Nicole Cotroneo, BS, on the Potential of Tebipenem to Treat Multidrug-Resistant UTIs

Nicole Cotroneo, BS, senior scientist at Spero Therapeutics, discusses her research on the activity of tebipenem against multidrug-resistant urinary tract infection-causing pathogens, which was presented at the European Congress of Clinical Microbiology and Infectious Diseases.

Interview transcript (modified slightly for readability):

Contagion®: What was your biggest takeaway from your research?

Nicole Cotroneo: In our poster we are discussing tebipenem's activity against UTI pathogens. As you may know, UTIs, or urinary tract infections, are commonly caused by E coli and Kleb pneumoniae and historically these have been managed with oral therapeutics such as cephalosporins, fluoroquinolones, and trimethoprim sulfamethoxazole. Not surprisingly, widespread use has been followed by development of resistance to these therapeutics and, in particular at the production of ESBLs, or extended spectrum beta lactamases, has been key in resistance to cephalosporins. We have found this is commonly accompanied by resistance to trimethoprim and fluoroquinolones, which reduces your oral therapeutic option. Tebipenem is a carbapenem and it's orally available as a prodrug. Carbapenems have excellent activity against these pathogens and in our poster, which describes a study that was run at JMI Laboratories, we explore the activity of tebipenem in vitro against some very well characterized ESBL-producers, some of which are also co-resistant to fluoroquinolones and trimeth-sulfa so tebipenem maintain excellent activity against these pathogens.

Contagion®: Why is the management and treatment of UTIs caused by ESBL-producing organisms so challenging?

Cotroneo: Managing these UTIs is very difficult probably because of a number of different factors, 1 of which is the global dissemination of the ST131 type of E coli and these are euro-pathogenic, they're virulent, and they're commonly producing ESBL and are co-resistant to trimethoprim sulfamethoxazole and fluoroquinolones. A second aspect is patients often experience recurring infections, which require treatment over and over again likely with the same classes of therapeutics and this creates selective pressure on the organisms to develop resistance mechanisms. A third factor may be industry attention to this problem. We have, as an industry, focused a lot of attention over the past decade in developing IV therapeutics to address carbapenem-resistant bacteria. This has created a bit of a gap in terms of the attention that's been put on developing oral therapeutics, which could help address this problem, so likely it's a combination of a number of factors and I'm sure there are more.

Contagion®: What is next for this line of research?

Cotroneo: What's next for tebipenem? We are very excited to be planning our phase 3 trial on complicated urinary tract infections and we are also in the process of launching a global surveillance program with JMI Laboratories where we will look at the activity of tebipenem in vitro against a global collection of contemporary Enterobacteriales, as well as other species in comparison to other therapeutics.

The poster, "Activity of tebipenem, an oral carbapenem, against multidrug-resistant urinary tract infection-causing pathogens with characterized resistance mechanisms collected in Europe and the United States in 2016," was presented April, 14, 2019, at ECCMID 2019.