Development of Pseudomonas aeruginosa resistance to norfloxacin during therapy.

Two elderly patients diagnosed with Pseudomonas aeruginosa urinary tract infections were treated with oral norfloxacin in the recommended dose of 400 mg q12h. Initially, antimicrobial susceptibility data indicated the organisms were sensitive to norfloxacin. Six to eight days into therapy urine cultures became positive for P. aeruginosa once again; this time, however, susceptibility reports indicated the organisms were now resistant to norfloxacin. Since cross-resistance among norfloxacin, other quinolones, and cephalosporins can occur, we recommend repeated urine cultures during and after norfloxacin therapy in elderly patients with complicated P. aeruginosa urinary tract infections.

Relationship between rate and extent of absorption of oral theophylline from Uniphyl brand of slow-release theophylline and resulting serum concentrations during multiple dosing.

The relationship between a standardized assessment of rate and extent of absorption of slow-release theophylline and serum concentrations during multiple dosing was examined in eight healthy adult volunteers. Each subject received single doses of a reference theophylline solution in addition to single and multiple doses of Uniphyl, a "once-a-day" theophylline formulation, administered after an overnight fast and after a large breakfast. Extent of absorption was similar during single and multiple dosing but was significantly greater when dose was taken after breakfast; 68 +/- 7% (mean +/- SEM) and 61 +/- 4% of administered doses were absorbed during single and multiple dosing, respectively, when breakfast was withheld, whereas 83 +/- 4% and 86 +/- 4% of administered doses were absorbed when single and multiple doses, respectively, followed breakfast. Observed mean serum concentrations during multiple dosing approximated values predicted from the single-dose study; mean peak serum concentrations averaged more than twice the tough for both predicted and observed values after both fasting and postprandial administration. These data demonstrate incomplete absorption of theophylline from Uniphyl with greater extent of absorption when Uniphyl is taken after food. The study also provides further documentation that characterization of rate and extent of absorption from single doses permit prediction of the mean serum concentration-time profile during multiple dosing at defined rates of theophylline elimination. This provides the potential to anticipate fluctuations in serum concentrations at clinically relevant elimination rates that deviate from the mean of samples typically used for study.