A 26-year-old recently married female is seen by you for a 2-day history of urinary urgency and mild "burning" on urination. On questioning, she also notes a slight vaginal discharge. She denies flank pain, hematuria, fevers, or chills.
A 26-year-old recently married female is seen by you for a 2-day history of urinary urgency and mild “burning” on urination. On questioning, she also notes a slight vaginal discharge. She denies flank pain, hematuria, fevers, or chills.
What is the differential diagnosis?
The differential diagnosis is broad as both infectious and non-infectious processes can cause symptoms of dysuria, frequency, urgency, and suprapubic pain. The top three would be a urinary traction infection (i.e. cystitis), urethritis (including gonorrhea, chlamydia, trichomoniasis, Candida, herpes simplex virus), and vaginitis. Other possible causes would include pelvic inflammatory disease, painful bladder syndrome (formerly known as interstitial cystitis), pregnancy, and structural urethral abnormalities
What findings on history and physical examination would you look for?
In all women of childbearing age, a complete sexual and menstrual history, including date of last menstrual period, should be taken. Often in women with typical urinary symptoms (dysuria, frequency, urgency, suprapubic pain, or hematuria), a physical exam is not warranted for diagnosis but if indicated, a complete abdominal and pelvic exam should be performed. Look for fever, cervical motion tenderness (Chandelier’s sign), vaginal discharge, vaginal or labial lesions, and costovertebral angle tenderness.
In young non-pregnant women, particularly in the absence of vaginal symptoms, typical symptoms of dysuria, frequency, urgency, suprapubic pain, or hematuria are highly suggestive of urinary tract infection (UTI).
Acute uncomplicated pyelonephritis is suspected in women with fevers, chills, flank pain, costovertebral tenderness to palpation, nausea and vomiting with or without the typical symptoms of cystitis.
Older women often already have non-specific urinary symptoms that may cloud the diagnosis of UTI including chronic urinary nocturia, incontinence, and general since of feeling unwell. However fever, acute dysuria, new or worsening urinary urgency, incontinence, frequency, gross hematuria, suprapubic or costovertebral tenderness, as well as changes in mental status are highly indicative and should prompt further testing.
What laboratory tests would you order?
The probability of cystitis is greater than 50% in women with any symptoms of urinary tract infection and greater than 90% in women who have dysuria and frequency without vaginal discharge or irritation1 ; often urinalysis or urine culture adds little diagnostic value in women with typical symptoms. If an office dipstick or routine urinalysis does not show pyuria, this should prompt the provider to order additional tests as this typically suggests a diagnosis other than UTI.
In this particular patient, given she has both typical urinary symptoms and vaginal discharge, I would order a urinalysis (dipstick or microscopy), urine culture, a urine pregnancy test, and perform a vaginal smear with microscopy. I would also consider STI screening for gonorrhea and chlamydia if history or exam findings were suggestive
When would order a urine culture?
Generally routine urine cultures are not necessary for management decisions. Additionally urine cultures can often miss low colony count UTI. However, because of the increasing prevalence of antimicrobial resistance among uropathogens causing uncomplicated cystitis, a urine culture may be warranted prior to initiation of therapy if symptoms are not characteristic of UTI. The culture could also be requested if symptoms persist or recur within 3 months following antimicrobial therapy, or if a complicated infection is suspected.2-3 Additionally urine culture and antimicrobial susceptibility testing should be performed in all women with acute pyelonephritis.
Urine dipstick testing reveals 3+ leukocyte esterase, 1+ blood, and negative for nitrites.
How would you interpret the dipstick findings?
Urine dipstick can readily detect the presence of leukocyte esterase (LE) and nitrite. It is the most accurate test for predicting UTI when positive either for LE or nitrite (sensitivity 75%, specificity 82%).1
Leukocyte esterase is the enzyme released by leukocytes and reflects pyuria. It has a sensitivity of 62--98% with specificity of 55-96%.3
Nitrite reflects the presence of Enterobacteriaceae, which converts urinary nitrate to nitrite. Although the nitrite test is fairly sensitive and specific for detecting >105 CFU of Enterobacteriaceae per mL of urine, it lacks adequate sensitivity for detection of lower colony counts and of other organisms so negative results should be interpreted with caution. It should also be noted that false positive results may be produced if the patient is using phenazopyridine (Pyridium) or recently ingested beets. 3
Suffice it to say that the results of the urine dipstick test prove less useful when the history is strongly suggestive of UTI since even negative results do not reliably rule out infection.
You make the presumptive diagnosis of cystitis
What are risk factors for developing cystitis?
Risk factors include recent sexual intercourse, recent spermicide use, a history of urinary tract infection, and a new partner. 4
What are the predominant infectious agents involved in uncomplicated UTIs?
The most common infectious agents in uncomplicated UTI’s consist mainly of Escherichia coli with other occasional species of Enterobacteriaceae, such as Proteus mirabilis and Klebsiella pneumonia, and other bacteria such as Staphylococcus saprophyticus. Rarely, other gram-negative and gram-positive species are isolated.3,4
Contamination can often be seen with isolation of lactobacilli, enterococci, Group B streptococci, and coagulase-negative staphylococci (other than S. saprophyticus) in otherwise healthy non-pregnant women.5
How would you manage the patient?
It is imperative that providers inquire about local antimicrobial susceptibility patterns of various uropathogens when considering empiric treatment of uncomplicated UTI. According to current IDSA (Infectious Diseases Society of America) guidelines for the treatment of uncomplicated cystitis in women 2, there are several viable options.
They include nitrofurantoin monohydrate/macrocrystals 100 mg BID x 5 days, trimethoprim-sulfamethoxazole 160/800 1 tab PO BID x 3 days (unless local resistance rates are greater than 20% or if used for UTI in previous 3 months), fosfomycin trometamol 3 gm single dose, or pivmecillinam 400mg BID x 5 days.
Consideration might also be given to the use of fluoroquinolones or B-lactams, but fluoroquinolones are known to have high resistance in some areas and B-lactams have lower efficacy than other agents and require close follow up. Additionally fluoroquinolones should not be used when resistance is known to exceed 10%.
Ultimately, the choice between these agents should be individualized and based on patient allergy and compliance history, local practice patterns, local community resistance prevalence, availability, cost, and patient and provider threshold for failure.
She responds to macrodantin 500 mg BID but develops recurrences 2 months and 5 months later, all rapidly responding to therapy.
What non-antibiotic preventive strategies are available for women with recurrent cystitis?
Depending on the individual circumstances of the patient, possible interventions would include the avoidance of spermicides, early post-coital voiding, and encouragement of a more liberal fluid intake. A common home remedy favored by patient is the use of cranberry juice or tablets. Although cranberry is felt to inhibit the adherence of uropathogens to uroepithelial cells, clinical studies on efficacy are limited by suboptimal study design
What antibiotic preventive strategies can be considered for such patients?
Prophylactic antibiotic use is highly beneficial for women who experience 2 or more symptomatic UTIs within 6 months or 3 or more over 12 months. Three strategies are commonly used for managing recurrent uncomplicated cystitis:6
1) Continuous prophylaxis: prescribing a 6- to 12-month course of daily antibiotic (e.g. trimethoprim-sulfamethoxazole (40 mg/200 mg), nitrofurantoin (50-100 mg), cefaclor (250 mg), cephalexin (125-250 mg), norfloxacin (200 mg), or ciprofloxacin(125 mg).
2) Post-coital prophylaxis: having the patient take a single dose of antibiotic after sexual intercourse (e.g. trimethoprim-sulfamethoxazole, nitrofurantoin, cephalexin, ciprofloxacin, norfloxacin, ofloxacin)
3) Intermittent self-treatment: permitting the patient to self-diagnosis and self-treat with a short course of an antibiotic (typically, trimethoprim-sulfamethoxazole or fluoroquinolone). This option is perhaps best reserved for selected patients who have clearly documented recurrent infections and who would be compliant with medical directions.
The strategy chosen would depend on the frequency and pattern of infection and patient preference. A referral to Urology might also be considered at this point for further evaluation and management.
When would you consider imaging studies of the upper urinary tract?
Urologic imaging studies are not of value in the great majority of patients with uncomplicated lower UTIs. Imaging studies would be a consideration in patients with persistent clinical symptoms after 48-72 hours of appropriate antibiotic therapy for acute uncomplicated UTI as well as patients with recurrent UTIs in whom the clinical or laboratory evaluation (e.g. persistent hematuria, etc.) is suggestive of complicating factors. Imaging studies are also a consideration in patients with pyelonephritis with severe or worsening illness as well as patients with two or more recurrences of pyelonephritis. 3,4,6
1. Bent S, Nallamothus BK, Simel DL, Fihn SD, Saint S. Does this women have an acute uncomplicated urinary tract infection? JAMA 2002;287(20):2701-2710
2. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases 2011;52(5):e103—e120
3. Takhar SS, Moran GJ: Diagnosis and management of urinary tract infections in the emergency department and outpatient settings. Infect Dis Clin N Am 2014;28:33—48
4. Hooton TM: Uncomplicated urinary tract infection. N Engl J Med 2012;366:1028-37.
5. Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med 2013;369:1883-91.
6. Hickling DR, Nitti VW: Management of recurrent urinary tract infections in healthy adult women. Rev Urol. 2013;15(2):41-48
About the Author
Dr. Kwok is a Health Sciences Clinical Instructor of Medicine, David Geffen School of Medicine at UCLA.