Efficacy of quinolones in preventing Staphylococcus aureus-induced abscess in mice.

The new fluoroquinolones clinafloxacin, CI-990 (PD 131112/PD 131628), sparfloxacin, and PD 138312 were bactericidal against Staphylococcus aureus with MICs > or = 4-fold lower than ciprofloxacin values. In a murine subcutaneous abscess model (subcutaneous/oral dosing) the new drugs displayed protective activities against five strains which were generally higher (up to 19-fold) than ciprofloxacin values.

In vitro evaluation of cefdinir (FK482), a new oral cephalosporin with enhanced antistaphylococcal activity and beta-lactamase stability.

Cefdinir (FK482), a new oral cephalosporin with enhanced beta-lactamase stability, was tested by microbroth dilution against respiratory, urogenital, and skin and skin-structure bacterial pathogens. Included were beta-lactamase (beta LAC)-producing and -nonproducing isolates. Activity was compared with that of other orally administered beta-lactams. Cefdinir minimum inhibitory concentrations for 90% of isolates MIC90s (microgram/ml) were < or = 0.5 versus beta LAC+/oxacillin-susceptible Staphylococcus, aureus, S. epidermidis, and S. saprophyticus; < or = 0.06 versus Streptococcus groups A and B, and Neisseria gonorrhoeae beta LAC+; 0.125 versus S. pneumoniae penicillin-susceptible and Proteus mirabilis beta LAC+; 0.25 versus beta LAC+ versus strains of Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, and K. oxytoca; 0.5 versus Haemophilus influenzae beta LAC-; 1 versus H. influenzae beta LAC+; 4 versus Legionella pneumophila beta LAC+; and 8 versus Enterococcus faecalis beta LAC-strains. Cefdinir was equally effective against both standard and high inocula of S. aureus strains producing A, B, C, or D beta LAC types. MICs were also generated versus quality-control reference strains.

In vivo therapeutic efficacy of cefdinir (FK482), a new oral cephalosporin, against Staphylococcus aureus and Haemophilus influenzae in mouse infection models.

Cefdinir (FK482), a new oral cephalosporin, displayed potent oral activity versus induced infections in mice. In studies using beta-lactamase-nonproducing (beta LAC-) and -producing (beta LAC+) Staphylococcus aureus strains, respective PD50s (in mg/kg) were 11 and 24 for preventing subcutaneous abscess and 2.7 and 2.3 for preventing lethal systemic infection. In studies using beta LAC- and beta LAC+ Haemophilus influenzae, respective PD50s were 5.8 and 3.1 for preventing lethal systemic infection. Time-kill studies versus H. influenzae showed that 6- to 12-mg/kg dosing was effective in reducing viable counts of these strains in blood by > or = 100-fold by 24 h after challenge. This in vivo performance was comparable to or exceeded values generated by cefaclor, cefpodoxime proxetil, and ampicillin.

In vitro antibacterial activities of PD 138312 and PD 140248, new fluoronaphthyridines with outstanding gram-positive potency.

PD 138312 and PD 140248 are new quinolones with high in vitro activities against a wide spectrum of bacterial species, notably including gram-positive isolates. The respective MICs (in micrograms per milliliter) of PD 138312 and PD 140248 capable of inhibiting > or = 90% of the strains were < or = 0.06 and < or = 0.06 for oxacillin-susceptible and -resistant staphylococci, streptococci (including Streptococcus pyogenes, S. agalactiae, S. pneumoniae, and viridans group streptococci), Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae; 0.125 and 0.03 for Legionella pneumophila; 0.25 and 0.125 for Listeria monocytogenes; 0.25 and 0.25 for Enterococcus faecalis; 0.5 and 0.06 for anaerobic gram-positive cocci; 0.5 and 0.25 for Acinetobacter spp.; 0.5 and 0.5 for members of the family Enterobacteriaceae (excluding Serratia marcescens); 2 and 0.5 for Bacteroides fragilis; 2 and 2 for Serratia marcescens and ciprofloxacin-resistant staphylococci; and 8 and 4 for Pseudomonas aeruginosa.