Comparative therapeutic efficacy of clinafloxacin in a Pseudomonas aeruginosa mouse renal abscess model.

A deep-seated Pseudomonas aeruginosa mouse kidney abscess model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral doses, twice daily for five consecutive days, clinafloxacin produced a 4 log decrease in mean bacterial count, the greatest decrease of all drugs tested. The same dosage regimen resulted in complete bacterial eradication in 88% of the kidneys.

Comparative therapeutic efficacy of clinafloxacin in leucopenic mice.

A cyclophosphamide-induced leucopenic mouse model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of ciprofloxacin and imipenem/cilastatin, two clinically relevant standard drugs. Acute systemic infections induced by Escherichia coli, Pseudomonas aeruginosa, a penicillin-resistant Staphylococcus aureus and a methicillin-resistant S. aureus (MRSA) were used to evaluate drug efficacy.

A novel rapid throughput phototolerance screen in mice.

A relatively simple, rapid throughput phototolerance screen in small animals would be very useful in early drug development. It could prioritize or select potential lead compounds from among a number of analogs with similar biological activities. This study describes an in vivo mouse phototolerance screen established for that purpose.

The synthesis, structure-activity, and structure-side effect relationships of a series of 8-alkoxy- and 5-amino-8-alkoxyquinolone antibacterial agents.

A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methyoxy and 8-ethoxy)-quionoline-3-carboxylic acids and 1-cyclopropyl-5-amino-6-fluoro-8-alkoxyquinoline-3-carboxylic acids has been prepared and evaluated for antibacterial activity. In addition, they were also compared to quinolones with classic substitution at C8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxicity assay. The series of 8-methoxyquinolones had antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria equivalent to the most active 8-substituted compounds (8-F and 8-Cl).

In vivo therapeutic efficacies of PD 138312 and PD 140248, two novel fluoronaphthyridines with outstanding gram-positive potency.

PD 138312 and PD 140248 are novel broad-spectrum 7-pyrrolidinyl fluoronaphthyridines with a cyclopropyl or a difluorophenyl substitution at the 1 positions, respectively. They have been demonstrated to have excellent in vitro activity against gram-positive organisms. These compounds were evaluated for their in vivo potencies against acute systemic infections in mice and in a mouse pneumococcal pneumonia model.