Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option

Abstract

Symptomatic urinary tract infections (UTIs) are a major public health concern in the developed world, accounting for almost 8 million annual outpatient and emergency department visits in the US alone, while also representing one of the most common hospital-acquired infections. The vast majority of uncomplicated UTIs are caused by the Gram-negative bacillus Escherichia coli, with other pathogens including enterococci, Staphylococcus saprophyticus, Klebsiella spp. and Proteus mirabilis. Effective management of UTIs in both the inpatient and outpatient settings has been complicated by the fact that many uropathogenic strains have developed resistance to antimicrobials, including cotrimoxazole (trimethoprim/sulfamethoxazole), the current first-line treatment for uncomplicated UTIs in the US and many other countries. In some countries, other antimicrobial therapies, such as trimethoprim and nitrofurantoin, are also used for treatment of uncomplicated UTIs. Antimicrobial resistance has been associated with an increased rate of clinical failure, and reports from Canada and the US indicate that the prevalence of cotrimoxazole resistance exceeds 15% and can be as high as 25%.The emergence and dissemination of antimicrobial resistance can be reduced with the use of agents that have favourable pharmacokinetic/pharmacodynamic profiles and convenient dose administration regimens that facilitate patient adherence and, therefore, pathogen eradication. Fluoroquinolones have been used successfully to treat a wide range of community- and hospital-acquired infections, and the rates of fluoroquinolone resistance have remained low. Use of fluoroquinolones is recommended for uncomplicated UTIs in areas where the incidence of cotrimoxazole resistance exceeds 10%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin is a widely used fluoroquinolone with high bactericidal activity against uropathogens and well established clinical efficacy in the treatment of UTIs. A new, extended-release formulation of ciprofloxacin (Cipro XR) provides systemic drug exposure comparable with that achieved with twice-daily administration of conventional, immediate-release ciprofloxacin, while also attaining higher maximum plasma concentrations with less interpatient variability. Therapeutic drug concentrations with extended-release ciprofloxacin are established immediately after dose administration and maintained throughout the 24-hour dosage interval, permitting convenient, once-daily treatment. Clinical trial results confirm that extended-release ciprofloxacin is as safely used and effective as the conventional, immediate-release formulation of ciprofloxacin in patients with uncomplicated UTIs, complicated UTIs or acute uncomplicated pyelonephritis. These findings support the use of extended-release ciprofloxacin as a well tolerated, effective and convenient therapy for UTIs, which may improve patients' adherence to therapy and, thereby, reduce the risk of infection recurrence and emergence of antimicrobial resistance.