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Uncomplicated urinary tract infection in women
Acute uncomplicated urinary tract infections (uUTIs) occur in non-pregnant women with normal genitourinary tracts.
These uUTIs are one of the most common bacterial infections, a frequent presenting complaint for women visiting their family practitioners. Short courses of antibiotic therapy are generally adequate treatment, and beginning empiric therapy without obtaining a urine specimen is recommended. The evolution of antimicrobial resistance in community-acquired Escherichia coli, however, requires continuing reevaluation of empiric antimicrobial therapy.
Widespread empiric use of antibiotics, while convenient, potentially contributes to development of antimicrobial resistance. With concerns about increasing resistance in common community-acquired infections, “antimicrobial stewardship” (using antibiotics in a way that helps limit development of resistance) must also be considered. This review addresses antimicrobial management of uUTIs in the context of evolving antimicrobial susceptibility and family practitioners’ use of guidelines for managing these infections.
For several decades, trimethoprim-sulfamethoxazole (TMP/SMX), or trimethoprim alone, have been first-line therapy for uUTI. These agents are effective as 3-day therapy, but adverse reactions, particularly allergic reactions to sulfa, sometimes occur and are occasionally serious. For women infected with susceptible E coli, cure rates of 90% to 95% are achieved with 3 days’ therapy.
Nitrofurantoin is a narrow-spectrum antimicrobial with no systemic activity. It is indicated only for treatment of uUTI caused by E coli and Staphylococcus saprophyticus, the two pathogensisolated from 95% of all uUTIs. Nitrofurantoin has been used for treating uUTIs for more than 50 years and has had continuing safety and efficacy. Early formulations were associated with substantial adverse effects of the gastrointestinal system, but the current macrocrystalline formulation is well tolerated. Nitrofurantoin cures 85% to 90% of uUTIs with a 7-day course,16 but only 70% to 80% of uUTIs when given as a 3-day course.
Fluoroquinolones including norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, and gatifloxacin, are effective as 3-day therapy and are well tolerated. For infection with susceptible organisms, outcomes with 3-day fluoroquinolone therapy are similar to outcomes with TMP/SMX: a 90% to 95% cure rate. Fluoroquinolones have been evaluated as single-dose therapy, but were shown to have limited efficacy against S saprophyticus with this abbreviated regimen, so single-dose therapy is not recommended. This class of antimicrobial is also important for treating many other infections, including severe infections of the urinary tract and other sites in the body.
Fosfomycin given as a single dose is also marketed for uUTI in North America. There is limited experience with this agent in Canada, but clinical trials suggest it is slightly less effective than other first-line agents, with a cure rate of about 70%. Cephalosporins have a role in treating urinary tract infections, particularly in pregnant women, but are not recommended for empiric therapy because of the relatively high rates of resistance and lower efficacy, especially with short-course therapy.
Evolution of resistance and choice of empiric therapy
The continuing evolution of antimicrobial resistance in community-acquired E coli requires repeated reassessment of recommendations for first-line empiric therapy for uUTI. Practitioners always need to balance antimicrobial selection for optimal patient outcome with the potential for contributing to further antimicrobial resistance through widespread empiric use. The prevalence of resistance at which first-line empiric therapy should be modified is unknown. The Infectious Diseases Society of America’s guidelines suggest that 10% to 20% is an appropriate benchmark, but acknowledge no specific data support this recommendation. Prescribing behaviour suggests that, over the past decade, primary care physicians have altered their approach to first-line therapy for uUTI: TMP/SMX prescriptions for uUTI have declined, while fluoroquinolone prescriptions have increased.
Level I evidence suggests that TMP/SMX, or trimethoprim by itself for women with sulfa allergies, remains optimal first-line empiric therapy where organisms are known or assumed to be susceptible. Thus, where resistance prevalence is lower than 20%, as it appears to be in Canada currently, TMP/SMX should remain the drug of choice for empiric therapy.29 Women with recurrent infections who have received TMP/SMX within 3 months are more likely to have resistant organisms, so alternative empiric therapy is likely appropriate for these patients39 (based on level II evidence).
When antimicrobial resistance or patients’ intolerance to TMP/SMX is of concern, nitrofurantoin, a fluoroquinolone, or fosfomycin are alternative medications. Level I evidence indicates that nitrofurantoin is an effective alternative for empiric therapy when given for 7 days. Use of nitrofurantoin also alleviates concerns about the emergence of resistance. Studies are exploring whether a 5-day course of nitrofurantoin therapy is as effective as a 7-day course. While fluoroquinolones are highly effective (based on level I evidence), widespread empiric use of these agents might promote antimicrobial resistance in organisms that cause severe infections, including organisms that cause infections outside the urinary tract, such as Streptococcus pneumoniae. It has been suggested that widespread empiric use of fluoroquinolones for uUTI should be avoided as a strategy for limiting resistance and prolonging the efficacy of this class of antibiotics for more serious infections. Fosfomycin has not been used much in North America, and the role of this agent remains unclear.
Conclusion
For treatment of uUTI, narrow-spectrum antimicrobials are appropriate, given the consistent bacteriology, and are preferred, given concerns about antimicrobial resistance. In most parts of Canada, TMP/SMX, trimethoprim alone, or nitrofurantoin are the agents of choice for uUTI. Use of narrow-spectrum antimicrobials is also consistent with the principles of antimicrobial stewardship. Use of broad-spectrum agents, such as the fluoroquinolones, might promote resistance that will negatively affect not only treatment of uUTI, but also treatment of other, more serious, infections. Fluoroquinolones should not be considered first-line therapy. The continuing evolution of antimicrobial resistance requires that timely information describing this resistance is generated and disseminated effectively to practitioners.