In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.

Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 µg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.

Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults.

An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy). The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%). The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each). Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were > or =10(3) cfu/mL. A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time.

In vitro activity of gemifloxacin against a broad range of recent clinical isolates from the USA.

The antibacterial potencies of gemifloxacin (SB-265805) and 13 comparator compounds were determined by broth microdilution against a panel of 645 Gram-positive and 995 Gram-negative organisms collected from various USA sites. Time-kill studies were performed and postantibiotic effect (PAE) was determined for several organisms using trovafloxacin and ciprofloxacin as comparator compounds. Based on MIC(90)s, gemifloxacin was the most potent compound tested against Gram-positive isolates: Streptococcus pneumoniae (MIC(90) 0. 016 mg/L), Streptococcus agalactiae (0.03 mg/L), Streptococcus pyogenes (0.03 mg/L), viridans streptococci (0.12 mg/L), methicillin-susceptible Staphylococcus aureus (0.03 mg/L), Staphylococcus epidermidis (2 mg/L), Staphylococcus saprophyticus (0. 016 mg/L) and Enterococcus faecalis (2 mg/L). Against Gram-negative isolates, the potency of gemifloxacin was equal to that of levofloxacin and ciprofloxacin and generally better than that of ofloxacin, grepafloxacin, trovafloxacin and nalidixic acid. MIC(90)s for gemifloxacin were: Haemophilus influenzae (6 h at 4 x MIC) and shorter PAEs with E. faecalis (0.1-0.6 h) and K. pneumoniae (0.1-0.2 h). In conclusion, gemifloxacin is a novel quinolone with a broad spectrum of antimicrobial activity. It has substantially improved potency against Gram-positive organisms, especially streptococci, for which gemifloxacin is generally at least eight- to 16-fold more potent than other quinolones tested. It retains the good Gram-negative activity seen with ciprofloxacin and levofloxacin and shows good bactericidal activity and prolonged PAEs.

In vitro antibacterial activity of gemifloxacin and comparator compounds against common respiratory pathogens.

This study investigated the in vitro potency of the novel quinolone agent gemifloxacin (SB-265805), in comparison with other quionolones, beta-lactams, macrolides and trimethoprim- sulphamethoxazole, against a panel of common respiratory pathogens. This panel comprised recent clinical isolates of Streptococcus pneumoniae (n = 347), Haemophilus influenzae (n = 256) and Moraxella catarrhalis (n = 184). Overall, the quinolones were highly active against H. influenzae and were the most potent agents against M. catarrhalis. Gemifloxacin was the most potent quinolone tested against all three species and was four- to 512-fold more potent against pneumococci than trovafloxacin, grepafloxacin, levofloxacin, ciprofloxacin, ofloxacin, gentamicin, cefuroxime, penicillin, ampicillin, clarithromycin, azithromycin or trimethoprim- sulphamethoxazole. Against 19 ofloxacin-intermediate and 52 ofloxacin-resistant strains of S. pneumoniae, gemifloxacin retained activity, and was the only agent tested with MICs of < or =0.5 mg/L. The results of this study demonstrate the excellent in vitro antibacterial activity of gemifloxacin against pathogens commonly associated with respiratory tract infections and suggest that gemifloxacin has significant potential in the treatment of such infections, including those caused by pneumococci considered resistant to other quinolones.

Escherichia coli ATCC 35218 as a quality control isolate for susceptibility testing of Haemophilus influenzae with haemophilus test medium.

Current National Committee for Clinical Laboratory Standards (NCCLS) susceptibility guidelines for quality control testing with Haemophilus influenzae do not include a beta-lactamase-producing strain that could detect the deterioration of the beta-lactamase inhibitor components of amoxicillin-clavulanic acid, ampicillin-sulbactam, and piperacillin-tazobactam. The objective of the study was to determine if comparable quality control results for Escherichia coli ATCC 35218, a beta-lactamase-producing strain, would be produced for the three beta-lactam-beta-lactamase inhibitor agents with Haemophilus test medium and Mueller-Hinton medium. The criteria used in this study to determine if Haemophilus test medium was acceptable for quality control testing of E. coli ATCC 35218 was that 100% of the results obtained with an antimicrobial agent-methodology combination needed to be within the acceptable NCCLS ranges established with Mueller-Hinton medium. The MIC testing results obtained by the broth microdilution and E-test methods with amoxicillin-clavulanic acid and piperacillin-tazobactam were all within the NCCLS ranges; however, the results obtained with ampicillin-sulbactam by both methods were not within the NCCLS ranges. Acceptable results were obtained by the disk diffusion methodology with ampicillin-sulbactam and piperacillin-tazobactam but not with amoxicillin-clavulanic acid. When performing susceptibility testing with H. influenzae with the beta-lactam-beta-lactamase inhibitors, in addition to quality control testing with H. influenzae ATCC 49247, testing of E. coli ATCC 35218 on Haemophilus test medium is an effective way to monitor the beta-lactamase inhibitors in some antimicrobial agent-methodology combinations.