Tanaz R. Ferzandi
History of present illness
A 42-year-old, premenopausal, healthy woman presents with new-onset urinary incontinence that has lasted for a week. She also complains of burning and irritation in the vagina and has used over-the-counter anti-fungal cream for a presumed yeast infection. She feels that the symptoms are getting worse and it is painful to urinate. She has some urinary urgency and supra- pubic tenderness, but denies any other discomfort. She denies any fever, chills, nausea, vomiting, or back pain. She has been recently reunited with her husband who has been overseas for the past two months on a job assignment. She has no other medical problems and her only prior surgery was a postpartum tubal ligation.
Physical examination
General appearance:Well-developed woman in no acute distress
Vital signs:
Pulse: 67 beats/min
Blood pressure: 130/60 mmHg Respiratory rate: 16 breaths/min BMI: 25 kg/m2
Abdomen:Soft, nontender, nondistended, no palpable masses
Back:No costo-vertebral tenderness Pelvic:
No lesions on external genitalia
No discharge or cervical lesions noted on speculum exam
Normal uterus and adnexa with no tenderness Laboratory studies:
Urine dipstick: ++ Nitrites, ++ leukocyte esterase, + blood
How would you manage this patient?
This patient has a urinary tract infection (UTI) based on her symptoms and the urine dipstick results obtained in clinic. Per current guidelines, she was given a prescription for nitrofur- antoin monohydrate 100 mg BID for 7 days [1]. As this was herfirst UTI, a urine culture was not sent and the patient was instructed to follow-up in 48–72 hours if her symptoms were not improved. She was also provided a urinary analgesic (phenazopyridine hydrochloride) to aid in symptom relief.
Urinary tract infections
More than half of all women will have at least one UTI in their lifetime, while 3–5% of women will have multiple recurrences.
The cost is staggering, if office visits are taken into account, with an estimated 3.5 billion dollars for evaluation and treat- ment in 2000 [2]. Risk factors include, but are not limited to, young age atfirst UTI, prior history of UTI, frequent or recent sexual activity, new sexual partner, use of diaphragm as contraception, use of spermicidal agents, increasing parity, diabetes mellitus, obesity, and urinary tract calculi [1]. UTIs typically involve fecalflora with the most common pathogens beingEscherichia coli(75–95% of all infections), Staphylococ- cus saprophyticus,Klebsiella pneumonia,Enterococcus faecalis, Streptococcus agalactiae(group B streptococcus), and Proteus mirabilis. In essence, these pathogens colonize the vagina and cause an ascending infection in the bladder via the urethra.
A UTI is considered uncomplicated if it occurs in a healthy premenopausal woman who is not pregnant and does not have a history of an anatomic abnormality of the urinary tract.
Cystitis is the term that captures an infection limited to the lower urinary tract, with symptoms of dysuria and urinary urgency. Asymptomatic bacteruria refers to the case of signifi- cant bacteruria without symptoms of infection. UTIs can be relapsing, meaning that the patient has an infection with the same organism after adequate therapy. Reinfection is defined as a UTI that occurs after the patient has cleared the initial infection with the previously isolated bacteria. Recurrent UTIs are defined as more than three UTIs in one year or more than two UTIs in six months.
Clinical presentation and symptomatology is important in the diagnosis of an uncomplicated case of acute cystitis.
Common symptoms include dysuria, urinary frequency and urgency, suprapubic pain, and hematuria. It is prudent to keep in mind that the differential diagnosis might include acute urethritis due to infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis, which also present with dysuria;
pain secondary to genital herpex simplex virus (type 1, type 2) can also cause similar symptoms. Therefore, patients with additional complaints of a vaginal discharge warrant a pelvic examination to rule out vaginitis or urethritis. A common office test helpful for diagnosis includes a clean-voided mid- stream urine sample and urinalysis by dipstick. Urine dipstick testing for leukocyte esterase or nitrite is a rapid and inexpen- sive method with a sensitivity of 75% and specificity of 82%;
however, the use of the dipstick as a surrogate has also come
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
into question [3]. In cases where there is a high suspicion for a UTI based on history and a negative dipstick, further testing is warranted as negative dipstick testing does not reliably rule out infection. Additional testing includes formal urinalysis and urine culture.
Formal urinalysis testing with microscopic identification of white blood cell count greater than or equal to 10/μL (pyuria) along with the presence of bacteria is highly suggestive of infection. Urine culture is very helpful in the diagnosis as well as antibiotic selection. The basic criterion of greater than or equal to 100 000 colony-forming units per millilitre (CFU/mL) of clean-catch urine for the diagnosis of UTI has been valid- ated repeatedly. Bacterial counts greater than or equal to 100 000 CFU/mL in two consecutive clean-catch urine samples allows differentiation between asymptomatic UTI and contam- ination (<100 000 CFU/mL). For infections withS. saprophy- ticusandCandidasp., the lower cut-offlevel of greater than or equal to 10 000 CFU/mL is commonly accepted. Contamin- ation is sometimes unavoidable and remains a pitfall in the diagnosis of UTI. Contamination is likely if only small numbers of bacteria or several bacterial species grow in urin- ary cultures. Lactobacilli, Corynebacteria sp., Gardnerella, alpha-haemolytic streptococci, and aerobes are considered urethral and vaginal contaminants. The presence of true infec- tion can be confirmed by urethral catheterization or more accurately by suprapubic aspiration [4]. Urine culture is not required for the diagnosis of uncomplicated cystitis, but is helpful in cases where the diagnosis is unclear or in situations where a patient has failed standard treatment.
Acute uncomplicated cystitis is a benign condition, and early resolution of symptoms is observed in 25–42% of women [2]. However, UTIs are one of the most common reasons for prescription of antimicrobials to otherwise healthy young women. In spite of study guidelines that are specific to the condition, selection of antimicrobials varies greatly, in the setting of greater resistance. Specific guidelines have focused on the treatment of premenopausal, nonpregnant women with no known urological abnormalities or comorbidities. Leading societies such as the American College of Obstetricians and Gynecologists (ACOG) and the Infectious Diseases Society of America (IDSA) have updated their guidelines in an effort to standardize and help prevent ongoing resistance. Below is a summary of those guidelines and the references are listed for further study [1,5].
First-line therapy
First-line therapy includes the following:
Nitrofurantoin monohydrate/macrocrystals 100 mg BID × 5–7 days, or:
Trimethoprim–sulfamethoxazole 160/800 mg (one DS tablet) BID × 3 days (avoid if resistance prevalence is known to be>20% or if used for UTI in past 3 months), or:
Fosfomycin trometamol3 g single dose (lower efficacy than for those listed above), or:
Pivmecillinam 400 mg BID × 5 days (currently not available in the United States).
Second-line therapy
Second-line therapy is as follows:
Fluoroquinolones (resistance prevalence high in some areas), or:
Beta-lactams (avoid ampicillin or amoxicillin alone; lower efficacy).
Continuous antimicrobial prophylaxis
A daily bedtime dose (except for fosfomycin) as follows:
Nitrofurantoin: 50–100 mg.
Trimethoprim–sulfamethoxazole: 40 mg and 200 mg.
Cephalexin: 124–250 mg.
Fosfomycin: 3 g sachet every 10 days.
Nitrofurantoin monohydrate/macrocrystals and trimethoprim- sulfamethoxazole 160/800 mg are the preferred drugs of choice in young, healthy women as empiric treatment. The former has a low resistance profile, while the latter is higher. Clinicians should be aware of their particular geographic regions’
susceptibilities. Additionally, nitrofurantoin monohydrate/
macrocrystals should be used with caution in patients with known glucose-6-phosphate dehydrogenase deficiency, as it can induce hemolytic anemia in rare instances.
Some guidelines, such as those proposed by the American Urological Association and the IDSA recommend that fluor- oquinolones be avoided due to the dramatic emergence of antibiotic resistance. In an era of greater antibiotic resistance, it is recommended that not all patients get empiric treatment routinely. For patients without a prior laboratory confirmed UTI, an office visit for urinalysis is appropriate prior to initi- ation of antibiotics. In patients with atypical symptoms or those who have had a recurrence of a UTI, treatment should be based on obtaining a urine culture. For those patients with recent treatment failures or re-infections, it is also recom- mended to obtain a follow-up culture within two weeks of completion of antibiotics to confirm resolution.
In patients with recurrent UTIs, the need for continuous antibiotic prophylaxis or postcoital prophylaxis should be assessed. Daily antibiotic prophylaxis for 6–12 months has been proved to be effective in the prevention of recurrent UTIs, even reducing the risk of recurrence by 95%, when compared with placebo [6]. The issue of prevention should also be discussed with patients, including hygiene practices. Interestingly, case control studies have shown no clear, significant associations between recurrent UTIs and precoital or postcoital voiding patterns, daily beverage consumption, frequency of urination, delayed voiding habits, wiping patterns, tampon use, douching, use of hot tubs, types of underwear, or body mass index [2]. Many patients use cranberry supplements in a variety of formulations, with mixed evidence to support its use. The theory behind cranberry use is
Case 85: New-onset incontinence in a 42-year-old woman
that it keeps the bacteria from adhering to the urothelium, due to its fructose and proanthocyanidins [5]. One study randomized patients who had recurrent UTIs to a combination of tablets, juice, and placebo. The conclusion of the study was that cran- berry tablets were the best in reduction of UTIs, followed by cranberry juice, and, lastly, placebo (P<0.05) [7].
Key teaching points
Patients with afirst presentation of a urinary tract infection should have an office evaluation with urinalysis to confirm diagnosis prior to initiating antibiotics.
Nitrofurantoin monohydrate/macrocrystals and trimethoprim–sulfamethoxazole 160/800 mg are the preferred drugs of choice in young, healthy women as empiric treatment.
Fluoroquinolones should be avoided as afirst-line therapy for acute uncomplicated cystitis.
Daily antibiotic prophylaxis for 6–12 months has been proved to be effective in the prevention of recurrent UTIs.
Urine culture is not required for the diagnosis of uncomplicated cystitis, but is helpful in cases where the diagnosis is unclear or in situations where a patient has failed standard treatment.
References
1. American College of Obstetricians and Gynecologists. Treatment of urinary tract infections in nonpregnant women.
Practice Bulletin, No. 91.Obstet Gynecol 2008;111(3):785–94.
2. Hooton TM. Uncomplicated urinary tract infection.N Engl J Med 2012;366:1028–37.
3. Khasriya R, Khan S, Lunawat R, et al.
The inadequacy of urinary dipstick and microscopy as surrogate markets of urinary tract infection in urological
outpatients with lower urinary tract symptoms without acute frequency and dysuria.J Urol2010:183;1843–7.
4. Franz M, Hửrl WH. Common errors in diagnosis and management of urinary tract infection. I: Pathophysiology and diagnostic techniques.Nephrol Dial Transplant1999;14(11):2746–53.
5. Gupta K, Hooton TM, Naber KG, et al.
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.Clin Infect Dis2011;52(5):
e103–20.
6. Hooton TM. Recurrent urinary tract infection in women.Int J Antimicrob Agents2001:17(4):259–68.
7. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections.
Cochrane Database Syst Rev2008, Issue 1. Art. No.: CD001321. DOI:
10.1002/14651858.CD001321.pub5.