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The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms. Additionally, the clinical impact of many new tests, including an understanding of how best to use them to inform optimal antibiotic prescribing, remains to be defined. This review summarizes the recent work of the ARLG toward addressing these unmet needs in the diagnostics field and describes future directions for clinical research aimed at curbing the threat of antibiotic-resistant bacterial infections.
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Infecciones por Bacterias Gramnegativas , Liderazgo , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Grampositivas , Farmacorresistencia Bacteriana , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Infecciones por Bacterias Gramnegativas/tratamiento farmacológicoRESUMEN
Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding initiative, the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, was developed to address the research gap in understanding the adoption of COVID-19 testing in underserved populations. This program is the single largest investment in health disparities and community-engaged research in the history of the NIH. The RADx-UP Testing Core (TC) provides community-based investigators with essential scientific expertise and guidance on COVID-19 diagnostics. This commentary describes the first 2 years of the TC's experience, highlighting the challenges faced and insights gained to safely and effectively deploy large-scale diagnostics for community-initiated research in underserved populations during a pandemic. The success of RADx-UP shows that community-based research to increase access and uptake of testing among underserved populations can be accomplished during a pandemic with tools, resources, and multidisciplinary expertise provided by a centralized testing-specific coordinating center. We developed adaptive tools to support individual testing strategies and frameworks for these diverse studies and ensured continuous monitoring of testing strategies and use of study data. In a rapidly evolving setting of tremendous uncertainty, the TC provided essential and real-time technical expertise to support safe, effective, and adaptive testing. The lessons learned go beyond this pandemic and can serve as a framework for rapid deployment of testing in response to future crises, especially when populations are affected inequitably.
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COVID-19 , Humanos , COVID-19/diagnóstico , Prueba de COVID-19 , SARS-CoV-2 , Poblaciones Vulnerables , PandemiasRESUMEN
BACKGROUND: Inappropriate antibiotic use is linked to the spread of antimicrobial resistance worldwide, but there are limited systemic data on antibiotic utilization in low- and middle-income countries. The purpose of this study was to evaluate the prevalence and patterns of antibiotic prescription in an ambulatory care setting in Sri Lanka. METHODS: This cross-sectional survey was conducted at the Outpatient Department of a public tertiary medical center in Southern Province, Sri Lanka from February to April 2019. Among consecutive outpatients presenting for care, questionnaires were verbally administered to a systematic random sample to capture information about patient demographics, illness characteristics, and visit outcomes. Prescription data were obtained from the outpatient pharmacy's electronic prescribing system. RESULTS: Of 409 surveyed patients, 146 (35.7%) were prescribed an antibiotic. The most frequently prescribed agents were amoxicillin (41 patients, 28.1% of antibiotic recipients) and first-generation cephalosporins (38, 26.0%). Respiratory indications were the most common reason for antibiotic use, comprising 69 (47.3%) of all antibiotic prescriptions. Antibiotics were prescribed for 66.1% of patients presenting with cough and 78.8% of those presenting with rhinorrhea or nasal congestion. Among all antibiotic recipients, 6 (4.1%) underwent diagnostic studies. CONCLUSIONS: A high prevalence of antibiotic prescription was observed, in particular for treatment of respiratory conditions. These data support the need for improved antimicrobial stewardship in the Sri Lankan outpatient setting.
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Atención Ambulatoria/estadística & datos numéricos , Antibacterianos/uso terapéutico , Prescripciones/estadística & datos numéricos , Enfermedades Respiratorias/tratamiento farmacológico , Adolescente , Adulto , Programas de Optimización del Uso de los Antimicrobianos , Niño , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Pautas de la Práctica en Medicina , Prevalencia , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/epidemiología , Sri Lanka/epidemiología , Centros de Atención Terciaria , Adulto JovenRESUMEN
BACKGROUND: 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.
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Antibacterianos/uso terapéutico , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Prescripción Inadecuada , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Hospitales Públicos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Pacientes Ambulatorios , Satisfacción del Paciente , Médicos , Investigación Cualitativa , Sri Lanka , Centros de Atención Terciaria , Adulto JovenRESUMEN
BACKGROUND: Antimicrobial overprescription is common for lower respiratory tract infections (LRTI), as viral and bacterial infections generally present with similar clinical features. Overprescription is associated with downstream antimicrobial resistance. This study aims to identify the prevalence and predictors of antibiotic prescription among patients hospitalized with viral LRTI. METHODS: A prospective cohort study was conducted among patients aged ≥1 year hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from 2018-2021. Demographic, clinical, and laboratory data were recorded. Nasopharyngeal and blood samples were collected for multiplex polymerase chain reaction testing for 21 respiratory pathogens and procalcitonin (PCT) detection, respectively. Demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests; significant variables (p<0.05) were further included in multivariable logistic regression models. The potential impact of biomarker testing on antibiotic prescription was simulated using standard c-reactive protein (CRP) and PCT cut-offs. RESULTS: Of 1217 patients enrolled, 438 (36.0%) had ≥1 respiratory virus detected, with 48.4% of these patients being male and 30.8% children. Influenza A (39.3%) and human rhinovirus/ enterovirus (28.3%) were most commonly detected. A total of 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics. Among children, neutrophil percentage (median 63.6% vs 47.6%, p = 0.04) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p = 0.003), crepitations/crackles (55.3% vs 21.6%, p<0.001), rhonchi/wheezing (42.9% vs 18.9%, p = 0.005), and chest x-ray opacities (27.4% vs 8.1%, p = 0.01) were associated with antibiotic prescription. Access to CRP and procalcitonin test results could have potentially decreased inappropriate antibiotic prescription in this study by 89.5% and 83.3%, respectively. CONCLUSIONS: High proportions of viral detection and antibiotic prescription were observed among a large inpatient cohort with LRTI. Increased access to point-of-care biomarker testing may improve antimicrobial prescription.
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Antibacterianos , Infecciones del Sistema Respiratorio , Humanos , Masculino , Femenino , Sri Lanka/epidemiología , Antibacterianos/uso terapéutico , Niño , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Adulto , Adolescente , Preescolar , Persona de Mediana Edad , Estudios Prospectivos , Prevalencia , Lactante , Hospitalización , Adulto Joven , Polipéptido alfa Relacionado con Calcitonina/sangre , Anciano , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
Influenza causes an estimated 3 to 5 million cases of severe illness annually, along with substantial morbidity and mortality, particularly in low- and middle-income countries (LMICs). Currently, Sri Lanka has no influenza vaccination policies and does not offer vaccination within the public healthcare sector. Therefore, we performed a cost-effectiveness analysis of influenza vaccine implementation for the Sri Lankan population. We designed a static Markov model that followed a population cohort of Sri Lankans in three age groups, 0-4, 5-64, and 65+ years, through two potential scenarios: trivalent inactivated vaccination (TIV) and no TIV across twelve-monthly cycles using a governmental perspective at the national level. We also performed probabilistic and one-way sensitivity analyses to identify influential variables and account for uncertainty. The vaccination model arm reduced influenza outcomes by 20,710 cases, 438 hospitalizations, and 20 deaths compared to no vaccination in one year. Universal vaccination became cost-effective at approximately 98.01% of Sri Lanka's 2022 GDP per capita (incremental cost-effectiveness ratio = 874,890.55 Rs/DALY averted; 3624.84 USD/DALY averted). Results were most sensitive to the vaccine coverage in the 5-64-year-old age group, the cost of the influenza vaccine dose in the 5-64-years-old age group, vaccine effectiveness in the under-5-years-old age group, and the vaccine coverage in the under-5-years-old age group. No value for a variable within our estimated ranges resulted in ICERs above Rs. 1,300,000 (USD 5386.15) per DALY adverted. Providing influenza vaccines was considered highly cost-effective compared to no vaccines. However, large-scale national studies with improved data are needed to better inform estimates and determine the impact of vaccination implementation.
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Background: We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania. Methods: We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use. Results: Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each). Conclusions: Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.
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Introduction: The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers. Methods: A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery. Results: Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them. Conclusion: A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.
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Prueba de COVID-19 , COVID-19 , Humanos , Estados Unidos , COVID-19/diagnóstico , COVID-19/epidemiología , Pandemias , Inestabilidad de Vivienda , Emigración e InmigraciónRESUMEN
Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens.
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Infecciones Bacterianas , Virosis , Humanos , Virosis/diagnóstico , Virosis/genética , Biomarcadores , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/genética , Cambodia , AustraliaRESUMEN
BACKGROUND: Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base. MAIN BODY: High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children < 1 year of age. In addition, observational data suggest that infections such as skin and soft tissue infections, rheumatic heart disease, acute respiratory illness, diarrheal illness, and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin. However, the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear. Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question. In addition to benefits, there are several important risks associated with MDA-azithromycin. Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects, idiopathic hypertrophic pyloric stenosis, cardiovascular side effects, and increase in chronic diseases such as asthma and obesity. Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms. Further, there is the risk for cross-resistance with other antibacterial agents, especially clindamycin. CONCLUSIONS: Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children < 5 years of age in certain under-resourced settings. However, there are significant potential risks that need to be considered when deciding how, when, and where to implement these programs. Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented.
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Tracoma , Buba , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Niño , Humanos , Administración Masiva de Medicamentos , Medición de Riesgo , Tracoma/epidemiologíaRESUMEN
Background: To develop effective antimicrobial stewardship programs (ASPs) for low- and middle-income countries (LMICs), it is important to identify key targets for improving antimicrobial use. We sought to systematically describe the prevalence and patterns of antimicrobial use in three LMIC hospitals. Methods: Consecutive patients admitted to the adult medical wards in three tertiary care hospitals in Tanzania, Kenya, and Sri Lanka were enrolled in 2018-2019. The medical record was reviewed for clinical information including type and duration of antimicrobials prescribed, indications for antimicrobial use, and microbiologic testing ordered. Results: A total of 3,149 patients were enrolled during the study period: 1,103 from Tanzania, 750 from Kenya, and 1,296 from Sri Lanka. The majority of patients were male (1,783, 56.6% overall) with a median age of 55 years (IQR 38-68). Of enrolled patients, 1,573 (50.0%) received antimicrobials during their hospital stay: 35.4% in Tanzania, 56.5% in Kenya, and 58.6% in Sri Lanka. At each site, the most common indication for antimicrobial use was lower respiratory tract infection (LRTI; 40.2%). However, 61.0% received antimicrobials for LRTI in the absence of LRTI signs on chest radiography. Among patients receiving antimicrobials, tools to guide antimicrobial use were under-utilized: microbiologic cultures in 12.0% and microbiology consultation in 6.5%. Conclusion: Antimicrobials were used in a substantial proportion of patients at tertiary care hospitals across three LMIC sites. Future ASP efforts should include improving LRTI diagnosis and treatment, developing antibiograms to direct empiric antimicrobial use, and increasing use of microbiologic tests.
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Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Adulto , Anciano , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Países en Desarrollo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
[This corrects the article DOI: 10.1371/journal.pntd.0010091.].
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Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection. Conclusions and Relevance: In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.
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Infecciones Bacterianas , COVID-19 , Virosis , Adulto , Bacterias , Infecciones Bacterianas/tratamiento farmacológico , COVID-19/diagnóstico , Niño , Femenino , Fiebre/diagnóstico , Expresión Génica , Humanos , Masculino , Polipéptido alfa Relacionado con Calcitonina , Virosis/diagnósticoRESUMEN
Coagulase-negative staphylococci (CoNS) are considered the most common cause of nosocomial bloodstream infections; yet, these species are frequently designated as contaminants in the absence of systemic signs and symptoms of infection. Immunocompromised patients or those with prosthetic devices are at increased risk for clinically significant bacteremia. With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in clinical practice, there has been improved specificity of CoNS isolate identification and further elucidation of underrecognized pathogenic species. Staphylococcus pettenkoferi was a novel CoNS species first identified in 2002 and thought to be misdiagnosed as other CoNS due to limitations in biochemical identification. There is increasing identification of S. pettenkoferi isolates; however, there are limited case reports of clinically significant S. pettenkoferi bacteremia and no reported cases within the United States. We present the first known case of S. pettenkoferi from an American intensive care unit.
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BACKGROUND: Healthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future. METHODS/PRINCIPAL FINDINGS: From June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/µL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization. CONCLUSIONS: One-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries.
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Dengue Grave/epidemiología , Dengue Grave/terapia , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Manejo de Caso , Niño , Estudios de Cohortes , Costo de Enfermedad , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Femenino , Hospitalización , Humanos , Masculino , Pacientes Ambulatorios/estadística & datos numéricos , Recuento de Plaquetas , Dengue Grave/sangre , Dengue Grave/virología , Sri Lanka/epidemiología , Atención Terciaria de Salud/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Antimicrobial resistance has been named as one of the top ten threats to public health in the world. Hospital-based antimicrobial stewardship programs (ASPs) can help reduce antimicrobial resistance. The purpose of this study was to determine perceived barriers to the development and implementation of ASPs in tertiary care centers in three low- and middle-income countries (LMICs). METHODS: Interviews were conducted with 45 physicians at tertiary care hospitals in Sri Lanka (n = 22), Kenya (12), and Tanzania (11). Interviews assessed knowledge of antimicrobial resistance and ASPs, current antimicrobial prescribing practices, access to diagnostics that inform antimicrobial use, receptiveness to ASPs, and perceived barriers to implementing ASPs. Two independent reviewers coded the interviews using principles of applied thematic analysis, and comparisons of themes were made across the three sites. RESULTS: Barriers to improving antimicrobial prescribing included prohibitively expensive antimicrobials, limited antimicrobial availability, resistance to changing current practices regarding antimicrobial prescribing, and limited diagnostic capabilities. The most frequent of these barriers in all three locations was limited drug availability. Many physicians in all three sites had not heard of ASPs before the interviews. Improved education was a suggested component of ASPs at all three sites. The creation of guidelines was also recommended, without prompting, by interviewees at all three sites. Although most participants felt microbiological results were helpful in tailoring antibiotic courses, some expressed distrust of laboratory culture results. Biomarkers like erythrocyte sedimentation rate and c-reactive protein were not felt to be specific enough to guide antimicrobial therapy. Despite limited or no prior knowledge of ASPs, most interviewees were receptive to implementing protocols that would include documentation and consultation with ASPs regarding antimicrobial prescribing. CONCLUSIONS: Our study highlighted several important barriers to implementing ASPs that were shared between three tertiary care centers in LMICs. Improving drug availability, enhancing availability of and trust in microbiologic data, creating local guidelines, and providing education to physicians regarding antimicrobial prescribing are important steps that could be taken by ASPs in these facilities.
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Programas de Optimización del Uso de los Antimicrobianos , Países en Desarrollo , Implementación de Plan de Salud , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/economía , Antibacterianos/provisión & distribución , Farmacorresistencia Bacteriana , Humanos , Kenia , Médicos , Investigación Cualitativa , Sri Lanka , Tanzanía , Centros de Atención TerciariaRESUMEN
BACKGROUND: The timing of and risk factors for intestinal colonization with multidrug-resistant Enterobacteriaceae (MDRE) are still poorly understood in areas with high MDRE carriage. We determined the prevalence, timing, and risk factors associated with MDRE intestinal colonization among infants in southern Sri Lanka. METHODS: Women and their newborn children were enrolled within 48 h after delivery in southern Sri Lanka. Rectal swabs were collected from women and infants at enrollment and 4-6 weeks later. Enterobacteriaceae were isolated and identified as MDRE (positive for extended-spectrum ß-lactamases or carbapenem resistant) using standard microbiologic procedures. We used exact methods (Fisher's exact and Kruskal-Wallis tests) and multivariable logistic regression to identify sociodemographic and clinical features associated with MDRE intestinal colonization. Whole-genome sequencing was performed on selected MDRE isolates to identify phylogroups and antibiotic resistance-encoding genes were identified with NCBI's AMRfinder tool. RESULTS: Overall, 199 post-partum women and 199 infants were enrolled; 148/199 (74.4%) women and 151/199 (75.9%) infants were reassessed later in the community. Twenty-four/199 (12.1%) women and 3/199 (1.5%) infants displayed intestinal colonization with MDRE at enrollment, while 26/148 (17.6%) women and 24/151 (15.9%) infants displayed intestinal colonization with MDRE at the reassessment. While there were no risk factors associated with infant colonization at enrollment, multivariable analysis indicated that risk factors for infant colonization at reassessment included mother colonized at enrollment (aOR = 3.62) or reassessment (aOR = 4.44), delivery by Cesarean section (aOR = 2.91), and low birth weight (aOR = 5.39). Of the 20 MDRE isolates from infants that were sequenced, multilocus sequence typing revealed that 6/20 (30%) were clustered on the same branch as MDRE isolates found in the respective mothers. All sequenced isolates for mothers (47) and infants (20) had at least one ESBL-producing gene. Genes encoding fosfomycin resistance were found in 33/47 (70%) of mothers' isolates and 16/20 (80%) of infants' isolates and genes encoding resistance to colistin were found in one (2%) mother's isolate. CONCLUSIONS: Our results suggest that a substantial proportion of infants undergo MDRE intestinal colonization within 6 weeks of birth, potentially due to postnatal rather than intranatal transmission.
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Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/epidemiología , Adulto , Enterobacteriaceae/efectos de los fármacos , Femenino , Hospitales de Enseñanza , Humanos , Recién Nacido , Masculino , Embarazo , Recto/microbiología , Sri Lanka/epidemiología , Secuenciación Completa del GenomaRESUMEN
Viruses 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.
Asunto(s)
Interferones/genética , Infecciones del Sistema Respiratorio/inmunología , Linfocitos T/fisiología , Virosis/genética , Virus/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Activación de Complemento , Femenino , Humanos , Inmunidad/genética , Interferones/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Transcriptoma , Adulto JovenRESUMEN
BACKGROUND: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI in cohorts of European and African descent. We determined classifier performance in a South Asian cohort. METHODS: Patients ≥15 years with fever and respiratory symptoms were enrolled in Sri Lanka. Comprehensive pathogen-based testing was performed. Peripheral blood ribonucleic acid was sequenced and previously developed signatures were applied: a pan-viral classifier (viral vs nonviral) and an ARI classifier (bacterial vs viral vs noninfectious). RESULTS: Ribonucleic acid sequencing was performed in 79 subjects: 58 viral infections (36 influenza, 22 dengue) and 21 bacterial infections (10 leptospirosis, 11 scrub typhus). The pan-viral classifier had an overall classification accuracy of 95%. The ARI classifier had an overall classification accuracy of 94%, with sensitivity and specificity of 91% and 95%, respectively, for bacterial infection. The sensitivity and specificity of C-reactive protein (>10 mg/L) and procalcitonin (>0.25 ng/mL) for bacterial infection were 100% and 34%, and 100% and 41%, respectively. CONCLUSIONS: Previously derived gene expression classifiers had high predictive accuracy at distinguishing viral and bacterial infection in South Asian patients with ARI caused by typical and atypical pathogens.
RESUMEN
BACKGROUND: Dengue is a major cause of acute febrile illness in Sri Lanka. Dengue has historically been considered an urban disease. In 2012-2013, we documented that acute dengue was surprisingly associated with self-reported rural residence in the Southern Province of Sri Lanka. METHODS: Patients admitted with an acute febrile illness were enrolled from June 2012-May 2013 in a cross-sectional surveillance study at the largest tertiary care hospital in the Southern Province. Acute dengue was diagnosed by serology and virology testing. Site visits were performed to collect residential geographical coordinates. Spatial variation in odds of acute dengue was modeled using a spatial generalized additive model predicted onto a grid of coordinate pairs covering the Southern Province. RESULTS: Of 800 patients, 333 (41.6%) had laboratory-confirmed acute dengue. Dengue was spatially heterogeneous (local probability of acute dengue 0.26 to 0.42). There were higher than average odds of acute dengue in the rural northeast of the Southern Province and lower than average odds in the urbanized southwest of the Southern Province, including the city Galle. CONCLUSIONS: Our study further affirms the emergence of dengue in rural southern Sri Lanka and highlights both the need for real-time geospatial analyses to optimize public health activities as well as the importance of strengthening dengue surveillance in non-urban areas.