To the Editor: In the Clinical Practice article by Fihn on acuteuncomplicated urinary tract infection in women (July 17 issue),1the recommendations for treatment appear to be somewhat outof date. First, the expected rates of clinical failure amongwomen treated with trimethoprim–sulfamethoxazole for acuteuncomplicated cystitis are now more secure and suggest thatfluoroquinolones or nitrofurantoin should be considered first-linetreatment in many parts of the United States. In an Israelistudy with a 29 percent rate of in vitro resistance to trimethoprim–sulfamethoxazole,the rate of clinical failure was 23 percent overall and 46 percentamong patients with pathogens that were resistant to trimethoprim–sulfamethoxazole.2Second, after the Infectious Diseases Society of America issuedits 1999 guidelines for the treatment of urinary tract infectionin women with acute uncomplicated pyelonephritis, it was demonstratedthat 7 days of ciprofloxacin therapy was superior to 14 daysof treatment with trimethoprim–sulfamethoxazole (largelybecause clinical failure among women treated with trimethoprim–sulfamethoxazolewas associated with the 18 percent rate of in vitro resistanceto trimethoprim–sulfamethoxazole in a study conductedin the United States between 1994 and 1997).3 These findingshave led to the recommendation in annual antimicrobial guidebooksthat the former treatment be used.4 Although better surveillancedata regarding resistance and studies of quality-of-life andcost outcomes are needed, the days of trimethoprim–sulfamethoxazoleas the treatment of choice for uncomplicated urinary tract infectionin women may be numbered.
David A. Talan, M.D. Olive View–UCLA Medical Center Sylmar, CA 91342 dtalan{at}ucla.edu
Editor's note: Dr. Talan reports having received grant supportand honorariums for lecturing from Bayer, Ortho McNeil, andAventis.
References
Fihn SD. Acute uncomplicated urinary tract infection in women. N Engl J Med 2003;349:259-266. [Free Full Text]
Raz R, Chazan Y, Kennes Y, et al. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Clin Infect Dis 2002;34:1165-1169. [CrossRef][ISI][Medline]
Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial. JAMA 2000;283:1583-1590. [Free Full Text]
Gilbert DN, Sande MA, Moellering RC, eds. The Sanford guide to antimicrobial therapy 2003. 33rd ed. Hyde Park, Vt.: Antimicrobial Therapy, 2003:23.
To the Editor: We were surprised to see that Fihn advocatedthe use of trimethoprim without a pregnancy test. Fihn mentionsthat trimethoprim is a known teratogen in animals and that coitusincreases the risk of cystitis. Coitus is associated with pregnancy.
At Charing Cross Hospital, we use cephalexin, a second-generationcephalosporin, for the treatment of uncomplicated urinary tractinfection in women. Although the cost of trimethoprim itselfis lower, the cost of trimethoprim plus a measurement of betahuman chorionic gonadotropin is higher than the cost of treatmentwith 500 mg of oral cephalexin twice daily three days per week.In addition, in our population, there is an 85 percent sensitivityto cephalexin and a 68 percent sensitivity to trimethoprim.
Rachel Hoey, F.R.C.S. Fey Probst, F.F.A.E.M. Charing Cross Hospital London W6 8RF, United Kingdom rhoey{at}hhnt.org
Dr. Fihn replies: As advocated by Dr. Talan and discussed inmy article, fluoroquinolones and nitrofurantoin are reasonablealternative treatments for acute cystitis when the local rateof resistance to trimethoprim–sulfamethoxazole is high.Dr. Talan cites a study from Israel in which the rate of resistanceapproached 30 percent and empirical therapy with trimethoprim–sulfamethoxazoleachieved a microbiologic cure in only 77 percent of women.1Higher cure rates would be expected in locales where the rateof resistance is lower. The critical question remains at whatlevel of ambient resistance trimethoprim–sulfamethoxazoleshould no longer be considered first-line therapy. Le and Millerconcluded that prescribing fluoroquinolones became cost effectivewhen resistance reached 22 percent, but they did not take intoaccount the public health concern about promoting resistanceto fluoroquinolones.2 In the United States, approximately 10percent of isolates of Escherichia coli from urine are resistantto fluoroquinolones, and the prevalence is rising.3 More liberaluse of these valuable agents could accelerate the emergenceof resistance. Drs. Hoey and Probst advocate treatment withcephalexin, citing low rates of resistance in London. Experiencewith cephalosporins in the United States, however, has beendisappointing, with resistance averaging 70 percent nationally.2Trimethoprim is definitely contraindicated in pregnancy, buta measurement of beta human chorionic gonadotropin will generallybe obtained, irrespective of the agent prescribed, if pregnancyis suspected because of the need for closer follow-up. However,treatment with a beta-lactam or a cephalosporin without a pregnancytest may be reasonable in some circumstances.
Dr. Talan also correctly points to the efficacy of a seven-daycourse of a fluoroquinolone for women with uncomplicated acutepyelonephritis. As his study showed, trimethoprim–sulfamethoxazoleis highly effective in women with sensitive organisms, althoughinformation on sensitivity is typically unavailable when treatmentis initiated.
I also wish to point out an error in my article in the firstsentence of the last paragraph on page 261: lines 4 and 5 shouldhave read, "can be safely treated as outpatients if they donot have complicating factors and signs of systemic toxicity,"rather than "if they do not have factors associated with anupper tract or complicated infection or signs of systemic toxicity,"as printed.
Stephan D. Fihn, M.D., M.P.H. Veterans Affairs Puget Sound Health Care System Seattle, WA 98108 sfihn{at}u.washington.edu
References
Raz R, Chazan B, Kennes Y, et al. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Clin Infect Dis 2002;34:1165-1169. [CrossRef][ISI][Medline]
Le TP, Miller LG. Empirical therapy for uncomplicated urinary tract infections in an era of increasing antimicrobial resistance: a decision and cost analysis. Clin Infect Dis 2001;33:615-621. [CrossRef][ISI][Medline]
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