In Vitro Activities of the Novel Cephalosporin LB 11058 against Multidrug-Resistant Staphylococci and Streptococci

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American Society for Microbiology

RESUMO

LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group. This study evaluated the in vitro activity and spectrum of LB 11058 against 1,245 recent clinical isolates, including a subset of gram-positive strains with specific resistant phenotypes. LB 11058 was very active against Streptococcus pneumoniae. The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime, or amoxicillin-clavulanate against both penicillin-intermediate and -resistant S. pneumoniae. LB 11058 was also very active against both β-hemolytic streptococci (MIC at which 90% of isolates were inhibited [MIC90], ≤0.008 μg/ml) and viridans group streptococci (MIC90, 0.03 to 0.5 μg/ml), including penicillin-resistant strains. Among oxacillin-susceptible Staphylococcus aureus, LB 11058 MIC results varied from 0.06 to 0.25 μg/ml (MIC50, 0.12 μg/ml), while among oxacillin-resistant strains LB 11058 MICs varied from 0.25 to 1 μg/ml (MIC50, 1 μg/ml). Coagulase-negative staphylococci showed an LB 11058 susceptibility pattern similar to that of S. aureus, with all isolates being inhibited at ≤1 μg/ml. LB 11058 also showed reasonable in vitro activity against Enterococcus faecalis, including vancomycin-resistant strains (MIC50, 1 μg/ml), and Bacillus spp. (MIC50, 0.25 μg/ml); however, it was less active against Enterococcus faecium (MIC50, >64 μg/ml) and Corynebacterium spp. (MIC50, 32 μg/ml). Against gram-negative pathogens, LB 11058 showed activity against Haemophilus influenzae (MIC90, 0.25 to 0.5 μg/ml) and Moraxella catarrhalis (MIC90, 0.25 μg/ml), with MICs not influenced by β-lactamase production. In conclusion, LB 11058 demonstrated a broad antibacterial spectrum and was highly active against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci.

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