Spotlight on Early-Stage Investigators

A primary goal of the ARLG is to train the next generation of researchers who will help support the mission of ARLG to reduce the public health threat of antibacterial resistance. Through the Mentorship Program, ARLG has funding and mentoring opportunities to researchers with a faculty appointment of less than five years. On this page, we spotlight our early-stage investigators (ESI).

Pranita D. Tamma, MD, MHS
Associate Professor of Pediatrics
Director of the Pediatric Antibiotic Stewardship Program
The Johns Hopkins Hospital

My initial introduction to the ARLG was as a recipient of an Early Stage Investigator Seed Grant. Since then, the ARLG has been very generous in providing me with opportunities for further involvement, including being a member of the Gram-negative Committee. In this role, I help establish the research agenda, provide feedback on proposed research studies, and review manuscripts from ARLG-funded research..

In 2014, I received funding from the ARLG to establish a Gram-negative bloodstream infection database from three hospitals: The University of Maryland Medical Center, The Johns Hopkins Hospital, and The Hospital of the University of Pennsylvania. This database includes information on close to 5,000 unique patients infected with Gram-negative bacteria. The main objective is to answer questions related to the clinical impact of antibiotic breakpoint changes.

Antibiotic breakpoints are established based on epidemiological cutoff values, pharmacokinetic-pharmacodynamic data, mathematical models, animal studies, and available clinical data. Unfortunately, there are often limited clinical data to inform breakpoint changes, so we rely mostly on in vitro and animal studies. By establishing a large database of patient-detailed data we hope to explore the impact established antibiotic breakpoints can have on patient outcomes to determine if breakpoint adjustments may be necessary.

Read more.

Thomas L. Holland, MD, MSc
Associate Professor
Department of Medicine, Division of Infectious Diseases
Duke University

I joined the ARLG in a role that might be best described as an early-career trialist. Over the years, my role has grown and evolved as I have been involved in more studies and part of the Gram-positive committee. Two of these efforts are:

  1. A set of projects around Staphylococcus aureus bloodstream infections. These infections are common and potentially deadly, but few trials have been done to try to determine the best treatment strategies for them. The ARLG has developed novel endpoints that improve trial feasibility and interpretation, including the desirability of outcome ranking (DOOR) and partial credit methods. Developed from a clinician survey and a patient-centered quality of life endpoint, we will use these endpoints in an upcoming interventional trial to test new treatment strategies.
  2. The Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE) Study. I had the opportunity to work with Tom Lodise, PhD, on PROVIDE, which was recently published in Clinical Infectious Diseases.

Read more.

Michael Woodworth, MD, MSc.
Assistant Professor, Division of Infectious Disease Infectious
Emory University
About my role in ARLG

I was awarded a two-year ARLG fellowship, which provides salary and tuition support for my research activities. My research primarily focuses on the use of microbiome therapeutics like fecal microbiota transplantation (FMT) for the eradication of intestinal multi-drug resistant organism (MDRO) colonization. My main efforts are concentrated on patient recruitment, and regulatory work related to a clinical trial of the safety of FMT for MDRO decolonization in renal transplant patients after infection.

With support from the ARLG, I have also been able to:

  • Experience hands-on wet-lab training in next generation sequencing
  • Better understand data science approaches to analyzing sequencing data
  • Complete a retrospective clinical outcome project for a cohort of more than 250 patients treated with FMT for recurrent Clostridioides difficile infection at Emory

Read more.

Sarah B. Doernberg, MD, MAS
Associate Professor
Medical Director of Adult Antibiotic Stewardship
University of California, San Francisco

I consider my role in ARLG as a “Trialist in Training.” I have been involved in the development and execution of protocols for three studiesMASTER GC: Performance of Nucleic Acid Amplification Tests for the Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in extragenital sites. This novel study involved collaboration with three manufacturers and input from the Food and Drug Administration (FDA) to evaluate performance of molecular diagnostic tests for extragenital gonorrhea and chlamydia. The primary goal was for the study results to support each company’s FDA application. This trial used the MASTERMIND (MASTER protocol for evaluating Multiple INfection Diagnostics) concept developed by the ARLG that is based on the following premise: One single participant can provide information and samples for the simultaneous evaluation of multiple diagnostics. The MASTER GC trial has completed enrollment of more than 2700 participants at nine sites. FDA submissions from the participating manufacturers and manuscripts from the scientists are underway.

Read more.

Ephraim Tsalik, MD, PhD
Duke University Medical Center
Associate Director of Diagnostics and MASTERMIND
(MASTER protocol for evaluating Multiple INfection

I have two primary roles in ARLG: 1) as a contributor and 2) and as recipient. As a recipient, I am the principal investigator for the Rapid Diagnostics in Categorizing Acute Lung Infections (RADICAL) study. ARLG has been a supporter of RADICAL from the project’s initial phase. We are currently in phase two of three expected phases. RADICAL-I focused on the development of a platform capable of measuring gene expression in a clinically meaningful way. RADICAL-II is testing the platform in a heterogeneous population with considerations for age, ethnicity, co-morbidities, and geographic location. We envision RADICAL-III as a clinical-utility study where real-time results will be used to determine the clinical value of the test in discriminating bacterial and viral infections.

Read more.

Judith A. Anesi, MD
Post-Doctoral Fellow and Attending Physician
Division of Infectious Diseases
University of Pennsylvania Perelman School of Medicine

I was awarded the ARLG Fellowship to study multidrug-resistant Gram-negative infections among solid-organ transplant recipients. More specifically, I am evaluating the clinical and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections among solid-organ transplant recipients. Solid- organ transplant recipients are particularly vulnerable to infection and can be the “canary in the coal mine” when new drug-resistant organisms are emerging. As a result, they represent an important piece of the global antimicrobial resistance puzzle. In order to minimize the morbidity and mortality related to these bacterial infections, it is important to study their clinical and molecular epidemiology. I have chosen to focus on ESBL-producing Enterobacteriaceae infections because they are the most common type of multidrug-resistant Gram-negative infections.

Read more.

Michael A. Liss MD, MAS, FACS
Assistant Professor of Urology
University of Texas Health San Antonio
Principal Investigator, Micro-FIRE (Microbiome of FluoroquInolone Resistant E. coli)

My early stage investigator (ESI) seed grants supports the Micro-FIRE. In this study, we are investigating the microbiome in men who harbor fluoroquinolone resistant (FQR) E. coli compared to those who do not harbor the organism. FQR E. coli is the main cause of transrectal ultrasound-guided prostate biopsy needle infections. Nearly one million biopsies are performed each year to diagnose prostate cancer, and sepsis rates have been steadily rising. We hope to understand the associated microbiome in this environment to identify pre/probiotics or other drugs to “decolonize” these men prior to prostate biopsy to reduce infection without increasing the use of antibiotics for prophylaxis. Although, we are investigating specifically FQR E. coli as applied to prostate biopsy infection, this research could also be applied to recurrent urinary tract infections.

Along with the ARLG, we are concerned that more antibiotics will be used to prevent infection leading to more resistance. We are seeking means to reduce infections by understanding the surrounding microenvironment.

Read more.

Jose M. Munita, MD
Associate Professor, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Chile 

Adjunct Assistant Professor and Director of International Research, Center for Antimicrobial Resistance and Microbial Genomics (CARMiG), UTHealth, Houston, TX
Principal Investigator, VENOUS (Vancomycin-resistant Enterococcus OUtcomes Study)

My ESI grant supports VENOUS, which is a prospective, multi-site observational cohort study to evaluate the outcomes of patients with bloodstream infections due to vancomycin-resistant enterococci (VRE). In addition, parallel collection of clinical isolates is underway with the idea of identifying genomic microbial determinants of outcomes in this population of patients.

The main goal of VENOUS is to answer critical gaps of knowledge regarding the clinical and microbial factors determining the outcomes of VRE bacteremia and the best therapeutic approaches to deal with these multidrug-resistant organisms.

Clinicians have limited options to treat deep-seated VRE infections due to the lack of quality data. Through VENOUS we expect to fill a long-lasting void of good-quality data, providing prospective information about clinical outcomes and their relationship with the genomic bacterial background.

Read more.