Management of acute uncomplicated urinary tract infection in adults

Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity and health care costs. Acute cystitis is a superficial infection of the bladder mucosa, whereas pyelonephritis involves tissue invasion of the upper urinary tract. Localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials. Because of the superficial nature of cystitis, single-dose and 3-day regimens have gained wide acceptance as the preferred methods of treatment. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to be more effective than those with beta-lactams, regardless of the duration. Acute pyelonephritis does not necessarily imply a complicated infection. Upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, and 14-day regimens are often used. We prefer to use antimicrobials that attain high renal tissue levels, such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women with frequently recurring infections can be successfully managed by continuous prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in compliant patients, by early self-administration of single-dose or 3-day therapy as soon as typical symptoms are noted. Our drug of choice for all these regimens is trimethoprim-sulfamethoxazole. Acute uncomplicated cystitis in adult men is very uncommon, but it is occasionally noted in homosexual men who practice insertive and intercourse or in heterosexual men whose partners have vaginal colonization with E. coli.     

Urinary tract infection: traditional pharmacologic therapies

Urinary tract infections (UTIs) are common bacterial infections, particularly in women. Antimicrobial therapy is seldom indicated for asymptomatic infection, but antimicrobial therapy is usually indicated for amelioration of symptoms. Management of acute uncomplicated UTI (cystitis) is generally straightforward, with a predictable distribution of uropathogens isolated. First-line treatment of acute uncomplicated UTI has traditionally involved a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) or TMP alone for patients with sulfa allergies. Increasing resistance among community-acquired Escherichia coli to TMP-SMX worldwide has led to a reassessment of the most appropriate empiric therapy for these infections. Alternative first-line agents include the fluoroquinolones, nitrofurantoin, and fosfomycin.Factors to be considered in the selection of appropriate antimicrobial therapy include pharmacokinetics, spectrum of activity of the antimicrobial agent, resistance prevalence for the community, potential for adverse effects, and duration of therapy. Ideal antimicrobial agents for UTI management have primary excretion routes through the urinary tract to achieve high urinary drug levels. In addition, there are special considerations in the management of UTI among selected populations, including postmenopausal and pregnant women, and for women with frequent recurrent UTIs.     

Urinary tract infections in the elderly population

Background

Urinary tract infections (UTIs) are a common problem in the elderly population. The spectrum of disease varies from a relatively benign cystitis to potentially life-threatening pyelonephritis.

Objective

This review covers the management of asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, antibiotic resistance, catheter-associated bacteriuria/symptomatic UTIs, and antibiotic prophylaxis for recurrent infections in elderly men and women.

Methods

Literature was obtained from English-language searches of MEDLINE (1966–April 2011), Cochrane Library, BIOSIS (1993–April 2011), and EMBASE (1970–April 2011). Further publications were identified from citations of resulting articles. Search terms included, but were not limited to, urinary tract infections, asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, antibiotic resistance, catheter associated urinary tract infections, recurrent urinary tract infections, and elderly.

Results

The prevalence of UTIs in elderly women depends on the location in which these women are living. For elderly women living in the community, UTIs compromise the second most common infection, whereas in residents of long-term care facilities (LTCFs) and hospitalized subjects, it is the number one cause of infection. The spectrum of patient presentation varies from classic signs and symptoms in the independent elderly population to atypical presentations, including increased lethargy, delirium, blunted fever response, and anorexia. Although there are few guidelines specifically directed toward the management of UTIs in the elderly population, therapy generally mirrors the recommendations for the younger adult age groups. When choosing a treatment regimen, special attention must be given to the severity of illness, living conditions, existing comorbidities, presence of external devices, local antibiotic resistance patterns, and the ability of the patient to comply with therapy.

Conclusions

Improved guidelines for the diagnosis and management of UTIs in the elderly population are needed. Better techniques to evaluate and prevent catheter-associated bacteriuria and UTIs await improved diagnostic modalities and catheter technologies. Alternative methods for prophylaxis of patients who suffer from recurrent infections must be found while minimizing the risk of developing or propagating antibiotic resistance.     

Urinary tract infections and antibiotic resistance

Urinary tract infections (UTI) are diseases which differ considerably regarding pathogenesis, natural history and management. Complicated UTI as well as uncomplicated acute pyelonephritis in women are managed with pretherapy urine and, possibly, blood culture. This is not the case, however, with the most frequent UTI, acute uncomplicated cystitis in women. Empirical management strategies, without pretherapy culture, are well established and widely used. The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMZ) and fluoroquinolones. E. coli cause the vast majority of these infections, and resistance to TMP-SMZ has been observed to increase considerably during the last decade. Data from Europe and Switzerland regarding resistance of etiologic agents causing acute uncomplicated cystitis are very limited. Indeed, these empirical management strategies have resulted in poor microbiological information, since only selected groups of women with UTI undergo urine culture. Data derived from laboratory isolates usually lack the necessary clinical and epidemiological correlations. Preliminary data allow some estimates of the clinical and microbiological success rates when treating TMP-SMZ resistant uropathogens with TMP-SMZ. TMP-SMZ should probably no longer be used if the prevalence of TMP-SMZ resistance among uropathogens causing acute uncomplicated cystitis is 20% or higher. In these cases, a fluoroquinolone during three days, amoxicillin-clavulanate during three to five days or nitrofurantoin during seven days should be given empirically. Non-antibiotic means of preventing UTI, such as increasing colonization resistance with lactobacilli, or the use of vaccines which provide inhibition of adherence of uropathogens to uroepithelial cells, show very promising experimental results. In order to survey and correct the value of our empirical strategies, more appropriate data on antimicrobial resistance and risk factors in the community are needed. This data can only be produced by a strong collaboration effort with networks of general practitioners.     

Treatment options for acute uncomplicated cystitis in adults

Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis.     

Antibiotic therapy for common infections

Several important points regarding the treatment of urinary tract infections should be made. Single-dose and short-course antibiotic therapy is appropriate only for women with acute bacterial cystitis due to E. coli. Studies comparing single-dose to full-course therapy have not been sufficiently designed to draw valid statistical conclusions, and only TMP/SMX is recommended at this time. Recurrent UTI in women is almost always due to reinfection, which is best managed by prophylactic antibiotics. Acute bronchitis and acute exacerbations of chronic bronchitis are often due to viral infections, and therefore antibiotic therapy is not always needed. In acute exacerbations of chronic bronchitis, the clearest success rates for antibiotic therapy have been in patients, who have all three of the following symptoms: increased dyspnea, increased sputum production, and sputum purulence. Mupirocin is an important addition to the agents used to treat bacterial skin infections due to streptococcal and staphylococcal strains. In impetigo, mupirocin has been demonstrated to be as effective or superior to oral erythromycin. In prostatitis, data on the fluoroquinolones appears impressive, but further comparative trials are needed. They may become first-line, empiric therapy. The newer oral antibiotics are not recommended as initial, empiric therapy in the outpatient management of common infections, with the possible exception of the treatment of prostatitis. These newer agents may be more important in the treatment of recurrent or resistant infections.     

Urinary tract infections: contemporary management

Urinary tract infections (UTIs) are an increasingly prevalent problem for women. The diagnosis and management of uncomplicated acute cystitis is relatively straightforward, while complicated and recurrent infections require more specialized assessment and treatment. This article will review the current management of UTIs.     

Urinary tract infections in adults

Urinary tract infections remain a significant cause of morbidity in all age groups. Recent studies have helped to better define the population groups at risk for these infections, as well as the most cost-effective management strategies. Initially, a urinary tract infection should be categorized as complicated or uncomplicated. Further categorization of the infection by clinical syndrome and by host (i.e., acute cystitis in young women, acute pyelonephritis, catheter-related infection, infection in men, asymptomatic bacteriuria in the elderly) helps the physician determine the appropriate diagnostic and management strategies. Uncomplicated urinary tract infections are caused by a predictable group of susceptible organisms. These infections can be empirically treated without the need for urine cultures. The most effective therapy for an uncomplicated infection is a three-day course of trimethoprim-sulfamethoxazole. Complicated infections are diagnosed by quantitative urine cultures and require a more prolonged course of therapy. Asymptomatic bacteriuria rarely requires treatment and is not associated with increased morbidity in elderly patients.     

Diagnosis and management of uncomplicated urinary tract infections

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 incidence of urinary tract infection has not changed substantially over the last 10 years, the diagnostic 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.     

Diagnosis and management of urinary tract infection and pyelonephritis

Urinary tract infections (UTIs) are the most common bacterial infections treated in the outpatient setting and range in severity from minimally symptomatic cystitis to severe septic shock in a wide array of patients. Diagnosis of uncomplicated cystitis can be inferred from history and physical, and confirmed by urinalysis. Appropriate antimicrobial therapy should rapidly improve symptoms in all UTIs. Treatment can be further tailored according to severity of illness, analysis of individualized risk factors, and antimicrobial resistance patterns. This article discusses treatment options in light of bacterial resistance in the twenty-first century.     

Isolation of fluoroquinolone-resistant rectal Escherichia coli after treatment of acute uncomplicated cystitis

OBJECTIVES: Given increasing rates of co-trimoxazole resistance among uropathogens causing acute uncomplicated cystitis, fluoroquinolones, nitrofurantoin and fosfomycin are often considered as alternative empirical therapy. The choice between these drugs should depend in part on whether they are associated with the isolation of drug-resistant microbial flora. We conducted a randomized treatment trial to assess the effects of ciprofloxacin, nitrofurantoin and fosfomycin on the rectal microbial flora of women with acute uncomplicated cystitis, including isolation of fluoroquinolone-resistant strains. METHODS: Pre-menopausal women presenting with acute uncomplicated cystitis were randomized to treatment with 3 days of ciprofloxacin, 7 days of nitrofurantoin, or a single dose of fosfomycin. Women were followed for 1 month for evaluation of clinical and microbiological responses as well as for isolation of resistant rectal E. coli. RESULTS: Sixty-two women (25 ciprofloxacin, 17 nitrofurantoin, 20 fosfomycin) were enrolled and eligible for analysis. All three regimens were well tolerated and resulted in >90% clinical and bacteriological cure. The prevalence of rectal E. coli was markedly decreased by ciprofloxacin and fosfomycin, but not by nitrofurantoin. One woman treated with ciprofloxacin had emergence of two ciprofloxacin-resistant rectal E. coli strains within 10 days of completing therapy. No emergence of resistance was observed in the other two treatment groups. CONCLUSIONS: This study demonstrates that fluoroquinolone-resistant E. coli remain infrequent in the rectal flora of women with uncomplicated cystitis in Seattle. However, a 3 day course of a fluoroquinolone for treatment of uncomplicated cystitis was followed by isolation of fluoroquinolone-resistant rectal E. coli in one patient.     

Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women

One hundred sixty-three women with uncomplicated acute lower urinary tract infections were included in a multicenter randomized study comparing cefpodoxime-proxetil (one 100-mg tablet twice daily) with trimethoprim-sulfamethoxazole (one double-strength tablet [160/800 mg] twice daily) for 3 days. A total of 30 women in both arms were excluded from the study for various reasons. At 4 to 7 days after the discontinuation of therapy, 62 of 63 (98.4%) cefpodoxime-proxetil recipients and 70 of 70 (100%) trimethoprim-sulfamethoxazole patients were clinically cured and demonstrated bacteriological eradication, respectively. At 28 days after treatment, 48 of 55 (87.3%) and 43 of 50 (86%) cefpodoxime-proxetil recipients as well as 51 of 60 (85%) and 42 of 50 (84%) trimethoprim-sulfamethoxazole recipients were clinically cured and demonstrated bacteriological eradication, respectively. Independently of the prescribed regimen, a significant difference (P < 0.001) in failure rates was observed only for patients with a previous history of three or more episodes of acute cystitis per year. With the exception of one patient in the trimethoprim-sulfamethoxazole arm who discontinued therapy because of gastrointestinal pain, both antimicrobials were well tolerated. In conclusion, cefpodoxime-proxetil treatment for 3 days was as safe and effective as trimethoprim-sulfamethoxazole for 3 days for the treatment of uncomplicated acute cystitis in women.     

Risk factors for trimethoprim-sulfamethoxazole resistance in patients with acute uncomplicated cystitis

Emerging antimicrobial resistance among uropathogens makes the management of acute uncomplicated cystitis increasingly challenging. Few prospective data are available on the risk factors for resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the drug of choice in most settings. In order to evaluate this, we prospectively enrolled women 18 to 50 years of age presenting to an urban primary care practice with symptoms of cystitis. Potentially eligible women provided a urine sample for culture and completed a questionnaire regarding putative risk factors for TMP-SMX resistance. Escherichia coli isolates were tested for clonal group A (CGA) membership by a fumC-specific PCR. Of 165 women with cystitis symptoms, 103 had a positive urine culture and were eligible for participation. E. coli was the predominant uropathogen (86%). Fifteen (14.6%) women had a TMP-SMX-resistant (TMP-SMX r) organism (all of which were E. coli). Compared with the women who had a TMP-SMX-susceptible organism, women in the TMP-SMX r group were more likely to have traveled (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.4 to 54.3; P < 0.001) and to be Asian (OR, 6.1; 95% CI, 1.0 to 36.4; P = 0.048). CGA was also independently associated with TMP-SMX resistance (OR, 105; 95% CI, 6.3 to 1,777.6; P = 0.001). No association with TMP-SMX resistance was demonstrated for the use of either TMP-SMX or another antibiotic in the past 3 months or with having a child in day care. Among these women with acute uncomplicated cystitis, Asian race and recent travel were independently associated with TMP-SMX resistance. TMP-SMX r isolates were more likely to belong to CGA. Knowledge of these risk factors for TMP-SMX resistance could facilitate the accurate selection of empirical therapy.     

Treatment of uncomplicated urinary tract infections in an era of increasing antimicrobial resistance

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.     

Addressing antibiotic resistance

Management of uncomplicated urinary tract infections (UTIs) has traditionally been based on 2 important principles: the spectrum of organisms causing acute UTI is highly predictable (Escherichia coli accounts for 75% to 90% and Staphylococcus saprophyticus accounts for 5% to 15% of isolates), and the susceptibility patterns of these organisms have also been relatively predictable. As a result, empiric therapy with short-course trimethoprim-sulfamethoxazole (TMP-SMX) has been a standard management approach for uncomplicated cystitis.However, antibiotic resistance is now becoming a major factor not only in nosocomial complicated UTIs, but also in uncomplicated community-acquired UTIs. Resistance to TMP-SMX now approaches 18% to 22% in some regions of the United States, and nearly 1 in 3 bacterial strains causing cystitis or pyelonephritis demonstrate resistance to amoxicillin. Fortunately, resistance to other agents, such as nitrofurantoin and the fluoroquinolones, has remained low, at approximately 2%. Preliminary data suggest that the increase in TMP-SMX resistance is associated with poorer bacteriologic and clinical outcomes when TMP-SMX is used for therapy. As a result, these trends have necessitated a change in the management approach to community-acquired UTI. The use of TMP-SMX as a first-line agent for empiric therapy of uncomplicated cystitis is only appropriate in areas where TMP-SMX resistance prevalence is <10% to 20%. In areas where resistance to TMP-SMX exceeds this rate, alternative agents need to be considered.     

Urinary tract infections in women

The clinical conditions that cause dysuria in women can usually be differentiated by the history and selected physical and laboratory examinations. Cystitis can be treated with short-course therapy in uncomplicated cases; pretreatment cultures are usually not necessary, since most infections are caused by Escherichia coli. Outpatient treatment of pyelonephritis is appropriate in selected patients. Follow-up culture after treatment of either cystitis or pyelonephritis is indicated to identify those patients requiring longer treatment or urologic evaluation. Recurrent urinary tract infections can be managed with postcoital antibiotics, long-term prophylaxis or patient self-administration of short-course therapy. Bacteriuria and pyelonephritis in pregnancy must be aggressively diagnosed and treated.     

Equal symptomatic outcome after antibacterial treatment of acute lower urinary tract infection and the acute urethral syndrome in adult women.

OBJECTIVE: To compare symptomatic outcome after antibacterial treatment in patients with acute lower urinary tract infection and the acute urethral syndrome. DESIGN: A multipractice study; patients registering symptoms prospectively for 3 days by means of a diary. SETTING: General practices in western Norway. SUBJECTS: 153 adult women with acute lower urinary tract symptoms. MAIN OUTCOME MEASURE: Patient's prospective registration of symptom distribution and duration after starting antibacterial treatment. RESULTS: Fifty-one patients with acute lower urinary tract infection and 58 patients with the acute urethral syndrome were included. There were no differences in age, history of urinary tract infection, actual symptoms, or symptom duration between the groups. Symptom duration was nearly identical in the two groups among those who became asymptomatic during the 3 days of registration, ranging from 1.2 days for urgency to 1.6 days for dysuria. Almost half of the patients in each group still had some symptom left after 3 days. CONCLUSIONS: Symptomatic outcome was equal after antibacterial treatment whether the patient was classified as having acute cystitis or the acute urethral syndrome. Consequently, the general practitioner may rely on symptoms alone when starting antibacterial treatment in adult women with suspected cystitis.     

Uncomplicated cystitis: diagnosis and treatment at college health centers.

The results of recent studies have led to valuable new recommendations regarding optimal diagnosis and treatment of acute uncomplicated cystitis in women. To investigate to what degree these recommendations have been incorporated into clinical practice, we conducted a survey of all college health centers belonging to the American College Health Association regarding their current management of suspected uncomplicated cystitis. Sixty-one percent responded. The results confirm that acute cystitis is indeed frequent among college women. Nonetheless, our data show that there is a wide variation in the approach to this common problem and that many centers have not yet adopted the new recommendations for optimal diagnosis and treatment. If we are to improve the management of uncomplicated cystitis in women, we must not only learn the best medical approaches, but we must also find reliable ways of transmitting this information to clinicians.     

Preliminary report on DU-6859a for urinary tract infection

The efficacy safety, and clinical value of DU-6859a, a novel new quinolone antimicrobial, were evaluated in a multicenter study. The subjects were selected from among patients aged 20 to 79 years with mild to moderate uncomplicated or complicated urinary tract infection (UTI). DU-6859a was administered orally after meals at a dose of 50–100 mg once or twice daily for 3–7 days. The clinical efficacy rate for all target infections was determined to be 88.5%, (100/113) by the attending physicians. The efficacy rate was 100% (21/21) for acute uncomplicated cystitis, 84.9% (62/73) for complicated cystitis, and 88.9% (16/18) for complicated pyelonephritis. The overall clinical efficacy rate and the eradication rate for urinary pathogens were determined according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents for UTI proposed by the Japanese UTI Committee. The rates were, respectively, 100% (9/9) and 100% (11/11) for acute uncomplicated UTI and 88.0% (66/75) and 91.2% (93/102) for complicated UTI. Clinical adverse reactions were experienced in seven (5/7%) out of 123 evaluable patients, but all symptoms were mild. Laboratory adverse reactions, such as slight elevations of GOT and/or GPT, were noted in 13 (12.1%) out of 107 evaluable patients. DU-6859a showed excellent clinical efficacy against acute uncomplicated and complicated UTI which reflected its high antibacterial activity in vitro and did not cause any clinically significant adverse reactions. These results show that DU-6859a is worthy of further clinical studies for the treatment of UTI.     

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money

CONTEXT: Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. OBJECTIVE: To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. DESIGN, SETTING AND PATIENTS: Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. RESULTS: The rate of adherence was 22.23% for nitrofurantoin (95% CI=19.81%, 24.65%), and 4.08% for ofloxacin (95% CI=2.88%, 5.28%). The average excess expenditure per case was 5.78 USD (US Dollar) with ofloxacin and 3.43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of approximately 19,000 USD. When extrapolated to the national population of 6.5 million, the loss due to inappropriate treatment of adult women is 190,000 USD. CONCLUSIONS: The lack of adherence to national and international guidelines with regard to the recommended duration of antibiotic treatment of UTI in women resulted in a significant and avoidable waste of health system resources. This study suggests that drug utilization analyses that concentrate solely on the choice of drug may be overlooking important information.