The expanding role of fluoroquinolones

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose.Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.     

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.     

Survey on antibiotic usage in the treatment of urinary tract infections

Ninety-two clinical microbiologists, infectious disease clinicians and clinicians with an interest in the management of urinary tract infections (UTIs) participated in an interactive session concerning the management of acute uncomplicated lower UTI. The antibacterials considered most appropriate as first-line agents were trimethoprim, co-trimoxazole, pivmecillinam, nitrofurantoin and fluoroquinolones. The current level of usage of fluoroquinolones for lower UTIs was, however, considered inappropriate by most delegates from a 'societal perspective', in terms of spread of resistance and potential impact on the environment.     

The etiology of urinary tract infection: traditional and emerging pathogens

The microbial etiology of urinary infections has been regarded as well established and reasonably consistent. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%). Klebsiella, Enterobacter, and Proteus species, and enterococci infrequently cause uncomplicated cystitis and pyelonephritis.The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. The etiology of UTI is also affected by underlying host factors that complicate UTI, such as age, diabetes, spinal cord injury, or catheterization. Consequently, complicated UTI has a more diverse etiology than uncomplicated UTI, and organisms that rarely cause disease in healthy patients can cause significant disease in hosts with anatomic, metabolic, or immunologic underlying disease. The majority of community-acquired symptomatic UTIs in elderly women are caused by E coli. However, gram-positive organisms are common, and polymicrobial infections account for up to 1 in 3 infections in the elderly. In comparison, the most common organisms isolated in children with uncomplicated UTI are Enterobacteriaceae. Etiologic pathogens associated with UTI among patients with diabetes include Klebsiella spp., Group B streptococci, and Enterococcus spp., as well as E coli. Patients with spinal cord injuries commonly have E coli infections. Other common uropathogens include Pseudomonas and Proteus mirabilis.Recent advances in molecular biology may facilitate the identification of new etiologic agents for UTI. The need for accurate and updated population surveillance data is apparent, particularly in light of concerns regarding antimicrobial resistance. This information will directly affect selection of empiric therapy for UTI.     

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.     

Urinary tract infections in women

Urinary tract infections in female patients are exceedingly common. One third of all women with an initial UTI demonstrate recurrence, and one third of those recurrences are in the first 6 months. The potential morbidity of RUTIs is high, especially in infants, the elderly, and pregnant patients. Uropathogenic bacteria reside in the rectal vault, colonize the vagina, and then ascend per the urethra into the bladder. These bacteria avidly adhere to uroepithelial cells using pili and can further ascend to the kidneys. Empiric treatment of an initial uncomplicated UTI is acceptable, but recurrences warrant a urine culture and possible radiographic evaluation. Fluoroquinolones are now first-line medications for UTIs, except in geographic areas where resistance to TMP-SMX is still low. Response to therapy should govern the need for additional treatment. Certain motivated patients with three or more UTIs per year should be considered for prophylaxis therapy.     

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.     

An update on the management of urinary tract infections in the era of antimicrobial resistance

Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- β -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin–tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs–producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance. Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options.     

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.     

Antibiotic resistance in isolates recovered from women with community-acquired urinary tract infections presenting to a tertiary care emergency department

ABSTRACTIntroduction:We sought to determine the antibiotic susceptibility of organisms causing community-acquired urinary tract infections (UTIs) in adult females attending an urban emergency department (ED) and to identify risk factors for antibiotic resistance.Methods:We reviewed the ED charts of all nonpregnant, nonlactating adult females with positive urine cultures for 2008 and recorded demographics, diagnosis, complicating factors, organism susceptibility, and risk factors for antibiotic resistance. Odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors were calculated.Results: Our final sample comprised 327 UTIs: 218 were cystitis, of which 22 were complicated cases and 109 were pyelonephritis, including 22 complicated cases. Escherichia coli accounted for 82.3% of all UTIs, whereas Staphylococcus saprophyticus accounted for 5.2%. In uncomplicated cystitis, 9.5% of all isolates were resistant to ciprofloxacin and 24.0% to trimethoprim-sulfamethoxazole (TMP-SMX). In uncomplicated pyelonephritis, 19.5% of isolates were resistant to ciprofloxacin and 36.8% to TMP-SMX. In UTI (all types combined), any antibiotic use within the previous 3 months was a significant risk factor for resistance to both ciprofloxacin (OR 3.34, 95% CI 1.16-9.62) and TMP-SMX (OR 4.02, 95% CI 1.48-10.92). Being 65 years of age or older and having had a history of UTI in the previous year were risk factors only for ciprofloxacin resistance. Conclusions:E. coli was the predominant urinary pathogen in this series. Resistance to ciprofloxacin and TMP-SMX was high, highlighting the importance of relevant, local antibiograms. Any recent antibiotic use was a risk factor for both ciprofloxacin and TMP-SMX resistance in UTI. Our findings should be confirmed with a larger prospective study.     

Urinary tract infections: diagnosis and management in the emergency department

With the emergence of increasing resistance to common antibiotics used to treat urinary tract infections (UTIs), including ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX), the choice of antibiotics for these infections has become more challenging. In this article, the authors review the evidence-based guidelines for the evaluation and treatment of cystitis and pyelonephritis in the emergency department. They review the pathophysiology and describe the initial diagnostic workup, spending some time discussing the urine dipstick. The authors discuss whether hospital antibiograms are useful in making the initial antibiotic choice. The treatment section reviews the current recommendations and also highlights the use of nitrofurantoin in the treatment of uncomplicated UTIs. The authors also discuss the appropriate use of ciprofloxacin and TMP-SMX in the treatment of UTIs.     

Evidence-Based Management of Urinary Tract Infections Across the Lifespan: Current Update

Urinary tract infections (UTIs) are common in a busy primary care setting, accounting for approximately 7 million office visits annually. These infections affect all ages and both sexes, with the highest prevalence in women. The key to management of the uncomplicated UTI depends on the correct diagnosis and pharmacologic agent. Other variables to consider when treating UTIs are uropathogen resistance patterns, patient population, and duration of therapy to name a few. This article presents an evidence-based approach to the diagnosis and treatment of UTIs across the lifespan.     

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.     

Epidemiology of urinary tract infections: incidence,morbidity, and economic costs

Urinary tract infections (UTIs) are considered to be the most common bacterial infection. According to the 1997 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, UTI accounted for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations. Nevertheless, it is difficult to accurately assess the incidence of UTIs, because they are not reportable diseases in the United States. This situation is further complicated by the fact that accurate diagnosis depends on both the presence of symptoms and a positive urine culture, although in most outpatient settings this diagnosis is made without the benefit of culture.Women are significantly more likely to experience UTI than men. Nearly 1 in 3 women will have had at least 1 episode of UTI requiring antimicrobial therapy by the age of 24 years. Almost half of all women will experience 1 UTI during their lifetime. Specific subpopulations at increased risk of UTI include infants, pregnant women, the elderly, patients with spinal cord injuries and/or catheters, patients with diabetes or multiple sclerosis, patients with acquired immunodeficiency disease syndrome/human immunodeficiency virus, and patients with underlying urologic abnormalities. Catheter-associated UTI is the most common nosocomial infection, accounting for >1 million cases in hospitals and nursing homes. The risk of UTI increases with increasing duration of catheterization. In noninstitutionalized elderly populations, UTIs are the second most common form of infection, accounting for nearly 25% of all infections.There are important medical and financial implications associated with UTIs. In the nonobstructed, nonpregnant female adult, acute uncomplicated UTI is believed to be a benign illness with no long-term medical consequences. However, UTI elevates the risk of pyelonephritis, premature delivery, and fetal mortality among pregnant women, and is associated with impaired renal function and end-stage renal disease among pediatric patients. Financially, the estimated annual cost of community-acquired UTI is significant, at approximately $1.6 billion.     

Management of asymptomatic bacteriuria in patients with diabetes mellitus

OBJECTIVE: To review the literature regarding the management of asymptomatic bacteriuria (ASB) in patients with diabetes mellitus. DATA SOURCES: A MEDLINE (1967-June 2003) and bibliographic search of the English-language literature was conducted using the search terms diabetes mellitus, asymptomatic, bacteriuria, and urinary tract infection. DATA SYNTHESIS: ASB occurs in diabetic women more commonly than in non-diabetics and is associated with an increased risk of symptomatic urinary tract infection (UTI) among patients with type 2 diabetes. Symptomatic UTIs tend to follow a more complicated course in diabetics. Despite these independent observations, antimicrobial therapy has not been shown to reduce symptomatic UTIs, pyelonephritis, or hospitalization for UTI. CONCLUSIONS: Available evidence does not support antimicrobial treatment of ASB among patients with diabetes mellitus.     

Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey

OBJECTIVES: To determine the risk factors for community-acquired ciprofloxacin-resistant Escherichia coli urinary tract infection (UTI). METHODS: The study was performed with isolates from community-acquired UTIs collected from 15 centres representing six different geographic regions of Turkey. All microbiological procedures were carried out in a central laboratory. Multivariate analysis was performed for detection of risk factors for resistance. Use of quinolones more than once within the last year, living in a rural area, having a urinary catheter, age >50 and complicated infections were included in the model as variables and logistic regression was performed. RESULTS: A total of 611 gram-negative isolates were studied: 321 were isolated from uncomplicated UTI and 290 were isolated from complicated UTI. E. coli was the causative agent in 90% of the uncomplicated UTIs and in 78% of the complicated UTIs (P < 0.001). Seventeen percent of E. coli strains isolated from uncomplicated cases and 38% of E. coli strains isolated from complicated UTI were found to be resistant to ciprofloxacin. In multivariate analysis, age over 50 [odds ratio (OR): 1.6; confidence interval (CI): 1.08-2.47; P = 0.020], ciprofloxacin use more than once in the last year (OR: 2.8; CI: 1.38-5.47; P = 0.004) and the presence of complicated UTI (OR: 2.4; CI: 1.54-3.61; P < 0.001) were found to be associated with ciprofloxacin resistance. Detection of strains of E. coli producing extended-spectrum beta-lactamase (ESBL) enzymes was two times more common in the patients who received ciprofloxacin than those who did not (15% versus 7.4%). CONCLUSIONS: The increasing prevalence of infections caused by antibiotic-resistant bacteria makes the empirical treatment of UTIs more difficult. One of the important factors contributing to these high resistance rates might be high antibiotic use. Urine culture and antimicrobial susceptibility testing are essential in Turkey for patients with UTI who have risk factors for resistance, such as previous ciprofloxacin use. Fluoroquinolone-sparing agents such as nitrofurantoin and fosfomycin should be evaluated as alternative therapies by further clinical efficacy and safety studies.     

Pathogenesis of urinary tract infections: an update

The pathogenesis of uncomplicated urinary tract infection (UTI) is complex and influenced by many host biological and behavioural factors and by properties of the infecting uropathogens. Most uncomplicated UTIs in women are not associated with underlying functional or anatomical abnormalities of the urinary tract, whereas sexual intercourse, spermicide use, a history of recurrent UTI and recent antimicrobial chemotherapy are important risk factors. A maternal history of UTI and young age at first UTI, as well as sexual intercourse and spermicide use, are risk factors for recurrent UTI in young women. In some young healthy women, especially those with 'low UTI risk' behaviour, features of pelvic anatomy appear to be associated with UTI risk. In postmenopausal women, anatomical and functional characteristics of the genitourinary tract are more strongly associated with UTI risk than in younger women. A genetic predisposition to recurrent UTI is suggested by the association of recurrent UTI in certain age groups with the ABH blood group non-secretor phenotype, a maternal history of UTI and early age at onset of UTI. Virulence determinants of uropathogens are much more important in the normal host than in the host who has a functional or anatomical abnormality of the genitourinary tract.     

Cost-effective management of complicated urinary tract infections

Complicated urinary tract infection (UTI), which often requires hospitalization or prolongs a hospital stay, presents numerous diagnostic and therapeutic challenges. Implementation of effective antimicrobial treatment is vital because of the risk of adverse sequelae due to persistence of infection, relapse, or reinfection. Further, the increasing resistance of common uropathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter species, can complicate the therapeutic outcome. Economic factors also mandate cost-effective therapy. The costs of managing adverse sequelae have placed a significant liability on an already overburdened health care system. Estimates for prolonged hospitalization due to nosocomial UTI are reported as high as $2 billion a year in the United States. When parenteral rather than oral antimicrobial therapy is used, additional health care costs approximate $1000 per day per patient. Given the resistance to commonly used medications and the risk of serious adverse sequelae, clinicians are seeking more appropriate therapy. New oral antimicrobial agents now permit outpatient management of complicated UTIs that formerly required hospitalization for prolonged treatment. Currently, quinolones are recommended as first-line agents for complicated UTI. Reviews of pharmacokinetics, antimicrobial activity, efficacy, and safety of these drugs have noted equipotence or superiority to other antimicrobials, including trimethoprim/sulfamethoxazole. When used appropriately, quinolones provide effective and safe therapy for complicated UTI and offer in vitro efficacy against a broad range of pathogens.