Pivya is a newly-approved antibiotic to treat urinary tract infections (UTIs)

Urinary tract infections (UTIs) are common infections that affect the urinary system, including the bladder, kidneys, ureters, and urethra. The most frequent symptoms of a UTI include a burning sensation during urination, frequent and urgent needs to urinate, cloudy or strong-smelling urine, and pain in the lower abdomen. If the infection spreads to the kidneys, symptoms can also include back pain, fever, and nausea. The prognosis for UTIs is generally good with prompt treatment, which usually involves a course of antibiotics to eliminate the infection. In addition to medication, increasing fluid intake and practicing good hygiene can help manage symptoms and prevent future infections.

Urinary tract infections (UTIs) tend to affect women more often than men for several anatomical and physiological reasons. Two principal reasons are:

• Shorter Urethra: Women have a shorter urethra than men, which means bacteria have a shorter distance to travel to reach the bladder. This makes it easier for pathogens to enter and establish an infection.
• Proximity to the Anus: The female urethra is closer to the anus, which is a source of bacteria like E. coli, a common cause of UTIs. This proximity increases the risk of bacteria being transferred from the anal area to the urethra.

UTIs are typically classified as uncomplicated or complicated. Uncomplicated UTIs occur in individuals who are otherwise healthy and have a structurally and functionally normal urinary tract. Complicated UTIs occur in a setting where factors make the infection more difficult to treat such as additional medical conditions, e.g. diabetes, weakened immunity, and kidney stones. The distinction between these types of UTIs is important because it influences the approach to treatment and management. Complicated UTIs generally pose more significant health risks and require more intensive medical management.

In April, the FDA approved a new antibiotic, pivmecillinam (Pivya), for treating uncomplicated urinary tract infections (UTIs) in women (Figure 1). Pivmecillinam has been used in Europe for over 40 years and will now be available in the US starting in 2025. Pivmecillinam, primarily used for uncomplicated UTIs in Europe, has been proven safe and effective through extensive use and clinical trials, with nausea and diarrhea as the most common side effects.

Pivmecillinam is a prodrug of mecillinam, an antibiotic that belongs to the penicillin class. Its mechanism of action specifically targets and inhibits penicillin-binding proteins (PBPs) which are essential for the synthesis of the bacterial cell wall. By binding to these PBPs, mecillinam disrupts the normal synthesis and assembly of the cell wall during bacterial multiplication. This disruption leads to the weakening of the bacterial cell wall and ultimately causes the bacterium to lyse and die.

The approval is significant as it marks the first new antibiotic for UTIs approved by the FDA in two decades, a period during which antimicrobial resistance has grown into a major health threat, linked to five million deaths globally. This development comes as the U.S. sees a dire need for new antimicrobials due to the rising challenge of drug-resistant infections, which are particularly prevalent in UTIs.

As a final aside, one reason for the shortage of new antibiotics is the lack of profit incentives to develop new antibiotics. The current crop of antibiotics are very effective except against pathogens that have developed resistance against a particular antibiotic. Despite the concern over the specter of "superbugs" that are resistant to all antibiotics, so far that scenario has not occurred with the vast majority of pathogens susceptible to at least one class of antibiotics. However, the possibility still exists especially given the overuse of antibiotics which can promoter antibiotic resistance in pathogens.

With this in mind, members of Congress have proposed the Pasteur Act which is a proposed piece of legislation in the United States aimed at combating the growing crisis of antimicrobial resistance. The central goal is to incentivize antibiotic development by moving to a subscription model instead of relying on sales volume (which may be low for a new antibiotic that is viewed as the last line of defense). Drug developers would receive a fixed payment from the government in exchange for guaranteed access to their antibiotics when needed.

Figure 1. The antibiotic pivmecillinam (tradename Pivya) was approved recently to treat uncomplicated urinary tract infections (UTIs) in women . It is the first new antibiotic for UTIs approved by the FDA in two decades. Pivmecillinam has been used safely in Europe for many years against uncomplicated UTIs.