Antibacterial Resistance Leadership Group (ARLG)

Antibiotic resistance is one of the greatest threats to human health worldwide. According to the Centers for Disease Control and Prevention (CDC), annually in the United States, more than 2.8 million people acquire serious bacterial infections that are resistant to antibiotics designed to treat those infections with at least 35,000 dying as a result. In the European Union, about 33,000 people die from these infections annually. A recent report from the Global Burden of Disease (GBD) Antimicrobial Resistance Collaborators estimated that more than a million deaths were attributable to bacterial infections that were resistant to antimicrobials in 2021. This number is projected to rise. In addition to undermining our ability to treat specific infections, antibiotic resistance also threatens the safety and effectiveness of many medical and surgical procedures that rely on having effective antibiotics to prevent infections. This includes patients undergoing chemotherapy for cancer, dialysis for renal failure, orthopedic procedures, cardiac and complex surgeries, treatment of rheumatoid arthritis, and organ and bone marrow transplantation. The Antibacterial Resistance Leadership Group (ARLG) is an international cooperative clinical research network funded by NIAID to prioritize, design, and execute clinical research that will impact the prevention, diagnosis and treatment of infections caused by antibiotic-resistant bacteria.

LEADERSHIP

Scott Evans, PhD, Director

Toshimitsu Hamasaki, PhD, Associate Director

Lauren Komarow, MS, Lead Statistical Manager

Guoqing Diao, PhD, Faculty Investigator

RESEARCH STAFF

Suzanne Angermeier, MS

Lizhao Ge, MAS

Yijie He, MS

Yixuan Li, PhD, MS

Wanying Shao, MS

Jiahe Tian, MS

Yike Wang, MS

Qihang Wu, MS

Lijuan Zeng, MHS

Shanshan Zhang, MS

SELECTED PUBLICATIONS OF STUDY RESULTS

Boutzoukas AE, Komarow L, Chen L, Hanson B, Kanj SS, Liu Z, Salcedo Mendoza S, Ordoñez K, Wang M, Paterson DL, Evans S, Ge L, Giri A, Hill C, Baum K, Bonomo RA, Kreiswirth B, Patel R, Arias CA, Chambers HF, Fowler VG, van Duin D; Multi-Drug Resistant Organism Network Investigators. International Epidemiology of Carbapenemase-Producing Escherichia coli. Clin Infect Dis. 2023 Aug 22;77(4):499-509. doi: 10.1093/cid/ciad288. PMID: 37154071; PMCID: PMC10444003.

Doernberg SB, Komarow L, Tran TTT, Sund Z, Pandori MW, Jensen D, Tsalik EL, Deal CD, Chambers HF, Fowler VG, Evans SR, Patel R, Klausner JD. Simultaneous Evaluation of Diagnostic Assays for Pharyngeal and Rectal Neisseria gonorrhoeae and Chlamydia trachomatis Using a Master Protocol. Clin Infect Dis. 2020;71(9):2314-22. doi: 10.1093/cid/ciz1105. PubMed PMID: 31734695; PMCID: PMC7713680.

Evans SR, Hujer AM, Jiang H, Hill CB, Hujer KM, Mediavilla JR, Manca C, Tran TT, Domitrovic TN, Higgins PG, Seifert H, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Sampath R, Hall T, Marzan C, Fowler VG, Jr., Chambers HF, Bonomo RA. Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III. J Clin Microbiol. 2017;55(1):134-44. Epub 2016/11/01. doi: 10.1128/JCM.01524-16. PubMed PMID: 27795336; PMCID: PMC5228224.

Evans SR, Tran TTT, Hujer AM, Hill CB, Hujer KM, Mediavilla JR, Manca C, Domitrovic TN, Perez F, Farmer M, Pitzer KM, Wilson BM, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Fowler VG, Jr., Chambers HF, Bonomo RA, Antibacterial Resistance Leadership G. Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against Pseudomonas aeruginosa: PRIMERS IV. Clin Infect Dis. 2018. Epub 2018/09/22. doi: 10.1093/cid/ciy801. PubMed PMID: 30239599; PMCID: PMC Journal – In Process.

Evans SR, Tran TTT, Hujer AM, Hill CB, Hujer KM, Mediavilla JR, Manca C, Domitrovic TN, Perez F, Farmer M, Pitzer KM, Wilson BM, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Fowler VG, Chambers HF, Bonomo RA, Antibacterial Resistance Leadership G. Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV. Clin Infect Dis. 2019;68(11):1823-30. doi: 10.1093/cid/ciy801. PubMed PMID: 30239599; PMCID: PMC6938201.

Lodise TP, Rosenkranz SL, Finnemeyer M, Evans S, Sims M, Zervos MJ, Creech CB, Patel PC, Keefer M, Riska P, Silveira FP, Scheetz M, Wunderink RG, Rodriguez M, Schrank J, Bleasdale SC, Schultz S, Barron M, Stapleton A, Wray D, Chambers H, Fowler VG, Holland TL. The emperor's new clothes: Prospective observational evaluation of the association between initial cancomycin exposure and failure rates among adult hospitalized patients with methicillin-resistant Staphylococcus aureus bloodstream infections (PROVIDE). Clin Infect Dis. 2020; 70:1536-1545.

Reyes J, Komarow L, Chen L, Ge L, Hanson BM, Cober E, Herc E, Alenazi T, Kaye KS, Garcia-Diaz J, Li L, Kanj SS, Liu Z, Onate JM, Salata RA, Marimuthu K, Gao H, Zong Z, Valderrama-Beltran SL, Yu Y, Tambyah P, Weston G, Salcedo S, Abbo LM, Xie Q, Ordonez K, Wang M, Stryjewski ME, Munita JM, Paterson DL, Evans S, Hill C, Baum K, Bonomo RA, Kreiswirth BN, Villegas MV, Patel R, Arias CA, Chambers HF, Fowler VG, Jr., Doi Y, van Duin D, Satlin MJ, Antibacterial Resistance Leadership G, Multi-Drug Resistant Organism Network I. Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study. Lancet Microbe. 2023;4(3):e159-e70. Epub 20230209. doi: 10.1016/S2666-5247(22)00329-9. PubMed PMID: 36774938; PMCID: PMC10016089.

Parmar K, Komarow L, Ellison DW, Filippov AA, Nikolich MP, Fackler JR, Lee M, Nair A, Agrawal P, Tamma PD, Souli M, Evans SR, Greenwood-Quaintance KE, Cunningham SA, Patel R, Antibacterial Resistance Leadership G. Interlaboratory comparison of Pseudomonas aeruginosa phage susceptibility testing. J Clin Microbiol. 2023;61(12):e0061423. Epub 20231114. doi: 10.1128/jcm.00614-23. PubMed PMID: 37962552; PMCID: PMC10729752.

Turner NA, Hamasaki T, Doernberg SB, Lodise TP, King HA, Ghazaryan V, Cosgrove SE, Jenkins TC, Liu C, Sharma S, Zaharoff S, Wahid L, Renard VJ, Cook P, Raad I, Hachem R, Chaftari AM, Sims M, DeMarco C, Miller LG, McCarthy MW, Morse CG, Lucasti C, Forrest GN, Cherabuddi K, Polk C, Fazili T, Rupp ME, Thompson GR 3rd, Kim K, Strnad L, Schnee AE, McKinnell JA, Ramesh M, Silveira FP, McCarty TP, Lee TC, McDonald EG, Paolino K, Wiegand K, Wall A, Riccobene T, Patel R, Rappo U, Evans S, Chambers HF, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group. Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial. JAMA. 2025 Aug 13:e2512543. doi: 10.1001/jama.2025.12543. Epub ahead of print. PMID: 40802264; PMCID: PMC12351474.

van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG, Jr., Paterson DL, Bonomo RA, Evans S, Antibacterial Resistance Leadership G. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018;66(2):163-71. Epub 2017/10/12. doi: 10.1093/cid/cix783. PubMed PMID: 29020404; PMCID: PMC5850032.

van Duin D, Arias CA, Komarow L, Chen L, Hanson BM, Weston G, Cober E, Garner OB, Jacob JT, Satlin MJ, Fries BC, Garcia-Diaz J, Doi Y, Dhar S, Kaye KS, Earley M, Hujer AM, Hujer KM, Domitrovic TN, Shropshire WC, Dinh A, Manca C, Luterbach CL, Wang M, Paterson DL, Banerjee R, Patel R, Evans S, Hill C, Arias R, Chambers HF, Fowler VG, Jr., Kreiswirth BN, Bonomo RA, Multi-Drug Resistant Organism Network I. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis. 2020;20(6):731-41. Epub 20200306. doi: 10.1016/S1473-3099(19)30755-8. PubMed PMID: 32151332; PMCID: PMC7473597.

Wang M, Ge L, Chen L, Komarow L, Hanson B, Reyes J, Cober E, Alenazi T, Zong Z, Xie Q, Liu Z, Li L, Yu Y, Gao H, Kanj SS, Figueroa J, Herc E, Cordova E, Weston G, Ananth Tambyah P, Garcia-Diaz J, Kaye KS, Dhar S, Munita JM, Salata RA, Vilchez S, Stryjewski ME, Villegas Botero MV, Iovleva A, Evans SR, Baum K, Hill C, Kreiswirth BN, Patel R, Paterson DL, Arias CA, Bonomo RA, Chambers HF, Fowler VG Jr, Satlin MJ, van Duin D, Doi Y. Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions. Clin Infect Dis. 2024 Feb 17;78(2):248-258. doi: 10.1093/cid/ciad556. PubMed PMID: 37738153; PubMed Central PMCID: PMC10874260.

RESEARCH METHODOLOGIES AND TOOLS

The ARLG SDMC has advanced the research field through the development and implementation of catalytic methodologies and free online tools, for the design and analyses of clinical trials, other intervention studies, and diagnostic accuracy studies, to address the challenges and meet the needs of the antimicrobial resistance research community.

Selected Methodologies for the Design and Analyses of Clinical Trials and Studies of Diagnostics Accuracy Developed by the ARLG SDMC
DOOR	Desirability of Outcome Ranking (DOOR): A patient-centric paradigm for the design, analysis, and interpretation of clinical trials and other research studies based on benefit-risk evaluation. The ARLG Innovations Working Group, an NIH-FDA collaboration with patient representatives, created standardized DOOR outcomes for use in trials for cUTI, cIAI, HABP/VABP, and ABSSSI. The Oak Ridge Institute for Science and Education (ORISE) DOOR fellowship provided an opportunity to leverage vast registrational trial data from the FDA Division of Anti-infective Products to advance DOOR outcome development. DOOR was applied in several studies including studies that have provided the basis for treatment guidelines for vancomycin dosing for MRSA, and provided the basis for treatment guidelines to use ceftazidime-avibactam instead of colistin for CRE. DOOR has been recommended in guidance from the Council for International Organizations of Medical Sciences for benefit-risk evaluation. The SDMC developed a recommended statistical analysis plan (SAP) for DOOR and offers a free online application for for researchers implementing DOOR analyses or designing studies utilizing the DOOR paradigm. https://methods.bsc.gwu.edu/
SMART COMPASS	Sequential, Multiple-Assignment, Randomized Trials for Comparing Personalized Antibiotic Strategies (SMART COMPASS): A clinical trial design for evaluating dynmic decision-making e.g., empiric and definitive treatment decisions. Adjustments are personalized, tailored to the circumstances encountered with individual patients as new information becomes available.
MASTERMIND	Master Protocol for Evaluating Multiple Infection Diagnostics (MASTERMIND):a diagnostic platform study design evaluating multiple diagnostics simultaneously within a single study, providing efficiencies of specimen collection and characterization, central study organization, standardization of methods and definitions, and common reference standards. MASTERMIND offers central trial organization, standardization of methods and definitions, and common reference standards. MASTERMIND was utilized to evaluate simultaneously the performance of nucleic acid amplification tests for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in extragenital sites. The study resulted in FDA clearance of the first two diagnostic tests for extragenital testing for these pathogens.
BED-FRAME / AWA	Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) and Average Weighted Accuracy (AWA):  a systematic and pragmatic approach to evaluate and compare diagnostic alternatives to aid in clinical decision-making. The relative importance of diagnostic errors and the prevalence are incorporated, allowing tailored decision-making depending on local, temporal, and treatment availability context. BED-FRAME and AWA methods were applied to design the RADICAL study that evaluated the utility of a host response–based diagnostic test in categorizing acute respiratory tract illness into bacterial vs. other etiology. BED-FRAME was used to evaluate rapid molecular diagnostics for detecting resistance associated with three critical priority pathogens identified by the World Health Organization (WHO): carbapenem-resistant (CR) Enterobacterales, CR P. aeruginosa, and CR A. baumannii. The SDMC developed a free online application for BED-FRAME / AWA analyses. https://extapps.bsc.gwu.edu/shinypubtst/arlg/BED_FRAME/
ITD	Intention-to-Diagnose (ITD): An analog to the intention-to-treat (ITT) principle in clinical trials that protects the foundation for inference in diagnostic test accuracy studies. Distinct research foci: pragmatic application accuracy, pragmatic scientific accuracy, and explanatory scientific accuracy are defined. Selection of appropriate analysis sets and the handling of invalid and indeterminate results depend on the specific focus. The SDMC developed a free online application for ITD analyses. https://extapps.bsc.gwu.edu/shinypubtst/arlg/ITD/
DOOR-MAT	Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT):  a framework for assessing antibiotic selection strategies in the presence of drug resistance.

SELECTED PUBLICATIONS OF STATISTICAL METHODOLOGIES

Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D,  Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015; 61:800-806

Evans SR, Follmann D. Using outcomes to analyze patients rather than patients to analyze Outcomes: A step toward pragmatism in benefit:risk evaluation. Stat Biopharm Res. 2016; 8:386-393.

Evans SR, Pennello G, Pantoja-Galicia N, Jiang H, Hujer AM, Hujer KM, Manca C, Hill C, Jacobs MR, Chen L, Patel R, Kreiswirth BN, Bonomo RA. Benefit-risk Evaluation for Diagnostics: A Framework (BED-FRAME). Clin Infect Dis. 2016; 63(6):812-7. PMID: 27193750 PMCID: PMC4996133

Evans SR, Powers J. Evaluating Anti-Infective Drugs in the Resistant Pathogen Setting: Can we Use External Controls? Stat Commun Infect Dis. 2017;9(1):20160003. doi: 10.1515/scid-2016-0003. Epub 2017 Mar 14. PMID: 28757914; PMCID: PMC5529043.

Evans SR, Follmann D, Liu Y, Holland T, Doernberg SB, Rouphael N, Hamasaki T, Jiang Y, Lok JL, Tran TTT, Harris AD, Fowler, Jr. VG, Boucher H, Kreiswirth BN, Bonomo RA, van Duin D, Paterson DL, Chambers H. Sequential Multiple Assignment Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART-COMPASS). Clin Infect Dis. 2019;68(11):1961–7. PMID: 30351426 PMCID: PMC6522685 DOI: 10.1093/cid/ciy912.

Evans SR, Patel R, Hamasaki T, Howard-Anderson J, Kinamon T, King HA, Collyar D, Cross HR, Chambers HF, Fowler VG, Boucher HW, Antibacterial Resistance Leadership G. The Future Ain't What It Used to Be...Out With the Old...In With the Better: Antibacterial Resistance Leadership Group Innovations. Clin Infect Dis. 2023;77(Suppl 4):S321-S30. doi: 10.1093/cid/ciad538. PubMed PMID: 37843122; PMCID: PMC10578048.

Evans SR, Pennello G, Zhang S, Li Y, Wang Y, Cao Q, Komarow L, Hamasaki T, Petrides V, Meier K, Galicia NP, Fowler VG Jr, Boucher HW, Doernberg SB, Banerjee R, Rigatto MH, Kreiswirth BN, Bonomo RA, Chambers HF, Patel R. Intention-to-diagnose and distinct research foci in diagnostic accuracy studies. Lancet Infect Dis. 2025 Aug;25(8):e472-e481. doi: 10.1016/S1473-3099(25)00070-2. Epub 2025 Mar 27. PMID: 40158520.

Hamasaki T, Evans SR. The Disability of Outcome ranking (DOOR). In: Buyse M, Verbeeck J, De Backer M, Deltuvaite-Thomas V, Saad ED, G M, editors. Handbook of Generalized Pairwise Comparisons: Methods for Patient-Centric Analysis, Boca Raton: Chapman & Hall/CRC; 2025. p. 280-95.

Liu Y, Tsalik EL, Jiang Y, Ko ER, Woods CW, Henao R, Evans SR. Average Weighted Accuracy (AWA): Pragmatic Analysis for a RADICAL Study. Clin Infect Dis.; 2020;70(12):2736–42.

Patel R, Tsalik EL, Petzold E, Fowler VG Jr, Klausner JD, Evans S; Antibacterial Resistance Leadership Group (ARLG). MASTERMIND: Bringing Microbial Diagnostics to the Clinic. Clin Infect Dis. 2017 Feb 1;64(3):355-360. doi: 10.1093/cid/ciw788. Epub 2016 Dec 7. PMID: 27927867; PMCID: PMC5894935.

Wilson BM, Jiang Y, Jump RLP, Colindres RV, Perez F, Bonomo RA, Evans SR. Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance. CID, 2021;73(2):344–50. DOI: 10.1093/cid/ciaa1769.