cefclidin and Disease-Models--Animal

We evaluated the effects of a novel cephalosporin, cefclidin (CFCL) and imipenem (IPM), on the eradication of bacteria from the urine, bladder stones and the kidneys, and also on the prevention of the infection stone formations, in our polymicrobial urinary tract infection model of rats associated with bladder stones using IMP-sensitive or IPM-resistant Pseudomonas aeruginosa and Proteus mirabilis as a causative pathogen. CFCL completely eradicated P. mirabilis from the urine and the stone in the short-term regimen (5 days). CFCL completely eradicated both IPM-sensitive P. aeruginosa and P. mirabilis from the urine, the stones and the kidneys as compared to IPM in the long-term regimen (11 days), reflecting the superior antibacterial activity of CFCL. CFCL also significantly prevented the development of infection stones as compared to IPM in the long-term regimen. There was no significant difference in the blood urea nitrogen (BUN) values between the CFCL or IPM-treated and the non-treated groups. The cumulative recovery rate of unchanged CFCL reached 47.3% of the total dosage (20 mg/kg) within 8 hours.

Topics: Animals; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Female; Imipenem; Kidney Calculi; Proteus Infections; Proteus mirabilis; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Urinary Bladder Calculi; Urinary Calculi; Urinary Tract Infections

Healthy volunteers, who were receiving intravenous injections of cefclidin (CFCL) with frequent concomitant use of fluorescein (F) and oxybuprocain (O) in the eyes for measurement of ocular tension, developed drug eruptions at the high frequency of 66.7%. The injection of CFCL alone induced the eruptions at an incidence of 2.8%. The cause of this high eruption rate was thought to be the simultaneous treatment with F and/or O. Therefore, we conducted experiments with CFCL-induced generalized rash (GR) in guinea pigs. Guinea pigs treated with F and O during both the phases of immunization and intraperitoneal elicitation developed CFCL rashes at a high frequency. This CFCL-rash was augmented by the treatment with F during either phase, but not by the treatment with O. Skin testing induced delayed type hypersensitivity (DTH) reaction to O in some animals, but the DTH to F was not induced in animals immunized with F in complete Freund's adjuvant. Furthermore, F augmented rashes induced not only by CFCL but also by other beta-lactam antibiotics such as cefsulodin and sulbenicillin. Accordingly, it is likely that F played a dominant role in the high incidence of drug eruptions during the volunteer trials with measurement of ocular tension.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Disease Models, Animal; Drug Eruptions; Drug Interactions; Fluoresceins; Guinea Pigs; Male