Diagnosis and treatment of acute uncomplicated cystitis

Diagnosis and Treatment of
Acute Uncomplicated Cystitis
University of Maryland School of Medicine, Baltimore, Maryland
Urinary tract infections are the most common bacterial infections in
women. Most urinary tract infections are acute uncomplicated cysti-
tis. Identifiers of acute uncomplicated cystitis are frequency and dys-
uria in an immunocompetent woman of childbearing age who has
no comorbidities or urologic abnormalities. Physical examination is
typically normal or positive for suprapubic tenderness. A urinaly-
sis, but not urine culture, is recommended in making the diagno-
sis. Guidelines recommend three options for first-line treatment
of acute uncomplicated cystitis: fosfomycin, nitrofurantoin, and
trimethoprim/sulfamethoxazole (in regions where the prevalence of
Escherichia coli
resistance does not exceed 20 percent). Beta-lactam
antibiotics, amoxicillin/clavulanate, cefaclor, cefdinir, and cefpo-
doxime are not recommended for initial treatment because of con-
cerns about resistance. Urine cultures are recommended in women
with suspected pyelonephritis, women with symptoms that do not
resolve or that recur within two to four weeks after completing treat-
ment, and women who present with atypical symptoms. (Am Fam
2011;84(7):771-776. Copyright 2011 American Acad-
emy of Family Physicians.)

Patient information:
A handout on treating a
bladder infection (cystitis),
written by the authors of
this article, is provided on
page 778.
Urinary tract infections (UTIs) to miss work or school.3 Additionally, up to are the most common bacterial one-half of those with acute uncomplicated infections in women, with one- cystitis also reported avoiding sexual activity half of all women experiencing for an average of one week.
at least one UTI in their lifetime.1 Most UTIs in women are acute uncomplicated cysti- Diagnosis
tis caused by Escherichia coli (86 percent), The history is the most important tool for Staphylococcus saprophyticus (4 percent), diagnosing acute uncomplicated cystitis, and Klebsiella species (3 percent), Proteus species it should be supported by a focused physical (3 percent), Enterobacter species (1.4 per- examination and urinalysis. It also is impor- cent), Citrobacter species (0.8 percent), or tant to rule out a more serious complicated Enterococcus species (0.5 percent).2 Although UTI. By definition, the diagnosis of acute acute uncomplicated cystitis may not be uncomplicated cystitis implies an uncompli-thought of as a serious condition, patients’ cated UTI in a premenopausal, nonpregnant quality of life is often significantly affected. woman with no known urologic abnormali-Acute uncomplicated cystitis results in an ties or comorbidities (Table 15).
estimated six days of discomfort leading to approximately 7 million office visits per include dysuria, frequent voiding of small year with associated costs of $1.6 billion.3,4 In one study of women with acute uncompli- cated cystitis, nearly one-half of participants fort is less common. The pretest probabil- reported that their symptoms caused them ity of UTI in women is 5 percent; however, Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2011 American Academy of Family Physicians. For the private, noncommer- [email protected] for copyright ques A
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The combination of new-onset frequency and dysuria, with the absence of vaginal discharge, is diagnostic for a urinary tract infection.
A urine culture is recommended for women with suspected acute pyelonephritis, women with symptoms that do not resolve or that recur within two to four weeks after the completion of treatment, and women who present with atypical symptoms.
First-line treatment options for acute uncomplicated cystitis include nitrofurantoin (macrocrystals; 100 mg twice per day for five days), trimethoprim/sulfamethoxazole (Bactrim, Septra; 160/800 mg twice per day for three days in regions where the uropathogen resistance is less than 20 percent), and fosfomycin (Monurol; a single 3-g dose).
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi-dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml. when a woman presents with the acute onset test in itself. In addition, the likelihood of of even one of the classic symptoms of acute acute uncomplicated cystitis is less if the uncomplicated cystitis, the probability of patient reports vaginal discharge or irrita-infection rises 10-fold to 50 percent.6 There- tion, both of which are more likely in women fore, presentation with one or more symp- with vaginitis or cervicitis. The new onset of toms may be viewed as a valuable diagnostic frequency and dysuria, with the absence of vaginal discharge or irritation, has a posi-tive predictive value of 90 percent for UTI.6 Table 1. Characteristics of
A prospective study of 796 sexually active Patients with Uncomplicated and
young women identified risk factors to help Complicated Urinary Tract Infections
diagnose UTI, including recent sexual inter-course, diaphragm use with spermicide, and Uncomplicated
Self-Diagnosis and Diagnosis
by Telephone
For many patients, access to care can be difficult. Two recent studies have shown Complicated*
History of childhood urinary tract infections UTI may be treated safely with telephone uncomplicated cystitis previously are usu- ally accurate in determining when they are Underlying metabolic disorder (e.g., diabetes having another episode. In one study of 172 Urologic abnormalities (e.g., stones, stents, indwelling catheters, neurogenic bladder, symptoms, and self-treated with antibiot- *—Urinary tract infections in men are usually 84 percent of the urine samples showed a uro- pathogen, 11 percent showed sterile pyuria, and only 5 percent were negative for pyuria and bacteriuria. Another small, randomized 772 American Family Physician
Volume 84, Number 7October 1, 2011 Cystitis
controlled trial compared outcomes of acute acute uncomplicated cystitis. Patients who uncomplicated cystitis in healthy women present with atypical symptoms of acute managed by telephone versus in the office.9 uncomplicated cystitis and those who do not There were no differences in symptom score respond to appropriate antimicrobial ther- or satisfaction. The authors concluded that apy may need imaging studies, such as com-the short-term outcomes of managing sus- pected UTIs by telephone were comparable rule out complications and other disorders. with those managed by usual office care.
International Clinical Practice Guidelines
Physical Examination and Diagnostic
In 2010, a panel of international experts updated the 1999 Infectious Diseases Society The physical examination of patients with of America (IDSA) guidelines on the treat-acute uncomplicated cystitis is typically nor- mal, except in the 10 to 20 percent of women Nitrites and leukocyte
with suprapubic tenderness.10 Acute pyelone- esterase on urine dipstick
phritis should be suspected if the patient is the literature, including the testing are the most accu-
ill-appearing and seems uncomfortable, par- rate indicators of acute
ticularly if she has concomitant fever, tachy- uncomplicated cystitis.
cardia, or costovertebral angle tenderness. The convenience and cost-effectiveness of women with uncomplicated urine dipstick testing makes it a common bacterial cystitis and pyelonephritis.16,17 The diagnostic tool, and it is an appropriate alter- IDSA collaborated with the European Soci- native to urinalysis and urine microscopy ety of Clinical Microbiology and Infectious to diagnose acute uncomplicated cystitis.11 Diseases, and invited representation from Nitrites and leukocyte esterase are the most diverse geographic areas and a wide variety accurate indicators of acute uncomplicated of specialties, including urology, obstetrics cystitis in symptomatic women.11 To avoid and gynecology, emergency medicine, fam-contamination, the convention is to use a ily medicine, internal medicine, and infec-midstream, clean-catch urine specimen to tious diseases. Levels-of-evidence ratings diagnose UTI; however, at least two studies were assigned to recommendations on the have shown no significant difference in num- use of antimicrobials for the treatment of ber of contaminated or unreliable results uncomplicated UTIs.
between specimens collected with and with-
out preparatory cleansing.12,13 Urine cultures Treatment
are recommended only for patients with sus-
No single agent is considered best for treating pected acute pyelonephritis; patients with acute uncomplicated cystitis according to symptoms that do not resolve or that recur the 2010 guidelines, and the choice between within two to four weeks after the comple- tion of treatment; and patients who present ized16 (Table 218,19). Choosing an antibiotic with atypical symptoms.11 A colony count depends on the agent’s effectiveness, risks of greater than or equal to 103 colony-forming adverse effects, resistance rates, and propen-units per mL of a uropathogen is diagnostic sity to cause collateral damage (i.e., ecologic of acute uncomplicated cystitis.14 However, adverse effects of antibiotic therapy that may studies have shown that more than 102 colony allow drug-resistant organisms to prolifer- forming-units per mL in women with typical ate, and the colonization or infection with symptoms of a UTI represent a positive cul- multidrug-resistant organisms). Addition- ture.15 Routine posttreatment urinalysis or ally, physicians should consider cost, avail-urine cultures in asymptomatic patients are ability, and specific patient factors, such as not necessary.
allergy history. On average, patients will Further studies beyond urinalysis and begin noting symptom relief within 36 hours urine cultures are rarely needed to diagnose of beginning treatment.2 October 1, 2011Volume 84, Number 7 American Family Physician 773
Table 2. Antimicrobial Agents for the Management of Acute
Uncomplicated Cystitis

Third§ Amoxicillin/clavulanate 500/125 mg twice per day for *—Estimated retail price of one course of treatment based on information obtained at http://www.drugstore.com (accessed May 11, 2011). ‚—May be available at discounted prices ($10 or less for one month’s treatment) at one or more national retail chains.
—Estimated cost to the pharmacist based on average wholesale prices in Red Book. Montvale, N.J.: Medical Eco-nomics Data; 2010. Cost to the patient will be higher, depending on prescription filling fee.
§—Not generally recommended because of relatively high rates of resistance. Third-tier options include beta-lactam antibiotics. Information from references 18 and 19. There are several first-line agents recom- effectiveness with a shorter duration of ther- mended by the IDSA for the treatment of apy.20 Fosfomycin may be less effective and acute uncomplicated cystitis (Figure 1).16 is not widely available in the United States.
Fluoroquinolones (i.e., ofloxacin, ciproflox- furantoin (macrocrystals) and fosfomycin acin [Cipro], and levofloxacin [Levaquin]) (Monurol) as first-line therapy.16 The follow- are considered second-tier antimicrobials, ing antimicrobials represent the first tier: and are appropriate in some settings, such as (1) nitrofurantoin at a dosage of 100 mg in patients with allergy to the recommended twice per day for five days; (2) trimethoprim/ agents. Although fluoroquinolones are effec- sulfamethoxazole (Bactrim, Septra) at a dos- tive, they have the propensity for collateral age of one double-strength tablet (160/800 damage, and should be considered for patients mg) twice per day for three days in regions with more serious infections than acute where the prevalence of resistance of com- uncomplicated cystitis. Certain antimicrobi- munity uropathogens does not exceed 20 als (i.e., beta-lactam antibiotics, amoxicillin/percent; and (3) fosfomycin at a single dose clavulanate [Augmentin], cefdinir [Omnicef], of 3 g. Note that the duration of therapy for cefaclor, and cefpodoxime) may be appro-nitrofurantoin has been reduced to five days priate alternatives if recommended agents compared with the previous IDSA guidelines cannot be used because of known resistance of seven days, based on research showing or patient intolerance. Despite wide use of 774 American Family Physician
Volume 84, Number 7October 1, 2011 Cystitis
cranberry products for treating UTIs, there is over the past several years.16 To preserve the no evidence to support their use in symptom- effectiveness of fluoroquinolones, they are not recommended as a first-tier option. Fos-fomycin and nitrofurantoin have retained Antimicrobial Resistance
high rates of in vitro activity in most areas.16 Because results of urine cultures are not mended as first-line therapy for acute uncom- plicated cystitis because of widespread E. coli uncomplicated cystitis, local resistance resistance rates above 20 percent. Fluoroqui- rates may not be available. Defaulting to nolone resistance usually is found to be below the annual antimicrobial sensitivity data 10 percent in North America and Europe, but with a trend toward increasing resistance tance rates based on a population that Choosing an Antimicrobial Agent for Empiric Treatment of Acute
Uncomplicated Cystitis

The rights holder did not grant the American Academy of Family Physicians the right to sublicense this material to a third party. For the missing item, see the original print ver-sion of this publication.
Figure 1. Algorithm for choosing an antimicrobial agent for empiric treatment of acute uncom-
plicated cystitis.
Adapted with permission from Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treat-ment 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 Dis. 2011;52(5):e104. October 1, 2011Volume 84, Number 7 American Family Physician 775
does not reflect women with simple acute uncompli- factors for symptomatic urinary tract infection in young women. N Engl cated cystitis (e.g., sicker patients, inpatients, patients of all ages, male patients). Several studies have been 8. Gupta K, Hooton TM, Roberts PL, Stamm WE. Patient-initiated treat- ment of uncomplicated recurrent urinary tract infections in young published that may help predict the likelihood of women. Ann Intern Med. 2001; 135(1): 9-16. E. coli resistance to trimethoprim/sulfamethoxazole 9. Barry HC, Hickner J, Ebell MH, Ettenhofer T. A randomized controlled in patients with acute uncomplicated cystitis. Use of trial of telephone management of suspected urinary tract infections in women. J Fam Pract. 2001; 50(7): 589-594. trimethoprim/sulfamethoxazole in the preceding three 10. Stamm WE. Urinary tract infections. In: Root RK, Waldvogel F, Corey to six months has been found to be an independent risk L, Stamm WE. Clinical Infectious Diseases: A Practical Approach. New factor for resistance in women with acute uncomplicated York, NY: Oxford University Press; 1999: 649-656. cystitis.22,23 In addition, two U.S. studies demonstrated 11. Colgan R, Hyner S, Chu S. Uncomplicated urinary tract infections in adults. In: Grabe M, Bishop MC, Bjerklund-Johansen, et al., eds. Guide- that travel outside the United States in the preceding lines on Urological Infections. Arnhem, The Netherlands: three to six months was independently associated with trimethoprim/sulfamethoxazole resistance.24,25 12. Bradbury SM. Collection of urine specimens in general practice: to clean or not to clean? J R Coll Gen Pract. 1988; 38(313): 363-365. The authors thank Kalpana Gupta, MD, for her review of the manuscript.
13. Lifshitz E, Kramer L. Outpatient urine culture: does collection technique matter? Arch Intern Med. 2000; 160(16): 2537-2540. The Authors
14. Stamm WE. Criteria for the diagnosis of urinary tract infection and for the assessment of therapeutic effectiveness. Infection. 1992; 20(suppl 3): RICHARD COLGAN, MD, is an associate professor and director of medical student education in the Department of Family and Community Medicine 15. Kunin CM. Guidelines for urinary tract infections. Rationale for a sepa- at the University of Maryland School of Medicine in Baltimore.
rate strata for patients with “low-count” bacteriuria. Infection. 1994; 22(suppl 1): S38-S40. MOZELLA WILLIAMS, MD, is an assistant professor and assistant director 16. Gupta K, Hooton TM, Naber KG, et al. International clinical practice of medical student education in the Department of Family and Community guidelines for the treatment of acute uncomplicated cystitis and pyelo- Medicine at the University of Maryland School of Medicine.
nephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Address correspondence to Richard Colgan, MD, University of Mary- Diseases. Clin Infect Dis. 2011; 52(5): e103-e120.
land School of Medicine, 29 South Paca St., Baltimore, MD 21201 17. Zalmanovici Trestioreanu A, Green H, Paul M, Yaphe J, Leibovici L. Anti- (e-mail: [email protected]). Reprints are not available from microbial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev. 2010; (10): CD007182. Author disclosure: No relevant financial affiliations to disclose.
18. Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005; 72(3): 451-456.
19. American College of Obstetricians and Gynecologists. ACOG Practice REFERENCES
Bulletin No. 91: treatment of urinary tract infections in nonpregnant women. Obstet Gynecol. 2008; 111(3): 785-794.
1. Nicolle LE. Epidemiology of urinary tract infection. Infect Med. 2001; 18: 20. Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course nitrofuran- toin for the treatment of acute uncomplicated cystitis in women. Arch 2. Gupta K, Scholes D, Stamm WE. Increasing prevalence of antimicrobial Intern Med. 2007; 167(20): 2207-2212. resistance among uropathogens causing acute uncomplicated cystitis in 21. Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract women. JAMA. 1999; 281(8): 736-738.
infections. Cochrane Database Syst Rev. 2000; (2): CD001322. 3. Colgan R, Keating K, Dougouih M. Survey of symptom burden in 22. Brown PD, Freeman A, Foxman B. Prevalence and predictors of trime- women with uncomplicated urinary tract infections. Clin Drug Investig. thoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli isolates in Michigan. Clin Infect Dis. 2002; 34(8): 1061-1066. 4. Foxman B. Epidemiology of urinary tract infections: incidence, morbid- 23. Metlay JP, Strom BL, Asch DA. Prior antimicrobial drug exposure: a risk ity, and economic costs. Am J Med. 2002; 113(suppl 1A): 5S-13S.
factor for trimethoprim-sulfamethoxazole-resistant urinary tract infec- 5. Nicolle L; AMMI Canada Guidelines Committee. Complicated urinary tions. J Antimicrob Chemother. 2003; 51(4): 963-970.
tract infection in adults. Can J Infect Dis Med Microbiol. 2005; 16(6): 24. Burman WJ, Breese PE, Murray BE, et al. Conventional and molecular epidemiology of trimethoprim-sulfamethoxazole resistance among uri- 6. Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman nary Escherichia coli isolates. Am J Med. 2003; 115(5): 358-364. have an acute uncomplicated urinary tract infection? JAMA. 2002; 25. Colgan R, Johnson JR, Kuskowski M, Gupta K. Risk factors for trime- thoprim-sulfamethoxazole resistance in patients with acute uncompli- 7. Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk cated cystitis. Antimicrob Agents Chemother. 2008; 52(3): 846-851.
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