Respiratory Tract Infections In Adults Research Articles

Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus.

Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals. However, elderly individuals develop severe respiratory disease on HMPV reinfection that leads to a high risk for morbidity and mortality. In this study, we developed a mouse model to mirror HMPV reinfection in elderly humans. C57BL/6J mice were infected with HMPV at 6-7 wk old, aged in-house, and rechallenged with high-dose virus at 70 wk. Aged rechallenged mice had profound weight loss similar to primary infected mice, increased lung histopathology, and accumulated cytotoxic CD8+CD44+CD62L-CD69+CD103+ memory cells despite having undetectable lung virus titer. When aged mice 14 mo postinfection (p.i.) or young mice 5 wk p.i. were restimulated with HMPV cognate Ag to mimic epitope vaccination, aged mice had an impaired CD8+ memory response. Convalescent serum transfer from young naive or 5 wk p.i. mice into aged mice on day of infection did not protect. Aged mice vaccinated with UV-inactivated HMPV also exhibited diminished protection and poor CD8+ memory response compared with young mice. These results suggest aged individuals with HMPV reinfection have a dysregulated CD8+ memory T cell response that fails to protect and exacerbates disease. Moreover, aged mice exhibited a poor memory response to either epitope peptide or UV-inactivated vaccination, suggesting that aged CD8+ T cell dysfunction presents a barrier to effective vaccination strategies.

Estimation of the Number of Respiratory Syncytial Virus-Associated Hospitalizations in Adults in the European Union.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated hospitalization is critical for planning RSV-related healthcare across Europe. We gathered RSV-associated hospitalization estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 European Union (EU) countries using nearest-neighbor matching, multiple imputations, and 2 sets of 10 indicators. On average, 158 229 (95% confidence interval [CI], 140 865-175 592) RSV-associated hospitalizations occur annually among adults in the EU (≥18 years); 92% of these hospitalizations occur in adults ≥65 years. Among 75-84 years, the annual average is estimated at 74 519 (95% CI, 69 923-79 115) at a rate of 2.24 (95% CI, 2.10-2.38) per 1000. Among ≥85 years, the annual average is estimated at 37 904 (95% CI, 32 444-43 363) at a rate of 2.99 (95% CI, 2.56-3.42). Our estimates of RSV-associated hospitalizations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalization estimate in adults was lower but of a similar magnitude to the estimate in young children (0-4 years): 158 229 (95% CI, 140 865-175 592) versus 245 244 (95% CI, 224 688-265 799).

Human Bocavirus in Childhood: A True Respiratory Pathogen or a "Passenger" Virus? A Comprehensive Review.

Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and lower respiratory tract infections in adults and children. However, its role as a respiratory pathogen is still not fully understood. It has been reported both as a co-infectious agent (predominantly with respiratory syncytial virus, rhinovirus, parainfluenza viruses, and adenovirus), and as an isolated viral pathogen during respiratory tract infections. It has also been found in asymptomatic subjects. The authors review the available literature on the epidemiology of HBoV, the underlying risk factors associated with infection, the virus's transmission, and its pathogenicity as a single pathogen and in co-infections, as well as the current hypothesis about the host's immune response. An update on different HBoV detection methods is provided, including the use of quantitative single or multiplex molecular methods (screening panels) on nasopharyngeal swabs or respiratory secretions, tissue biopsies, serum tests, and metagenomic next-generations sequencing in serum and respiratory secretions. The clinical features of infection, mainly regarding the respiratory tract but also, though rarely, the gastrointestinal one, are extensively described. Furthermore, a specific focus is dedicated to severe HBoV infections requiring hospitalization, oxygen therapy, and/or intensive care in the pediatric age; rare fatal cases have also been reported. Data on tissue viral persistence, reactivation, and reinfection are evaluated. A comparison of the clinical characteristics of single infection and viral or bacterial co-infections with high or low HBoV rates is carried out to establish the real burden of HBoV disease in the pediatric population.

Viral etiology of lower respiratory tract infections in adults in the pre-COVID-19 pandemic era: A cross-sectional study in a single center experience from Cameroon.

Respiratory viruses are responsible for the majority of lower respiratory tract infections (LRTIs) worldwide. However, there is a gap on the epidemiology of viral LRTIs in adults in sub-Saharan African countries. In Cameroon, like in other countries, the role of viral respiratory pathogens in the etiology of LRTIs in adults is helpful for clinical management. This study aimed to determine the viral aetiologies of LRTIs among hospitalized adults in a reference center for respiratory diseases in the town of Yaounde in Cameroon and its surroundings. A cross-sectional study was conducted from January 2017 to January 2018 at Jamot Hospital in Yaounde (Cameroon). Clinical and demographic information; BAL and sputa were collected from hospitalized patients meeting LRTI case definitions. The clinical samples were investigated for respiratory pathogens with a commercial Reverse Transcriptase Real-Time Polymerase Chain Reaction (RT-PCR) targeting 21 viruses, cultures for bacterial and fungal infections. The 77 included adult patients with LRTIs had an appropriate clinical sample for microbial investigations. A viral agent was detected in 22.1% (17/77) samples. The main viruses detected included rhinovirus (10/77), coronavirus (hCoV-OC43 and hCoV-229E), and influenza A virus (3/77 each). A concomitant viral and bacterial co-infection occurred in 7.8% of patients (6/77) while viral co-infection occurred in one patient (1.3%). No Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) was detected in clinical samples. Most patients were under antimicrobials before getting diagnosed. Respiratory viruses account for 22.1% of LRTIs in hospitalized patients in this study. Despite prior antimicrobial therapy and delay, rhinovirus, coronavirus and influenza A virus were the most detected in patients in the pre-COVID-19 pandemic era in a single center experience from Cameroon.

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).

Immunoinformatics aided approach for predicting potent cytotoxic T cell epitopes of respiratory syncytial virus

Respiratory syncytial virus (RSV) is an infectious viral pathogen that causing serious respiratory infection in adults and neonates. The only approved therapies for RSV are the monoclonal antibodies palivizumab and its derivative motavizumab. Both treatments are expensive and require a hospital setting for administration. A vaccine represents a safe, effective and cheaper alternative for preventing RSV infection. In silico prediction methods have proven to be valuable in speeding up the process of vaccine design. In this study, reverse vaccinology methods were used to predict the cytotoxic T lymphocytes (CTL) epitopes from the entire proteome of RSV strain A. From amongst 3402 predicted binders to 12 high frequency alleles from the Immune Epitope Database (IEDB), 567 had positive processing scores while 327 epitopes were predicted to be immunogenic. A thorough examination of the 327 epitopes for possible antigenicity, allergenicity and toxicity resulted in 95 epitopes with desirable properties. A BLASTp analysis revealed 94 unique and non-homologous epitopes that were subjected to molecular docking across the 12 high frequency alleles. The final dataset of 70 epitopes contained 13 experimentally proven and 57 unique epitopes from a total of 11 RSV proteins. From our findings on selected T-cell-specific RSV antigen epitopes, notably the four epitopes confirmed to exhibit stable binding by molecular dynamics. The prediction pipeline used in this study represents an effective way to screen the immunogenic epitopes from other pathogens. Communicated by Ramaswamy H. Sarma

Characterization of viral pathogens associated with symptomatic upper respiratory tract infection in adults during a low COVID-19 transmission period.

The epidemiology of respiratory tract infections (RTI) has dramatically changed over the course of the COVID-19 pandemic. A major effort in the clinical management of RTI has been directed toward diagnosing COVID-19, while the causes of other, common community RTI often remain enigmatic. To shed light on the etiological causes of RTI during a low COVID-19 transmission period in 2021, we did a pilot study using molecular testing for virologic causes of upper RTI among adults with respiratory symptoms from Almaty, Kazakhstan. Adults presenting at two public hospitals with respiratory symptoms were screened using SARS-CoV-2 PCR on nasopharyngeal swabs. A subset of RTI+, COVID-19-negative adults (n = 50) was then tested for the presence of common RTI viruses and influenza A virus (IAV). Next generation virome sequencing was used to further characterize the PCR-detected RTI pathogens. Of 1,812 symptomatic adults, 21 (1.2%) tested SARS-CoV-2-positive. Within the COVID-19 negative outpatient subset, 33/50 subjects (66%) had a positive PCR result for a common community RTI virus, consisting of human parainfluenza virus 3-4 (hPIV 3-4) in 25/50 (50%), rhinovirus (hRV) in 2 (4%), hPIV4-hRV co-infection in four (8%) and adenovirus or the OCR43/HKU-1 coronavirus in two (4%) cases; no IAV was detected. Virome sequencing allowed to reconstruct sequences of most PCR-identified rhinoviruses and hPIV-3/human respirovirus-3. COVID-19 was cause to a low proportion of symptomatic RTI among adults. Among COVID-negative participants, symptomatic RTI was predominantly associated with hPIV and hRV. Therefore, respiratory viruses other than SARS-CoV-2 should be considered in the clinical management and prevention of adult RTI in the post-pandemic era.

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

IntroductionFifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations. MethodsWe conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework. ResultsNine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from −10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from −8 to 3% for PPV23 and 9 to 12% for PCV13. ConclusionsOverall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.

Duration of antibiotic therapy for common respiratory infections in adults

Antibiotic therapy is not recommended for the majority of adult outpatients with a respiratory tract infection. When antibiotic therapy is mandatory, its duration should be as short as possible in order to avoid side effects and reduce costs. This literature review summarises the recommendations for new, shorter courses of antibiotics. The recommended duration of antibiotic treatment for community-acquired pneumonia, chronic obstructive pulmonary disease exacerbation and acute otitis media is now 5 days, 6 days for pharyngitis and between 5 and 7 days for sinusitis. These recommendations do not apply to severe or complicated infections, infections with resistant agents or in immunosuppressed patients.

Detection of the Mycobacterium avium complex in dogs with lymphadenitis.

Mycobacterium avium complex (MAC) is connected to human immunosuppressive diseases, including HIV-AIDS, and may pose a zoonotic threat. MAC causes lymphadenopathy in children, respiratory infection in adults, and generalized infection in immunocompromised individuals. Infection with nontuberculous Mycobacteria (NTM) in humans is now primarily brought on by MAC. Recently, MAC members have emerged as pathogenic organisms for animals and humans. While dogs are generally resistant to mycobacterial infections, there have been some cases of infection that result in systemic or disseminated diseases. The organisms can be transmitted to dogs through oral contact, and their faeces can be a possible source of infection for dog owners. It is important to note that this ailment is zoonotic, especially if infected pet dogs are in prolonged contact with their humans. The study was planned to demonstrate the occurrence of MAC organisms and other Mycobacteria in dogs associated with lymphadenopathy cases with special emphasis on lymphadenitis. A total of 123 samples (100 lymph node aspirates, 15 lymph node tissues, and 8 blood samples) from 83 dogs suspected of lymphadenitis accompanied by gastroenteritis, chronic skin infections, immunosuppression, chronic pulmonary diseases, and other chronic undiagnosed diseases were studied. The samples were processed for cytological and microscopic examination by Ziehl-Neelsen staining. Following the decontamination procedure, the aspiration and lymph node tissue samples were inoculated into Middlebrook 7H11 media for up to 8 weeks. The aspirated material was also directly used for molecular detection by triplex-nested polymerase chain reaction (nPCR) assay. A cytological study revealed pyogranulomatous inflammation of the lymph node tissue. Impression smears from lymph node tissues displayed the presence of acid-fast organisms. Out of 83 cases of dogs, 8 were found to be positive for Mycobacterium spp. Among those 8 positive cases, 3 were confirmed to belong to MAC, and 5 belonged to the Mycobacterium tuberculosis complex (MTB complex). MAC and MTB are the underestimated bacteria that could be the causative agents of lymphadenitis in animals.

Antibiotic treatment of respiratory tract infections in adults in Norwegian general practice.

To analyse the prevalence of respiratory tract infection (RTI) episodes with and without antibiotic prescriptions in adult patients in Norwegian general practice during the period 2012-2019. Observational study linking data from the Norwegian Control and Payment for Health Reimbursements Database and the Norwegian Prescription Database. Episodes of acute RTIs in patients aged 18 years or older were identified and linked to antibiotic prescriptions dispensed within 7 days after diagnosis. We analysed annual infection rates and antibiotic prescription rates and antibiotics prescribed for the different RTI conditions. RTI episode rate per 1000 inhabitants was 312 in 2012 and 277 in 2019, but showed no linear trend of change during the study period (P = 0.205). Antibiotic prescription rate decreased from 37% of RTI episodes in 2012 to 23% in 2019 (P < 0.001). The reduction in prescribing was most pronounced for episodes coded with ICPC-2 symptom diagnoses, as well as upper RTIs, influenza, acute bronchitis and sinusitis. Prescriptions for phenoxymethylpenicillin decreased from 178 746 in 2012 to 143 095 in 2019, but increased as proportion of total antibiotic prescriptions from 40% in 2012 to 53% in 2019 (P < 0.001). This study demonstrates stable RTI episode rates and reduced antibiotic prescription rates for RTIs for adults in Norwegian general practice 2012-2019. We also observed a shift towards relatively more use of phenoxymethylpenicillin and less broad-spectrum antibiotics. These changes are in line with the aims of the Norwegian strategy against antibiotic resistance.

Executive summary of Chinese expert consensus for topical application of anti-microbial agents for lower respiratory tract infection in adults.

Executive summary of Chinese expert consensus for topical application of anti-microbial agents for lower respiratory tract infection in adults.

Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial

ObjectiveTo determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in...

Lung Effects of Household Air Pollution

Biomass fuel smoke, secondhand smoke, and oxides of nitrogen are common causes of household air pollution (HAP). Almost 2.4 billion people worldwide use solid fuels for cooking and heating, mostly in low- and middle-income countries. Wood combustion for household heating is also common in many areas of high-income countries, and minorities are particularly vulnerable. HAP in low- and middle-income countries is associated with asthma, acute respiratory tract infections in adults and children, chronic obstructive pulmonary disease, lung cancer, tuberculosis, and respiratory mortality. Although wood smoke exposure levels in high-income countries are typically lower than in lower-income countries, it is similarly associated with accelerated lung function decline, higher prevalence of airflow obstruction and chronic bronchitis, and higher all-cause and respiratory cause-specific mortality. Household air cleaners with high-efficiency particle filters have mixed effects on asthma and chronic obstructive pulmonary disease outcomes. Biomass fuel interventions in low-income countries include adding chimneys to cookstoves, improving biomass fuel combustion stoves, and switching fuel to liquid petroleum gas. Still, the impact on health outcomes is inconsistent. In high-income countries, strategies for reducing biomass fuel-related HAP are centered on community-level woodstove changeout programs, although the results are again inconsistent. In addition, initiatives to encourage home smoking bans have mixed success in households with children. Environmental solutions to reduce HAP have varying success in reducing pollutants and health problems. Improved understanding of indoor air quality factors and actions that prevent degradation or improve pollutedindoor air may lead to enhanced environmental health policies, but health outcomes must be rigorously examined.

Comparison of sputum specimens and nasopharyngeal swab specimens for diagnosis of acute human metapneumovirus-related lower respiratory tract infections in adults.

To detect human metapneumovirus, tests besides reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens are less accessible. Immunochromatography assays are rapid and simple without the need of any special equipment but sometimes are insufficiently sensitive. This study describes the usefulness of immunochromatography assays to detect human metapneumovirus in adult patients with human metapneumovirus-related acute lower respiratory tract infection using sputum specimens. This prospective single-center study enrolled adults and adolescents aged ≥16 years with signs and symptoms of an acute respiratory illness who were diagnosed with acute lower respiratory tract infection. The presence of human metapneumovirus infection was confirmed by seroconversion. Immunochromatography assays and real-time RT-PCR were performed to compare the efficacy of nasopharyngeal swab specimens and sputum specimens. Comparative results were obtained via McNemar's test. Overall, 337 patients were recruited in this study; 63 (18.7%) patients were seroconverted. Sputum specimens showed significantly higher positivity rates than nasopharyngeal swab specimens with both immunochromatography assays (p=0.0008) and real-time RT-PCR (p=0.014). Among 29 patients with pneumonia who had concordant positive real-time RT-PCR results for both nasopharyngeal swab specimens and sputum specimens, 21 (72.4%) had a higher viral load in the sputum specimens. Sputum specimens are more useful in detecting human metapneumovirus than nasopharyngeal swab specimens in adult patients with acute lower respiratory tract infection.

Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: A Delphi study

ABSTRACT Recurrent infections of upper and lower respiratory tract have an important clinical and economic impact, which can be reduced through appropriate preventive measures, including the use of immunomodulating agents, such as OM-85, which proved to be effective and safe in both adults and children. Although OM-85 can be useful for the prevention of respiratory tract infections, it is still underused in clinical practice. In order to evaluate the level of awareness of the disease burden of recurrent respiratory infections in adults and children and to assess the level of agreement on the prophylactic and therapeutic approach to the disease, including the use of immunomodulants, a Delphi study was performed. A board of six experts in the field of respiratory infections was appointed to elaborate a series of statements covering four main topics (disease, prevention, OM-85, and future strategies), which were thereafter voted by a panel of 30 experts. Results showed that prevention is unanimously recognized as the most important intervention to reduce disease burden, and the use of immunomodulation to improve the effectiveness of vaccination is gaining increasing favor among clinicians. In this respect, OM-85 is recognized as the most studied immunomodulating agent currently available, whose efficacy and safety make it a valuable tool to optimize the management of recurrent respiratory infections in both adults and children. In particular, the combined use of OM-85 and influenza vaccine was recognized as an effective and safe approach to improve the current prevention strategies in order to reduce the burden of recurrent respiratory infections.

Utility of Polymerase Chain Reaction in Nasopharyngeal Swabs for Identifying Respiratory Bacteria Causing Community-Acquired Pneumonia.

ABSTRACTTimely identification of a pathogen in lower respiratory tract infections (LRTI) can support appropriate antibiotics use. The difficulty of obtaining lower respiratory tract (LRT) samples limits the utility of point-of-care syndromic molecular assays. We assessed the performance of the FilmArray Pneumonia plus panel (FilmArray PP) in nasopharyngeal (NP) swab for detection of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Patients in the study included retrospectively consenting adults who attended the emergency department of Lausanne University Hospital between February 2019 and August 2020 for a community-acquired LRTI, with available NP swab and a high-quality LRT sample. These samples were tested with the FilmArray PP (cutoff of ≥104 copies/mL). Positive (PPA) and negative percent agreement (NPA) of FilmArray PP in NP swab were calculated, using (i) FilmArray PP in LRT sample and (ii) standard microbiological tests as reference standards. To assess the performance of a lower detection cutoff, NP samples were also tested with an in-house PCR (cutoff of ≥10 copies/mL) for S. pneumoniae and H. influenzae. Overall, 118 patients were included. FilmArray PP in LRT sample and standard microbiology tests detected S. pneumoniae in 19/118 and 12/118, H. influenzae in 44/118 and 19/118, and M. catarrhalis in 14/118 and 0/118, respectively. Using LRT FilmArray PP as reference, PPA and NPA of FilmArray PP on NP were 58% and 100% for S. pneumoniae, 61% and 100% for H. influenzae, and 57% and 99% for M. catarrhalis. Using standard diagnostic tests as reference, PPA and NPA were 58% and 96% for S. pneumoniae, 74% and 87% for H. influenzae, and indefinite and 92% for M. catarrhalis. Using a lower cutoff on NP (≥102 copies/mL), PPA was 68% for S. pneumoniae and 77% for H. influenzae with LRT FilmArray PP as reference. FilmArray PP in NP swabs has a limited PPA for identifying the most common etiologies of community-acquired LRTI irrespective of the reference standard, preventing its use for withholding antibiotics. The PCR detection cutoff does not explain the low PPA. The excellent NPA suggests the use of NP PCR results for rapidly targeted antimicrobial therapy.IMPORTANCE Timely identification of a pathogen in patients with lower respiratory tract infections is of paramount importance to avoid inappropriate antibiotic prescription. We aimed to evaluate the performance of a rapid syndromic molecular assay in nasopharyngeal swabs for identifying the most common bacterial causes of lower respiratory tract infections in adults (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). Our data show that nasopharyngeal molecular assay has a good concordance with lower respiratory tract sample when positive but not when negative. A positive result is therefore concordant with a lower respiratory tract infection and can be used to target antibiotics. Nevertheless, a negative result does not have a good concordance, so it cannot be used to withhold antibiotics. Our findings illustrate the potential utility of these easily collected samples for the management of patients with lower respiratory tract infections.

Prescribing of common outpatient antibiotics for respiratory infections in adults amid the COVID-19 pandemic in Brazil

Background: Inappropriate antibiotic use for SARS-CoV-2 infection has the potential to increase the burden of antibiotic resistance. Brazil experienced spread of a new SARS-CoV-2 variant in the fourth quarter (Q4) of 2020, resulting in the highest case counts in Latin America, raising concerns of antibiotic overuse. To better understand antibiotic use during the COVID-19 pandemic, we evaluated prescribing changes in antibiotics commonly used for outpatient respiratory infections (amoxicillin-clavulanate, azithromycin, and levofloxacin or moxifloxacin [AALM]) among adults aged ≥20 years in Brazil in 2020 versus 2019. Methods: We analyzed the IQVIA MIDAS medical data set for AALM prescribing by age group (20–39, 40–59, 60–64, 65–74, ≥75 years), comparing Q4 2020 rates to those in Q4 2019. We estimated crude rate ratios and 95% CIs using prescription number as the numerator (assuming Poisson counts) and age-adjusted population as the denominator. We also determined the most common prescribing specialties for each antibiotic across both time points. Results: Compared to Q4 2019, Q4 2020 azithromycin prescribing increased among all ages, ranging from 90.7% (95% CI, 90.0%–91.4%) in those aged 20–39 years to 927.2% (95% CI, 912.9%–941.7%) in those aged 65–74 years (Fig. 1). Amoxicillin-clavulanate prescribing decreased for most ages, ranging from −78.4% (95% CI, −78.7% to −78.1%) in those aged 60–64 years to −25.8% (95% CI, −26.6% to −25.0%) in those aged 65–74 years. Prescribing of levofloxacin or moxifloxacin decreased for most ages, ranging from −39.1% (95% CI, −39.4% to −38.8%) in those aged 20–39 years to −16.9% (95% CI, −18.1% to −15.7%) in those aged 60–64 years. For those aged ≥75 years, prescribing of amoxicillin-clavulanate and levofloxacin or moxifloxacin increased by 13.2% (95% CI, 11.9%–14.5%) and 43.1% (95% CI, 41.7%–44.5%), respectively. In Q4 2019 and Q4 2020, the 2 most common prescribing specialties for azithromycin were general practice (48%–50% of prescriptions) and gynecology (19%–25%). Compared to Q4 2019, infectious disease specialists in Q4 2020 saw the largest decline in percentage of azithromycin prescriptions (10% to 1%) and surgeons saw the largest increase (0% to 7%). General practitioners were also the most common prescribers of the remaining antibiotics (43%–54%), followed by gynecology for levofloxacin or moxifloxacin (25%–29%) and otolaryngology for amoxicillin-clavulanate (14%–20%). Conclusions: Despite decreases in prescribing of amoxicillin-clavulanate and respiratory fluoroquinolones for most adults, azithromycin prescribing increased dramatically across all adults during the COVID-19 pandemic. Targeting inappropriate outpatient antibiotic use in Brazil, particularly azithromycin prescribing among general practitioners, gynecologists, and surgeons, may be high-yield targets for antibiotic stewardship.Funding: NoneDisclosures: None

Clinical Outcome of Viral Respiratory Tract Infections in Hospitalized Adults in Norway: High Degree of Inflammation and Need of Emergency Care for Cases With Respiratory Syncytial Virus.

BackgroundThe clinical features and outcomes of viral respiratory tract infections (RTIs) in adults have not been thoroughly studied, especially the respiratory syncytial virus (RSV) disease burden. It has become apparent that outbreaks of RSV in the elderly are associated with increased hospitalization rates. However, little data exists on the severity of such viral RTIs in adults, particularly the need for hospitalization, respiratory support and intensive care.MethodsWe conducted a retrospective observational single-center study at Østfold Hospital Trust, Norway, during three winter seasons 2015–2018. Patients ≥18 years with either influenza A, influenza B, RSV A/B, human metapneumovirus, parainfluenza virus 1–4 or adenovirus detected in respiratory specimens were included, if they were hospitalized 14 days prior or following the detection date, with signs of RTI. Hospital records on treatment and outcome were investigated, as well as mortality of all causes up to 30 days from discharge.ResultsOf the 1222 infection events that were included, influenza A was the most frequent virus detected (39%), while 179 infection events (14.6%) were due to RSV. Influenza B counted for 24% of the infection events, human metapneumovirus 13%, parainfluenza virus 9% and adenovirus 1%. Patients admitted with RSV more often suffered from COPD and congestive heart failure than patients with influenza A. In addition, RSV patients were overrepresented in the urgent response NEWS score (National Early Warning Score) category ≥5. RSV patients also showed signs of more severe inflammation, with WBC ≥11.1 × 109/L and CRP >100 mg/L, and they were more often treated with antibiotic agents during their hospital stay. However, we found no differences in the need for ICU admission or mortality.ConclusionPatients with RSV had more often high values for markers of inflammation and elevated NEWS score when compared to patients hospitalized with other common respiratory viruses. Taken into account that they suffered more frequently from comorbidities like COPD, these patients needed hospitalization more urgently. These findings highlight the need for further investigations on RSV disease in adults and the elderly.

Nonsteroidal anti-inflammatory drugs in acute viral respiratory tract infections: An updated systematic review.

In this systematic review, we aimed to assess the efficacy and safety of nonsteroidal anti‐inflammatory drugs (NSAIDs) in treating respiratory tract infections in adults and children. PubMed, Scopus, Web of Science, Cochrane, and Embase databases were searched. A total of 34 randomized clinical trials were included in this systematic review. We assessed the risk of bias of all included studies using the Cochrane tool for risk of bias assessment. The evidence on ibuprofen, naproxen, aspirin, diclofenac, and other NSAIDs were rated for degree of uncertainty for each of the study outcomes and summarized using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Our findings suggest that high‐quality evidence supports the use of NSAIDs to reduce fever in both adults and children. However, the evidence was uncertain for the use of NSAIDs to reduce cough. Most studies showed that NSAIDs significantly relieved sore throat. The evidence for mortality and oxygenation is limited. Regarding the adverse events, gastrointestinal discomfort was more frequently reported in children. For adults, our overall certainty in effect estimates was low and the increase in gastrointestinal adverse events was not clinically significant. In conclusion, NSAIDs seem to be beneficial in the outpatient management of fever and sore throat in adults and children. Although the evidence does not support their use to decrease mortality nor improve oxygenation in inpatient settings, the use of NSAIDs did not increase the rate of death or the need for ventilation in patients with respiratory tract infections. Further studies with a robust methodology and larger sample sizes are recommended.