How to select the right drugs for UTIs
The development of antibiotics in the late 1930s represents the single most important advance in the management of UTIs. At the time of its introduction, antimicrobial therapy was expected by many clinicians to reduce UTI risk to nothing more than a historic footnote. Yet these infections are a leading cause of patient morbidity and a primary reason for office visits. In the United States, UTI management accounts for nearly 7 million office visits per year plus approximately 1 million visits to emergency departments. Prostatitis accounts for another 2 million office visits.
Widespread use of antimicrobial therapy over the past decades has contributed to shifts in the causative organisms for UTIs. These shifts are characterized in two ways: by the emerging awareness of causative pathogens and by the evolution of treatment-resistant variants. This constantly evolving spectrum of uropathogens demands repeated reassessment of recommendations for empiric therapy. Current treatment guidelines for genitourinary infections (discussed later in this review) advocate taking into account safety, cost, and expected efficacy, considering infection etiology and regional variability in bacterial resistance. However, antimicrobial stewardship — the use of antibiotics with an eye toward limiting future resistance development — should also be paramount in judicious treatment selection. An additional consideration is the need to minimize “collateral damage” — the effect of antibiotics on nontarget systems or tissues.
Principles for antibiotic selection
Treatment for UTIs and chronic bacterial prostatitis (CBP) is often initially empiric, with selection of an appropriate agent based on multiple variables that include pharmacokinetics, safety, antimicrobial spectrum of activity, evidence from clinical trials, and local patterns of resistance. Agents used to treat cystitis and complicated UTIs need to achieve urinary levels exceeding the pathogen's minimum inhibitory concentration. Due to the risk for urosepsis, attainment of bactericidal levels in plasma is also important in the treatment of complicated UTIs and acute pyelonephritis, while efficacy in treating these more serious infections mandates effective tissue penetration as well. To attain high levels in the prostate and, specifically, the prostate fluid for effective management of CBP, an antimicrobial agent must have high lipid solubility, low serum protein binding, and be nonionized in biologic fluids.1 Maintenance of therapeutic concentrations for an extended duration in target tissues and fluids is also requisite for optimizing efficacy, as well as reducing dosing frequency — an aspect that is commonly understood to enhance patient compliance.
Clearly, agents used to treat UTIs and CBP should provide predictable coverage of expected pathogens. Ideally, however, they should do so without adversely affecting normal vaginal and bowel flora. Treatments that eradicate uropathogens but not commensal organisms from vaginal and intestinal reservoirs are associated with reduced risks of urinary tract reinfection, vaginal yeast infections, and antibiotic-associated diarrhea.2
The ideal antimicrobial spectrum of agents for treating UTIs varies according to the intended use. In uncomplicated UTIs, Escherichia coli is by far the predominant pathogen (80%-90%) followed in frequency by Staphylococcus saprophyticus (5%-15%).3,4 In complicated UTIs and CBP, E. coli is also a frequent isolate, but both infections have a more diverse etiology than uncomplicated UTIs, with gram-positive organisms (Enterococcus spp.,Staphylococcus spp.) playing a more prominent role.4-6 Therefore, while an appropriate agent for the treatment of uncomplicated UTIs may have a fairly narrow spectrum of activity, greater broad-spectrum coverage is important for empirically selected antibiotics used to treat complicated UTIs and CBP.