Pharmacologic Basis for the Treatment of Pyelonephritis

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Even though physicians have been treating UTIs for 60 years, there has been no standardized approach regarding the rational choice of antimicrobial agents and optimal treatment duration for these infections. This review discusses the pharmacologic basis for the treatment of UTIs. Although most antibiotics concentrate well in the urine and can eradicate most of the sensitive uropathogens that cause lower UTI, antibiotics given for the treatment of pyelonephritis must concentrate and kill bacteria embedded within the renal parenchyma. Investigators once believed that antibiotics must concentrate in sufficient amounts in the urine of infected patients to be effective in treating pyelonephritis. In fact, the efficacy of an antibiotic in the treatment of pyelonephritis is proportional to its capacity to converge in high concentration not only in urine but also in the renal parenchyma because serum and urine levels of antibiotics are poor predictors of the intrarenal levels. Other factors should also be taken into consideration in the management of UTIs, such as the time of day antibiotics are given because significant time-dependent differences have been observed in the pharmacokinetics and rate of excretion in urine of several antibiotics. Finally, the authors review the recent development in the inflammatory response in the urinary tract that may explain the clinical features of UTI and may be useful in the diagnosis as well as better management of UTI.