Diagnosing UTI Complications in Mothers and Newborns

Urinary tract infections (UTIs) are one of the most common bacterial infections that occur in humans. Over 50% of women become infected with a UTI at least once in their lives, with up to 10% of women suffering from yearly infections⁵. Recurrence rates are high in UTIs, almost 50% of women who contract a UTI experience reinfection or relapse within one year of the initial infection⁵. Men are four times less likely to contract a UTI due to a longer urethra seen in men when compared with women.

Infections occur in the urinary organs and structures which can be categorized by the site of infection: cystitis (bladder), pyelonephritis (kidney) and bacteriuria (urine)⁵. So-called, uncomplicated UTIs are sited only in the bladder, however, UTIs are highly likely to cause secondary infections, commonly in the kidneys. Pyelonephritis has been shown to result in renal scarring and in some cases, subsequent renal failure². There are various species of bacteria responsible for UTIs, which have different mechanisms of infection and virulence. However, most species have surface adhesins which function like hooks, attaching the bacteria to the urothelial mucosal surface, and colonizing the bladder. From here, the bacteria can ascend the ureters, reaching the kidney and causing secondary infections².

Under normal conditions, the innate immune system actions an inflammatory response to the infection site. However, some species of bacteria that cause UTI can inhibit or delay the immune response resulting in secondary infections in the ureters and kidneys where the risk of severe renal defects is considerable, and the bacteria have direct access to the bloodstream².

Common symptoms of UTI include:

• Frequent urination
• Painful urination
• Incomplete voiding of the bladder
• Pelvic, back, and/or abdominal pain
• Haematuria
• Lethargy
• Nausea and/or vomiting
• Fever

Antibiotic therapies are effective and aim to facilitate the immune response and inhibit the spread of the infection to the kidneys and upper urinary tract. Although these treatments are usually effective, antimicrobial resistance (AMR) has become a global crisis encompassing all medical disciplines³. This resistance to antibiotics can occur through several mechanisms such as dysregulation of protein expression, structural modifications, and mutations to name a few¹¹.

Bacteria are capable of some level of intrinsic resistance, or insensitivity, to antibiotics through the production of various enzymes designed to degrade the drug or inhibit its mechanism¹¹. Mutations found in the genome of bacterial species are often responsible for the resistance they display. These mutations commonly alter the bacterial binding sites used by antibiotics, therefore inhibiting their action. Some bacteria produce enzymes, which alter the chemical structure of the antibiotic, again, inhibiting them from binding to the antibiotic. Other examples include horizontal gene transfer and biofilm formation¹⁰.

One study reported in 2019, that AMR was the twelfth leading cause of death when compared with a susceptible infection counterfactual⁹. The same study went on to show that AMR had the highest mortality rate in low to middle-income countries providing evidence that AMR is an even bigger problem in the most impoverished parts of the world. New techniques such as CRISPR-Cas9 and antibiotic re-sensitization methods are at the forefront of the fight against AMR, however, the scale of the problem warrants taking all possible action to elevate the risk posed by AMR⁸.

UTI During Pregnancy

UTIs are a common occurrence in pregnancy with one hospital reporting over 15% of pregnant women being diagnosed with some form of UTI⁴. Diagnosis can usually be confirmed by a bacterial growth of over 105 counts/ml in urine^{4, 12, 13}. Many hormonal and anatomical changes occur in a woman’s body during pregnancy that create favorable conditions for UTI. Firstly, the glomerular filtration rate is altered, causing an increase in glucose concentration and pH of the urine³. The urethral dilation, smooth muscle relaxation, enlarged mechanical compression of the uterus, and increased plasma volume result in lower urinary concentration and increased bladder size leading to urinary tract reflux and urine stagnation. These conditions are favorable for the proliferation of bacterial infections¹.

Diagnosis of UTIs in pregnant women can be complicated. For example, the increased frequency of urination experienced could also be caused by additional pressure placed on the woman’s bladder by the baby, or the abdominal pain indicative of a UTI could be interpreted as Braxton Hicks contractions and vice versa³. There are several established risk factors associated with UTI in pregnancy including advanced maternal age, diabetes, sickle cell anemia, history of UTI, urinary tract abnormalities, and various immunodeficiencies³. Other reports claim that UTI in pregnancy is more common in women with hypothyroidism and women who are carrying their first child⁴.

Bacterial Species Responsible for UTI

There are a multitude of bacterial species responsible for UTIs, the most common is Escherichia coli (E. coli), followed by group B streptococcus (GBS), enterococcus, and Klebsiella pneumonia. Escherichia coli infections are categorized as either enteric or extraintestinal (ExPEC). Of the latter, there are two main culprits: neonatal meningitis E. coli (NMEC) and uropathogenic E. coli (UPEC)². These infections can exist in the gut and spread, colonizing other parts of the host such as the blood or central nervous system, causing other potentially severe infections. Of these strains, UPEC is responsible for around 80% of both symptomatic and asymptomatic UTIs. UPEC strains have been associated with acute renal damage and are thought to encourage bacterial growth and persistence by inhibiting or delaying the innate immune response².

Maternal and Perinatal UTI Complications

UTI complications in mothers and children have long been debated. However, there is sufficient evidence to support several prognostic claims. Preterm delivery is a major complication associated with UTI and has been well studied. Preterm neonates face a high risk of fatality with up to 1 million babies dying every year due to premature labor⁶. Those that survive are at risk of developing one or more of the following health defects¹:

• Lung problems
• Diabetes
• Heart Disease
• Hearing loss
• Visual impairment
• Learning disabilities
• Behavioral problems
• Cerebral palsy

The risk of preterm birth in women who suffered from a single UTI was increased when compared to women who had no infection during their pregnancy but recurrent UTIs did not increase the risk³. Risk of low birth weight has been shown to increase by 50% in women who suffered symptomatic UTIs compared to those who remained uninfected throughout their pregnancy; this risk can be mitigated through antibiotic therapy. The same treatments did not show any significant ameliorative effects on preterm birth⁴. Women who contract a UTI during pregnancy are also at a higher risk of various conditions such as preeclampsia, postpartum endometritis, sepsis¹, hypertensive disorders, anemia and amnionitis⁴.

Asymptomatic UTIs, also known as asymptomatic bacteriuria (ASB), are not known to cause as drastic primary effects on pregnancy as seen with symptomatic infections. Despite this, ASB can spread and colonize in the kidneys. At this point, pyelonephritis is likely to occur, increasing the risk of severe renal scarring⁴ and advanced risk of preterm birth³. In these cases, it is common to treat the patient with antibiotics to reduce the risk of a secondary, symptomatic infection. While these treatments are effective at limiting the progression of the infection, overuse of antibiotics is a primary factor contributing to antimicrobial resistance⁴.

Screening and Treating UTI Complications

Women who are not pregnant and show no risk factors can be tested for UTI through a simple urine dipstick. The presence of leukocyte and absence of nitrite can be considered a positive UTI diagnosis. However, where complications are likely, a urine culture is required. Cultures can be carried out on blood or MacConkey agar and require preservation of the sample in boric acid, or in a refrigerator, for 24 hours prior to testing. This culture can then be isolated and used to identify the strain of bacteria causing the infection⁷.

Species identification is imperative in maternal UTIs. Different species have different levels of sensitivity to the various antibiotics available. E. coli, for example, shows 93% sensitivity to Nitrofurantoin but is only 86% sensitive to Fosfomycin. Selection of the correct treatment can ameliorate symptoms rapidly and reduce the possible complications for both mother and baby⁴. Many species of bacteria known to be responsible for UTIs have displayed resistance to antibiotics. Group B streptococcus has been shown to be 42% resistant to clindamycin⁴. The selection of antibiotics available to clinicians treating maternal UTI are already limited as many antibiotics have been associated with increased risk of miscarriage and birth defects independent of UTI¹.

With the patient in mind, Randox provides clinicians with both laboratory and near patient testing solutions. Bringing to the market, to help eliminate distress and improve testing turnaround times, the Randox Urinary Tract Infection Array. It has the ability to detect 30 bacterial, fungal, and associated antibiotic resistance markers from a single urine sample in under four hours. This multiplex diagnostic tool can help detect specific bacterial and fungal strains known to cause UTI allowing laboratories to confidently diagnose patients in a timely manner, aiding with targeted treatments and helping to reduce risk of complications.

The Ongoing UTI Battle

Maternal UTI is a very common problem resulting in many fatalities and morbidities worldwide. It is crucial to identify and characterize these infections to limit the negative effects seen to both mothers and their children. Quick and efficient screening is paramount in the battle against bacteria to allow the prescription of targeted treatment. While antibiotics are often an effective weapon against UTIs, care should be taken when prescribing these treatments to pregnant women due to the potential adverse effects that have been reported. Furthermore, unnecessary treatments using antibiotics should be avoided at all costs due to the increasingly serious issue of antimicrobial resistance.

References

1.Eslami V, Belin S, Sany T, Ghavami V, Peyman N. The relationship of health literacy with preventative behaviours of urinary tract infection in pregnant women. Journal of Health Literacy. 2022;6(4):22-31. doi:https://doi.org/10.22038/jhl.2021.59768.1183

2.Bien J, Sokolova O, Bozko P. Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage. International Journal of Nephrology. Published online 2012:1-15. doi:https://doi.org/10.1155/2012/681473

3.Werter DE, Kazemier BM, van Leeuwen E, et al. Diagnostic work-up of urinary tract infections in pregnancy: study protocol of a prospective cohort study. BMJ Open. 2022;12(9):e063813. doi:https://doi.org/10.1136/bmjopen-2022-063813

4.Balachandran L, Jacob L, Al Awadhi R, et al. Urinary Tract Infection in Pregnancy and Its Effects on Maternal and Perinatal Outcome: A Retrospective Study. Cureus. 2022;14(1). doi:https://doi.org/10.7759/cureus.21500

5.Bono MJ, Reygaert WC. Urinary Tract Infection. Nih.gov. Published 2018. https://www.ncbi.nlm.nih.gov/books/NBK470195/

6.World Health Organization. Preterm birth. Who.int. Published February 19, 2018. Accessed February 8, 2023. https://www.who.int/news-room/fact-sheets/detail/preterm-birth

7.Sinawe H, Casadesus D. Urine Culture. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK557569/

8.Schrader SM, Botella H, Vaubourgeix J. Reframing antimicrobial resistance as a continuous spectrum of manifestations. Current Opinion in Microbiology. 2023;72:102259. doi:https://doi.org/10.1016/j.mib.2022.102259

9.Murray CJ, Ikuta KS, Sharara F, et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet. 2022;399(10325):629-655. doi:https://doi.org/10.1016/S0140-6736(21)02724-0

10.Ali J, Rafiq QA, Ratcliffe E. Antimicrobial resistance mechanisms and potential synthetic treatments. Future Science OA. 2018;4(4):FSO290. doi:https://doi.org/10.4155/fsoa-2017-0109

11.Nelson DW, Moore JE, Rao JR. Antimicrobial resistance (AMR): significance to food quality and safety. Food Quality and Safety. 2019;3(1):15-22. doi:https://doi.org/10.1093/fqsafe/fyz003

12.Myers AL. Curbside Consultation in Pediatric Infectious Disease : 49 Clinical Questions. Slack; 2012:4.

13.Oie S, Kamiya A, Hironaga K, Koshiro A. Microbial contamination of enteral feeding solution and its prevention. American Journal of Infection Control. 1993;21(1):34-38. doi:https://doi.org/10.1016/0196-6553(93)90205-i

7. Sinawe H, Casadesus D. Urine Culture. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK557569/