The nonrecirculating isolated perfused rat liver was used to study biliary antibiotic excretion by the liver in a steady-state, controlled environment in which bile flow, bile salt output, and antibiotic delivery were maintained under constant conditions. The effects of piperacillin, ampicillin, and gentamicin on bile flow and bile salt output were analyzed; none altered bile salt output, and only high concentrations of piperacillin (100 micrograms/mL) increased bile flow. The ratio of antibiotic concentration in bile and perfusate depended on the type of antibiotic and perfusate concentration. Piperacillin infusions at perfusate concentrations of 50 or 100 micrograms/mL (in the presence of 60 microM taurocholate) yielded bile to perfusate ratios of 112 +/- 10 versus 49 +/- 3, respectively. Using similar perfusate, the concentration ratios for ampicillin (20 micrograms/mL) and gentamicin (10 micrograms/mL) were only 3.4 +/- 0.5 and 0.5 +/- 0.1, respectively. By altering the perfusate to contain either 60 microM or 240 microM taurocholate, we found variance in bile salt output from 27 +/- 1 to 115 +/- 2 mumol/h, yet this alteration had little effect on the output of ampicillin (perfusate concentration of 20 micrograms/mL), 73 +/- 7 versus 74 +/- 12 micrograms/h, or piperacillin (perfusate concentration 100 micrograms/mL), 10 +/- 1 versus 11 +/- 2 mg/h. Thus, it appears ampicillin and piperacillin are excreted into bile at high concentrations by bile salt-independent pathways. Partial biliary obstruction (6 cm H2O) results in significant decreases in bile volume. Infusion of 50 micrograms/mL of piperacillin resulted in increased biliary flow that approached nonobstructed values. Obstruction resulted in significant decreases in bile piperacillin concentration. Whether the choleretic effect of high concentrations of piperacillin has any clinical significance in nonobstructed or obstructed conditions remains to be established.

The efficacy of ciprofloxacin (Bay o 9867), a promising new quiiolone, was compared with the efficacy of azlocillin plus tobramycin in rabbits with experimentally induced Pseudomonas aeruginosa endocarditis. The MBCs of ciprofloxacin, azlocillin, and tobramycin against the test strain were 0.5, 8, and 4 JLg/ml respectively.Ciprofloxacin at a concentration of 50 mg/kg or azlocillin at a concentration of 200 mg/kg in combination with tobramycin at a concentration of 5 mg/kg was administered intramuscularly at 8-h intervals for 4 days. Both regimens produced median peak serum bactericidal titers of 1:8. The concentrations of ciprofloxacin, azlocillin, and tobramycin in serum, 1.8 ± 0.7, 154 ± 48, and 9.1 ± 2.4 ,g/ml (mean ± standard deviation), respectively, closely approximated concentrations found in humans after accepted dosages. At the end of treatment, the titers of P. aeruginosa were 3.0 ± 1.6 log10 CFU/g of vegetation (mean ± standard deviation) for recipients of ciprofloxacin and 3.2 ± 1.3 log10 CFU/g of vegetation for recipients of azlocillin plus tobramycin. These values compared with control titers of 7.3 ± 1.6 CFU/g. These data indicate that at the doses used, ciprofloxacin was as effective as azlocillin plus tobramycin in the treatment of P. aeruginosa endocarditis in rabbits. Since the latter drug combination has proven efficacy, ciprofloxacin deserves further evaluation in the therapy of systemic infections in animal models and in humans.Ciprofloxacin (Bay o 9867) is a new quinolone carboxylic acid derivative currently being developed for oral and parenteral use (19). Like nalidixic acid, to which it is structurally related, it is active against most members of the family Enterobacteriaceae in vitro. However, ciprofloxacin is much more active against these organisms and also has an extended spectrum of activity against Pseudomonas aeruginosa, Neisseria gonorrhoeae, Staphylococcus aureus, Haemophilus influenzae, and a wide variety of other organisms (3,7,8,10,19 851, 1983). Because of its broad spectrum, potency, and oral efficacy, ciprofloxacin could be useful for oral treatment of systemic infections that in the past required parenteral therapy (e.g., osteomyelitis). Because of the remarkable susceptibility of Pseudomonas sp. to ciprofloxacin, parenteral use of this quinolone might offer advantages over currently available therapy for such infections, in which resistance, drug allergy, and drug toxicity are frequent problems.The observations described above on the antimicrobial activity and pharmacology of ciprofloxacin led us to compare the activity of this quinolone with that of azlocillin plus tobramycin, a combination which has previously been * Corresponding author. t Present address: Instituto Di Clinica, Delle Malattie Infettive, Policlinico S. Matteo, Universita Di Pavia, 27100 Pavia, Italy. shown to be an effective regimen in this model (14) of experimentally induced P. aeruginosa endocarditis in rabbits. MATERIALS AND METHODSIn vitro studies. All 149 P. aeruginosa strains studied were ...