Correlation between pharmacokinetic/pharmacodynamic parameters and efficacy for antibiotics in the treatment of urinary tract infection

Antibiotic treatment of urinary tract infection (UTI) depends on the antibiotic being able to inhibit the growth or to kill the bacteria present in the urinary tract. The pharmacokinetics of antibiotics in the urinary tract including the kidneys, the bladder and the prostate are briefly reviewed. The conclusion is that high urinary antibiotic concentrations can eradicate bacteria in the urine, but in the kidney tissue levels must surpass the MIC of the infecting pathogen to achieve effect. Pharmacodynamic studies in UTI are relatively scarce, but recent studies have shown, that as for other types of infections, beta-lactam antibiotic treatment of UTI depends on the T(>MIC), i.e. the time the antibiotic concentration remains above the MIC. This counts for activity against bacteria in the kidneys as well as in the urine. Bacterial counts in the bladder are curiously resistant to the activity of most antibiotics. For drugs with concentration dependent time-kill activity such as the fluoroquinolones and the aminoglycosides, the effect in UTIs is dependent on the peak/MIC ratio or AUC/MIC ratio. The aminoglycosides are difficult to evaluate in this context, since they are bound in high concentrations to the renal cortex. For clinical studies the author reviews the literature for aminopenicillins (ampicillin and amoxycillin) as representatives of beta-lactam antibiotics. Data from 16 studies of uncomplicated UTI encompassing 20 treatment groups showed a significant correlation between the cumulative T(>MIC) and bacteriological cure, such that a cumulative T(>MIC) of 30 h was necessary for a maximal cure rate of 80-90%. Incorporating these data including the T(>MIC) for the aminopenicillins, the optimal dose with minimal consumption of drug can be calculated, i.e. for amoxycillin 500 mg TID for 4 days. Further research is needed to calculate optimal dosages for other types of antibiotics, especially in order to prevent development of resistance.