Ciprofloxacin is a new antibacterial agent of the 4-quinolone group. With an agar dilution technique we compared its activity on 365 clinical isolates with those of norfloxacin, nalidixic acid, ampicillin, mezlocillin, cefadroxil, cefuroxime, ceftazidime, ceftriazone , cefotaxime, latamoxef (moxalactam), and gentamicin. Ciprofloxacin was overall the most active agent tested against aerobic Gram-negative species, with the MIC90 values for all species being below 1 mg/l (excepting Providencia stuartii with 4 mg/l), and the large majority being below 0.12 mg/l. Many of the strains were selected on the basis of resistance to beta-lactam agents or gentamicin, and ciprofloxacin was also active against these. There was little difference in the activity of ciprofloxacin at inocula of 10(4) or 10(6) cfu. Strains with higher MIC's of the related agents norfloxacin and nalidixic acid were less susceptible to ciprofloxacin . Ciprofloxacin was less active against Gram-positive species (typical MIC90 values were 0.5 or 1 mg/l) and obligate anaerobes (4 mg/l for Bacteroides fragilis). The activity of ciprofloxacin in broth dilution tests was little affected by pH over the range 6.0-8.0, or by human serum or tissue fluid; its activity was reduced by the presence of urine. Binding to human serum protein was 20-28%. Ciprofloxacin was rapidly bacterial in broth at concentrations near to its MICs. By exposure to subinhibitory concentrations of ciprofloxacin it was possible to increase its MIC for bacteria in daily subcultures. The final MIC values after ten days were often about 16-fold greater than those observed initially.

Identification of Capnocytophaga facilitates appropriate, and in most cases effective, antimicrobial therapy.

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Levels of ciprofloxacin in serum and sputum were studied for eight patients with cystic fibrosis who were infected with Pseudomonas aeruginosa. Patients were studied in a steady state on a dosage of 500 mg every 8 h. Peak levels in serum ranged from 1.27 to 5.6 mg/liter (mean, 3.16 +/- 1.27), and absorption was rapid, the time to peak concentration ranging from 0.5 to 3.0 h (mean, 1.5 +/- 0.9). The antibiotic penetrated sputum well, achieving areas under the curve of approximately 46% of those obtained in serum.

Aims-This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. Methods-Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.30/o topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. Results-Intracorneal concentrations of ofloxacin (geometric mean 0-81 mg kg-1) were significantly higher than both ciprofloxacin (0-60 mg kg-1; p=0.048) and norfloxacin (0.54 mg kg-1; p=0.012).Ciprofloxacin and norfloxacin concentrations did not differ significantly (p=0*33).Conclusions-Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin. (BrJ Ophthalmol 1995; 79: 606-609)

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease.

The pharmacokinetics of cefotaxime were investigated in human volunteers given constant intravenous infusions, intravenous bolus, and intramuscular doses of the drug. After intravenous dosing, the plasma levels of cefotaxime declined in a biphasic manner with a terminal half-life varying between 0.92 and 1.65 hr. Moreover, the pharmacokinetics were linear up to at least a 2.0 g dose for volume of distribution based on area (23.3-31.3 l), plasma clearance (249-2.88 ml/min), and renal clearance (151-177 ml/min). Renal tubular secretion of intact cefotaxime and each of its metabolites was demonstrated by its interaction with probenecid, although the ratio of drug to metabolites ultimately excreted in urine after probenecid was similar to that seen normally (54 +/- 6, 19 +/- 4, 6.5 +/- 0.7 and 5.5 +/- 0.7% for cefotaxime, DACM, M2, and M3, respectively, when calculated as a percentage of the dose). The observed half-lives of DACM, M2, and M3 were 2.3 +/- 0.4, 2.2 +/- 0.1 and 2.2 hr, respectively. However, when the true half-life of DACM was calculated (0.83 +/- 0.23 hr) it was not only significantly shorter than that observed but also shorter than that for intact cefotaxime. The plasma clearance of DACM (744 +/- 226 ml/min) was much higher than that of cefotaxime while the volume of distribution was of a similar order (56 +/- 24 l). When administered intramuscularly, there was good absorption of cefotaxime from the site of injection (92-94%) giving maximum plasma levels of the drug of between 30 and 35 mg/l at approximately 40 min after dosing. Thereafter, the plasma levels of cefotaxime declined in a monophasic manner with a half-life (1.0-1.2 hr) similar to that of the terminal half-life seen after intravenous administration. Lidocaine had no significant effect on either its absorption or elimination kinetics.

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.