Novel Diagnostics to Improve Antimicrobial Stewardship for Acute Respiratory Tract Infections in Resource-Limited Settings

改善资源有限环境下急性呼吸道感染抗菌药物管理的新型诊断方法

• 批准号: 10092816
• 负责人: GAYANI TILLEKERATNE
• 金额: $ 16.68万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-07 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092816
• 关键词: Acute; Antibiotic Resistance; Antibiotics; Antigens; Area; Award; Bacterial Infections; Bioinformatics; Biological Assay; Biological Markers; Characteristics; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Communicable Diseases; Country; Diagnosis; Diagnostic; Diagnostic tests; Enrollment; Epidemiology; Etiology; European; Fever; Five-Year Plans; Foundations; Frequencies; Funding; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genomics; Goals; Hospitals; Immune response; Income; Infection; Influenza; Infrastructure; Inpatients; Intervention Trial; Knowledge; Laboratories; Language; Legionella pneumophila; Logistic Regressions; Measures; Mentors; Mentorship; Microbiology; Minority; Outpatients; Patients; Performance; Peripheral; Physicians; Play; Polymerase Chain Reaction; Population; Positioning Attribute; Reference Standards; Research; Research Personnel; Resources; Respiratory Tract Infections; Role; South Asian; Specificity; Sri Lanka; Streptococcus pneumoniae; Structure; Syndrome; Teaching Hospitals; Technology; Testing; Training; Uncertainty; Universities; Urine; Viral; Whole Blood; Work; adjudicate; antigen test; antimicrobial; base; cohort; density; genetic signature; global health; improved; mRNA sequencing; novel; novel diagnostics; pathogen; procalcitonin; prospective; respiratory; respiratory pathogen; response; skill acquisition; skills; tertiary care

Project Summary/ Abstract Acute respiratory tract infections (ARTIs) are a leading cause of antibiotic overuse worldwide. Rapid, accurate identification of a pathogen can reduce antibiotic overuse for ARTIs, but is not always possible with available diagnostics. In low- or middle-income countries (LMICs), ARTI diagnosis is further complicated by limited laboratory infrastructure. Previously, the applicant showed that providing access to rapid antigen-based influenza testing in a LMIC setting was associated with a significant decrease in antibiotic use; however, the majority of influenza-positive patients still received antibiotic prescriptions. Physicians later cited diagnostic uncertainty regarding bacterial infection as a major reason for antibiotic over-prescription. To more effectively minimize antibiotic use for ARTIs, diagnostics that broadly classify infections as bacterial or viral may play an important role. The long-term goal of the applicant is to become an independent investigator developing effective strategies for using novel diagnostics to improve antimicrobial stewardship in LMIC settings. The work proposed in this application will be carried out in a LMIC with the objectives of 1) defining the epidemiology of ARTIs, 2) refining a novel host-based gene expression assay that differentiates between viral and bacterial ARTIs, and 3) determining the performance characteristics of procalcitonin and gene signatures at differentiating between viral and bacterial ARTIs. To accomplish these goals, the applicant will carry out the project under the mentorship of experts in genomics, infectious disease diagnostics, antibiotic resistance/ stewardship, and global health. The proposed Specific Aims will be carried out at a tertiary care hospital in Sri Lanka and include the following: 1) Determine the frequency distribution of viral and bacterial respiratory infections among patients with acute febrile respiratory illness, 2) Refine a gene expression classifier to distinguish viral and bacterial ARTIs, and 3) Prospectively enroll a cohort of ARTI patients to assess the performance characteristics of procalcitonin and gene expression classifiers at differentiating between viral and bacterial ARTIs. By conducting this work, the applicant proposes to fill an important gap in knowledge regarding the applicability of host-based technologies for diagnosing ARTIs in a South Asian, LMIC population. The proposed comprehensive five-year plan includes didactic sessions, hands-on laboratory and bioinformatics work, antimicrobial stewardship and clinical trials training, and structured mentorship to develop the candidate as an independent and successful researcher. The completion of these aims and the acquisition of skills during the training period would place the applicant in a competitive position to apply for future R01 funding. By the conclusion of the award period, the applicant will have contributed significantly to the knowledge of how host-based technologies perform at diagnosing ARTIs in a South Asian, LMIC setting, and will be poised to become a leader in developing effective strategies for improving the rational use of antibiotics in resource-limited settings.

项目摘要/摘要

项目成果

Point-prevalence survey of outpatient antibiotic prescription at a tertiary medical center in Sri Lanka: opportunities to improve prescribing practices for respiratory illnesses.

• DOI: 10.1186/s12879-021-05804-6
• 发表时间: 2021-01-21
• 期刊: BMC infectious diseases
• 影响因子: 3.7
• 作者: Zhang HL;Bodinayake C;Wijayaratne GB;Jayatissa P;Piyasiri DLB;Kurukulasooriya R;Sheng T;Nagahawatte A;Woods C;Tillekeratne LG
• 通讯作者: Tillekeratne LG

Opportunities for Improving Antimicrobial Stewardship: Findings From a Prospective, Multi-Center Study in Three Low- or Middle-Income Countries.

• DOI: 10.3389/fpubh.2022.848802
• 发表时间: 2022
• 期刊: FRONTIERS IN PUBLIC HEALTH
• 影响因子: 5.2
• 作者: Muro, Florida J.;Lyamuya, Furaha S.;Kwobah, Charles;Bollinger, John;Bodinayake, Champica K.;Nagahawatte, Ajith;Piyasiri, Bhagya;Kurukulasooriya, Ruvini;Ali, Shamim;Mallya, Rose;Rolfe, Robert;Ruwanpathirana, Anushka;Sheng, Tianchen;ostbye, Truls;Drew, Richard;Kussin, Peter;Woods, Christopher W.;Anderson, Deverick J.;Mmbaga, Blandina T.;Tillekeratne, L. Gayani
• 通讯作者: Tillekeratne, L. Gayani

Colonization with multidrug-resistant Enterobacteriaceae among infants: an observational study in southern Sri Lanka.

• DOI: 10.1186/s13756-021-00938-3
• 发表时间: 2021-04-30
• 期刊: Antimicrobial resistance and infection control
• 影响因子: 5.5
• 作者: Meredith HR;Kularatna S;Nagaro K;Nagahawatte A;Bodinayake C;Kurukulasooriya R;Wijesingha N;Harden LB;Piyasiri B;Hammouda A;Wiegmann BM;Nicholson BP;Joyce M;Woods CW;Van Vliet AHM;Thakur S;Tillekeratne LG
• 通讯作者: Tillekeratne LG

Barriers to implementing antimicrobial stewardship programs in three low- and middle-income country tertiary care settings: findings from a multi-site qualitative study.

• DOI: 10.1186/s13756-021-00929-4
• 发表时间: 2021-03-25
• 期刊: Antimicrobial resistance and infection control
• 影响因子: 5.5
• 作者: Rolfe R Jr;Kwobah C;Muro F;Ruwanpathirana A;Lyamuya F;Bodinayake C;Nagahawatte A;Piyasiri B;Sheng T;Bollinger J;Zhang C;Ostbye T;Ali S;Drew R;Kussin P;Anderson DJ;Woods CW;Watt MH;Mmbaga BT;Tillekeratne LG
• 通讯作者: Tillekeratne LG

Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

斯里兰卡面临严重登革热风险的儿童和成人的结果：疾病负担高的国家进行门诊病例管理的机会。

• DOI: 10.1371/journal.pntd.0010091
• 发表时间: 2021-12
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Bodinayake CK;Nagahawatte AD;Devasiri V;Dahanayake NJ;Wijayaratne GB;Weerasinghe NP;Premamali M;Sheng T;Nicholson BP;Ubeysekera HA;Kurukulasooriya RM;de Silva AD;Østbye T;Woods CW;Tillekeratne LG
• 通讯作者: Tillekeratne LG