Browsing by Subject "Respiratory Tract Infections"
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Item Open Access Antibiotic overuse for acute respiratory tract infections in Sri Lanka: a qualitative study of outpatients and their physicians.(BMC Fam Pract, 2018-03-01) Tillekeratne, L Gayani; Bodinayake, Champica K; Dabrera, Thushani; Nagahawatte, Ajith; Arachchi, Wasantha Kodikara; Sooriyaarachchi, Anoji; Stewart, Kearsley; Watt, Melissa; Østbye, Truls; Woods, Christopher WBACKGROUND: Acute respiratory tract infections (ARTIs) are a common reason for antibiotic overuse worldwide. We previously showed that over 80% of outpatients presenting to a tertiary care hospital in Sri Lanka with influenza-like illness received antibiotic prescriptions, although almost half were later confirmed to have influenza. The purpose of this qualitative study was to assess Sri Lankan patients' and physicians' attitudes towards ARTI diagnosis and treatment. METHODS: Semi-structured interviews were conducted with 50 outpatients with ARTIs and five physicians in the Outpatient Department (OPD) at a large, public tertiary care hospital in southern Sri Lanka. Interviews were audio-recorded, transcribed, and analyzed for themes related to ARTI diagnosis and treatment. RESULTS: Patients frequently sought ARTI care in the public sector due to the receipt of free care and the perception that government hospitals carried a sense of responsibility for patients' health. Patients reported multiple medical visits for their illnesses of short duration and many indicated that they were seeking care in the OPD while at the hospital for another reason. While patients generally expected to receive medication prescriptions at their visit, most patients were not specifically seeking an antibiotic prescription. However, more than 70% of patients received antibiotic prescriptions at their OPD visit. Physicians incorrectly perceived that patients desired antibiotics or "capsules," a common formulation of antibiotics dispensed in this outpatient setting, and cited patient demand as an important cause of antibiotic overuse. Physicians also indicated that high patient volume and fear of bacterial superinfection drove antibiotic overuse. CONCLUSIONS: Patients in this study were seeking medication prescriptions for their ARTIs, but physicians incorrectly perceived that antibiotic prescriptions were desired. High patient volume and fear of bacterial superinfection were also important factors in antibiotic overuse. Training of physicians regarding guideline-concordant management and dealing with diagnostic uncertainty, education of patients regarding ARTI etiology and management, and systematic changes in the public outpatient care structure may help decrease unnecessary antibiotic prescriptions for ARTIs in this setting.Item Open Access Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review.(International journal of molecular sciences, 2020-02) Carugati, Manuela; Morlacchi, Letizia Corinna; Peri, Anna Maria; Alagna, Laura; Rossetti, Valeria; Bandera, Alessandra; Gori, Andrea; Blasi, Francesco; Working Group, IfaltRespiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipients.Item Open Access Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.(The Lancet. Infectious diseases, 2023-04) Tsalik, Ephraim L; Rouphael, Nadine G; Sadikot, Ruxana T; Rodriguez-Barradas, Maria C; McClain, Micah T; Wilkins, Dana M; Woods, Christopher W; Swamy, Geeta K; Walter, Emmanuel B; El Sahly, Hana M; Keitel, Wendy A; Mulligan, Mark J; Tuyishimire, Bonifride; Serti, Elisavet; Hamasaki, Toshimitsu; Evans, Scott R; Ghazaryan, Varduhi; Lee, Marina S; Lautenbach, Ebbing; TRAP-LRTI Study Group; Antibacterial Resistance Leadership GroupBackground
Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.Methods
We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273.Findings
Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066).Interpretation
Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration.Funding
National Institute of Allergy and Infectious Diseases, bioMérieux.Item Open Access Host gene expression classifiers diagnose acute respiratory illness etiology.(Sci Transl Med, 2016-01-20) Tsalik, Ephraim L; Henao, Ricardo; Nichols, Marshall; Burke, Thomas; Ko, Emily R; McClain, Micah T; Hudson, Lori L; Mazur, Anna; Freeman, Debra H; Veldman, Tim; Langley, Raymond J; Quackenbush, Eugenia B; Glickman, Seth W; Cairns, Charles B; Jaehne, Anja K; Rivers, Emanuel P; Otero, Ronny M; Zaas, Aimee K; Kingsmore, Stephen F; Lucas, Joseph; Fowler, Vance G; Carin, Lawrence; Ginsburg, Geoffrey S; Woods, Christopher WAcute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.Item Open Access Host-Based Diagnostics for Acute Respiratory Infections.(Clinical therapeutics, 2019-10) Ross, Melissa H; Zick, Brittany L; Tsalik, Ephraim LPURPOSE:The inappropriate use of antimicrobials, especially in acute respiratory infections (ARIs), is largely driven by difficulty distinguishing bacterial, viral, and noninfectious etiologies of illness. A new frontier in infectious disease diagnostics looks to the host response for disease classification. This article examines how host response-based diagnostics for ARIs are being used in clinical practice, as well as new developments in the research pipeline. METHODS:A limited search was conducted of the relevant literature, with emphasis placed on literature published in the last 5 years (2014-2019). FINDINGS:Advances are being made in all areas of host response-based diagnostics for ARIs. Specifically, there has been significant progress made in single protein biomarkers, as well as in various "omics" fields (including proteomics, metabolomics, and transcriptomics) and wearable technologies. There are many potential applications of a host response-based approach; a few key examples include the ability to discriminate bacterial and viral disease, presymptomatic diagnosis of infection, and pathogen-specific host response diagnostics, including modeling disease progression. IMPLICATIONS:As biomarker measurement technologies continue to improve, host response-based diagnostics will increasingly be translated to clinically available platforms that can generate a holistic characterization of an individual's health. This knowledge, in the hands of both patient and provider, can improve care for the individual patient and help fight rising rates of antibiotic resistance.Item Open Access Maternal Effects of Respiratory Syncytial Virus Infection during Pregnancy.(Emerg Infect Dis, 2015-11) Wheeler, Sarahn M; Dotters-Katz, Sarah; Heine, R Phillip; Grotegut, Chad A; Swamy, Geeta KGiven the illness and deaths caused by respiratory syncytial virus (RSV) infection during the first year of life, preventing infant RSV infections through maternal vaccination is intriguing. However, little is known about the extent and maternal effects of RSV infection during pregnancy. We describe 3 cases of maternal RSV infection diagnosed at a US center during winter 2014. Case-patient 1 (26 years old, week 33 of gestation) received a diagnosis of RSV infection and required mechanical ventilation. Case-patient 2 (27 years old, week 34 of gestation) received a diagnosis of infection with influenza A(H1N1) virus and RSV and required mechanical ventilation. Case-patient 3 (21 years old, week 32 of gestation) received a diagnosis of group A streptococcus pharyngitis and RSV infection and was monitored as an outpatient. Clarifying the effects of maternal RSV infection could yield valuable insights into potential maternal and fetal benefits of an effective RSV vaccination program.Item Open Access Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center Experience of Two Cases.(The American journal of case reports, 2017-07-31) Bedoya, Armando; Glisinski, Kristen; Clarke, Jeffrey; Lind, Richard N; Buckley, Charles Edward; Shofer, ScottBACKGROUND Recurrent respiratory papillomatosis (RRP), caused by human papillomavirus (HPV), is the most common benign neoplasm of the larynx and central airways. RRP has a significant impact on quality life and high annual costs to healthcare. Currently, there is no cure for RRP, leading to repeated debulking operations for symptomatic palliation. Various local adjuvant therapies have also been studied with mixed efficacy. HPV oncogene products increase expression of vascular endothelial growth factor (VEGF) providing a potential target for treatment of RRP. Bevacizumab, a recombinant monoclonal antibody that inhibits VEGF, has shown efficacy in patients with localized disease. CASE REPORT We present two cases of extensive airway and parenchymal RRP successfully managed with systemically administered bevacizumab, a recombinant monoclonal antibody that inhibits VEGF. CONCLUSIONS Bevacizumab has shown efficacy in patients with localized disease, but here we illustrate the potential of bevacizumab for patients with extensive parenchymal burden as well as provide a brief review of the literature.Item Open Access The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.(Frontiers in immunology, 2021-01) Tsalik, Ephraim L; Fiorino, Cassandra; Aqeel, Ammara; Liu, Yiling; Henao, Ricardo; Ko, Emily R; Burke, Thomas W; Reller, Megan E; Bodinayake, Champica K; Nagahawatte, Ajith; Arachchi, Wasantha K; Devasiri, Vasantha; Kurukulasooriya, Ruvini; McClain, Micah T; Woods, Christopher W; Ginsburg, Geoffrey S; Tillekeratne, L Gayani; Schughart, KlausViruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.Item Open Access Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.(Frontiers in immunology, 2019-01) Rawlings, Stephen A; Heldt, Sven; Prattes, Juergen; Eigl, Susanne; Jenks, Jeffrey D; Flick, Holger; Rabensteiner, Jasmin; Prüller, Florian; Wölfler, Albert; Neumeister, Peter; Strohmaier, Heimo; Krause, Robert; Hoenigl, MartinBackground: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.