PCR Testing Is the Future of Treating UTIs During Pregnancy

Urinary Tract Infections (UTI’s) are one of the most common diagnoses an expecting mother receives during pregnancy. This tends to make clinicians view this as a routine aspect of care, but UTI’s often lead to significant patient discomfort, risk of long-term harm, antibiotic overuse, and excessive health expenditure. To help change these outcomes, it’s critical to understand the pathophysiology of UTI’s during pregnancy, what level of risk they carry, how they’re contributing to a rising prevalence of antibiotic resistance, and what providers can do to streamline care and improve their patients’ lives. 

Why do UTIs occur during pregnancy?

The best treatment plans begin with a thorough understanding of how UTIs occur in the pregnant mother. The key pathophysiology revolves around changes to the urinary tract itself. According to research, "Ureteral dilation is seen due to compression of the ureters from the gravid uterus. Hormonal effects of progesterone also may cause smooth muscle relaxation leading to dilation and urinary stasis, and vesicoureteral reflux increases."¹ 

Put simply, the anatomical pressure of the fetus along with hormonal changes leads to enlargement of the urinary tract and the easier entry of bacteria. This results in a slow or backwards flow of urine that is one of the main risk factors for bacterial overgrowth.

UTI’s can occur in all women during pregnancy but are more common in nulliparous patients (women who have never been pregnant) and those with existing urinary tract abnormalities. 

Why do UTIs during pregnancy matter?

The commonplace nature of UTIs in expecting mothers has a tendency to lull providers into standard treatment rhythms. But for all its mundanity-inducing prevalence, there are significant risks associated with contracting a UTI during pregnancy. Infections can lead to chorioamnionitis, premature rupture of membranes, and fetal growth restriction. 

At the most extreme ends, Dr. Horsager-Boehrer, a leading Gynecologist from UT Southwestern, notes that "if left untreated during pregnancy, a UTI can progress to serious infection that can lead to preterm labor, premature delivery, or even fetal loss."²

The types of UTIs and the dangers they each pose during pregnancy.

Dr. Horsager-Boehrer continues on to describe the three primary types of UTIs:

1. Asymptomatic infections are those that don't trigger any symptoms - they're found in around 7% of expecting mothers. "An untreated asymptomatic infection has a 25% chance of advancing to the next level of UTI – your bladder and then your kidney."

2. Cystitis infections are those that have spread to the bladder and cause the infamous combination of pain when urinating, increased urinary frequency and the feeling of urinary urgency. 

3. Pyelonephritis infections are those that directly affect the kidneys, which can cause some of the more serious issues like "septic shock, anemia, excess lung fluid, and pre-term labor. It typically includes the symptoms of cystitis, plus nausea, fever, chills, and pain in your lower back and sides."

How antibiotics are being misused in this vulnerable population.

In light of these considerable risks, physicians for decades have classically taken an empirical treatment approach which means using an in-office urinalysis and prescribing an antibiotic based on their knowledge of which pathogens are most likely to be the culprit. Then, they wait for a urine culture to result with the actual pathogen so they can "tailor" the right antibiotic to the right bug. But Harvard Health's Dr. Lisa Bebell weighs in on some frightening recent findings, 

"At some point, most people have taken a course of trimethoprim/sulfamethoxazole (Bactrim) or ciprofloxacin (Cipro), two common antibiotics used for UTIs. However, in the last few years it has become clear that the likelihood these antibiotics will kill most UTIs is dropping rapidly… one in three uncomplicated UTIs in young healthy women are Bactrim-resistant and one in five are resistant to five other common antibiotics. Pretty scary, since we (the medical community) used to feel confident that writing a prescription for Bactrim was a sure recipe for cure."^{3 4 5}

How PCR can help in the fight for antibiotic stewardship.

The situation described above puts physicians in a challenging spot. UTIs during pregnancy are dangerous enough to warrant rapidly responding with a treatment plan, but antibiotic overuse is leading to stronger, more resistant pathogens. And since the development of new antibiotics doesn't offer many hopeful answers in the short term, the public discussion has turned to antimicrobial stewardship - i.e, being more responsible with antibiotic prescribing habits. One of the central tenets of this concept is making sure to only give antibiotics that match the disease-causing organism. 

This is exactly what physicians are attempting to do when they send urine off for a culture and sensitivity, which tells them what the pathogen is and what specific antibiotics work best against it. That said, the inherent difficulty when doing this is the amount of time it takes for culture findings to return to the physician. 

Normally results only begin to come back around 2-3 days after receipt in the lab, with 5 days needed for them to fully mature. By this point, the patient may have been on the wrong antibiotics for a few days, leading to a persistent infection, predisposition to antibiotic resistance, and the potential for gaps in communication when it comes time to get the patient on the right medication.

So does a better solution exist? If the challenge is time-to-specific-treatment, is there anything that can be done to shorten how long it takes to personalize therapy? Thankfully, due to the advances in the world of molecular diagnostics, Polymerase Chain Reaction (PCR) tests offer the possibility of getting the same results in under 2 hours. This leads to prescriber confidence of giving the right drug, right away, before the patient even leaves the office.

PCR rises to the thresholds for safe, personalized care.

The COVID-19 pandemic has led many to discover the efficiency and reliability of PCR testing, which analyzes for the genetic components of various microorganisms. However, PCR's ability to detect pathogens and their antibiotic resistant genes is not limited to SARS-CoV-2, but is already being actively used in a broad array of pathogenic testing, including for urine samples. 

Researchers for Urology found that "PCR detected uropathogens in 326 patients (56%, 326/582), while urine culture detected pathogens in 217 patients (37%, 217/582)." This led them to conclude that "multiplex PCR is non-inferior to urine culture for detection and identification of bacteria. Further investigation may show that the accuracy and speed of PCR to diagnose UTI can significantly improve patient outcomes."⁶

So for physicians that are contemplating how to be champions for timelier care that furthers the goals of antibiotic stewardship, many are turning to PCR. For vulnerable populations like pregnant women, PCR carries the potential for decreased patient suffering and better health outcomes.

References

1. Habak PJ, Griggs, Jr RP. Urinary Tract Infection In Pregnancy. [Updated 2021 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537047/" 
2. https://utswmed.org/medblog/utis-during-pregnancy/
3. https://www.health.harvard.edu/blog/antibiotic-resistant-urinary-tract-infections-are-on-the-rise-2019101417982
4. Frazee BW, Trivedi T, Montgomery M, Petrovic DF, Yamaji R, Riley L. Emergency Department Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Many Patients Have No Identifiable Risk Factor and Discordant Empiric Therapy Is Common. Ann Emerg Med. 2018 Oct;72(4):449-456. doi: 10.1016/j.annemergmed.2018.05.006. Epub 2018 Jul 3. PMID: 29980462.
5. Klevens, R. M., Edwards, J. R., Richards, C. L., Jr, Horan, T. C., Gaynes, R. P., Pollock, D. A., & Cardo, D. M. (2007). Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public health reports (Washington, D.C. : 1974), 122(2), 160–166. https://doi.org/10.1177/003335490712200205
6. Wojno KJ, Baunoch D, Luke N, Opel M, Korman H, Kelly C, Jafri SMA, Keating P, Hazelton D, Hindu S, Makhloouf B, Wenzler D, Sabry M, Burks F, Penaranda M, Smith DE, Korman A, Sirls L. Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients. Urology. 2020 Feb;136:119-126. doi: 10.1016/j.urology.2019.10.018. Epub 2019 Nov 9. PMID: 31715272."