Roundup From ECCMID: New Anti-Viral and Bacterial Drugs of Interest

Paul G. Auwaerter, MD


June 05, 2023

This transcript has been edited for clarity.

Hello. This is Paul Auwaerter with Medscape Infectious Diseases.

I had the pleasure of attending this year's European Clinical Congress of Microbiology and Infectious Diseases held in Copenhagen (ECCMID). I thought I would touch on a few things that caught my interest. Obviously, this is idiosyncratic. It was a huge meeting — over 14,000 people were in attendance, and many excellent sessions and posters were presented.

One presentation I want to mention briefly was about the rather remarkable effects of the pandemic on invasive group A streptococcus infections. Six years of data from the United Kingdom that covered the pandemic years showed that on average, there were 350 cases per year pre-pandemic, but in 2021, the number of cases fell to 29. The number of cases then rebounded in 2022 to 690. This clearly reflects the impact of social mitigation measures and, perhaps, the lack of viral upper respiratory infections that might drive invasive streptococcal disease. There was also some discussion on increasing tetracycline, erythromycin, and clindamycin resistance among Group A streptococci isolates, which is relevant when treating severely ill patients who might be penicillin allergic. Of course, all isolates were still penicillin-sensitive.

New Drugs of Interest

Data from a phase 3 trial of ensitrelvir, a novel protease inhibitor that does not require ritonavir, and has already received emergency use authorization in Japan for COVID-19, was also presented. The data suggests that there was sound inhibition of the virus with lack of detectable virus and shorter durations of viral culture. Of 70 patients who were infected with mild, moderate, or asymptomatic disease who were placed on the drug, fewer had symptoms compared with patients who were given a placebo. Ensitrelvir was granted Fast track authorization from the Us Food and Drug Administration (FDA), and additional clinical trials are in progress.

Also discussed at the meeting were two bacterial drugs you may be hearing about soon. One is gepotidacin, a novel drug that inhibits DNA replication by binding to two different topoisomerases, which is somewhat similar to the fluoroquinolones. The drug shows broad-spectrum activity against gram-positive and gram-negative bacteria, anaerobes, and Neisseria gonorrheae. Data from two phase 3 noninferiority trials (EAGLE 2 and EAGLE 3) comparing gepotidacin with nitrofurantoin in uncomplicated urinary tract infection (UTI) were presented.

Of course, it compared well, which isn't surprising. However, this is one of the first trials I've seen using the new composite endpoint from the FDA in uncomplicated UTI, a composite of both clinical and microbiological success. Both drugs scored far lower for the composite endpoint, at 50% and 47% for gepotidacin and nitrofurantoin, respectively, indicating that gepotidacin is noninferior, even though their clinical and microbiologic success rates independently were higher. Of interest, 98% of the enrollees did not require an additional antibiotic. The meaning of this new composite metric is indeed interesting; whether it's still a worthwhile approach moving ahead is something that remains to be seen.

The second drug discussed that I think may be useful is a new combination drug called sulbactam-durlobactam. Sulbactam, of course, is a component of ampicillin-sulbactam. But durlobactam is a novel beta-lactamase inhibitor that will hopefully be able to treat some carbapenem-resistant organisms and acinetobacter. Globally, according to in vitro studies and collections, there's only about 4% resistance to this novel drug.

Researchers presented results of the phase 3 ATTACK trial looking at carbapenem-resistant acinetobacter infections, among others, and found that sulbactam-durlobactam performed better than colistin for mortality, clinical cure, and microbiologic cure as well as having less nephrotoxicity. Admittedly comparison with colistin is a pretty low bar to achieve, but this drug will be reviewed soon by the FDA, so we'll get a closer look at the data, and we'll be able to see whether this drug may have a role in treating incredibly difficult to treat infections such as acinetobacter.

The Remarkable Story of a Remarkable Achievement

I want to close by mentioning one of the keynote lectures at ECCMID, given by Thomas Harrison, MD, professor of infectious diseases and medicine, deputy director of the Institute for Infection and Immunity, and lead for the Centre of Global Health. He recounted the remarkable story of over 20 years of work in Africa trying to improve the treatment of cryptococcal meningitis. In these low-resource settings, over many years of conducting many trials, Harrison was able to shift treatment from the gold standard of 2 weeks of amphotericin with 5-fluorocytosine (5-FC), to oral fluconazole, to a 1-week course of amphotericin with 5-FC.

Last year, he published a study that harnessed the long half-life of liposomal amphotericin B such that a single dose of liposomal amphotericin B plus 5-FC followed by fluconazole was noninferior to more extensive regimens. Given the issues of infusing an intravenous drug in a low resource setting, this study provided lowered costs and shifted mortality rates from over 75% historically to about 25%. This is a truly remarkable achievement and a testament to Dr. Harrison and his active clinical trial team and the many others dedicated to improving care in often challenging settings.

Thank you so much for listening. Hopefully, this was of interest. Stay tuned for additional Medscape videos and blogs. Thank you.

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