title: In vitro activities of the novel cephalosporin LB 11058 against multidrug-resistant Staphylococci and Streptococci.
abstract: 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 beta-hemolytic streptococci (MIC at which 90% of isolates were inhibited [MIC(90)], </=0.008 micro g/ml) and viridans group streptococci (MIC(90), 0.03 to 0.5 micro g/ml), including penicillin-resistant strains. Among oxacillin-susceptible Staphylococcus aureus, LB 11058 MIC results varied from 0.06 to 0.25 micro g/ml (MIC(50), 0.12 micro g/ml), while among oxacillin-resistant strains LB 11058 MICs varied from 0.25 to 1 micro g/ml (MIC(50), 1 micro g/ml). Coagulase-negative staphylococci showed an LB 11058 susceptibility pattern similar to that of S. aureus, with all isolates being inhibited at </=1 micro g/ml. LB 11058 also showed reasonable in vitro activity against Enterococcus faecalis, including vancomycin-resistant strains (MIC(50), 1 micro g/ml), and Bacillus spp. (MIC(50), 0.25 micro g/ml); however, it was less active against Enterococcus faecium (MIC(50), >64 micro g/ml) and Corynebacterium spp. (MIC(50), 32 micro g/ml). Against gram-negative pathogens, LB 11058 showed activity against Haemophilus influenzae (MIC(90), 0.25 to 0.5 micro g/ml) and Moraxella catarrhalis (MIC(90), 0.25 micro g/ml), with MICs not influenced by beta-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.
authors.affiliation: The JONES Group/JMI Laboratories, North Liberty, Iowa 52317, USA. sader@jmilabs.com
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: David M
authors.initials: DM
authors.lastname: Johnson
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects; D006193:Haemophilus influenzae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D013210:Staphylococcus / Q000187:drug effects*; D013291:Streptococcus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C481663:LB 11058