Understanding the Need for New UTI Treatments

Defining UTIs

According to the Mayo Clinic, a urinary tract infection is a bacterial infection in any part of the urinary tract, including the kidneys, ureters, bladder, and urethra, with the majority of infections beginning in and including the bladder and urethra. Frequent or recurring UTIs are defined as two infections within six months or three or more infections within one year.

Symptoms

While many varying symptoms and complications are associated with a UTI, common symptoms may include an overactive bladder, dysuria, albuminuria, hematuria, and pelvic pain.

Beyond the typical symptoms associated with UTI, additional symptoms may be experienced depending on the affected part of the urinary tract. If the infection has traveled to the kidneys, patients may experience back or side pain, fever, chills, nausea, and vomiting. An affected bladder yields feelings of pelvic pressure, lower stomach pain, dysuria, and hematuria. Urethral infections are characterized by burning with urination and discharge.

Symptoms with Aging

According to Geisinger, UTI symptoms can change as the patient ages. Older patients may experience additional symptoms such as confusion, irritability, hallucinations, sudden changes in behavior, fatigue, dizziness, and more frequent falls — symptoms often associated with dementia.

A weakened immune system in older individuals can make it easier for infection to spread to the kidneys, causing sepsis which can lead to the cognitive symptoms seen in the elderly. Beyond immunity, a weaker pelvic floor or incontinence can make older patients more susceptible to UTIs. Additionally, urinary catheters, which are more common in elderly patients, may increase the probability that a UTI goes untreated until the late stages, as it can make recognizing early symptoms difficult.

Causes

As a bacterial infection, UTIs occur when opportunistic bacteria invade the urinary tract through the urethra and spread upward toward the bladder and kidneys. StatPearls defines a UTI as greater than “100,000 colony forming units (CFUs)/mL of urine associated with typical acute symptoms of dysuria, urgency, frequency, or suprapubic pain. However, more than 100 CFUs of E. coli with typical acute urinary symptoms has a positive predictive value of about 90%, suggesting that a lower CFU threshold may be more appropriate in diagnosing simple and recurrent UTIs.”

Urethral infections can happen when GI bacteria from the anus spread to the urethra. According to the Mayo Clinic, in women, “an infection of the urethra can also be caused by sexually transmitted infections. They include herpes, gonorrhea, chlamydia, and mycoplasma. This can happen because women's urethras are close to the vagina."

Although the most common bacterium that causes UTIs is E. coli, a common GI bacterium, other kinds of bacteria can still cause UTIs.

Risk Factors

While multiple risk factors are associated with an increased risk of developing a UTI, the primary risk factor is anatomy. Many sources cite the length of the urinary tract as the reason behind this increased risk. Because women have a shorter urinary tract, the female anatomy allows for a more accessible and quicker path for bacteria to travel.

Additional risk factors may include sexual activity, specific birth control methods — namely, using a diaphragm and spermicide — menopause, blockages in the urinary tract, suppressed immune systems, catheter use, and a history of urinary tract problems.

Many factors may increase the risk of UTIs, such as anatomical defects, vesicoureteral reflux (VUR), cystoceles and pelvic organ prolapse, functional defects, lesions, and urinary stasis. Additional risk factors for recurring infections include the following:

• atrophic vaginitis
• chronic diarrhea
• genetic predisposition
• frequent intercourse
• incomplete bladder emptying
• new or multiple sexual partners
• urinary incontinence
• spermicide use
• poor personal hygiene

Diagnosis

If a patient is suspected of having a UTI, many providers will run a urine dipstick test, which can be done in the doctor’s office. Essentially, after the provider collects a urine sample, it is tested with a pH paper-like strip to determine if the patient has ketones, blood, and other factors in their urine. Despite the convenience of this diagnostic method, it can be inaccurate and useless if a patient has taken over-the-counter medication to treat the symptoms of UTIs.

A urinalysis can be used to confirm a urine dipstick or in cases where one is not an option. In this case, the urine sample is sent out for a laboratory analysis that identifies the presence of white blood cells, red blood cells, or bacteria.

According to a study published in American Family Physician, “using a urine dipstick test instead of urinalysis to detect urinary tract infections (UTIs) can decrease the time needed to make a diagnosis; however, the diagnostic accuracy of urine dipsticks varies, depending on the standards used. Many experts have recommended urinalysis to confirm urine dipstick test results.”

Some research may contradict this statement; however, many providers opt to continue with a uranalysis due to potential inconclusive tests.

A urine culture is required for a differential diagnosis identifying the type of bacteria causing the infection. This can provide healthcare professionals with additional insights into which medications are most effective. For patients with recurring UTIs, a urine culture is required to differentiate between reinfection and relapse. Additionally, urine cultures can help with antibiotic stewardship as it prevents the same antibiotic from being written if it is unnecessary.

Doctors may also choose to do imaging or conduct a cystoscopy to rule out structural issues when a patient has recurrent UTIs. Medical imaging may include an MRI or a CT, with or without contrast, which can show providers if there is a structural problem. Imaging is called for when patients have a history of kidney stones, persistent hematuria, or relapsing infections.

In addition, a cystoscopy — a procedure where a scope is inserted into the urethra and passed into the bladder — may also be used to detect a structural issue.

Recurrence vs Relapse

Many people confuse UTI recurrence with a relapse. A recurrent infection occurs when a patient is infected multiple times by different bacteria each time. If the same bacteria reinfect a patient, it is called relapse. A relapse typically indicates an inadequately treated infection caused by a secondary source, such as an abscess or urinary stone.

Authors in StatPearls emphasize the importance of defining the infection, saying, “it is important to differentiate rapid reinfection (a different organism) from a relapse (the same organism which was not completely treated). A relapse is further defined as a recurrence within two weeks of completing therapy with the same organism. It is considered reinfection if the new infection is more than two weeks after completion of therapy even if the organism is the same.”

Treatments

While the standard treatment method for UTIs is a dose or round of antibiotics, an individualized treatment plan can depend on the infection's complexity, frequency, and cause. According to the Mayo Clinic, the most common medications for UTI are trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS), fosfomycin (Monurol), nitrofurantoin (Macrodantin, Macrobid, Furadantin), cephalexin, and ceftriaxone.

Treating acute uncomplicated UTIs is a relatively simple process. After the necessary tests, first-line treatments are prescribed, which may include 100 mg of nitrofurantoin twice daily for 5–7 days, 160/800 mg of trimethoprim–sulfamethoxazole twice daily for three days, or 3 mg of fosfomycin one time.

When those medications are unavailable or cannot be used, providers may opt for beta-lactams such as 500 mg of amoxicillin–clavulanate, 300 mg of cefdinir, 500 mg of cefadroxil, or 100 mg of cefpodoxime may be given twice a day for 5–7 days.

Fluoroquinolones, a group of strong antibiotics including ciprofloxacin and levofloxacin, are typically not advised for uncomplicated UTIs as they are associated with many risks. However, if no other treatment method is available, a doctor may prescribe them. A severe infection may require IV antibiotics delivered at an in-patient facility.

Those who get frequent UTIs are familiar with the perceived benefit of cranberry extract and cranberry juice. While there is no definitive evidence that cranberries may prevent or alleviate symptoms of a UTI, many believe it has some beneficial properties. Since cranberry juice is associated with few risks and contraindications, most providers believe that if patients find it helpful, they should go ahead and use it. 

StatPearls states, “The use of cranberry products is somewhat controversial, but so far, a benefit has not yet been definitively established. Cranberries are thought to work by providing proanthocyanidins, which decrease bacterial adherence to the urothelium. While this sounds attractive, commercially available cranberry products have limited amounts of proanthocyanidins. The bottom line is that it is suggested for whatever benefit it might provide but advise patients that it is unclear sure how much it will ultimately help.”

For frequent UTIs, providers may consider prescribing long-term low-dose antibiotics, postcoital antibiotics, and vaginal estrogen therapy. These treatment methods and their indications vary based on age, sex, lifestyle, and cause of infection.

The Need for New Treatment Methods

While the standard course of treatment for UTIs is similar to most bacterial infections, the frequency of recurrent infections presents some concerns for patients, providers, and public health experts. It is well understood that repetitive antibiotic usage is associated with increased rates of antibiotic resistance, posing a threat to public health. Pharmaceutical companies, researchers, and providers are constantly searching for new options to minimize repetitive prescriptions of the same antibiotic.  

Gepitidacin

In a press release earlier this month by GSK, the company claimed that it may have developed a new antibiotic, gepitidacin, which is comparable to nitrofurantoin in treating UTIs. It states that this is a “triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and equally and independently binds to two different Type II topoisomerase enzymes.” The medication has been shown to work against E. coli and Staphylococcus saprophyticus, including those resistant to current antibiotic treatments.

As the company prepares its New Drug Application for the FDA and continues with the approval process, urologists, primary care providers, and other healthcare professionals who treat UTIs regularly will wait in anticipation of the FDA decision and the potential rollout of this new tool.