On July 17, the Food and Drug Administration (FDA) approved a new three-drug regimen to treat complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI), both of which can be especially problematic for people living with HIV.
The antibacterial drug is a combination of imipenem and cilastatin (which were previously existing drugs) and one new drug, relebactam. The new combination is marketed under the brand name Recarbrio by Merck & Co. Over the last few years, the public health agencies (Centers for Disease Control and Prevention [CDC], National Institutes of Health, and FDA) have been ringing the alarm bells about the growing threat of bacteria that are resistant to our current panoply of antimicrobial drugs, and FDA expressed some celebration of this newly approved drug to treat people with difficult-to-treat UTIs and IAIs.
The drug was given approval after two clinical trials, one for cUTI and one for cIAI, and demonstrated safety in participants who received the drug, according to the FDA press release. The determination of efficacy was based on previous trials of the two older drugs, imipenem and cilastatin, and in vitro studies and animal models studying relebactam. The drug was given priority review and ultimately given expedited approval, a process the FDA allows for antibacterial and antifungal drugs approved to treat "serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act," the release stated.
According to the CDC, UTIs are the most common infection in people -- and in recent years, there has been an increase in the number of drug-resistant UTIs. On July 13, just days before the FDA approved this new treatment, The New York Times reported that complicated UTIs have become such a problem in New York City that the New York City Department of Health "introduced a new mobile phone app this month that gives doctors and nurses access to a list of strains of urinary tract infections and which drugs they are resistant to."
UTIs can be caused by a number of bacterial infections, and they are more common in the vaginal urinary tract than they are in the penile urinary tract. Annually, about 6 million patient visits to doctors or emergency departments in the U.S. are due to UTIs. IAIs can also be caused by a range of different infections, but they can involve appendicitis and sepsis and are more likely to be fatal.
Treating UTIs and IAIs in people with compromised immune systems, like people living with HIV, is particularly important. And while there was more research dedicated to the connection of UTIs in people living with HIV prior to the introduction of antiretroviral therapy in the United States, it still remains an issue. Anecdotally, I personally have heard several cisgender women living with HIV state that a recurring or persistent UTI was one of the symptoms that led to their HIV diagnosis.
A 2018 study looked at the factors associated with having a UTI for people living with HIV. Of 608 patients living with HIV who received care at a Warsaw, Poland, clinic who had at least one urine culture, 141 tested positive for a UTI. The factors that were most associated with having a UTI were having contracted HIV through means other than homosexual sex and female gender. Having a higher nadir CD4 count decreased the odds of urinary tract infection. But no differences were observed in people who were on antiretroviral therapy. While having access to lifesaving antiretrovirals is still vitally important, the work to increase the options in the pipeline of antibiotics for drug-resistant strains of bacteria is still critical for people living with HIV.
"The FDA remains focused on facilitating the development of safe and effective new antibacterial drugs to give patients more options to fight serious infections," Ed Cox, M.D., M.P.H., director for the Office of Antimicrobial Products in FDA's Center for Drug Evaluation and Research, stated in the release. "It is important that the use of Recarbrio be reserved for situations when there are limited or no alternative antibacterial drugs for treating a patient's infection."