The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens

Abstract

Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection

“…Additionally, an initial acute infection has a 25–40% chance of a recurrent UTI (rUTI) within six months, even with appropriate antibiotic treatment (Czaja et al, 2009; Foxman et al, 2000; Stamm et al, 1991). Further confounding this problem, UPEC, which cause ~80% of such infections, are becoming increasingly antibiotic resistant (Boucher et al, 2009; Chen et al, 2012; Stamm, 2002). Multidrug resistant UPEC increase the risk of UTIs progressing to life-threatening septicemia (Wagenlehner et al, 2015).…”

Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections

“…A recent meta-analysis examined multiple cUTI trials before ASPECT-cUTI and identified microbiological eradication rates at the TOC visit in the microbiological intent-to-treat population of 81% for doripenem, 79% for levofloxacin, and 80.5% for imipenem-cilastatin, confirming that levofloxacin has a place in the armamentarium for cUTI [21]. In an era of increasing and evolving antibiotic resistance, however, decisions about clinical usefulness must be made at the local hospital and individual patient level [22]. …”

A Comparative Study of Efficacy of Pefloxacin Versus Pefloxacin and Alkalinising Agent in the Treatment of Urinary Tract Infection

“…2 Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprimsulfamethoxazole-resistant uropathogens. 3 Among the floroquinolones, pfloxacin is commonly prescribed for the treatment of UTI.…”