Wong-Beringer Gains Grant from Merck

Annie Wong-Beringer, associate dean for research affairs and professor of clinical pharmacy at USC Mann, received a $364,140 grant from Merck for her project “Differentiating antibiotics for the treatment of ESBL-Enterobacterales by their propensity to drive the in vitro and in-human evolution of carbapenem resistance with associated clinical outcomes.”

ESBL stands for extended-spectrum beta-lactamases, a diverse group of enzymes that destroy the effectiveness of many commonly used antibiotics. Meanwhile, Enterobacterales are a large order of bacteria that frequently cause infections in the community as well as healthcare settings. Infections caused by ESBL-producing Enterobacterales have increased by 32% since the COVID-19 pandemic.

As such, ESBL-producing Enterobacterales is a major factor in rising antibiotic resistance with the parallel increase in the use of broad-spectrum antibiotics. Wong-Beringer’s research aims for better strategies to limit the emergence of antibiotic resistance.

Her current project focuses on carbapenems, which are among the few antibiotics still able to treat ESBL-Enterobacterales. However, the more they are used, the more ESBLs evolve to overcome their effectiveness as well. Clinicians currently select antibiotics for treatment by considering factors such as the antimicrobial activity, dosing schedule, side effects, and cost of the drug but not its propensity to drive the bacterium’s ability to develop resistance through genetic changes. Wong-Beringer is examining two species of Enterobacterales, E. coli and K. pneumoniae, to determine exactly what drives carbapenem resistance. The findings will better inform treatment selection to reduce resistance and improve patient outcomes.

“We have available for this proposed investigation a large collection of ESBL-producing E. coli and K. pneumoniae strains curated over a 10-year period with accompanying clinical data with treatment details and outcomes from patients who were hospitalized for repeated infections and who were treated with a carbapenem or a carbapenem-alternative agent,” Wong-Beringer says.  

“This proposal aims to test our hypothesis by taking a translational approach that combines clinical observations with in vitro testing to explore the molecular basis underlying the different potential for antibiotics to drive the evolution of carbapenem resistance in ESBL-producing E. coli and K. pneumoniae causing recurrent infections in patients.” 

In 2017 alone, an estimated 197,400 cases of ESBL-Enterobacterales occurred in hospitals, causing 9,100 estimated deaths in the United States, according to the Centers for Disease Control and Prevention.

Wong-Beringer, whose clinical practice and research is at Huntington Hospital in Pasadena, has served as principal investigator on numerous research studies on antimicrobial resistance and bacterial virulence and their impact on patient outcomes. Her research focuses on host immune response during infections and the key pathogens: Pseudomonas aeruginosa, ESBL- and carbapenem-resistant Enterobacterales, and Staphylococcus aureus.