Urinary Tract Infections

Medical Student Clinical Pearl

Rob Hanlon, Med 1

Dalhousie Medicine New Brunswick, Class of 2021

Reviewed by: Dr David Lewis

Urinary tract infections (UTIs) are common in both the inpatient and outpatient settings. As such, it is important to understand the etiology, pathogenesis, and treatment of such infections. This post will focus primarily on uncomplicated UTIs, bacteriology and pathogenesis, treatment options with consideration for drug resistance.

Types of UTIs: 

The term UTI encompasses different infections. These include asymptomatic bacteriuria, acute uncomplicated cystitis, recurrent cystitis, complicated UTI, catheter-associated asymptomatic bacteriuria, catheter-associated UTI, prostatitis, and pyelonephritis. ¹ There are two broad classifications: uncomplicated and complicated.

Uncomplicated UTIs refer to infections occurring in individuals with normal urinary tracts; meaning they have no structural or neurological issues, such as neurogenic bladder. These are differentiated into lower (bladder and urethra) and upper (ureters and kidneys) urinary tract infections; cystitis and pyelonephritis respectively. ² Typical symptoms of cystitis include dysuria, urinary frequency and urgency, suprapubic pain, and hematuria. Symptoms of pyelonephritis include fever, chills, flank pain, costovertebral angle tenderness, and nausea/vomiting. ³

Risk factors of uncomplicated UTIs include being female (proximity of urethral opening to anus), frequent sexual intercourse, history of recurrent UTIs, use of spermicide-coated condoms, diaphragms, obesity, and diabetes. ³ Menopause also increases the risk for UTIs as the decrease in estrogen causes the walls of the urinary tract to thin, which decreases resistances to bacteria. ⁴ Uncomplicated UTIs do occur in men; albeit, less frequently than women. Risk factors in men include anal intercourse (fecal bacteria), lack of circumcision, and benign prostatic hyperplasia. ⁵

Complicated UTIs refer to infections that are typically more severe and difficult to treat. This type of infection can be seen in people with structural abnormalities impairing the flow of urine, catheter use or other foreign bodies, renal transplantation, and kidney/bladder dysfunction.⁴

Bacteriology and Pathogenicity:

It is important to note that recently the urinary tract has been found to be colonized by a normal microbiome, similar in concept to the gut and vaginal lumens. The urinary tract has traditionally been thought to be a sterile lumen. Changes in the bacterial make-up may contribute to a disease state in the urinary tract.⁶ There is more research needed to fully appreciate how changes to the normal bacteria contribute to disease and specifically to UTIs. There is ongoing research to determine how the microorganisms become pathological and if the normal flora can be a source of a pathological process.⁶ There is research indicating possible alternative treatments such as probiotics and dietary modifications that can impact urinary tract diseases.⁶ The impact of antibiotics on the normal urinary tract bacteria is also a current research topic.⁶ Clinically, the presence of UTI symptoms would indicate that there is a pathological process present and, when indicated, antibiotics as first-line treatments are still recommended.

There are two mechanism by which bacteria enter the urinary tract, these are ascending infections and haematogenous infections. The ascending mechanism occurs when perineal/fecal bacteria enter the urethra and travel up towards the bladder/kidneys. The haematogenous route occurs when bacteria from the blood enter the kidneys.⁷

Bacteria causing UTIs are termed uropathogens. The common UTI causing organisms are gram negative Klebsiella spp., Escherichia coli, and Proteus spp., and gram positive Enterococci spp. and Staphylococcus saprophyticus. E. coli being the most common uropathogen; seen in 80% of cases. More opportunistic organisms can be isolated in complicated UTIs, such as Pseudomonas spp. and fungal Candida spp.^{4 8}

Uropathogenic E. coli (UPEC) strains contain virulence factors that allow them to colonize the urinary tract. Fimbriae are filamentous cell surface extensions that allow the bacteria to adhere to the uroepithelium and promote invasion into the tissue. Other surface molecules include flagella that allow the bacteria to mobilize up the urinary tract. ⁹ UPEC also produce toxins such as haemolysin, which damage epithelial cells and induce inflammatory responses (causing UTI symptoms). Factors allowing adherence of UPEC to uroepitehlium are paramount, as urine could wash away the bacteria. Other virulence factors allow the bacteria to thrive and grow. ⁷

Klebsiella spp. and Proteus spp. are other gram negative uropathogens that also produce fimbriae. Klebsiella produce polysaccharide capsules that prevent host defense phagocytosis.⁷  It also produces an enzyme called urease, produced by Proteus spp. as well, which hydrolyzes urea into ammonia and CO₂. The bacteria use ammonia as a source of nitrogen for metabolism. The enzymatic process also increases the pH of the urinary tract and leads to the formation of renal stones. ¹⁰

Proteus

Pseudomonas aeruginosa is a gram-negative commonly associated with nosocomial acquired UTIs, especially when catheters are in place. Its major virulence factor is the production of biofilms, which protect it from host defenses and many antimicrobials. ⁷ Staphylococcus saprophyticus is a gram-positive bacterium that also produces biofilms, as well as a specific epithelial adhesion protein called lipoteichoic acid. ¹¹

Although some of these uropathogens have similar virulence mechanisms, it is important to understand the different types of pathogens and their virulence factors because different antimicrobials target specific parts of the bacteria and the bacteria can be resistant to specific treatment options.

Treatment with Consideration for Antimicrobial Resistance

Multiple factors must be considered when choosing treatment options for UTIs in order to determine the risk of increased drug resistance. Patients are considered to be at a higher risk of drug resistance if, within the last three months, they have been found to have a multidrug resistant strain in their urine, they have been admitted to a hospital or other care facility, used broad-spectrum antibiotics, or have a travel history to areas known for resistant strains. ³

For low risk patients, treatments for uncomplicated cystitis include nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin. Choosing which drug depends on the individual’s allergies, local rates of resistance, and availability. If the patient has used one of these drugs within the last three months, the remaining two drugs are possible options. ³ If first-line treatments are not an option, then an oral beta-lactam, such as amoxicillin-clavulanate is appropriate. If allergic to this, then a fluoroquinolone such as ciprofloxacin can be used.³

Table 1: Drugs and dosages for empiric treatment of uncomplicated cystitis. ³

For higher risk patients, a urine culture and antimicrobial susceptibility testing should be ordered. First-line treatments (see above) can be used as empiric treatments until test results are obtained. However, if the patient is unable to take these treatments, test results should be obtained prior initiating treatment. ³

For complicated UTIs, such as catheter infections, treatment depends on the severity of the illness. Urine culture and susceptibility testing should be performed. In the case of a catheter infection, it should be removed and a sample from the catheter should be cultured. ¹² If the catheterized patient requires treatment prior to obtaining test results, treatment should cover gram-negative bacilli. Third-generation cephalosporins can be used in this case. Critically ill patients should be put on broad spectrum antibiotics such as carbapenems and vancomycin, in order to cover pseudomonas and methicillin-resistant Staphylococcus aureus infections respectively. ¹³

Local (New Brunswick, Canada) Information on Antimicrobial Treatment of UTIs can be found here:

Antibiotic Guidelines and Infection Resources

This is not an exhaustive description of infection types, treatments, or resistance mechanisms. This post focused on uncomplicated UTIs and their treatments because they are commonly seen in the clinical setting. An in-depth patient history is crucial for understanding the possible causes of a UTI and for developing a differential diagnosis. These should be included alongside test results when evaluating treatment options.

References:

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11. Raul Raz, Raul Colodner, Calvin M. Kunin. Who are you: Staphylococcus saprophyticus? Clinical Infectious Diseases. 2005;40(6):896-898. http://www.jstor.org/stable/4463165. doi: 10.1086/428353.
12. Fekete T. Catheter-associated urinary tract infection. Retrieved from: https://www.uptodate.com/contents/catheter-associated-urinary-tract-infection-in-adults?source=see_link#H123172989. Updated 2016.
13. Hooton T, Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. Retrieved from: https://www.uptodate.com/contents/acute-complicated-urinary-tract-infection-including-pyelonephritis-in-adults?source=see_link#H12414288. Updated 2017.