Respiratory viral infections in children with cancer and febrile neutropenia and children undergoing hematopoietic stem cell transplantation.

PURPOSE OF REVIEW: The scope of this review is to understand the epidemiology and potential role of respiratory viral infections in children with cancer and febrile neutropenia, as well as in children, undergoing hematopoietic stem cell transplantation. Early detection of respiratory viral infections through molecular diagnostic techniques has allowed recent randomized clinical studies to advance the possibility of more rational use of antimicrobials in this susceptible population. RECENT FINDINGS: Progress has been made in the early detection of respiratory viruses in episodes of fever and neutropenia in children with cancer. In selected patients who meet specific clinical safety criteria and have negative bacterial cultures, it has been possible to safely and effectively discontinue antimicrobials. This has been validated in recent randomized clinical studies. However, more evidence is still needed for a similar indication in children, undergoing hematopoietic stem cell transplantation with viral respiratory infection episodes. SUMMARY: Understanding the role of respiratory viral infections in populations of immunocompromised children may contribute to a more rational use of antimicrobials and, in the near future, may help to decrease antimicrobial resistance in this susceptible population.

Understanding antibiotic knowledge, attitudes, and practices: a cross-sectional study in physicians from a Colombian region, 2023.

BACKGROUND: Antibiotic resistance has been identified as a global health threat. Knowledge, attitudes, and inappropriate prescription practices of antibiotics by physicians play a crucial role in this problem. In Colombia, research addressing this issue is scarce. METHODS: A cross-sectional study involving 258 physicians was conducted. A scale with questions on sociodemographic aspects, level of education, satisfaction with antibiotic education received, and knowledge, attitudes, and practices was administered. The scale was designed for each item to be analyzed individually or as a total score ranging from 0 to 100 (0 being the lowest and 100 the highest). RESULTS: 31.5% of physicians rated the education received on antibiotics as fair to poor. The knowledge score was 80.1 (IQR 70.5-87.5); however, 25.2% agreed to some extent that amoxicillin is useful in treating most respiratory infections, and 15% agreed that antibiotics are effective in treating upper respiratory infections. Attitudes scored 80.2 (IQR 75.0-86.5), with 99% stating that bacterial resistance is a public health problem in Colombia, but only 56.9% considering it a problem affecting their daily practice. Practices scored 75.5 (IQR 68.8-81.2), and 71.7% affirmed that if they refuse to prescribe antibiotics to a patient who does not need them, the patient can easily obtain them from another physician. General practitioners were found to have lower scores in all three indices evaluated. CONCLUSION: The study reveals enduring misconceptions and concerning practices in antibiotic prescription, particularly among general practitioners. Enhancing knowledge necessitates the implementation of continuous medical education programs that focus on updated antibiotic guidelines, and resistance patterns. Fostering positive attitudes requires a culture of trust and collaboration among healthcare professionals. Practical enhancements can be realized through the establishment of evidence-based prescribing guidelines and the integration of regular feedback mechanisms. Moreover, advocating for the inclusion of antimicrobial stewardship principles in medical curricula is crucial, emphasizing the significance of responsible antibiotic use early in medical education.

Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. OBJECTIVE: To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease. METHODS: CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3). RESULTS: In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. CONCLUSIONS: Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Effect of carbohydrates on the adhesion of Bordetella bronchiseptica to the respiratory epithelium in rabbits.

This study proposes an ecological approach for preventing respiratory tract infections caused by Bordetella bronchiseptica in mammals using a mixture of carbohydrates. In an in vivo study, 51-day-old New Zealand rabbits were treated with a solution containing 1 × 107 CFUs of B. bronchiseptica and 250 µg of one of the following carbohydrates: N acetylglucosamine (GlcNAc), N acetylgalactosamine (GalNAc), alpha methyl mannose (AmeMan), alpha methyl glucose (AmeGlc) and sialic acid (Neu5AC). Positive (B. bronchiseptica) and negative (Physiological Saline Solution (PSS)) controls were included. Animals treated with GlcNAc or AmeGlc showed no clinical signs of infection and exhibited a significant reduction (p < 0.05) in the severity of microscopic lesions evaluated in the nasal cavity and lung compared with the positive controls. Additionally, the presence of bacteria was not detected through microbiological isolation or PCR in the lungs of animals treated with these sugars. Use of a mixture of GlcNAc and AmeGlc resulted in greater inhibition of microscopic lesions, with a significant reduction (p < 0.05) in the severity of these lesions compared to the results obtained using individual sugars. Furthermore, the bacterium was not detected through microbiological isolation, Polymerase Chain Reaction (PCR) or indirect immunoperoxidase (IIP) in this group.

Factors Associated with Inhaled Bronchodilator and Oral Corticosteroid Use in Young Children with First Lower Respiratory Tract Infection.

OBJECTIVES: To examine factors associated with claims for and potential overuse of inhaled bronchodilators (IBs) and oral corticosteroids (OCSs) for children <2 years old at first lower respiratory tract infections (LRTIs). STUDY DESIGN: Retrospective cohort study using Colorado All Payer Claims data from 2009 through 2019. Children with asthma were excluded. Primary outcomes were 1) IB and 2) OCS claims within 7 days of index LRTI. Primary predictors were previous IB or OCS claims for each outcome respectively. Covariates included demographics, atopy, family history of asthma, complex chronic conditions, prior inhaled corticosteroid claim, and location of index LRTI. Separate multivariable logistic regression models were used for each outcome. RESULTS: Of 10 194 eligible children, 1468 (14.4%) had an IB and 741 (7.3%) an OCS claim at or within 7 days of index LRTI. Index LRTIs were most often at outpatient visits (64%). Adjusting for covariates, prior IB prescription was associated with the IB outcome (aOR 1.9; 95% CI 1.3, 2.8), and prior OCS prescription was associated with the OCS outcome (AOR 2.2; 95% CI 1.7, 2.9). Other variables associated with either outcome included age, sex, insurance, location, and atopy. Prior inhaled corticosteroid claim, asthma family history, and complex chronic conditions were not associated with either outcome. CONCLUSIONS: This study identifies factors that might serve as opportunities for de-implementation strategies for IB and OCS overuse in young children with LRTI.

Utility of Respiratory Pathogen Panels in the Outpatient Oncology Setting.

Oncology patients presenting for outpatient evaluation of a respiratory tract infection (RTI) are often tested for a variety of viruses with a respiratory pathogen panel (RPP) in addition to influenza and SARS-CoV-2. This triad of testing is expensive and uncomfortable because it requires 2 nasal swabs. Little evidence supports the use of an RPP in outpatient settings, but it is routinely ordered. This retrospective chart review analyzed 183 RPPs performed at Jefferson between April 2020 and November 2021 in outpatient oncology patients presenting with RTI. Data collected included patient demographics, symptoms, and exam findings at time of RPP, additional testing completed, results of RPP, antibiotic and antiviral use before and after RPP results, and patient outcomes 30 days after RPP. Descriptive statistics were calculated. Of the 183 RPPs analyzed, 16.9% (31) were positive for at least 1 respiratory virus. Fifty-two patients (28.4%) started antibiotics before results of the RPP. Of those, 2 patients (3.8%) had a change in antibiotic plan after RPP results returned. Zero patients were started on antiviral medication before results of the RPP. One patient started antiviral treatment after RPP results returned. In total, only 3 patients (1.6%) had an RPP-driven change in medication management. This study suggests limited utility in use of RPPs for oncology patients presenting to the office with RTI symptoms. Targeted testing with a single nasal swab for influenza, RSV, and SARS-CoV-2 may be more clinically relevant. The authors hope to use these data to implement a quality improvement initiative to reduce RPP utilization in this population.

[Use of antibiotics, in a pediatric hospital, for respiratory infection and diarrheal disease]. / Uso de antibióticos, en hospital pediátrico, para infección respiratoria y enfermedad diarreica.

Background: The World Health Organization (WHO) reports an increasing unjustified use of antibiotics in the treatment of Acute Respiratory Infections (ARI) and Acute Diarrheal Diseases (ADD) in children under five years of age. This has generated problems such as polypharmacy and the inappropriate use of antibiotics; characterized by incorrect dosage, use in viral infections, prescription inconsistent with clinical guidelines. Objective: To analyze the prescription of antibiotics, their diagnostic-therapeutic congruence, as well as the correct filling of the medical prescription, in a tertiary level hospital in Mexico. Material and methods: Observational, descriptive cross-sectional study. The electronic medical prescriptions made during the period January-December 2017 with a clinical diagnosis of ARI and EDA were analyzed. Results: Of a total of 21,446 boys and girls under five years of age, 10,233 prescriptions were issued for the treatment of ARI and ADD diagnoses. 80% of the prescriptions complied with the items indicated in the electronic file. Conclusions: The prescription of antibiotics showed a prudent use of antibiotics both in the management of acute diarrheal diseases and in the management of acute respiratory diseases. Diagnostic-therapeutic congruence was found in most of the cases in the prescriptions analyzed.

Introducción: la Organización Mundial de Salud (OMS) reporta un creciente uso injustificado de antibióticos en el tratamiento de las infecciones respiratorias agudas (IRA) y las enfermedades diarreicas agudas (EDA) en menores de cinco años de edad. Lo anterior ha generado problemas como la polifarmacia y el uso inapropiado de antibióticos, caracterizado por dosis incorrectas, uso en infecciones virales y prescripción incongruente con las directrices clínicas. Objetivo: analizar la prescripción de antibióticos, su congruencia diagnóstico-terapéutica, así como el correcto llenado de la receta médica, en un hospital de tercer nivel de México. Material y métodos: estudio transversal observacional, descriptivo. Se analizó las recetas médicas electrónicas realizadas durante el periodo enero-diciembre de 2017 con diagnóstico clínico de IRA y EDA. Resultados: de un total de 21,446 niños y niñas menores de cinco años se otorgaron 10, 233 recetas para el tratamiento de los diagnósticos de IRA y EDA. El 80% de las recetas cumplieron con de los rubros indicados en el expediente electrónico. Conclusiones: la prescripción de antibióticos mostró un uso prudente de antibióticos tanto en el manejo de las enferdades diarreicas agudas como en el manejo de las enfermedades respiratorias agudas. Se encontró, en la mayoría de los casos, congruencia diagnóstico-terapéutica en las prescripciones analizadas.

Prescribing of Outpatient Antibiotics Commonly Used for Respiratory Infections Among Adults Before and During the Coronavirus Disease 2019 Pandemic in Brazil.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

The HRA2pl fusion peptide exerts in vitro antiviral activity against human respiratory paramyxoviruses and pneumoviruses.

Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory infections reported by the Secretariat of Health, in 2019. The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza-2 (hPIV-2) are responsible for many respiratory infections. Currently, palivizumab, a monoclonal antibody against the fusion protein F, is the treatment of choice against hRSV infections. This protein is being studied for the design of antiviral peptides that act by inhibiting the fusion of the virus and the host cell. Therefore, we examined the antiviral activity of the HRA2pl peptide, which competes the heptad repeat A domain of the F protein of hMPV. The recombinant peptide was obtained using a viral transient expression system. The effect of the fusion peptide was evaluated with an in vitro entry assay. Moreover, the effectiveness of HRA2pl was examined in viral isolates from clinical samples obtained from patients with infections caused by hRSV, hMPV, or hPIV-2, by evaluating the viral titer and the syncytium size. The HRA2pl peptide affected the viruses' capacity of entry, resulting in a 4-log decrease in the viral titer compared to the untreated viral strains. Additionally, a 50% reduction in the size of the syncytium was found. These results demonstrate the antiviral potential of HRA2pl in clinical samples, paving the way toward clinical trials.

Impact of the multiplex molecular FilmArray Respiratory Panel on antibiotic prescription and clinical management of immunocompromised adults with suspected acute respiratory tract infections: A retrospective before-after study.

This study aimed to assess the impact of the implementation of a rapid multiplex molecular FilmArray Respiratory Panel (FRP) on the medical management of immunocompromised patients from a community general hospital. We conducted a single-center, retrospective, and before-after study. Two periods were evaluated: before the implementation of the FRP (pre-FRP) from April 2017 to May 2018 and after the implementation of the FRP (post-FRP) from January to July 2019. The inclusion criteria were immunocompromised patients over 18 years of age with suspected acute respiratory illness tested by conventional diagnostic methods (pre-FRP) or the FilmArray™ Respiratory Panel v1.7 (post-FRP). A total of 142 patients were included, 64 patients in the pre-FRP and 78 patients in the post-FRP. The positive detection rate was significantly higher in the post-FRP (63% vs. 10%, p<0.01). There were more patients receiving antimicrobial treatment in the pre-FRP compared with the post-FRP period (94% vs. 68%, p<0.01). A decrease in beta-lactam (89% vs. 61%, p<0.01) and macrolide (44% vs. 13%, p<0.01) prescriptions were observed in the post-FRP. No differences were observed in oseltamivir use (22% vs. 13%, p=0.14), changes in antimicrobial treatment, hospital admission rate, days-reduction in droplet isolation precautions, hospital length of stay (LOS), admission to intensive care unit (ICU), LOS in ICU, treatment failure and 30-day mortality. The implementation of the FRP impacted patient care by improving diagnostic yield and optimizing antimicrobial treatment in immunocompromised adult patients.

Current and emerging pharmacological treatments for respiratory syncytial virus infection in high-risk infants.

INTRODUCTION: The human respiratory syncytial virus (hRSV) is the leading cause of respiratory infections in children, older adults, and patients with comorbidities. Since the hRSV discovery, multiple efforts have been made to generate therapies that control the devastating effects on the population at risk in winter. AREAS COVERED: This article describes the development of different drugs and treatments approved for use in the risk-population against hRSV infection. In addition, an exhaustive bibliographical review is presented here describing new candidate molecules under evaluation and showing promising results in different assays in animal models and clinical studies. Additionally, we highlight antiviral molecules, monoclonal antibodies, and nanobodies among the new candidate treatments. EXPERT OPINION: hRSV is a major burden for the health systems, promoting their collapse worldwide. Therefore, developing new therapies is an essential goal to decrease hospitalization rates caused by hRSV infection in high-risk populations. For this, injecting resources and exploring new targets in addition to the F protein is an interesting alternative to achieve this goal.

Quinones as Promising Compounds against Respiratory Viruses: A Review.

Respiratory viruses represent a world public health problem, giving rise to annual seasonal epidemics and several pandemics caused by some of these viruses, including the COVID-19 pandemic caused by the novel SARS-CoV-2, which continues to date. Some antiviral drugs have been licensed for the treatment of influenza, but they cause side effects and lead to resistant viral strains. Likewise, aerosolized ribavirin is the only drug approved for the therapy of infections by the respiratory syncytial virus, but it possesses various limitations. On the other hand, no specific drugs are licensed to treat other viral respiratory diseases. In this sense, natural products and their derivatives have appeared as promising alternatives in searching for new compounds with antiviral activity. Besides their chemical properties, quinones have demonstrated interesting biological activities, including activity against respiratory viruses. This review summarizes the activity against respiratory viruses and their molecular targets by the different types of quinones (both natural and synthetic). Thus, the present work offers a general overview of the importance of quinones as an option for the future pharmacological treatment of viral respiratory infections, subject to additional studies that support their effectiveness and safety.

Prevalence, outcomes, and predictors of multidrug-resistant nosocomial lower respiratory tract infections among patients in an ICU.

OBJECTIVE: To determine the prevalence, outcomes, and predictors of multidrug-resistant nosocomial lower respiratory tract infections (LRTI) in patients in an ICU. METHODS: This was an observational cohort study involving patients with nosocomial LRTI (health care-associated pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia). Data were prospectively collected between 2015 and 2019. The multidrug-resistant pathogens (MDRPs) identified in the isolates studied included resistant to extended-spectrum cephalosporin-resistant and carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus at microbiological diagnosis. RESULTS: During the study period, 267 patients in the ICU were diagnosed with LRTI, microbiological confirmation of LRTI having been obtained in 237. Of these, 146 (62%) had at least one MDRP isolate. Patients infected with MDRP were found to have poorer outcomes than patients infected with susceptible strains, such as prolonged mechanical ventilation (18.0 days vs. 12.0 days; p < 0.001), prolonged ICU length of stay (23.0 days vs.16.0 days; p < 0.001), and higher mortality (73% vs. 53%; p < 0.001) when compared with patients infected with susceptible strains. Hospital length of stay ≥ 5 days (OR = 3.20; 95% CI: 1.39-7.39; p = 0.005) and prolonged use vasoactive drugs (OR = 3.15; 95% CI: 1.42-7.01; p = 0.004) were independent predictors of LRTI caused by MDRPs (LRTI-MDRP). The presence of LRTI-MDRP was found to be an independent predictor of death (OR = 2.311; 95% CI: 1.091-4.894; p = 0.028). CONCLUSIONS: Prolonged use of vasoactive drugs and prolonged hospital length of stay were independent predictors of LRTI-MDRP in this population of critically ill patients with very poor outcomes.

Antibiotic stewardship with upper respiratory tract infection patients at student health centers: Providers' communication experiences and strategies.

BACKGROUND: Effective provider-patient communication can improve antibiotic stewardship in primary care, but providers find it challenging to discuss antibiotics with patients. This study, focused on college student health centers, examines patients' tactics for obtaining antibiotics for upper respiratory tract infections and providers' communication strategies for improving patient understanding and reducing demand. METHODS: Health care providers (N = 103) employed at student health centers on large and primarily residential college campuses in the U.S. completed an online survey. RESULTS: Providers perceived patients as wanting antibiotics in approximately 50% of upper respiratory tract infection visits and noted multiple patient tactics to obtain them, including reports of prior prescribing, suggested diagnoses, and direct requests. Providers used multiple strategies to manage patient demand, including explanation of the diagnosis, antibiotic utility and risks, and treatment plan. DISCUSSION: This study extends prior research indicating that patients exercise a range of influence tactics to obtain antibiotics, and thereby create discomfort for providers. The study also elucidates providers' efforts to counter these influence tactics and steward antibiotics by educating patients. CONCLUSIONS: Additional research is needed to specify the most effective ways for providers to respond to patients' influence tactics, including the best approaches to explaining diagnosis, treatment, and antibiotic resistance.

OM-85 BV in pediatric recurrent respiratory tract infections: a cost-utility analysis.

BACKGROUND: Despite the growing evidence on efficacy, little is known regarding the cost-utility of Vaxom/Imocur (OM-85 BV) supplementation to decrease the probability of recurrent respiratory tract infections in OM-85 BV to reduce the incidence of recurrent respiratory tract infections in children. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of OM-85 BV in a patient aged 1-6 with a history of recurrent respiratory tract infections. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated using the willingness-to-pay defined for Colombia of US$5180 per QALY. The time horizon defined was six months. Costs were estimated from a societal perspective. RESULTS: The expected annual cost per patient with OM-85 BV was US$843 and with placebo was US$1167. The QALYs per person estimated with OM-85 BV was 0.91 and with placebo was 0.89. CONCLUSION: In conclusion, our study shows that OM-85 BV is a cost-effective strategy to reduce the incidence of recurrent respiratory tract infections in children. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Country data on AMR in Mexico in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review AMR in Mexico and initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rises in AMR and to improve patient outcomes. METHODS: National AMR initiatives in Mexico, antibiotic use and prescribing, and availability of susceptibility data, particularly the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used in Mexico for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) were also reviewed, along with local antibiotic availability. Insights from a local clinician were sought to contextualize this information. CONCLUSIONS: The Mexican national AMR strategy was published in 2018. This comprised similar objectives to the Global Action Plan from the World Health Assembly (2015) and was compulsory, requiring full compliance from members of the National Health System. Historically, antibiotic consumption in Mexico has been high, however, between 2000 and 2015, consumption fell, in sharp contrast to the majority of countries. Mexico lacks a national surveillance network for AMR, however there are several ongoing global surveillance studies providing local antibiotic susceptibility data. International and local antibiotic prescribing guidelines for CA-RTIs are used. A more standardized inclusive approach in developing local guidelines, using up-to-date local surveillance data of isolates from community-acquired infections, could make guideline use more locally relevant. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development in Mexico and improve patient outcomes.

Country data on AMR in Brazil in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review the situation with respect to AMR in Brazil and initiatives addressing it. Identifying areas where more information is required will provide a call to action to minimize any further rises in AMR within Brazil and to improve patient outcomes. METHODS: National initiatives to address AMR, antibiotic use and prescribing in Brazil, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infections (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines for CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) commonly used locally were also reviewed, along with local antibiotic availability. CONCLUSIONS: In Brazil there have been some initiatives addressing AMR such as the National Action Plan for AMR, established in 2018. Antibiotic consumption in Brazil is high but a ban on over-the-counter sales of antibiotics has led to a decrease in consumption. Local antibiotic susceptibility testing needs to be increased and the Survey of Antibiotic Resistance (SOAR) study in Brazil will provide useful data for pathogens causing CA-RTIs. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Brazil, could make guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical outcomes for patients.