RESEARCH

Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea and is associated with significant morbidity and mortality. We have conducted multiple investigations evaluating therapies for severe, complicated, and recurrent C. difficile infection (CDI). We demonstrated a potential role for the use of tigecycline in patients with severe disease who are unable to tolerate oral therapies and are too ill for surgical intervention (Britt, et al. 2014). Current efforts are focused on prospectively evaluating the efficacy and safety of bezlotoxumab, a monoclonal antibody to C. difficile toxin B, for the prevention of CDI recurrence in high-risk populations (NCT03880539).

One of the most significant public health achievements of the last quarter-century has been the introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection, which has led to profound improvements in HIV-associated mortality. Secondary to this increased life expectancy, persons living with HIV (PLWH) are now more commonly succumbing to the same non-infectious complications that plague uninfected individuals. In a study led by Dr. Nimish Patel (PI, University of California-San Diego), we have evaluated the impact of drug-drug interactions, polypharmacy, and pill burden on achievement of cardiometabolic disease goals among HIV-infected patients (Malek, et al. 2017 and Ahmed, et al. 2019). As part of this ongoing collaboration, we are continuing to study elimination of hepatitis C virus (HCV) in HIV-coinfected patients.

Urinary tract infection (UTI) is the most common infectious complication following kidney transplantation. In collaboration with Dr. Timothy Horwedel (PI, Barnes-Jewish Hospital) and Dr. Daniel Brennan (Johns Hopkins Hospital, formerly Washington University in St. Louis School of Medicine), we uncovered that recurrent UTIs were associated with significantly poorer graft and patient outcomes compared to non-recurrent UTI and no UTI (Britt, et al. 2017). We are continuing to evaluate the comparative effectiveness of treatment options for infections in immunosuppressed patient populations.

Despite significant advances in medical care, sepsis and septic shock continue to be major causes of death in intensive care units (ICUs). There is increasing evidence to support the short- and long-term detrimental effects of immune cell dysregulation in sepsis. We are involved in multiple projects aimed at defining immunophenotypes, biomarkers, and immunoadjuvant therapies for sepsis.

We work in close collaboration with the laboratory of Dr. Molly Steed as part of the University of Kansas Medical Center Antimicrobial Pharmacokinetics/Pharmacodynamics Translational Research Laboratory (ASTRAL), which specializes in the application of in vitro PK/PD models of infection to optimize the use of antimicrobial agents for the treatment of infections due to multidrug-resistant organisms (MDROs). Current collaborative efforts are focused on evaluating the activity of novel treatment regimens against a variety of multidrug-resistant Gram-positive and Gram-negative pathogens.