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.

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The MICs and MBCs of 21 antimicrobial agents were determined for 103 strains of Listeria monocytogenes isolated in the UK and 27 strains of other Listeria species. Ampicillin, penicillin, azlocillin, imipenem, gentamicin, netilmicin, amikacin, erythromycin, rifampicin, trimethoprim, clindamycin and vancomycin had good activity, while cephalothin, chloramphenicol, ciprofloxacin and ofloxacin were less active, and cefuroxime, enoxacin, norfloxacin and fosfomycin were the least active. Tetracycline had good activity against many strains, but the MIC was high for some. Unlike the other Listeria species tested, Listeria ivanovii was susceptible to fosfomycin. Inoculum size and media employed were shown to affect the MBC, tryptose phosphate broth yielding higher MBCs than Mueller-Hinton or Isosensitest broths.

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.

The activity of enoxacin against 362 clinical bacterial isolates in comparison with norfloxacin, nalidixic acid, ampicillin, latamoxef (moxalactam) and gentamicin was tested by an agar dilution method. Typical MICs for enterobacteria lay between 0.12 and 1.0 mg/l. Enterobacter spp. and Serratia spp. tended to be more resistant. Enoxacin was also active against Pseudomonas aeruginosa (mean MIC 0.5 mg/l) and highly active against fastidious Gram-negative aerobes. Typical MICs for Staphylococcus aureus were 1-2 mg/l while streptococci were more resistant (16-32 mg/l). Enoxacin had no useful activity against Bacteroides fragilis and Clostridium perfringens. Enoxacin was generally more active at pH 8 than pH 6, and in broth than in urine. It was bactericidal in its action. Daily serial passage from growth in broth containing enoxacin caused decreased sensitivity which was limited to four- to 16-fold greater than the original MIC. Enoxacin was about half as active as norfloxacin against enterobacteria, equally active against staphylococci, and some two to four times less active against streptococci.