Distinguishing between complicated and uncomplicated UTI is important because the duration of antimicrobial therapy is typically longer in complicated

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1 CONCISE REVIEW FOR CLINICIANS TREATMENT OF UNCOMPLICATED URINARY TRACT INFECTIONS Treatment of Uncomplicated Urinary Tract Infections in an Era of Increasing Antimicrobial Resistance LOREN G. MILLER, MD, MPH, AND ANGELA W. TANG, MD In the past few years, notable advances have occurred in our understanding of the epidemiology and clinical importance of drug resistance among uropathogens that cause uncomplicated urinary tract infections (UTIs) or cystitis. Guidelines recommend trimethoprim-sulfamethoxazole for empirical treatment of uncomplicated UTI unless trimethoprim-sulfamethoxazole resistance in a community exceeds 10% to 20%. The rationale for this 10% to 20% cutoff appears to be related to clinical and economical considerations and to concerns about the emergence of fluoroquinolone-resistant bacteria. In patients with uncomplicated UTIs caused by uropathogens resistant to trimethoprim-sulfamethoxazole who were treated with this drug combination, clinical outcomes were clarified recently and found to be suboptimal (<60% clinical cure). Following guidelines for empirical treatment of uncomplicated UTIs is problematic. Surveillance of antimicrobial resistance among uropathogens that cause uncomplicated UTIs is performed rarely. Hospital antibiograms provide data on resistance among bacteria that cause community-associated UTIs; however, antibiograms overestimate drug resistance among uropathogens that cause UTIs and may mislead clinicians about the prevalence of local resistance. We review options for management of uncomplicated UTIs in light of these considerations. Mayo Clin Proc. 2004;79(8): IDSA = Infectious Diseases Society of America; UTI = urinary tract infection Urinary tract infections (UTIs) in women are a common problem in primary care settings. Of women between ages 20 and 40 years, 25% to 35% have had a UTI. 1 In the United States each year, physicians write approximately 11.3 million prescriptions for adult women with UTIs, and the cost of treatment has been estimated at $1.6 billion. 1 Unfortunately, drug resistance among uropathogens has increased steadily during the past several decades, resulting in more complex treatment choices. Since the publication of guidelines for the treatment of uncomplicated UTIs (also From the Division of Infectious Diseases and the Research and Education Institute, Harbor-UCLA Medical Center, Torrance, Calif (L.G.M.); and Department of Medical Education, St Mary Medical Center Internal Medicine Residency Training Program, Long Beach, Calif (A.W.T.). Dr Miller has received honoraria for serving on the Speakers Bureau for Bristol-Myers Squibb Co. A question-and-answer section appears at the end of this article. Individual reprints of this article are not available. Address correspondence to Loren G. Miller, MD, MPH, Division of Infectious Diseases, Harbor-UCLA Medical Center and Harbor-UCLA Research and Education Institute, 1124 W Carson St, Box 466, Torrance, CA ( lgmiller@rei.edu) Mayo Foundation for Medical Education and Research known as cystitis) and pyelonephritis by the Infectious Diseases Society of America (IDSA) in 1999, 2 major advances have occurred in our understanding of the epidemiology and clinical importance of drug resistance in these infections. These advances warrant reexamination of the guidelines regarding the diagnosis and management of uncomplicated UTIs, noting especially the relationship between these infections and the increasing antimicrobial resistance among uropathogens. We review the diagnosis and management of uncomplicated UTIs and focus on recent advances. DIAGNOSIS OF UNCOMPLICATED UTIS Symptoms of UTIs are encountered commonly in primary care settings. Typical symptoms include increased urinary frequency, urgency, and dysuria, although all 3 symptoms may not be present. 3,4 Up to 25% of women with uncomplicated UTIs have hematuria, which resolves typically with successful management of the infection. 4 Of note, dysuria also can be present in conditions such as urethritis (most commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae) and vaginitis (eg, fungal, atrophic, and bacterial). 3 If the patient history and the physical examination are not consistent with UTI, then diagnostic tests for these other conditions should be pursued. Some authors believe that the presence of symptoms such as dysuria and increased urinary frequency in a woman with risk factors for sexually transmitted infections should prompt consideration of diagnostic testing for Chlamydia infection. 4 In the outpatient setting, UTI may be diagnosed by history alone or by confirmatory urinalysis. Leukocyte esterase testing on dipstick has a reasonably good sensitivity (75%-96%) and specificity (>90%) for detecting 5 to 25 white blood cells per high-power field. 5 Urinary dipstick test results for nitrite are positive in 60% to 90% of UTIs; this test has a specificity greater than 90%. 5 If test results are negative and UTI is still suspected, microscopic examination of urine for leukocytes may increase detection rates and help assess collection techniques. 3 Ideally, very few or no epithelial cells should be present in a properly collected sample because contamination of specimens with these cells is associated with increased leukocytes and may result in false-positive test results

2 Distinguishing between complicated and uncomplicated UTI is important because the duration of antimicrobial therapy is typically longer in complicated infections. According to the IDSA and others, 2,3,7 an uncomplicated UTI, by definition, lacks features of a complicated UTI. The presence of diabetes mellitus, immunocompromised conditions, pregnancy, urinary tract obstruction (eg, strictures, neurogenic bladder), or unusual pathogens (eg, Pseudomonas aeruginosa, Mycoplasma species) in a woman with UTI categorizes the infection as complicated. Some argue that pyelonephritis in the absence of these abnormalities is considered an uncomplicated infection, 8 although categorizing pyelonephritis as uncomplicated can be confusing because this infection requires a longer course of therapy. Others consider pyelonephritis a complicated infection. 9 In men, UTIs are considered complicated (and are beyond the scope of this article) because they are associated frequently with prostate enlargement and impairment of anterograde urinary flow. Finally, some consider older age (>65 years) and prolonged prodromal symptoms (>14 days) to be complicating factors. 8,9 In this review, we focus primarily on uncomplicated lower UTIs, excluding pyelonephritis. Escherichia coli is the most common causative organism of uncomplicated UTIs, accounting for 80% of cases. 3 The remainder of uncomplicated UTIs are caused primarily by Staphylococcus saprophyticus, Proteus mirabilis, and Klebsiella species. Because the organisms responsible for outpatient uncomplicated UTIs are predictable, the IDSA recommends that urine culture not be performed for these infections. 2 Rather, cultures are reserved for complicated cases and treatment failures. 2,3 This recommendation, although prudent for conserving resources in the management of uncomplicated UTIs, is limiting because it hampers surveillance of drug resistance among uropathogens that cause uncomplicated UTIs; cultures are rarely used in this setting. ANTIMICROBIAL THERAPY The 1999 IDSA guidelines recommend that trimethoprimsulfamethoxazole, double strength, 1 tablet twice a day orally for 3 days, is the treatment of choice for uncomplicated UTIs. A 3-day course eradicates approximately 95% of uncomplicated infections. 3 One-day courses of trimethoprim-sulfamethoxazole are associated with lower rates of cure (approximately 85%) and are not recommended as first-line treatment. 2,3 Courses of 5, 7, or 14 days have no advantage over 3-day courses because the probability of cure is not increased and adverse drug effects are more likely with longer courses. 2 The longer courses (7-14 days) are reserved for pyelonephritis and complicated infections. Patients allergic to sulfa drugs may be treated with trimethoprim, 100 mg twice daily, which appears to have a similar efficacy to trimethoprim-sulfamethoxazole for uncomplicated UTIs. 2 Trimethoprim-sulfamethoxazole has some advantages over β-lactam antibiotics such as amoxicillin and cephalexin. First, cure rates are higher with trimethoprim-sulfamethoxazole, even when drug resistance is noncontributory. 2 Second, trimethoprim-sulfamethoxazole use for uncomplicated UTIs is associated with a decreased risk of subsequent UTI over the ensuing months, which has been attributed to the ability of this drug combination to eradicate gastrointestinal colonization of uropathogens. 2 The IDSA recommends that when trimethoprimsulfamethoxazole resistance exceeds 10% to 20% in the community, empirical treatment of UTIs should be switched from trimethoprim-sulfamethoxazole to another agent, of which the fluoroquinolones have the greatest efficacy. However, this recommendation has 2 important limitations: (1) The rationale for the 10% to 20% cutoff is not well delineated. Although not explicitly stated, the guidelines suggest that this cutoff was chosen on the basis of clinical cure percentages and perhaps because of treatment costs becoming unacceptably high when trimethoprim-sulfamethoxazole resistance exceeds the 10% to 20% threshold. (2) The guidelines raise concern that empirical use of fluoroquinolones may contribute to the emergence of fluoroquinolone-resistant bacteria. 2 Some have questioned this threshold from the perspective of health care cost. A cost-based model developed by Le and Miller 10 found that fluoroquinolones become less expensive when trimethoprim-sulfamethoxazole resistance exceeds 22% in the community. Trimethoprim-sulfamethoxazole becomes more costly at higher levels of resistance primarily because of treatment failures, repeated visits to physicians, and associated laboratory testing. A subsequent cost analysis performed by other investigators had similar findings and found that the threshold of trimethoprimsulfamethoxazole resistance at which fluoroquinolone therapy becomes less expensive was 19% to 21%. 11 Although these models provide important information regarding selection of empirical treatment, they do not consider other factors that may influence these decisions, such as societal costs (eg, days lost from work or school due to UTIs) and the effect that antibiotic use (particularly fluoroquinolones) has on antibiotic susceptibility in the community. Another limitation of the IDSA guideline is that most communities have limited data on resistance rates of uropathogens, especially among uncomplicated UTIs (see the Antibiotic Resistance Among Pathogens That Cause Uncomplicated UTIs section). 1049

3 Fluoroquinolones are extremely effective agents for the treatment of UTIs, and like trimethoprim-sulfamethoxazole, they eliminate gastrointestinal colonization of uropathogens. Fluoroquinolones are more costly than trimethoprim-sulfamethoxazole, but medication costs are offset somewhat by lower failure rates in settings of high levels of trimethoprim-sulfamethoxazole resistance. Currently, several commonly used and commercially available fluoroquinolones are approved for treatment of uncomplicated UTIs and pyelonephritis in the United States. These include ciprofloxacin, levofloxacin, gatifloxacin, norfloxacin, and ofloxacin, although the latter 2 are now used less frequently. 12 Moxifloxacin, another commonly used fluoroquinolone, is not approved for treatment of UTIs and is not an ideal agent for this infection because of its hepatic metabolism and minimal urinary concentrations relative to other fluoroquinolones. 12 Gemifloxacin, a recently approved fluoroquinolone for the treatment of respiratory tract infections, has shown efficacy in treatment of UTIs but has not yet been approved for this indication (as of summer 2004). 13 The IDSA recommends 3-day courses of treatment for uncomplicated UTIs. 2 Single-dose fluoroquinolones have been studied; in general, the single-dose treatment has had a slightly lower cure rate and higher rates of adverse effects compared with the 3-day regimens. 2,3 Although some single-dose regimens appear as effective as 3-day regimens, 14 this approach may have limitations; symptoms of UTI may last several days after effective therapy is initiated, 15 and persistent symptoms may trigger revisits to physicians. Published experiences of outcomes of singledose therapy outside clinical trials are lacking. Other treatment options for UTI include amoxicillin, 500 mg 3 times daily, and first-generation cephalosporins (eg, cephalexin, 500 mg 4 times daily), but physicians should realize that β-lactams are somewhat less effective than trimethoprim-sulfamethoxazole and are associated with more adverse drug effects. 2 Nitrofurantoin, 100 mg 4 times daily (or nitrofurantoin macrocrystals, 100 mg twice daily), can be used for uncomplicated UTIs. However, this medication has extremely poor penetration into tissues; it should not be used for pyelonephritis and probably should be limited only to treatment of uncomplicated UTIs. 16 The efficacy of nitrofurantoin is inferior to that of trimethoprim-sulfamethoxazole and fluoroquinolones, and most experts recommend a longer course (eg, 7 days) of this antibiotic for uncomplicated UTIs. 2,16 Although used rarely in the United States, fosfomycin is approved as a single oral 3-g dose for uncomplicated UTIs. However, the efficacy of fosfomycin is lower than that of the traditional 3- day trimethoprim-sulfamethoxazole or fluoroquinolone regimens. 2 Because resistance to fosfomycin is extremely rare in the United States, it may have a role in multidrug-resistant infections or for patients with multiple drug allergies. ADJUNCTIVE THERAPY Women are increasingly seeking alternative treatments for common ailments such as uncomplicated UTIs. The role of additional hydration is unclear. Hydration enhances anterograde flow of urine through the urinary tract, a protective mechanism against uropathogens, and may remove uropathogens by bladder emptying. However, there is concern that hydration may lead to lower levels of antibiotics and host antibacterial substances normally found in the urine, which may hinder eradication. 17 Cranberries and other berries in the genus Vaccinium contain proanthocyanidins, which in vitro prevent uropathogens from adhering to urinary epithelium. 18,19 However, no evidence suggests that these agents provide clinical benefit in the treatment of acute infections. Cranberry products have shown value only in reduction of (largely asymptomatic) bacteriuria 20 and in prophylaxis in women with recurrent infections. 21 ANTIBIOTIC RESISTANCE AMONG PATHOGENS THAT CAUSE UNCOMPLICATED UTIS In the remaining sections, we focus on resistance to trimethoprim-sulfamethoxazole because IDSA guidelines suggest that resistance to this agent has the most important clinical significance. Determining how much trimethoprimsulfamethoxazole resistance exists among uropathogens that cause uncomplicated UTIs is problematic; data on which to base our antibiotic choices are scant. One of the most readily available pieces of information for clinicians regarding local drug resistance among bacteria is a hospital antibiogram, which quantifies drug resistance seen at the hospital microbiology laboratory during a particular year or portion thereof. However, hospital antibiograms have limitations. Antibiograms may lump together inpatient with outpatient isolates as well as urinary with respiratory, wound, and other isolates. Also, some hospital antibiograms consider multiple isolates from the same patient as separate isolates. Because multiple sampling from the same patient probably is done during treatment failures and these instances may be associated with antimicrobial resistance, some antibiograms may overestimate drug resistance. Antibiotic resistance is more prevalent in the inpatient than in the outpatient setting ; therefore, antibiograms tend to overestimate antibiotic resistance in an ambulatory setting. Finally, even antibiograms that separate inpatient from outpatient isolates and urinary pathogens from nonurinary pathogens may be limited because their data on the preva- 1050

4 lence of resistance among uropathogens in outpatients reflect resistance only among patients whose urine is cultured, which excludes patients with uncomplicated UTIs. To what degree antibiograms overestimate resistance among uropathogens that cause uncomplicated UTIs in the outpatient setting is poorly understood. A recent investigation in New Zealand found 19% trimethoprim resistance among E coli reported by the hospital microbiology laboratory but only 11% resistance among uropathogens that cause uncomplicated UTIs. 22 In an investigation from Singapore, 46% of E coli from the hospital mircrobiology laboratory was resistant to trimethoprim-sulfamethoxazole. However, only 21% of E coli from a prospective survey of 2 outpatient clinics was resistant to trimethoprimsulfamethoxazole (of note, most but not all patients had uncomplicated UTIs). 24 Therefore, although hospital antibiograms can provide useful information for assessing inpatient drug resistance, they can substantially overestimate drug resistance among uncomplicated UTIs. TRENDS IN ANTIBIOTIC RESISTANCE AMONG UROPATHOGENS Unfortunately, drug resistance is increasing among uropathogens that cause uncomplicated UTIs. An investigation from Seattle that used administrative data to retrospectively identify patients with uncomplicated UTIs found that trimethoprim-sulfamethoxazole resistance was increasing: among uropathogens, resistance increased from 8% in 1992 to 16% in Also, temporal increases in drug resistance to ampicillin, cephalothin, and trimethoprim alone were observed. In Michigan, a prospective surveillance of drug resistance among pathogens that cause uncomplicated UTIs found that trimethoprim-sulfamethoxazole resistance increased from 8% in to 16% in Besides investigations performed for research purposes, few if any surveillances are performed in the United States to monitor drug resistance among pathogens that cause uncomplicated UTIs. However, an impressive investigation from 16 European countries and Canada of drug resistance among pathogens that cause uncomplicated UTIs was published recently. 27 In this survey, drug resistance among uropathogens varied widely from country to country. However, several important trends emerged. Resistance to ampicillin was high (18%-54%), as was resistance to trimethoprim (9%-27%) and sulfamethoxazole (16%- 49%). Resistance to antibiotics that are used only for lower UTIs (fosfomycin, nitrofurantoin, and mecillinam, which is not used in the United States) was low, generally less than 3%. Uncomplicated infections are the most common type of UTI; therefore, surveillance of drug resistance among these infections in additional locales is needed, as is longitudinal surveillance of resistance trends in general. CLINICAL IMPORTANCE OF IN VITRO DRUG RESISTANCE Because many antibiotics are concentrated in the urine, the predictive value of in vitro resistance among uropathogens when treating in vivo UTIs has been questioned. 28 On average, levels of trimethoprim and sulfamethoxazole found in urine are 35 and 3 times, respectively, the levels found in serum. 17,28,29 Most cutoffs between drug susceptibility and resistance were developed not on the basis of clinical correlations, but instead for identification of drug levels associated with clinical dosing that would achieve minimum inhibitory concentrations in the serum to treat serious infections adequately. 17 Curing UTIs has been shown to be more closely associated with urinary rather than serum antibiotic concentrations. 30 However, resistance cutoffs for urinary pathogens often are based on serum cutoffs despite notable differences in peak concentration of antibiotic between urine and serum. 31,32 In infections at some body sites, in vitro drug resistance does not necessarily equate with clinical failure. For example, in pneumonia caused by penicillin-resistant Streptococcus pneumoniae, treatment with penicillins may be effective against many strains of penicillin-resistant S pneumoniae because the high antibiotic concentrations achieved in target organ tissues are sufficient to kill many drug-resistant strains. 33 Unfortunately, this does not appear to be the case with uncomplicated UTIs caused by organisms resistant to trimethoprim-sulfamethoxazole. Until recently, outcomes of patients with UTIs were based primarily on microbiological rather than clinical end points. 10,28 In a recent investigation of women with uncomplicated UTIs, the likelihood of cure was compared in patients with resistant vs sensitive infections that were treated with trimethoprim-sulfamethoxazole. Patients whose infections were caused by a uropathogen sensitive to trimethoprim-sulfamethoxazole had a 96% likelihood of clinical cure compared with only a 55% likelihood of cure in those infected with an organism resistant to trimethoprimsulfamethoxazole. 26 A similar investigation revealed comparable results: 88% of women infected with an organism sensitive to trimethoprim-sulfamethoxazole were cured, whereas only 54% of women infected with a pathogen resistant to trimethoprim-sulfamethoxazole were cured. 34 Using these success and failure rates weighted for the size of studies, 26,34 treatment with trimethoprim-sulfamethoxazole for uncomplicated UTIs in communities with 0% resistance to trimethoprim-sulfamethoxazole would result 1051

5 in an 89% likelihood of cure. When there is 10% community resistance, an 86% likelihood of cure would be expected with trimethoprim-sulfamethoxazole treatment. An 82% likelihood of cure would be expected when there is 20% community resistance, and a 79% likelihood of cure when there is 30% resistance. As noted previously, when a trimethoprim-sulfamethoxazole resistant uropathogen causes a UTI, the likelihood of clinical cure is 54% to 55%. 26,34 How comparable is this percentage to other suboptimal treatments? An investigation in which women with uncomplicated UTI were randomized to antimicrobial therapy or placebo showed that 54% of patients in the placebo group had resolution of symptoms. 35 Although methods and patient populations among these studies differed and cross-investigational comparisons of likelihood of cure should be done with much trepidation, it is nevertheless notable that patients with organisms resistant to trimethoprim-sulfamethoxazole who were treated with this drug combination had likelihoods of cure similar to those in the placebo group. Therefore, it appears that trimethoprim-sulfamethoxazole provides little or no benefit for patients with UTIs when uropathogens have in vitro resistance to this drug combination. WHO IS AT RISK OF TRIMETHOPRIM- SULFAMETHOXAZOLE RESISTANCE? Several investigations have examined predictors of drug resistance among uropathogens. Easily identifiable clinical characteristics associated with trimethoprim-sulfamethoxazole resistance have included recent antibiotic exposures, recent hospitalization, diabetes mellitus, 3 or more UTIs in the past year, and possibly use of oral contraceptives or estrogen-replacement drugs. 26 Armed with this information and any data on antibiotic resistance in uropathogens of local outpatients, clinicians must judge whether trimethoprim-sulfamethoxazole or an alternative antibiotic should be used empirically. Use of fluoroquinolones may be prudent for patients with these risk factors for drug resistance. Unfortunately, trimethoprim-sulfamethoxazole resistance among uropathogens is not the only resistance of concern. Worldwide fluoroquinolone resistance among urinary pathogens is increasing. Recent surveillances from Slovenia and Spain found the proportion of fluoroquinolone-resistant uropathogens to be 20% and 22%, respectively, among adult outpatients. 36,37 The exact cause of this increase is unclear but probably reflects the over-thecounter availability of antibiotics in some countries and/or the use of fluoroquinolones in animal feed and the subsequent transmission of fluoroquinolone-resistant organisms from animals to humans. 38 Regardless, effort should be intensified to minimize unnecessary use of these agents to prevent the emergence of drug resistance. Finally, data are extremely limited on outcomes of patients infected with fluoroquinolone-resistant pathogens. 10,39-44 Given the importance of these agents in the treatment of UTIs, research should be performed to better define the likelihood of cure with fluoroquinolone therapy stratified by drug susceptibility and resistance. SUMMARY Although a 3-day course of trimethoprim-sulfamethoxazole is still recommended as first-line empirical therapy for uncomplicated UTIs in communities with high rates of trimethoprim-sulfamethoxazole resistance, fluoroquinolones and other agents should be considered as alternatives. Unfortunately, accurate data are scant regarding resistance levels in uropathogens in uncomplicated UTIs, and the level of trimethoprim-sulfamethoxazole resistance that necessitates conversion to empirical use of other agents for uncomplicated UTIs is controversial. Improved surveillance of resistance among uropathogens that cause uncomplicated UTIs would help clinicians make informed decisions regarding the empirical treatment of uncomplicated UTIs. Future research should focus on better defining the clinical importance of antibiotics other than trimethoprimsulfamethoxazole, such as fluoroquinolones. Also, the effect of fluoroquinolones for UTIs on the emergence of fluoroquinolone-resistant organisms needs to be better understood. We thank Kiran Bharadwa for her critical review of the submitted manuscript. REFERENCES 1. Foxman B, Barlow R, D Arcy H, Gillespie B, Sobel JD. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000; 10: Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Clin Infect Dis. 1999;29: Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med. 1993;329: Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287: Wallach J. Interpretation of Diagnostic Tests. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; Walter FG, Gibly RL, Knopp RK, Roe DJ. 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Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial. JAMA. 2000;283: Hooton TM, Winter C, Tiu F, Stamm WE. Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women. JAMA. 1995;273: McCarty JM, Richard G, Huck W, et al, Ciprofloxacin Urinary Tract Infection Group. A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Am J Med. 1999;106: Gomolin IH, Siami PF, Reuning-Scherer J, Haverstock DC, Heyd A, Oral Suspension Study Group. Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim-sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection. J Am Geriatr Soc. 2001;49: Newsom SW, Murphy P, Matthews J. A comparative study of ciprofloxacin and trimethoprim in the treatment of urinary tract infections in geriatric patients. J Antimicrob Chemother. 1986;18(suppl D): Iravani A, Klimberg I, Briefer C, Munera C, Kowalsky SF, Echols RM. A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection. J Antimicrob Chemother. 1999;43(suppl A): Questions About Treatment of Uncomplicated UTI 1. Which one of the following antibiotics or antibiotic classes may have a lower cure rate in the treatment of an uncomplicated UTI when used as 3-day therapy compared with longer (eg, 7-day) courses of therapy? a. Amoxicillin b. Trimethoprim-sulfamethoxazole c. Fluoroquinolones d. Nitrofurantoin e. Cephalexin 1053

7 2. Which one of the following represents the approximate likelihood of clinical cure of an uncomplicated UTI caused by a uropathogen resistant to trimethoprim-sulfamethoxazole and treated with this drug combination? a. 1% to 10% b. 30% to 40% c. 50% to 60% d. 70% to 80% e. 90% to 100% 3. Which one of the following regarding cranberry juice in the treatment of UTIs is false? a. Has shown therapeutic value in the treatment of acute UTIs b. Has shown therapeutic value in the prevention of UTIs c. Has reduced bacteriuria in patients with asymptomatic bacteriuria d. Contains compounds that in vitro prevent uropathogens from adhering to urinary epithelium e. Contains proanthocyanidins, believed to be the compounds that provide the juice s effect against urinary compounds 4. Which one of the following risk factors is not predictive of trimethoprim-sulfamethoxazole resistance among uropathogens? a. Recent antibiotic exposure b. Recent hospitalization c. Diabetes mellitus d. Estrogens or oral contraceptives e. Employment as a health care worker 5. Which one of the following statements regarding treatment of uncomplicated UTIs is false? a. Treatment with β-lactams, such as amoxicillin and cephalexin, is associated with lower likelihood of cure compared with treatment with trimethoprimsulfamethoxazole b. Treatment with β-lactams, such as amoxicillin and cephalexin, is associated with lower likelihood of adverse effects compared with treatment with trimethoprim-sulfamethoxazole c. Resistance to fosfomycin among uropathogens is uncommon in the United States d. Resistance to trimethoprim-sulfamethoxazole among uropathogens appears to be increasing in the United States e. When using nitrofurantoin, the likelihood of cure using 3-day therapy is inferior to that of 7-day therapy Correct answers: 1. d, 2. c, 3. a, 4. e, 5. b 1054