scholarly journals In Vitro Activity of Cephalosporin RWJ-54428 (MC-02479) against Multidrug-Resistant Gram-Positive Cocci

2002 ◽  
Vol 46 (2) ◽  
pp. 321-326 ◽  
Author(s):  
Alan P. Johnson ◽  
Marina Warner ◽  
Michael Carter ◽  
David M. Livermore

ABSTRACT RWJ-54428 (MC-02479) is a novel cephalosporin that binds to penicillin-binding protein (PBP) PBP 2′ (PBP 2a) of methicillin-resistant staphylococci. Its in vitro activity was assessed against 472 gram-positive cocci, largely selected as epidemiologically unrelated isolates with multidrug resistance. The MIC at which 50% of isolates are inhibited (MIC50) and MIC90 of RWJ-54428 for methicillin-resistant Staphylococcus aureus (MRSA) were 1 and 2 μg/ml, respectively, whereas they were 0.5 and 0.5 μg/ml, respectively, for methicillin-susceptible S. aureus. The MIC50 and MIC90 were 1 and 4 μg/ml, respectively, for methicillin-resistant coagulase-negative staphylococci (MRCoNS), whereas they were 0.25 and 1 μg/ml, respectively, for methicillin-susceptible isolates. The highest MICs for MRSA and MRCoNS isolates were 2 and 4 μg/ml, respectively. The MIC50 and MIC90 of RWJ-54428 for Enterococcus faecalis were 0.5 and 1 μg/ml, respectively, but they were 4 and 8 μg/ml, respectively, for Enterococcus faecium. For penicillin-susceptible, -intermediate, and -resistant pneumococci, the MIC90s of RWJ-54428 were 0.03, 0.25, and 0.5 μg/ml, respectively, with the highest MIC for a pneumococcus being 1 μg/ml, recorded for a strain for which penicillin and cefotaxime MICs were 8 and 4 μg/ml. MICs for Lancefield group A, B, C, and G streptococci were ≤0.008 μg/ml; those for viridans group streptococci, including isolates not susceptible to penicillin, were from 0.015 to 0.5 μg/ml. RWJ-54428 did not select resistant mutants of MRSA or enterococci in challenge experiments and has the potential to be useful for the treatment of infections caused by gram-positive cocci.

2005 ◽  
Vol 49 (9) ◽  
pp. 3933-3936 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Wojciech Kamysz ◽  
Carmela Silvestri ◽  
Alberto Licci ◽  
...  

ABSTRACT The in vitro activity of uperin 3.6, alone or combined with six antibiotics, against gram-positive cocci, including Rhodococcus equi, methicillin-resistant staphylococci, and vancomycin-resistant enterococci, was investigated. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when uperin 3.6 was combined with clarithromycin and doxycycline.


2006 ◽  
Vol 50 (6) ◽  
pp. 2255-2257 ◽  
Author(s):  
Paul A. Wickman ◽  
Jennifer A. Black ◽  
Ellen Smith Moland ◽  
Kenneth S. Thomson

ABSTRACT The in vitro activity of the novel quinolone DX-619 was compared to those of currently available quinolones against U.S. clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Streptococcus pyogenes, and Streptococcus pneumoniae. DX-619 was the most potent quinolone overall, indicating possible utility as an anti-gram-positive quinolone.


2004 ◽  
Vol 48 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Helio S. Sader ◽  
David M. Johnson ◽  
Ronald N. Jones

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 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.


2000 ◽  
Vol 44 (3) ◽  
pp. 802-805 ◽  
Author(s):  
Dwight Hardy ◽  
Daniel Amsterdam ◽  
Lionel A. Mandell ◽  
Coleman Rotstein

ABSTRACT The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistantStaphylococcus epidermidis isolates, and coagulase-negative staphylococci.


2013 ◽  
Vol 41 (3) ◽  
pp. 213-217 ◽  
Author(s):  
Russell Hope ◽  
Aiysha Chaudhry ◽  
Rachael Adkin ◽  
David M. Livermore

2010 ◽  
Vol 36 (2) ◽  
pp. 111-113 ◽  
Author(s):  
Carmen Betriu ◽  
Esther Culebras ◽  
María Gómez ◽  
Fátima López-Fabal ◽  
Iciar Rodríguez-Avial ◽  
...  

1999 ◽  
Vol 10 (2) ◽  
pp. 122-127 ◽  
Author(s):  
Donald E Low ◽  
Joyce de Azavedo ◽  
Canadian Bacterial Surveillance Network ◽  
Ross Davidson

OBJECTIVE: To determine the in vitro activity of cefepime against multidrug-resistant Gram-negative bacilli and Gram-positive cocci obtained from an ongoing cross-Canada surveillance study.DESIGN: Clinical isolates of aerobic Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, viridans group streptococci andStreptococcus pneumoniaewere collected from laboratories serving hospitals, nursing homes and physician offices in the community from across Canada during 1996 and 1997. Laboratories were asked to submit only clinically relevant nonduplicate isolates for susceptibility testing. In vitro antimicrobial susceptibility testing was carried out on all isolates of Gram-negative and viridans group streptococci.S pneumoniaewere characterized as penicillin susceptible, intermediately resistant or highly resistant. Nonsusceptible isolates were defined as being intermediately or highly resistant (minimal inhibitory concentrations [MIC] greater than 0.06 mg/L). Only isolates ofS pneumoniaethat were nonsusceptible to penicillin were selected for further study. MICs were determined using a microbroth dilution technique according to the National Committee of Clinical Laboratory Standards.RESULTS: A total of 727 Gram-negative bacilli samples were collected. No resistance to cefepime was detected withCitrobacter freundii,Serratia marcescens,Morganella morganiiandEnterobacterspecies. Of these strains,Enterobacterspecies andC freundiiwere the most resistant to ceftazidime, cefotaxime and ceftriaxone with MIC90Sof 32 mg/L or greater and resistance rates of 6% or greater. Resistance rates ofPseudomonas aeruginosaandAcinetobacterspecies to cefepime were 4.8% and 3%, respectively. The two organisms had similar rates of resistance to ceftazidime. Less than 3% of the Gram-negative bacilli were resistant to imipenem and meropenem. There were 153 viridans group streptococci, of which 22 (14.4%) were resistant to penicillin. Of 1287S pneumoniaesamples, 193 (15%) were nonsusceptible to penicillin. Cefepime, ceftriaxone and cefotaxime had comparable activity against all isolates of viridans group streptococci andS pneumoniae.CONCLUSIONS: Cefepime demonstrated excellent in vitro activity against Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, and had equal or superior activity versus comparator beta-lactams against all isolates of viridans group streptococci andS pneumoniae.


Sign in / Sign up

Export Citation Format

Share Document