Drug and vaccine development for the treatment and prevention of urinary tract infections

Urinary tract infections (UTI) are one of the most common bacterial infections, with roughly eleven-million cases reported in the U.S. each year that cost an estimated $5 billion annually (1, 2). More than one in every two women will experience at least one UTI in her lifetime, and nearly one in three women will have received antibiotic treatment for a UTI before age 24 (3, 4). The clinical manifestations of symptomatic UTI include infection-induced inflammation of the urethra (urethritis), urinary bladder (cystitis), and kidneys (pyelonephritis) and are diagnosed by the presence of high levels of bacteria in the urine (bacteriuria) with concomitant symptoms. Symptoms of cystitis include frequent urination, burning sensation and pain during urination (dysuria), suprapubic pain and/or lower abdominal discomfort, and cloudy and/or bloody, foul-smelling urine. Symptoms of pyelonephritis include the presence of bacteriuria and pyuria (white blood cells in the urine) that is accompanied by flank pain and fever, but may or may not include other symptoms of cystitis. The vast majority of UTI manifest as cystitis and urethritis, affecting primarily the lower urinary tract, but this can potentially lead to bacterial ascension to the kidneys and pyelonephritis, particularly in pregnant women, diabetics, and children with vesicoureteral reflux (VUR) (5, 6). As a result, renal scarring and loss of function is a potentially serious complication of any UTI, particularly in infants, where diagnosis of UTI may be delayed.