Diagnosis and treatment of acute uncomplicated cystitis
Diagnosis and Treatment of Acute Uncomplicated Cystitis RICHARD COLGAN, MD, and MOZELLA WILLIAMS, MD 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 Physician. 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,
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quests. 771 Cystitis SORT: KEY RECOMMENDATIONS FOR PRACTICE
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 7 ◆ October 1, 2011Cystitis
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, 2011 ◆ Volume 84, Number 7American Family Physician 773 Cystitis 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 7 ◆ October 1, 2011Cystitis
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, 2011 ◆ Volume 84, Number 7American Family Physician 775 Cystitis
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
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INFORME TECNICO BROMEFLOX ® Producto : BROMEFLOX ® contiene en su formula por cada adición de más Fluor logre una mayor eficacia Combinación de un antibiótico con un muco lítico b ) Mecanismo Acción : indicado para el tratamiento de infecciones aviares causadas por bacterias Gram. positivas , Las quinolonas y fluorquinolonas tienen su sitio de acción en la
obesity reviews Obesity Management Recent advances in adaptive thermogenesis: potential implications for the treatment of obesity S. L. J. Wijers, W. H. M. Saris and W. D. van Marken LichtenbeltDepartment of Human Biology, Nutrition andToxicology Research Institute Maastricht,Large inter-individual differences in cold-induced (non-shivering) and diet-induced adaptive thermogenesis exi