Diagnosis and Treatment of Urinary Tract Infections: A Case-Based Mini-Review, Part 2
Eiyu Matsumoto, MB; Jennifer R. Carlson, PA-C; and Alice Xu, MD
Matsumoto E, Carlson JR, Xu A. Diagnosis and treatment of urinary tract infections: a case-based mini-review, part 2. Consultant. 2017;57(9):526-529.
ABSTRACT: Urinary tract infection (UTI) remains one of the most common indications for prescribing antimicrobial medications in the outpatient setting. Despite the extensive need for treatment of UTIs, the antimicrobial resistance rate has been rising, which has limited the therapeutic options. Application of basic knowledge can not only cure UTIs but also prevent Clostridium difficile colitis and the development of multidrug-resistant organisms. For these reasons, primary care providers need to be knowledgeable and proficient in the diagnosis and management of UTIs. Three clinical cases, each with their own teaching points, are presented in this review.
KEYWORDS: Urinary tract infection, cystitis, pyelonephritis, prostatitis, asymptomatic bacteriuria, antibiotics
Editor’s note: Part 1 of this article appeared in the August 2017 issue of Consultant. Read it at https://www.consultant360.com/articles/diagnosis-and-treatment-urinary-tract-infections-case-based-mini-review.
Urinary tract infection (UTI) is the most common bacterial infection encountered in the ambulatory care setting in the United States, accounting for 8.6 million visits (84% by women) in 2007.1 Acute cystitis is more common than acute pyelonephritis, with an estimated ratio of 28 cases of cystitis to 1 case of pyelonephritis.2
UTI is classified as either uncomplicated or complicated. In general, uncomplicated UTI refers to an acute illness of cystitis or pyelonephritis in healthy, premenopausal, nonpregnant women with no history to suggest abnormalities of the urinary tract.3 Complicated UTIs are those occurring in patients with a structural or functional abnormality of the genitourinary tract.4 The pathogenesis of UTI is periurethral mucosal colonization of pathogens that ascends the urethra to the bladder. Enteric organisms such as Escherichia coli are the most common culprits.
Acute cystitis usually manifests with dysuria, urinary frequency, urgency, suprapubic pain, hematuria, or combinations of these symptoms. Pyelonephritis should be suspected when a patient has fever, chills, flank pain, costovertebral angle tenderness, or nausea and vomiting in addition to symptoms of cystitis.5 Pyuria and bacteriuria are diagnostic. Dipstick testing is useful to assess the presence of leukocyte esterase and nitrites. Leukocyte esterase is an enzyme released by leukocytes and indicates the presence of pyuria. Nitrites are metabolic products converted from nitrates by enteric organisms (eg, E coli). Of note, Enterococcus and Candida species do not produce nitrites. Urine culture testing is performed to determine the presence of bacteriuria and antimicrobial susceptibility.
Acute uncomplicated cystitis is a benign condition that rarely progresses to severe disease, even if untreated. Thus, the primary goal of treatment is to ameliorate symptoms.4 On the other hand, pyelonephritis can rapidly progress to urosepsis. Although most episodes of acute uncomplicated pyelonephritis are now treated in the outpatient setting, hospital admission should be considered if there is hemodynamic instability or any complicating factor such as diabetes, renal stones, or pregnancy. Other factors to consider for hospital admission include the patient’s inability to tolerate oral medications or a concern regarding nonadherence to treatment.4
Despite the extensive need for treatment of UTIs, the antimicrobial resistance rate has been increasing, which has limited the therapeutic options. For these reasons, primary care providers need to be knowledgeable about and proficient in the diagnosis and management of UTIs.
A 75-year-old man presented with a 3-day history of dysuria, urinary frequency, hesitancy, dribbling of urine, and transient hematuria. He denied fever, chills, nausea, vomiting, scrotal pain, or back pain. He is not sexually active. Urine dipstick test results were positive for leukocyte esterase and nitrates. The patient was prescribed a 7-day course of nitrofurantoin empirically for suspected cystitis. In 24 hours, urine culture results were positive for E coli, susceptible to all tested antimicrobial agents. The patient’s symptoms resolved in a few days. What would be the best next course of action?
Discussion. UTI in men without an indwelling urethral catheter is uncommon, but the incidence and severity of UTI increase substantially among men older than 60 years.6,7 UTI is the most common cause of bacteremia in older men.8 Recurrent infection is common among the older population.7
All cases of UTI in men should be classified as complicated, whereas most UTIs in healthy younger women are classified as uncomplicated. As men age, they may acquire more structural and functional abnormalities of the urinary tract that impair the normal voiding process. The most common of these is benign prostatic hyperplasia (BPH). Other common causes are listed in the accompanying Table.4
The choice of antimicrobial treatment depends on the clinical presentation. For cystitis, the various available options include nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), and ciprofloxacin or levofloxacin, typically for 7 days. In acute pyelonephritis, ciprofloxacin or levofloxacin, ceftriaxone, or gentamicin is used for 7 to 14 days.9
Once a male patient is confirmed to have a first UTI, evaluation of the upper and lower urinary tract is recommended given the high prevalence of urologic abnormalities among men who present with UTI.9 The digital rectal examination (DRE) is useful in evaluating the size and texture of the prostate. Residual urine volume should be assessed by means of noninvasive ultrasonography. Although there is no clear cutoff, a residual volume exceeding 100 mL raises suspicion for a urinary tract obstruction distal to the bladder.10
Either computed tomography (CT) with intravenous contrast or ultrasonography is the diagnostic modality of choice in evaluating the anatomy of the urogenital tract. These investigations are especially high-yield in febrile UTI cases. One study showed that 15 of 85 men in Sweden who presented with febrile UTI were discovered to have previously unrecognized abnormalities in the urinary tract that required surgical intervention.11 These abnormalities included BPH with obstruction, urethral stricture, bladder or renal stones, and bladder cancer.11 If bladder cancer is suspected, urine specimens may undergo further cytology analysis for malignant cells. Cystoscopy typically is the next step.
Outcome of the case. The patient underwent a DRE and bladder ultrasonography scanning, which revealed a smooth but enlarged prostate without nodularity. His bladder urine residual volume was 250 mL. CT scans showed mild bilateral hydronephrosis but revealed no calculi, mass, or ureteric strictures. He received a diagnosis of complicated cystitis secondary to BPH. After starting a regimen of tamsulosin, his urinary tract symptoms improved. To date, he has had no recurrence of UTI.
A 25-year-old woman with past medical history significant for remote UTIs presented with dysuria, urinary frequency, urgency, and a one-time episode of hematuria. She denied fever, chills, nausea, vomiting, or back pain. She reported that she did not feel particularly sick and stated that she was not pregnant. She had no recent history of surgical procedures or hospitalizations. Urine dipstick test results were positive for leukocyte esterase and nitrates. She was presumed to have an uncomplicated UTI and was prescribed a 5-day course of nitrofurantoin. Two days after her presentation, urine culture results were positive for Pseudomonas aeruginosa, resistant to ciprofloxacin. How would you manage this case?
Discussion. Pseudomonas species are ubiquitous gram-negative bacteria, and P aeruginosa is the most important species in human infections.12 P aeruginosa is among the main pathogens in community-onset health-care–associated UTI.13 In a surveillance study conducted from 2009 to 2010, P aeruginosa was the second most common pathogen in catheter-associated UTIs, accounting for 11.3% of all cases in the United States.14 It also is a very common pathogen in intensive care and long-term acute care settings.15,16
In contrast, UTI from P aeruginosa is rare in the community, with an occurrence rate of 1% to 4%.13 However, the positivity of this pathogen in urine culture in community-onset UTI has some implications. Studies have revealed that Pseudomonas UTI is suggestive of underlying urologic conditions such as prostatitis, urinary tract obstruction, a history of urologic procedures or neurogenic bladder, and prior UTI treatment. Many of these risk factors suggest that the patients have had health care exposure; therefore, these infections may not be community-acquired but are likely health-care–associated.12
The antimicrobial resistance rate is high among P aeruginosa strains. Only 2 antimicrobial classes, fluoroquinolones and fosfomycin, are effective as oral options. Among fluoroquinolones, ciprofloxacin and levofloxacin are well known to have activity against susceptible P aeruginosa strains. Although it is not widely recognized, fosfomycin can have activity against P aeruginosa in varying degrees.17 The antibiotic penetration of fosfomycin in the lower urinary tract is excellent, and it can be an effective option if the P aeruginosa strain is susceptible to it.
Outcome of the case. Despite having denied any recent health care contact (hospital admissions, surgical procedures, urinary catheter placements, antibiotic prescriptions), the patient did mention having had 7 UTI episodes since childhood. She received a diagnosis of P aeruginosa cystitis. Additional testing for fosfomycin sensitivity was requested, the results of which confirmed susceptibility a few days later.
The patient was instructed to take fosfomycin orally as 3 g of powder mixed with at least ½ cup of water every 3 days for a total of 3 doses, after which her symptoms resolved. Urine human chorionic gonadotropin testing was not done, since fosfomycin is known to be safe in pregnancy. In light of the patient’s community-onset P aeruginosa UTI and her history of frequent UTIs, she was referred her a urology clinic to rule out anatomic or functional problems in her genitourinary tract.
An 82-year-old man taking tamsulosin for BPH presented with a 2-day history of dysuria. He reported that he had had 3 UTIs in the past 2 months. A review of his medical records revealed that he had had 3 positive urine culture results for pan-susceptible E coli 7 weeks ago, 4 weeks ago, and again 2 weeks ago. He had experienced dysuria, perianal discomfort, and cloudiness of urine intermittently during these episodes, but he denied fever, chills, and flank pain. He had received 10 days of ciprofloxacin for the first episode, 10 days of nitrofurantoin for the second episode, and 10 days of TMP-SMX for the third and most recent episode.
At the current visit, urine dipstick test results were positive for leukocyte esterase and nitrates. Urine culture grew E coli that was pan-susceptible (including to ciprofloxacin). Results of CT scan with contrast of the abdomen/pelvis were unremarkable.
What is the most likely diagnosis and treatment approach?
Discussion. In the absence of fever, this elderly patient with BPH presenting with recurrent UTI is unlikely to have pyelonephritis. Identification of the same E coli strain in repeated urine cultures raises several possibilities, including asymptomatic bacteriuria, infected nephrolithiasis, abscess, and chronic prostatitis.
Asymptomatic bacteriuria is a microbiologic diagnosis determined with the results of a urine specimen that has been collected in a manner to minimize contamination and that has been transported to the laboratory in a timely fashion to limit bacterial growth. Asymptomatic bacteriuria occurs not only in women but also in men,18 particularly those who have diabetes (0.7%-11%),19 who are elderly persons in the community (3.6%-19%),20 and elderly persons in a long-term care facility (15%-40%).21 Our patient presented with positive urine culture results and correlating symptoms; therefore, this is not a case of asymptomatic bacteriuria.
UTI from a nidus of infection is another possibility. Infected nephrolithiasis in the ureter or the bladder can present with recurrent UTI from the same bacterial strain. Renal abscess resulting from severe pyelonephritis also can present with persistent bacteriuria from the same strain until its resolution. CT imaging can help rule out these anatomic problems.
Chronic prostatitis should be in the differential diagnosis in men with recurrent UTI. Chronic bacterial prostatitis is characterized by repeatedly positive urine culture results for the same organism strain.22 In contrast with acute bacterial prostatitis (which is characterized by abrupt-onset fever, chills, dysuria, and the striking physical finding of severe prostate tenderness), patients with chronic prostatitis are often asymptomatic between episodes of bacteriuria. The prostate is usually normal on DRE. Often, the bacterial strain remains antibiotic-sensitive on culture tests repeated after multiple antibiotic courses.23
A diagnosis of chronic bacterial prostatitis can be confirmed by means of culture of the prostatic fluid with the use of classic Meares-Stamey 4-glass test.9 In this test, the patient voids the first 10 mL of urine (the urethral specimen; VB1) into a collection glass. After the patient voids approximately 200 mL, a midstream specimen (bladder urine; VB2) is collected. After the bladder has been emptied, expressed prostatic secretions (EPS) are obtained after prostatic massage. The first 10 mL of urine voided after massage (VB3) is considered to be prostatic washout. The presence of the same bacteria in the EPS and VB3 samples as in the VB1 and VB2 samples is highly diagnostic of bacterial prostatitis. Growth of gram-negative bacilli in the VB1 specimen without substantial growth in the other samples is diagnostic of urethral colonization. Unfortunately, sensitivity and specificity have not been well established.
The prostate is unique in that only limited classes of antibiotic can penetrate it effectively. The first-line therapy for chronic prostatitis is a fluoroquinolone for 4 to 6 weeks, which generally results in microbiologic cure rates of 70% or more.24,25 Of note, tendinopathy with prolonged fluoroquinolone use has been reported frequently, prompting the Food and Drug Administration to mandate a black-box warning on the package labeling. Patients should be informed about the risks and benefits of the use of this class of medication.
Outcome of the case. In the light of the recurrent UTI symptoms, the multiple positive urine cultures for the same organism type, and the negative CT findings, the most likely diagnosis was chronic prostatitis. The patient deferred a DRE. Empiric treatment with ciprofloxacin for 6 weeks was prescribed, after which his symptoms resolved.
Eiyu Matsumoto, MB, is a clinical assistant professor in the Department of Internal Medicine, Division of Infectious Diseases, at the University of Iowa Carver College of Medicine in Iowa City, Iowa.
Jennifer R. Carlson, PA-C, is a physician assistant at the Iowa City Veterans Affairs Health Care System in Iowa City, Iowa.
Alice Xu, MD, is a third-year resident in the Department of Internal Medicine at University of Iowa Hospitals and Clinics in Iowa City, Iowa.
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- Kärkkäinen U-M, Ikäheimo R, Katila M-L, Siitonen A. Recurrence of urinary tract infections in adult patients with community-acquired pyelonephritis caused by E. coli: a 1-year follow-up. Scand J Infect Dis. 2000;32(5):495-499.
- Hooton TM. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028-1037.
- Nicolle LE; AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005;16(6):349-360.
- Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287(20):2701-2710.
- Nicolle LE. Urinary tract infections in the elderly. Clin Geriatr Med. 2009;25(3):423-436.
- Foxman B, Klemstine KL, Brown PD. Acute pyelonephritis in US hospitals in 1997: hospitalization and in-hospital mortality. Ann Epidemiol. 2003;13(2):144-150.
- Lark RL, Saint S, Chenoweth C, Zemencuk JK, Lipsky BA, Plorde JJ. Four-year prospective evaluation of community-acquired bacteremia: epidemiology, microbiology, and patient outcome. Diagn Microbiol Infect Dis. 2001;41(1-2):15-22.
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- May M, Brookman-Amissah S, Hoschke B, Gilfrich C, Braun K-P, Kendel F. Post-void residual urine as a predictor of urinary tract infection—is there a cutoff value in asymptomatic men? J Urol. 2009;181(6):2540-2544.
- Ulleryd P, Zackrisson B, Aus G, Bergdahl S, Hugosson J, Sandberg T. Selective urological evaluation in men with febrile urinary tract infection. BJU Int. 2001;88(1):15-20.
- D’Agata E. Pseudomonas aeruginosa and other Pseudomonas species. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Vol 2. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 221.
- Aguilar-Duran S, Horcajada JP, Sorlí L, et al. Community-onset healthcare-related urinary tract infections: comparison with community and hospital-acquired urinary tract infections. J Infect. 2012;64(5):478-483.
- Sievert DM, Ricks P, Edwards JR, et al; National Healthcare Safety Network (NHSN) Team and Participating NHSN Facilities. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1-14.
- Venier A-G, Lavigne T, Jarno P, et al. Nosocomial urinary tract infection in the intensive care unit: when should Pseudomonas aeruginosa be suspected? Experience of the French national surveillance of nosocomial infections in the intensive care unit, Rea-Raisin. Clin Microbiol Infect. 2012;18(1):E13-E15.
- Chitnis AS, Edwards JR, Ricks PM, Sievert DM, Fridkin SK, Gould CV. Device-associated infection rates, device utilization, and antimicrobial resistance in long-term acute care hospitals reporting to the National Healthcare Safety Network, 2010. Infect Control Hosp Epidemiol. 2012;33(10):993-1000.
- Sastry S, Doi Y. Fosfomycin: resurgence of an old companion. J Infect Chemother. 2016;22(5):273-280.
- Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654.
- Zhanel GG, Harding GK, Nicolle LE. Asymptomatic bacteriuria in patients with diabetes mellitus. Rev Infect Dis. 1991;13(1):150-154.
- Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am. 2003;17(2):367-394.
- Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am. 1997;11(3):647-662.
- Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA. 1999;282(3):236-237.
- McGowan CC, Krieger J. Prostatitis, epididymitis, and orchitis. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Vol 1. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 112.
- Giannarini G, Mogorovich A, Valent F, et al. Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial. J Chemother. 2007;19(3):304-308.
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