Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in-vitro activity of gemifloxacin, a new fluoroquinolone, against a wide range (c. 700) of recent clinical isolates, was compared with that of three other fluoroquinolones and other relevant agents. Gemifloxacin inhibited 90% of the Enterobacteriaceae strains at 0.5 mg/L or less, exceptions being Serratia spp. (MIC(90) 1 mg/L) and strains possessing a putative mechanism of resistance to fluoroquinolones. Ninety per cent of Pseudomonas aeruginosa were inhibited by 4 mg/L. Gemifloxacin had good activity against respiratory pathogens, with 90% of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis being inhibited by 0.06 mg/L or less. Staphylococcus aureus (MSSA) were highly susceptible (MIC(90) 0.06 mg/L) but MRSA less susceptible (MIC(90) 8 mg/L) to gemifloxacin. Enterococcus spp. were markedly more susceptible to the study agent than to ciprofloxacin. Gemifloxacin showed good activity against Bacteroides fragilis (MIC(90) 0.5 mg/L) and anaerobic cocci. A tentative in-vitro breakpoint of 0.5 mg/L was studied using a 1 microg disc content for all genera except Pseudomonas where a 5 microg disc content was employed. The false sensitivity reporting rate was 0.5% and false resistance rate was 6.0%, which was considered acceptable. In conclusion, gemifloxacin is a highly active fluoroquinolone that should prove clinically useful in the treatment of a wide range of infections. Susceptibility testing criteria have been developed that should prove robust in a clinical laboratory.
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PMID:The in-vitro activity and tentative breakpoint of gemifloxacin, a new fluoroquinolone. 1055 86

Potent investigational fluoroquinolones require convenient, but accurate, diagnostic tests for initially applied clinical trials. For this purpose, gemifloxacin (formerly SB-265805, LB20304a) was tested by the reference dilution tests and standardized disk diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS) to establish interpretive criteria. For rapid-growing pathogens, 986 organisms were tested by broth microdilution MIC, and 5- and 10-microgram disk diffusion tests. Correlation (r) between 5- and 10-microgram disk zone diameters was 0.99 (y = -0.12 to 0.99x) and the preferred 5-microgram disk zone/MIC scattergram produced a regression of y = 14.8 to 0.41x (r = 0.93). At potential pharmacodynamics (Cmax = 1.3 micrograms/mL for 320 mg dose) validated breakpoints of < or = 0.5 microgram/mL for susceptible and > or = 2 micrograms/mL for resistant, correlate zones of > or = 17 mm and < or = 13 mm produced rare serious interpretive errors (0.1%) and 96.7% absolute categorical agreement. For 304 Streptococcus pneumoniae and 305 strains of other streptococci, the same breakpoints produced 100 and 99.1% categorical accuracy even when testing levofloxacin-resistant (MIC, > or = 4 micrograms/mL) strains. Interpretive breakpoints were proposed for Hemophilus influenzae (300 strains tested), with complete correlation between tests. Etest (AB BIODISK, Solna, Sweden) was compared in all experiments with the fastidious species and showed a trend toward higher values (twofold). Gemifloxacin in vitro susceptibility test methods seem to be accurate and with very acceptable intermethod agreement, supported by previously reported functional quality control guidelines.
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PMID:Development of in vitro susceptibility testing methods for gemifloxacin (formerly LB20304a or SB-265805), an investigational fluoronaphthyridone. 1062 34

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 (</=0.008 mg/L), Moraxella catarrhalis (0.008 mg/L), Escherichia coli (0.016 mg/L), Klebsiella pneumoniae (0.25 mg/L), Klebsiella oxytoca (0.25 mg/L), Enterobacter cloacae (1 mg/L), Enterobacter aerogenes (0.25 mg/L), Proteus spp. (4 mg/L), Serratia spp. (1 mg/L), Citrobacter freundii (2 mg/L), Morganella morganii (0.12 mg/L), Pseudomonas aeruginosa (8 mg/L), Stenotrophomonas maltophilia (4 mg/L) and Acinetobacter spp. (32 mg/L). Gemifloxacin was bactericidal for all organisms studied at 2 and 4 x MIC. The PAE for most strains was in the range 0.7-2.5 h at 2 and 4 x MIC, although longer PAEs were observed with H. influenzae, P. aeruginosa and Proteus vulgaris (>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.
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PMID:In vitro activity of gemifloxacin against a broad range of recent clinical isolates from the USA. 1082 27

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.
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PMID:In vitro antibacterial activity of gemifloxacin and comparator compounds against common respiratory pathogens. 1082 28

The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI.
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PMID:Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection. 1082 37

Gemifloxacin is a fluoroquinolone antibacterial agent which has an enhanced affinity for topoisomerase i.v.. It has potent activity against most Gram-positive bacteria, particularly Streptococcus pneumoniae. Gemifloxacin is over 30-fold more active than ciprofloxacin and 4- to 8-fold more active than moxifloxacin against this pathogen. Gemifloxacin has excellent activity against Haemophilus influenzae and Moraxella catarrhalis, and is unaffected by beta-lactamase production. It is generally 2-fold less active than ciprofloxacin against most Enterobacteriaceae. Atypical respiratory pathogens (Legionella, Mycoplasma and Chlamydia spp.) are highly susceptible to gemifloxacin. Preliminary results from phase II trials show that oral gemifloxacin 320 mg/day produced bacteriological responses of 94.7% in patients with acute exacerbations of chronic bronchitis and 95% of patients with uncomplicated urinary tract infections. Adverse events included nausea, abdominal pain, headache and mild rash in patients and healthy volunteers treated with gemifloxacin 320 mg/day. Gemifloxacin has a low potential for mild phototoxicity (comparable to that of ciprofloxacin).
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PMID:Gemifloxacin. 1085 45

The ability to identify agents with the optimal combination of potency, pharmacokinetics and pharmacodynamics should help to maximize bacteriological cure and thus minimize the potential for selection and spread of resistance. Gemifloxacin demonstrated excellent correlation between efficacy and the AUC0-24h/MIC ratio whereas there was little correlation with time above MIC. Thus, gemifloxacin is similar to other quinolones in that it is the amount of drug present, not the frequency of administration, that determines antibacterial effect. In a neutropenic murine thigh model of infection, caused by Gram-negative bacilli, a AUC0-24h/MIC ratio of approximately 100 was necessary to protect >90% of the animals, which is similar to data reported previously for other quinolones. However, in order to achieve the same protection in an immunocompetent murine infection caused by Streptococcus pneumoniae, the AUC-24h/MIC ratio was approximately 25. The magnitude of this AUC0-24h/MIC ratio did not alter for strains exhibiting penicillin or macrolide resistance. Importantly, when gemifloxacin was examined against strains of S. pneumoniae with well-characterized ciprofloxacin resistance (including mutations in gyrase, parC and parE as well as efflux strains) there was little impact on the in vivo efficacy. Overall, the data showed a trend towards a decrease in the AUC0-24h/MIC ratio for these more resistant strains. The lower AUC0-24h/MIC ratio was especially noticeable for the efflux mutants suggesting that the quinolone efflux mechanism may be down-regulated in vivo and may be of minimal relevance to the clinical activity of gemifloxacin against S. pneumoniae. The efficacy of gemifloxacin, in comparison with other oral agents used to treat respiratory infections, has also been evaluated in a rat model using doses, and therefore AUC0-24h/MIC ratios, that approximate those in man. These data confirm the excellent activity of gemifloxacin against strains of Haemophilus influenzae and S. pneumoniae, including those demonstrating penicillin, macrolide and quinolone resistance.
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PMID:Pharmacodynamics to combat resistance. 1099 96

Gemifloxacin is a new fluoroquinolone that has been shown to possess a broad spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms including methicillin-susceptible and methicillin-resistant staphylococci, Streptococcus pneumoniae, Haemophilus influenzae and most members of the family Enterobacteriaceae. The aim of the present study was to investigate the effect of gemifloxacin on the human intestinal microflora. Gemifloxacin was given in oral doses of 320 mg for 7 days to 10 healthy subjects and 5 subjects received a once-daily dose of matched placebo for 7 days. Faecal samples were collected prior to administration (days -8 and -6), during the administration period (days 2 and 4) and after withdrawal of administration (days 8, 11, 21, 28 and 56). In the aerobic intestinal microflora the numbers of enterobacteria were suppressed during the gemifloxacin administration and the numbers of enterococci and streptococci were also decreased. No other aerobic microorganisms were affected. In the anaerobic microflora the numbers of anaerobic cocci and lactobacilli were suppressed during the gemifloxacin administration while no other changes occurred. The microflora was normalized 49 days after the administration of gemifloxacin had stopped. No selection or overgrowth of resistant bacterial strains or yeasts occurred. The ecological impact of gemifloxacin was shown to be selective and similar to that of ciprofloxacin, levofloxacin and ofloxacin.
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PMID:Impact of gemifloxacin on the normal human intestinal microflora. 1123

The in vitro activity of gemifloxacin (SB-265805) was compared with that of other fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300 clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L inhibited all microorganisms tested. MIC(90) values of gemifloxacin, trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC(90) values of the same fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L, respectively.
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PMID:Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with other fluoroquinolones against respiratory tract pathogens. 1132 84

The in vitro activity of gemifloxacin, a new fluoroquinolone, was compared to three marketed fluoroquinolones; ciprofloxacin, levofloxacin and ofloxacin against over 4,000 recent clinical isolates covering 29 species isolated in the United States and Canada between 1997-1999. Based on MIC(90)s, gemifloxacin was the most potent fluoroquinolone tested against a majority of Gram-positive isolates: Streptococcus pneumoniae, penicillin resistant S. pneumoniae, macrolide resistant S. pneumoniae, ciprofloxacin non-susceptible (MIC > or = 4 microg/mL) S. pneumoniae, S. pyogenes, S. agalactiae, viridans streptococci, Enterococcus faecalis, methicillin susceptible Staphylococcus aureus, methicillin resistant S. aureus, S. epidermidis, S. hemolyticus, and S. saprophyticus. Against Enterobacteriaceae and aerobic non-Enterobacteriaceae Gram-negatives, gemifloxacin was usually comparable to ciprofloxacin and levofloxacin and more potent than ofloxacin for the following species: Citrobacter freundii, Enterobacter aerogenes, E. cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, P. vulgaris, Providencia stuartii, Serratia marcescens, Acinetobacter lwoffii, A. baumannii, Burkholderia cepacia, Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Gemifloxacin was generally 16-64 fold more potent than the other fluoroquinolones tested against Gram-positive organisms and retains excellent activity comparable with ciprofloxacin and levofloxacin against a majority of Gram-negative pathogens.
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PMID:Comparative in vitro activity of gemifloxacin, ciprofloxacin, levofloxacin and ofloxacin in a North American surveillance study. 1144 64


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