Urinary Tract Infections

Introduction

Urinary tract infection (UTI) is one of the most common infectious diseases, both in ambulatory and hospital settings, and is a major cause of antimicrobial use. This is especially relevant in the era of increasing antimicrobial resistance, and in particular, resistance developing in the Gram-negative organisms, which cause most UTI episodes. In many locations, it is increasingly difficult to select an empiric agent for UTI treatment that is reliably active, without major toxicities, and with robust evidence from clinical trials. Additional challenges in treating UTI are recognizing the distinct clinical syndromes included within the broad category of UTI and being aware of key management differences such as drug selection, therapy duration, and route of administration. The spectrum of distinct entities included under the umbrella of “UTI” ranges from simple cystitis, to pyelonephritis, to life-threatening urosepsis, making appropriate treatment of UTI more challenging than often appreciated.

Finally, it is critical to recognize that 30% to 50% of “UTI” episodes are actually asymptomatic bacteriuria mistakenly labeled as UTI and that any antimicrobial therapy given to these patients confers the risk of harm with no benefit. This chapter will focus on practical definitions of the commonly encountered UTI syndromes and highlight important principles of diagnosis and treatment for each entity.

Microbiology

Escherichia coli is the most important organism in the UTI world, but its relative importance fluctuates based on the specific UTI syndrome and the age and sex of the patient. In the case of uncomplicated cystitis in a premenopausal woman, E. coli is the causative organism for >90% of cases, with the remainder accounted for by Staphylococcus saprophyticus and a smattering of non– E. coli Enterobacteriaceae. Defining clonal strains of E. coli and their epidemiology is an ongoing area of research and is clinically relevant in that rapid expansion of specific clones can lead to widespread emergence of clinically relevant phenotypes, such as fluoroquinolone resistance and extended-spectrum β-lactamase production, both of which are important to consider when choosing empiric antimicrobial therapy, especially in a critically ill patient. In postmenopausal women, and especially in elderly men, non– E. coli organisms become more common causes of UTI. Although E. coli is still the most common organism isolated from the urine of symptomatic patients, in many cases, it is only a plurality, with non– E. coli organisms together comprising a majority. The specific organisms are not crucial to commit to memory, but a few general principles should be noted. Gram-negative organisms predominate, including Enterobacteriaceae such as Klebsiella , Enterobacter , and Citrobacter , but others such as Pseudomonas aeruginosa are also encountered, especially in patients with recent hospital exposure. Gram-positive organisms are less likely, but enterococci can be isolated from men, and Staphylococcus aureus should also be considered in a patient with hospital exposure.

Other than knowing the relative importance of Gram-negative organisms, the most important tools for a provider regarding UTI treatment is knowledge of how to access a current antibiogram and the ability to obtain a urine Gram stain to help guide empiric therapy. The urine Gram stain can be particularly useful in a patient with a prior history of methicillin-resistant S. aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) colonization; if such a patient presents with symptoms of pyelonephritis, a urine Gram stain showing only Gram-negative bacilli eliminates the need for empiric therapy targeting those previously isolated organisms and can greatly simplify therapy. Consulting a local antibiogram is essential in selecting an optimal empiric therapy for all UTI syndromes, but in particular for high-acuity syndromes such as pyelonephritis and urosepsis. At a facility where resistance to fluoroquinolones among Gram-negative organisms is below 10%, ciprofloxacin for a patient hospitalized with pyelonephritis is reasonable. If the same patient were to present at a facility with fluoroquinolone resistance rates for Gram-negatives exceeding 25%, ciprofloxacin as empiric therapy would be a questionable choice and could lead to harm.

Sex Differences

The epidemiology of UTI differs by sex, with UTI being far more common in premenopausal women relative to similarly aged men. The shorter urethra in women is believed to contribute to the increased risk of UTI, with bacteria having a shorter distance to travel to reach the bladder. Among postmenopausal women and similarly aged men, rates of UTI are comparable, largely due to rising incidence among men. This is attributed to the increasing frequency of prostatic hypertrophy and to the development of other comorbid conditions such as renal calculi, other prostatic diseases such as cancer, diabetes mellitus, chronic kidney disease, and others. This accumulation of conditions negates the protection accorded by the longer male urethra and whatever other factors may account for the lower rate of UTI in younger men relative to their female counterparts.

Sex differences are relevant in both the diagnosis and treatment of UTI. As mentioned previously, the microbiology of UTI in men is varied and unpredictable, such that a urine culture should always be obtained. In women, the microbiology is so predictable that in the absence of high rates of resistance, a urine culture is superfluous for UTI managed in the ambulatory setting. Among hospitalized patients, urine culture is advisable for all patients with a UTI syndrome to ensure active therapy in these acutely ill patients. Treatment differences between men and women include the fact that known or suspected prostatic involvement may influence drug selection (ideally with an agent known to penetrate prostatic tissue) and that treatment duration is generally longer for men than for women.

Classification of Urinary Tract Infections