In vitro antimicrobial activity of RU-59863, A C-7 catechol substituted cephalosporin

Abstract

The in vitro activity of RU-59863, a so-called “fifth generation” catechol cephalosporin, was evaluated against 606 bacterial isolates and compared with the activities of cefotaxime, ceftazidime, cefepime, and cefpirome. RU-59863 demonstrated a broad spectrum of inhibition and superior overall activity than comparators when tested against Enterobacteriaciae (MIC 90 S , 0.015 to 2 μg/ml), Pseudomonas aeruginosa (MIC 90, 0.5 μg/ml), Stenotrophomonas maltophilia (MIC 90, 0.25 μg/ml), Acinetobacter ssp. (MIC 90, 4 μg/ml), and oxacillin-susceptible Staphylococcus ssp. (MIC 90 S , 0.5 to 8 μg/ml). Potent RU-59863 activity was also observed against beta-haemolytic and viridans gr. streptococci (MIC 90 S , 0.12–0.5 μg/ml), Streptococcus pneumoniae (MIC 90 S , 0.03 to 0.5 μg/ml), Haemophilus influenzae (MIC 90, 0.06 μg/ml), and Neisseria gonorrhoeae (MIC 90, 0.06 μg/ml). RU-59863 demonstrated marginal potency against Enterococcus faecalis (MICs 2 to 16 μg/ml) and was inactive against Enterococcus faecium (MIC 90, > 128 μg/ml). Oxacillin-resistant staphylococci were not inhibited by RU-59863 (MIC 90S, 32 to 128 μg/ml). Among the cephalosporins tested, RU-59863 performed best versus ceftazidime-resistant Bush group 1 isolates and strains producing extended spectrum β-lactamases. RU-59863 was also effective against many fluoroquinolone-, aminoglycoside-, and imipenem-resistant isolates. RU-59863 seems to be a significant advance in cephalosporin chemistry and activity, especially against Gram-negative pathogens resistant to current β-lactam therapeutic agents. Further studies of human pharmacokinetics and against clinical infections are encouraged.