Pharmacists Play Key Role When Individualizing Treatments for UTIs

Pharmacy Times^® interviewed Marilyn N. Bulloch, PharmD, BCPS, FCCM, SPP, associate clinical professor and director of strategic operations at the Harrison College of Pharmacy, Auburn University, on urinary tract infections (UTIs) and the current treatment landscape. She discussed the common symptoms that patients often face and how health care professionals might navigate treating based on co-occurring conditions, what other drugs they are taking, and allergies. Gepotidacin (GSK) is currently undergoing evaluation for FDA approval in the UTI space and Bulloch described its potential efficacy in other infections.

Pharmacy Times^®: Can you introduce yourself?

Marilyn N. Bulloch, PharmD, BCPS, FCCM, SPP: Sure, I'm Marilyn [N.] Bullock. I'm an associate clinical professor of pharmacy practice and the director of strategic operations at Auburn University's Harrison College of Pharmacy.

Pharmacy Times: What are the most common symptoms of urinary tract infections (UTIs) and how do recurrent infections affect a patient’s quality of life?

Bulloch: This is something that affects 50% to 60% of women, at least in their lifetime, and it certainly can affect men, I see a lot of men in my practice with UTIs. It has to be one of the most uncomfortable infections I think a person can have. Burning is a very common symptom, and that burning can be intense—and absolutely miserable—you could have this increased frequency of urgent urination, this feeling like you have to urinate even when your bladder is empty....and those are sort of the bigger symptoms, and certainly, if the infection gets more complicated, you can have pain, as you get older, we'll see one of the first symptoms is altered mental status. So, [patients will] come in and [health care professionals] will want to work [with] them for all kinds of things from a neurologic perspective, and it's a UTI.

So, [UTIs are] a very, very uncomfortable infection, and when you think about quality of life—in addition to the obvious physical impact—having [these] frequent urges that are going to cause disrupted sleep...because you're going to feel like you need to go in the middle of the night several times, you're going to feel very tired. That might be from the infection itself, or the fact that you're not sleeping at night because you're waking up several times.

There's also this emotional impact: when are you going to get your next infection, [and] maybe for some patients who have recurrent UTIs, frustration that the UTI is not going away, there could be impact on self-confidence and body image, especially if you do have that foul odor in the urine, you can have a lot of stress because of it. If you're symptomatic, you've gotta find time to go to the doctor and get medicine and then go to the pharmacy.

From a social standpoint, this is something that really does disrupt work and school attendance...there's this anxiety that you need to know where the bathroom is, because you don't know when you're going to have to go. It can affect sexual activity for both men and women, there's a lot of concerns there, there's a lot of embarrassment with it, it can complicate making plans. And then, as I mentioned before, there's the time with medical appointments and the financial burden that goes into it. So, from a quality-of-life standpoint, it's a lot.

Pharmacy Times: Currently, what are some standard treatments for UTIs?

Bulloch: I think some of it does depend on age, gender, and comorbidity, but for uncomplicated UTIs, particularly in women, the guidelines—which are a little bit dated—have 3 first-line antibiotics. [Sulfamethoxazole/trimethoprim] (Bactrim; Amneal Pharmaceuticals), which a lot of [health care professionals] hesitate to use because about concerns with the kidneys, rash, and hyperkalemia. And also, one of the reasons we don't use it as much is because local resistance. It has to be below a 20% threshold before you're really supposed to use it.

One that's more frequently used probably has nitrofurantoin (Furadantin; Casper Pharma), which [has] broader acceptance, but it can be harder to use that in patients, especially as they get older, because you have to have a creatinine clearance of at least 30 for it to get into the urine and for it to work.

And then the last one is fosfomycin (Monurol; Allergan, Inc.), which I don't see used in the US a lot. It's a one-and-done treatment, there are obviously some advocates for its use, but where Bactrim and nitrofurantoin were generic for longer...and so, I think why would you use this expensive drug when you could use these 2 cheap ones? So, I just don't think that it ever gained that popularity in the US. Plus, there's some data [that] suggest it's not as good as nitrofurantoin.

In the hospital, we'll see a lot of third-generation syphilis...there are other options—like oral beta-lactams and fluoroquinolones—but you want to reserve those for specific circumstances, particularly when your patient can't take one of those first-line agents. You don't want to use fluoroquinolones unless you have to—which is a change from when I was in school—but it does have a lot of collateral damage, so we try to reserve them for only when we have to use them.

Pharmacy Times: What is the pharmacist’s role in the treatment of UTIs?

Bulloch: One of the biggest issues I see in practice is that first-line and second-line antibiotics are written for incorrect directions—and I'm not really sure where that misstep occurs in the educational process. Often, [antibiotics] are prescribed for longer than they need to be, at least for uncomplicated UTIs. Sometimes for complicated UTIs, I see antibiotics prescribed for much shorter than they need to be prescribed for. Either way, under- or over-treating can contribute to the development of resistance and intolerance in a patient.

I think it's important to understand patient selection. Often, prescribers know what to give to it what I call an "easy patient," someone who is otherwise healthy, they don't have allergies, no big drug interactions, no conflicting or co-occurring conditions. Where my role is and where our pharmacists' roles[are] is in the patients who are not as straightforward. They have several allergies and they have a drug interaction, or maybe their kidney function rules out the use of this drug, and all of a sudden...and it can be very complex, and this is actually a norm of patients as they age: you get older, your kidney function declines, you're taking more drugs, you have more co-occurring conditions which could interact with the antibiotic choices, [and] that's where we come in. We help individualize therapy when it's not easy.

Pharmacy Times: Any final or closing thoughts?

Bulloch: One, I think it's important for pharmacists to understand, [gepotidacin (GSK)] is also being looked at for gonorrhea, [which] right now is treated with ceftriaxone (Rocephin; Genentech USA), because we don't have a lot of oral options. And I don't know if you've ever received intramuscular ceftriaxone—[it's] not the most comfortable medication—so, this would give you an oral option now.

While it's not being studied right now for other sources of infection...the spectrum of bacteria includes some really impressive medications, including [methicillin-resistant Staphylococcus aureus], Streptococcus, [Moraxella] catarrhalis, and Clostridium perfringens...so, I would not be surprised if they get approved for UTIs [and] if the manufacturer doesn't then try to pursue or evaluate it in the management of other types of infections, like skin and soft tissue infections, and pneumonia. And a really interesting coverage—Yersinia pestis, the [Bubonic plague], which I don't see here in Alabama, but they have a few patients out west that have it every year—and then tuberculosis, which I do see here in Alabama. So, I think that that...we're seeing a lot more resistance in tuberculosis.

And then there's other pathogens, which depending on where you practice, you may not be as familiar with, but there's one called Stenotrophomonas, which I call it a "bully" because it really impacts patients who have been sick for a long time or who are immunocompromised. And again, we don't have a lot of options available for [that] and very few oral options...it would not be surprising to me if they started to evaluate to see if this drug could be used in more places than just for a UTI.

One of the things we don't know, and I think that this is equally important...we know [gepotidacin has] been studied in cystitis, [but] we don't know how it will work for pyelonephritis (pyelo), which is a more severe form of UTI. And we as pharmacists and clinicians need to remember when we're treating infections, it's not just about pathogen coverage, but tissue penetration. And that's not to say it won't work for pyelo, we just don't know. There's been nonhuman studies that suggest it might be effective for pyelo, but I think until we know that for sure in humans, we need to reserve its use there. I don't think that we need to broadly use it for any type of UTI.