Diagnosis and Management of

Uncomplicated Urinary Tract Infections

SUSAN A. MEHNERT-KAY, M.D., University of Oklahoma College of MedicineTulsa, Tulsa, Oklahoma

Most uncomplicated urinary tract infections occur in women who are sexually active, with far
fewer cases occurring in older women, those who are pregnant, and in men. Although the inci-
dence of urinary tract infection has not changed substantially over the last 10 years, the diagnos-
tic criteria, bacterial resistance patterns, and recommended treatment have changed. Escherichia
coli is the leading cause of urinary tract infections, followed by Staphylococcus saprophyticus.
Trimethoprim-sulfamethoxazole has been the standard therapy for urinary tract infection;
however, E. coli is becoming increasingly resistant to medications. Many experts support using
ciprofloxacin as an alternative and, in some cases, as the preferred first-line agent. However,
others caution that widespread use of ciprofloxacin will promote increased resistance. (Am Fam
Physician 2005;72:451-6,458. Copyright American Academy of Family Physicians.)

U
Patient information: ncomplicated urinary tract phyticus is less common than E. coli, it is

A handout on urinary tract infections (UTIs) are one of more aggressive. Approximately one half of
infections, written by the
author of this article, is the most common diagnoses in patients infected with S. saprophyticus pres-
provided on page 458. the United States. In 1997, an ent with upper urinary tract involvement,
estimated 8.3 million physician office visits and these patients are more likely to have
were attributed to acute cystitis.1 A U.S. and recurrent infection.3
Canadian study showed that approximately
one half of all women will have a UTI in their Diagnosis
lifetimes, and one fourth will have recurrent Uncomplicated UTI occurs in patients who
infections.2 The health care costs associ- have a normal, unobstructed genitourinary
ated with UTIs exceed 1 billion dollars3,4; tract, who have no history of recent instru-
therefore, any advance in the diagnosis and mentation, and whose symptoms are confined
treatment of this entity could have a major to the lower urinary tract. Uncomplicated
economic impact. Streamlining the diagnos- UTIs are most common in young, sexually
tic process could also decrease morbidity and active women. Patients usually present with
improve patient outcomes and satisfaction. dysuria, urinary frequency, urinary urgency,
and/or suprapubic pain. Fever or costoverte-
Epidemiology bral angle tenderness indicates upper urinary
Escherichia coli is the most common cause tract involvement. Studies show that no labo-
of uncomplicated UTI and accounts for ratory tests, including urinalysis and culture,
approximately 75 to 95 percent of all infec- can predict clinical outcomes in women
tions.2-5 A longitudinal study6 18 to 70 years of age who present with
of 235 women with 1,018 UTIs acute dysuria or urgency.7 Dipstick urinaly-
Escherichia coli is the most
found that E. coli was the only sis, however, is a widely used diagnostic tool.
common cause of uncom-
causative agent in 69.3 percent A dipstick urinalysis positive for leukocyte
plicated urinary tract
of cases and was a contrib- esterase and/or nitrites in a midstream-void
infections and accounts
uting agent in an additional specimen reinforces the clinical diagnosis
for approximately 75 to
2.4 percent of cases. Staphylo of UTI. Leukocyte esterase is specific (94 to
95 percent of all infections. coccus saprophyticus is a distant 98 percent) and reliably sensitive (75 to
second, accounting for only 96 percent) for detecting uropathogens
5 to 20 percent of infections. Other Entero- equivalent to 100,000 colony-forming units
bacteriaceae, such as Klebsiella and Proteus, (CFU) per mL of urine.5 Nitrite tests may
occasionally cause UTI.2,3,5 Although S. sapro be negative if the causative organism is not

August 1, 2005 Volume 72, Number 3 www.aafp.org/afp American Family Physician 451
Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2005 American Academy of Family Physicians. For the private, noncommercial
use of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.
 SORT: Key Recommendations for Practice

Evidence
Clinical recommendation rating References

A three-day course of trimethoprim-sulfamethoxazole (TMP/SMX; C 24

Bactrim, Septra) is recommended as empiric therapy of uncomplicated
urinary tract infections (UTIs) in women, in areas where the rate of
resistance Escherichia coli are less than 20 percent.
Fluoroquinolones are not recommended as first-line treatment of C 24
uncomplicated UTIs in order to preserve their effectiveness for
complicated UTIs.
Use of beta-lactam antibiotics is not recommended for the routine C 24
treatment of uncomplicated UTIs because of limited effectiveness.
For treatment of uncomplicated urinary tract infections in older women, B 25
consider short or longer (three to 10 days) courses of antibiotics.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented

evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For more infor-
mation about the SORT evidence rating system, see page 363 or http://www.aafp.org/afpsort.xml.

nitrate-reducing (e.g., enterococci, S. sap alone after phone triage by a nurse. These
rophyticus, Acinetobacter). Therefore, the guidelines have reduced doctor visits and
sensitivity of nitrite tests ranges from 35 to laboratory tests without increasing adverse
85 percent, but the specificity is 95 percent.8 outcomes.7 A study9 of these guidelines found
Nitrite tests can also be false negative if the that women treated by telephone triage had
urine specimen is too diluted.3 Microscopic a 95 percent satisfaction rate. The study also
hematuria may be present in 40 to 60 percent found that if these guidelines were used for
of patients with UTI.3 147,000 women ages 18 to 55 years who were
Routine urine cultures are not necessary enrolled in the plan, it could save an estimated
because of the predictable nature of the $367,000 annually.9 A much smaller study10
causative bacteria. However, urinalysis may comparing telephone triage with office visits
be appropriate for patients who fail initial for treating symptomatic cystitis showed no
treatment. Current literature suggests that difference in symptom improvement scores
a colony count of 100 CFU per mL has a or overall patient satisfaction.
sensitivity of 95 percent and a specificity
of 85 percent,3 but the Infectious Diseases Treatment
Society of America (IDSA) recommends Many studies in the last decade have focused
using a colony count of 1,000 CFU per mL on the treatment length of standard thera-
(80 percent sensitivity and 90 percent speci- pies. A study11 comparing a three-day course
ficity) for symptomatic patients.3,5 A cutoff of ciprofloxacin (Cipro) 100 mg twice daily,
of 100,000 CFU per mL defines asymptom- ofloxacin (Floxin) 200 mg twice daily, and
atic bacteriuria. Physicians may have to trimethoprim-sulfamethoxazole (TMP-
request that sensitivities be performed on SMX; Bactrim, Septra) 160/800 mg twice
low-count bacteria if low counts are not the daily, found that all three had comparable
standard in their community. efficacy in managing uncomplicated UTI.
After reviewing existing data on uncompli- Another study12 comparing a short course
cated cystitis, the Group Health Cooperative (three days) of ciprofloxacin (100 mg twice
of Puget Sound implemented evidencebased daily) with the more traditional seven-day
guidelines for treating adult women with course of TMP-SMX (160/800 mg twice
acute dysuria or urgency.7 These guidelines daily), and nitrofurantoin (Furadantin) (100
support treating women based on symptoms mg twice daily) found that ciprofloxacin had

452 American Family Physician www.aafp.org/afp Volume 72, Number 3 August 1, 2005
 Uncomplicated Urinary Tract Infections

superior bacteriologic eradication rates after IDSA guidelines recommend the use of fluo-
short-term follow-up (four to six weeks). roquinolones (e.g., ciprofloxacin, fleroxacin
All three medications had similar eradica- [not available in the United States], norflox-
tion rates immediately after therapy.12 The acin [Noroxin], and ofloxacin) as first-line
study12 also found that treatment failures agents in communities with greater than
associated with nitrofurantoin were more 10 to 20 percent resistance rates to TMP-
common in nonwhite women older than SMX.17 An economic analysis4 found that a
30 years, but researchers were unable to three-day regimen of ciprofloxacin was more
account for this difference. cost-effective than a three-day regimen of
E. colis resistance to TMP-SMX is an TMP-SMX if the resistance rate to that drug
increasing problem across the United States.13 was 19.0 percent or greater.4 A study13 com-
A recent article14 that reviewed data from paring the newest formulation of extended-
The Surveillance Network (TSN) database release ciprofloxacin (500 mg daily for three
reported that E. coli had an overall resistance days) with traditional ciprofloxacin (250 mg
rate of 38 percent to ampicillin, 17.0 percent twice daily for three days) showed equivalent
to TMP-SMX, 0.8 percent to nitrofurantoin, clinical cure rates. A 1995 study18 comparing
and 1.9 to 2.5 percent to fluoroquinolones. multidose regimens of ciprofloxacin showed
The article14 also reported that E. coli strains that the minimal effective dosage was 100 mg
resistant to TMP-SMX had a 9.5 percent twice daily. Another study19 compared a
rate of concurrent ciprofloxacin resistance single 400-mg dose of gatifloxacin (Tequin),
versus a 1.9 percent rate of concurrent resis- with three-day regimens of gatifloxacin
tance to nitrofurantoin. Another review15 of (200 mg twice daily) and ciprofloxacin
data from TSN (January through September (100 mg twice daily). The single-dose therapy
2000) found that 56 percent of E. coli isolates had a clinical response rate equivalent to the
were susceptible to all tested drugs includ- two three-day regimens. Gatifloxacin is also
ing ampicillin, cephalothin (Keflin), nitro- expected to be 1,000 times less likely than
furantoin, TMP-SMX, and ciprofloxacin. older fluoroquinolones to become resistant
Among the tested antimicrobials, E. coli had because of its 8-methoxy structure.19
the highest resistance rate to ampicillin (39.1 Fosfomycin (Monurol) is another treat-
percent), followed by TMP-SMX (18.6 per- ment option for patients with UTI. The U.S.
cent), cephalothin (15.6 percent), ciprofloxa- Food and Drug Administration (FDA) indi-
cin (3.7 percent), and nitrofurantoin (1.0 cates fosfomycin for the treatment of women
percent).15 Resistance rates varied by region with uncomplicated UTI. A study20 compar-
of the country. Of the more than 38,000 iso- ing a single dose of fosfomycin
lates, 7.1 percent had a multidrug resistance.15 (3 g) with a seven-day course of Fluoroquinolones have
A 1999 regional analysis16 of the United nitrofurantoin (100 mg twice become popular treat-
States showed that resistance to TMP-SMX daily) showed similar bacterio- ments for patients with
was highest in the Western-Southern-Cen- logic cure rates (60 versus 59
uncomplicated urinary
tral regions, with a 23.9 percent resistance percent, respectively).20 Fosfo-
tract infections because of
rate. The Pacific and Mountain regions had mycin is bactericidal and con-
Escherichia colis emerging
a 21.8 percent resistance rate, and the South centrates in the urine to inhibit
resistance to other com-
Atlantic region had a 19.7 percent resistance the growth of pathogens for
mon medications.
rate.16 Resistance rates in southern Europe, 20
24 to 36 hours. When fos-
Israel, and Bangladesh reportedly have been fomycin entered the market
as high as 30 to 50 percent.4 in 1997, unpublished studies submitted
Fluoroquinolones have become popular to the FDA found that it was significantly
treatments for patients with uncomplicated less effective in eradicating bacteria than
UTI because of E. colis emerging resistance seven days of ciprofloxacin or 10 days of
to other common medications. The reported TMP-SMX (63 percent, 89 percent, and
resistance rate of E. coli to ciprofloxacin is 87 percent eradication rates, respectively).21
still very low at less than 3 percent.13 The Cephalosporins, including cephalexin

August 1, 2005 Volume 72, Number 3 www.aafp.org/afp American Family Physician 453
 table 1
Antimicrobial Agents for the Management of Uncomplicated UTIs

Dosage Duration Pregnancy

Drug (mg) Frequency (days) Cost per day* category

TMP-SMX 160/800 Twice daily Three $3.88 (Bactrim DS) C

(Bactrim, Septra) $4.00 (Septra)
Ciprofloxacin 250 Twice daily Three $10.15 (tablet) C
(Cipro)
Extended-release 500 Daily Three $8.66 C
ciprofloxacin
(Cipro XR)
Nitrofurantoin 100 Twice daily Seven to 10 $17.13 B
(Furadantin)
Fosfomycin 3,000 Daily One $36.49 B
(Monurol) (3 g)
Cephalexin 250 Four times daily Seven to 10 $6.59 (250 mg) B
(Keflex) 500 Twice daily Seven to 10 $6.47 (500 mg)
Gatifloxacin 400 Single dose One $9.57 (400 mg) C
(Tequin) 200 Twice daily Three $9.57 (200 mg) C

URI - urinary tract infection; TMP-SMX = trimethoprim-sulfamethoxazole.

*Cost for complete course of therapy, based on average wholesale cost, based on Red Book, Montvale, N.J.:
Medical Economics Data, 2004.
One double-strength tablet.

(Keflex), cefuroxime (Ceftin), and cefixime that women with cystitis should increase
(Suprax), can also manage UTIs. Increasing their fluid intake, and some doctors specu-
resistance, however, has limited their effec- late that increased fluid may be detrimental
tiveness.2 The broad spectrum of this class because it may decrease the urinary concen-
also increases the risk of vulvovaginal can- tration of antimicrobial agents.17
didiasis. Cephalosporins are pregnancy cat-
older women
egory B drugs, and a seven-day regimen can
be considered as a second-line therapy for Treating older women who have UTIs requires
pregnant women.2 Table 1 summarizes the special consideration. A recent study23 com-
possible treatments in patients with UTI. pared a 10-day course of ciprofloxacin (250
mg twice daily) with a 10-day course of
nonpharmacologic therapies TMP-SMX (160/800 mg twice daily). The
Physicians commonly recommend nonphar- study, which included 261 outpatient and
macologic options (e.g., drinking cranberry institutionalized women with an average
juice or water) to patients with cystitis. A age of approximately 80 years, showed a 96
Cochrane review22 found insufficient evi- percent bacteriologic eradication rate with
dence to recommend the use of cranberry ciprofloxacin compared with an 80 percent
juice to manage UTI. eradication rate with TMP-SMX for the three
Similarly, no scientific evidence suggests most common isolates.23 Although the IDSA
did not study postmenopausal women specif-
ically, its review found that evidence supports
The Author the use of a seven-day antibiotic regimen for
SUSAN A. MEHNERT-KAY, M.D., is a clinical assistant professor at the University older women. The three-day therapy had a
of Oklahoma College of Medicine-Tulsa. She received her medical degree at the higher failure rate when compared with the
University of Oklahoma College of Medicine-Tulsa, where she also completed a seven-day regimen.24 A Cochrane review25
family medicine residency. found insufficient evidence to recommend
Address correspondence to Susan A. Mehnert-Kay, M.D., 1111 S. St. Louis Ave.,
for or against short- versus long-term (seven
Tulsa, OK 74120. (e-mail: Susan-mehnert@ouhsc.edu). Reprints are not available to 10 days) treatment of uncomplicated UTIs
from the author. in older women.

454 American Family Physician www.aafp.org/afp Volume 72, Number 3 August 1, 2005
 Uncomplicated Urinary Tract Infections
Management of Uncomplicated Urinary Tract Infections
Patient with dysuria, urinary frequency,
urinary urgency, or suprapubic pain

Is the patient postmenopausal?

Yes No

Is there a complicating factor Is the patient pregnant?

(e.g., sulfa allergy, TMP-SMX
[Bactrim, Septra] failure)?
Yes No

Yes No Nitrofurantoin, 100 mg twice Is there a complicating

daily for seven days; fosfomycin factor (e.g., sulfa allergy,
Ciprofloxacin (Cipro), 250 mg TMP-SMX, (Monurol), 3-g single dose; or TMP-SMX failure)?
twice daily for seven days; or 160/800 mg cephalexin (Keflex), 250 mg
nitrofurantoin (Furadantin), twice daily for four times daily or 500 mg
100 mg twice daily for seven days* seven days* twice daily for seven days Yes No

Ciprofloxacin, 250 mg twice TMP-SMX,

daily for three days; or 160/800 mg,
nitrofurantoin,100 mg twice daily for
twice daily for seven days three days)

*Drugs administered orally.

One double-strength tablet.

Figure 1. Algorithm for the management of uncomplicated urinary tract infections. (TMP-SMX = trimethoprim-
sulfamethoxazole.)

men three-day course of double-strength TMP-

The incidence of UTI in men ages 15 to SMX as empiric therapy in areas where E.
50 years is very low, and little evidence coli resistance rates are below 20 percent.
exists on treating them. Risk factors include Second, although it recognizes that they
homosexuality, intercourse with an infected have efficacy rates similar to TMP-SMX, the
woman, and lack of circumcision. The lim- IDSA does not recommend fluoroquino-
ited available data are similar on two key lones as universal first-line agents because of
points. First, the data show that men should resistance concerns. Third, the IDSA recom-
receive the same treatment as women with the mends a seven-day course of nitrofurantoin
exception of nitrofurantoin, which has poor or a single dose of fosfomycin as reasonable
tissue penetration.17 Second, a minimum of treatment alternatives. Finally, the IDSA
seven days is the recommended treatment does not recommend the use of beta-lactams
length, because the likelihood of complicat- because multiple studies have shown them
ing factors is higher than in women.5,17 to be inferior when compared with other
treatments.23
Recommendations Figure 1 is an algorithm for the manage-
After reviewing the available clinical data as ment of uncomplicated UTIs.
of 1999 and classifying it by quality of evi-
The author thanks Karen Malnar, R.N., C.C.R.C., and
dence, the IDSA published guidelines for the Dana Carroll, Pharm.D., for assisting her with this article.
use of antimicrobial agents to treat women
with UTI.24 The American Urological Asso- Members of various family medicine departments
develop articles for Practical Therapeutics. This article
ciation and the European Society of Clini- is one in a series coordinated by the Department of
cal Microbiology and Infectious Diseases Family Medicine at the University of Oklahoma College
have endorsed these guidelines,2,17 which of Medicine, Tulsa, Okla. Coordinator of the series is
John Tipton, M.D.
can be summarized into four main recom-
mendations. First, the IDSA recommends a Author disclosure: Nothing to disclose.

August 1, 2005 Volume 72, Number 3 www.aafp.org/afp American Family Physician 455
Uncomplicated Urinary Tract Infections

ceptibility of antimicrobial-resistant urinary Escherichia

REFERENCES coli isolates to fluoroquinolones and nitrofurantoin.
Clin Infect Dis 2003;36:183-7.
1. National Institutes of Health. National Kidney and Uro-
logic Diseases Information Clearinghouse (NKUDIC). 15. Sahm DF, Thornsberry C, Mayfield DC, Jones ME, Kar-
Accessed online May 4, 2005, at: http://kidney.niddk. lowsky JA. Multidrug-resistant urinary tract isolates of
nih.gov. Escherichia coli: prevalence and patient demographics
in the United States in 2000. Antimicrob Agents Che-
2. Nicolle LE. Urinary tract infection: traditional pharma-
mother 2001;45:1402-6.
cologic therapies. Dis Mon 2003;49:111-28.
16. Seifert R, Weinstein DM, Li-McLeod J. National preva-
3. Faro S, Fenner DE. Urinary tract infections. Clin Obstet
lence of Escherichia coli resistance to trimethoprim-
Gynecol 1998;41:744-54.
sulfamethoxazole: managed care implications in the
4. Perfetto EM, Gondek K. Escherichia coli resistance treatment of urinary tract infections. J Manag Care
in uncomplicated urinary tract infection: a model for Pharm 2001;7:132. Accessed online May 4, 2005, at:
determining when to change first-line empirical antibi- http://www.amcp.org/data/jmcp/jmcp_2001_7_2.pdf.
otic choice. Manag Care Interface 2002;15:35-42.
17. Naber KG. Treatment options for acute uncompli-
5. Hooton TM, Stamm WE. Diagnosis and treatment of cated cystitis in adults. J Antimicrob Chemother
uncomplicated urinary tract infection. Infect Dis Clin 2000;46(suppl 1):S23-7.
North Am 1997;11:551-81.
18. Iravani A, Tice AD, McCarty J, Sikes DH, Nolen T,
6. Vosti KL. Infections of the urinary tract in women: a Gallis HA, et al., for the Urinary Tract Infection Study
prospective, longitudinal study of 235 women observed Group. Short-course ciprofloxacin treatment of acute
for 1-19 years. Medicine (Baltimore) 2002;81:369-87. uncomplicated urinary tract infection in women. The
7. Stuart ME, Macuiba J, Heidrich F, Farrell RG, Braddick minimum effective dose [published correction appears
M, Etchison S. Successful implementation of an evi- in Arch Intern Med 1995;155:871]. Arch Intern Med
dence-based clinical practice guideline: acute dysuria/ 1995;155:485-94.
urgency in adult women. HMO Pract 1997;11:150-7. 19. Richard GA, Mathew CP, Kirstein JM, Orchard D,
8. Orenstein R, Wong ES. Urinary tract infections in adults. Yang JY. Single-dose fluoroquinolone therapy of acute
Am Fam Physician 1999;59:1225-34, 1237. uncomplicated urinary tract infection in women: results
9. Saint S, Scholes D, Fihn SD, Farrell RG, Stamm WE. The from a randomized, double-blind, multicenter trial
effectiveness of a clinical practice guideline for the comparing single-dose to 3-day fluoroquinolone regi-
management of presumed uncomplicated urinary tract mens. Urology 2002;59:334-9.
infection in women. Am J Med 1999;106:636-41. 20. Stein GE. Comparison of single-dose fosfomycin and
10. Barry HC, Hickner J, Ebell MH, Ettenhofer T. A random- a 7-day course of nitrofurantoin in female patients
ized controlled trial of telephone management of sus- with uncomplicated urinary tract infection. Clin Ther
pected urinary tract infections in women. J Fam Pract 1999;21:1864-72.
2001;50:589-94. 21. Fosfomycin for urinary tract infections. Med Lett Drugs
11. McCarty JM, Richard G, Huck W, Tucker RM, Tosiello Ther 1997;39:66-8.
RL, Shan M, et al.; for the Ciprofloxacin Urinary Tract 22. Jepson RG, Mihaljevic L, Craig J. Cranberries for treat-
Infection Group. A randomized trial of short-course ing urinary tract infections. Cochrane Database Syst Rev
ciprofloxacin, ofloxacin, or trimethoprim/ sulfamethox- 2000;(2):CD001322.
azole for the treatment of acute urinary tract infection 23. Gomolin IH, Siami PF, Reuning-Scherer J, Haverstock
in women. Am J Med 1999;106:292-9. DC, Heyd A, for the Oral Suspension Study Group.
12. Iravani A, Klimberg I, Briefer C, Munera C, Kowalsky Efficacy and safety of ciprofloxacin oral suspension
SF, Echols RM. A trial comparing low-dose, short- versus trimethoprim-sulfamethoxazole oral suspension
course ciprofloxacin and standard 7 day therapy with for treatment of older women with acute urinary tract
co-trimoxazole or nitrofurantoin in the treatment of infection. J Am Geriatr Soc 2001;49:1606-13.
uncomplicated urinary tract infection. J Antimicrob 24. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer
Chemother 1999;43(suppl A):S67-75. AJ, Stamm WE. Infectious Diseases Society of America
13. Henry DC Jr, Bettis RB, Riffer E, Haverstock DC, (IDSA). Guidelines for antimicrobial treatment of uncom-
Kowalsky SF, Manning K, et al. Comparison of once- plicated acute bacterial cystitis and acute pyelonephritis
daily extended-release ciprofloxacin and conventional in women. Clin Infect Dis 1999;29:745-58.
twice-daily ciprofloxacin for the treatment of uncom- 25. Lutters M, Vogt N. Antibiotic duration for treating
plicated urinary tract infection in women. Clin Ther uncomplicated, symptomatic lower urinary tract infec-
2002;24:2088-104. tions in elderly women. Cochrane Database Syst Rev
14. Karlowsky JA, Thornsberry C, Jones ME, Sahm DF. Sus- 2002;(3):CD001535.

456 American Family Physician www.aafp.org/afp Volume 72, Number 3 August 1, 2005