Effective Treatments of UTI-Is Intravesical Therapy the Future?

Abstract

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics.

Keywords: antibiotic; intravesical; urinary tract infection; urothelium.

Figure 1

Typical blood plasma antibiotic concentration–time profile after oral administration. The delivered dose is absorbed from the gastrointestinal tract while undergoing simultaneous elimination. Before the concentration peaks (C_max), absorption proceeds at a faster rate than elimination until the absorbable dose is depleted and the drug undergoes distribution across the body compartments and is eliminated by hepatic metabolism and/or renal excretion. MIC: minimum inhibitory concentration; AUC: area under the plasma concentration–time curve.

Figure 2

Mean plasma and urine concentrations of ciprofloxacin after a single oral dose of 500 mg ciprofloxacin. ∆: plasma; O: urine. Urinary concentrations are plotted against the middle of the collection time ranges. Data are redrawn from [30].