gemifloxacin and Gram-Positive-Bacterial-Infections

The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10x MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Quinolones; Thiazoles

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.

Topics: Anti-Infective Agents; Bacteria; Canada; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Naphthyridines

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 -resistant Staphylococcus epidermidis isolates, and coagulase-negative staphylococci.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Bacteremia; Ciprofloxacin; Fluoroquinolones; Gemifloxacin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Piperazines; Quinolines

Gemifloxacin (GEMI), formerly SB-265805 and LB20304, is a newer fluoroquinolone with broad-spectrum activity against a wide variety of bacterial pathogens. The present investigation extended earlier observations by sampling an additional 6790 gram-positive organisms from more than 50 medical centres on three continents. The reference broth microdilution method with recommended medium supplements was used throughout. Selected results (number strains tested; MIC90 for GEMI/trovafloxacin in mg/l; % < or = 1 mg/l for GEMI/trovafloxacin) were: Staphylococcus aureus (3672; 2/2; 86/85), S. epidermidis (404; 1/>4; 92/71), Enterococcus faecalis (630; 4/>4; 76/66), E. faecium (216; > 4/>4; 15/11), Streptococcus pneumoniae (300; 0.06/0.25; 100/97), beta-haemolytic streptococci (150; 0.06/0.25; 100/100) and viridans group streptococci (150; 0.12/0.25; 99/97). Gemifloxacin appeared equal or superior to trovafloxacin in its overall gram-positive spectrum of activity pending a choice of the susceptible breakpoint concentration. Continued in vitro, pharmacodynamic and clinical investigations of gemifloxacin appear warranted.

Topics: Anti-Infective Agents; Europe; Fluoroquinolones; Gemifloxacin; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Naphthyridines; North America; South America