage form of amoxicillin-clavulanate 14:1, as well as to defining the category of patients to whom it is advisable to prescribe the high-dose amoxicillin-clavulanate.

Фармакоэпидемиологический анализ применения антимикробных препаратов при заболеваниях нижних дыхательных путей в пульмонологическом отделении многопрофильного стационара Республики Таджикистан

Aim. Assessment of the use of antimicrobial drugs (AD) in the pulmonary department of a multifield hospital (MH), the Republic of Tajikistan. Materials and methods. A retrospective analysis of medical prescriptions of patients who were treated in the pulmonary department of the Sughd Regional Clinical Hospital (city of Khojend, the Republic of Tajikistan) in 2011–2018 was carried out. The use of AD was evaluated in total, by groups in accordance with the WHO ATC/DDD index: penicillins, cephalosporins, aminoglycosides, fluoroquinolones, tetracyclines, and other antibiotics, as well as separately by international nonproprietary names of drugs. The measurable unit was the number of grams of an active substance, followed by the calculation of the indicators DDD/100 bed-days and percentage of total DDD. Results. Significant changes in the structure of AD used for the initial antibacterial therapy of respiratory tract infections during the study period were revealed. There is a marked tendency to reduce the use of AD of the penicillin family and macrolides, with the transition to monotherapy with cephalosporins of the 3rd generation (ceftriaxone) and partially with fluoroquinolones. Conclusion. Monitoring the use of AD in hospital departments on basis of the ATC/DDD methodology allows to make strategic decisions regarding the tactics of antibacterial therapy, determine the orientation of administrative measures and improve the range of antibacterial agents with the introduction of the modern effective drugs into practice in the future.

Rational antibiotic therapy of respiratory tract infections in a primary care setting

Rational antibiotic therapy of respiratory tract infections in a primary care setting

The protocol of empirical antimicrobial therapy of the inpatient hospital of the National Medical and Surgical Center n. a. N. I. Pirogov (fourth edition, 2018)

The protocol of empirical antimicrobial therapy (AMT) in the National Medical &amp; Surgical Center n. a. N. I. Pirogov is a part of antimicrobial stewardship program, implemented in 2013. The protocol is based on local antimicrobial resistance data, takes into account features of the hospital and contains the decision-making process for risk stratification of antibiotic-resistant microorganisms, for start, choice, removal of AMT and its results assessment, as well as differentiated algorithms of empirical antibiotic therapy for respiratory tract infections, skin and soft tissues infections, urinary tract infections, bloodstream infections, intra-abdominal infections, periprosthetic joint infection, central nervous system infection, infections in neutropenic patients, treatment regimens for antibiotic-associated colitis. The protocol is updated annually, the fourth edition of the protocol is presented.

Рациональная антибактериальная терапия при инфекциях дыхательных путей у детей в аспекте предупреждения антимикробной резистентности

Рациональная антибактериальная терапия при инфекциях дыхательных путей у детей в аспекте предупреждения антимикробной резистентности

Probiotics for Modification of the Incidence or Severity of Respiratory Tract Infections.

There is increasing interest in probiotics for therapy and prevention of infectious diseases. There are no published trials of probiotics as therapy for respiratory tract infections (RTIs) in children or adults. There is low quality, inconsistent evidence for the efficacy of probiotics for prevention of RTIs or ventilator-associated pneumonia or for modification of the severity of RTIs.

Результаты тестирования педиатров по вопросам антибактериальной терапии при инфекциях дыхательных путей

Результаты тестирования педиатров по вопросам антибактериальной терапии при инфекциях дыхательных путей

Probiotics for Modification of the Incidence or Severity of Respiratory Tract Infections.

There is increasing interest in probiotics for therapy and prevention of infectious diseases. There are no published trials of probiotics as therapy for respiratory tract infections (RTIs) in children or adults. There is low quality, inconsistent evidence for the efficacy of probiotics for prevention of RTIs or ventilator-associated pneumonia or for modification of the severity of RTIs.

Pharmacoepidemiological analysis of the use of antibacterial drugs in the pulmonary department of the multi-specialty hospital of the Republic of Tajikistan

The uncontrolled and excessive use of antibiotics in infectious diseases significantly reduces the effectiveness of the drug therapy, increases the risk of adverse reactions, increases the cost of treatment and, most importantly, promotes the growth and spread of antibiotic resistance. Monitoring of the consumption of this group of drugs for systemic use is one of the most important methods used in the system of measures to improve prescribing practices of this group. Aim . To analyze the consumption of antimicrobial agents in the pulmonary department of the multi-specialty hospital using the DDD-methodology. Materials and methods . The retrospective descriptive analysis of prescribing pharmacotherapy for patients being treated in the pulmonary department of the Sughd regional clinical hospital (Khujand, Tajikistan) was performed. Using the ATC/DDD-methodology the consumption of antimicrobial agents was studied. As a unit of measurement the grams of the active substance was used with the subsequent calculation of the indicator of DDD/100 bed-days and the percentage of the total DDD. Results and discussion . The DDD-analysis of the consumption of antimicrobial drugs on the example of the pulmonary department of the multi-specialty hospital showed a significant change in the structure of the drug consumption in this group for the starting antibiotic therapy of respiratory tract infections over the past five years. A clear downward tendency was identified in the consumption of drugs of penicillin and macrolides with the transition to monotherapy with cephalosporins of the 3-rd generation (ceftriaxone) and partially fluoroquinolones. Conclusions . Monitoring of the consumption of antimicrobials in in-patient departments using the ATC/DDD-methodology allows to make strategic decisions concerning the tactics of antibiotic treatment of diseases according to the department specialization, as well as to determine the direction of administrative measures for further improvement of the range of antibacterial drugs introducing modern effective products into practice and optimizing the consumption of antibiotics in each specific department.

Effects 4.5 years after an interactive GP educational seminar on antibiotic therapy for respiratory tract infections: a randomized controlled trial.

The few studies assessing long-term effects of educational interventions on antibiotic prescription have produced conflicting results. Our aim was to assess the effects after 4.5 years of an interactive educational seminar designed for GPs and focused on antibiotic therapy in respiratory tract infections (RTIs). The seminar was expected to decrease antibiotic prescriptions for any diagnosis. We conducted a randomized controlled parallel-group trial in a Paris suburb (France), with GPs as the randomization unit and prescriptions as the analysis unit. The intervention occurred in September 2004 and the final assessment in March 2009. Among 203 randomized GPs, 168 completed the study, 70 in the intervention group and 98 in the control group. Intervention GPs were randomized to attending only a 2-day interactive educational seminar on evidence-based guidelines about managing RTIs or also 1 day of problem-solving training. The primary outcome was the percentage of change in the proportion of prescriptions containing an antibiotic for any diagnosis in 2009 versus 2004. An intention-to-treat sensitivity analysis was performed using multiple imputation. After 4.5 years, absolute changes in the primary outcome measure were -1.1% (95% confidence interval: -2.2 to 0.0) in the intervention group and +1.4% (0.3-2.6) in the control group, yielding an adjusted between-group difference of -2.2% (-2.7 to -1.7; P < 0.001). Both intervention modalities had significant effects, and multiple imputation produced similar results. A single, standardized and interactive educational seminar targeting GPs significantly decreased antibiotic use for RTIs after 4.5 years.