Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular activity of ABT-773 against Legionella pneumophila was compared with azithromycin and ciprofloxacin using HL-60 cells. Against L. pneumophila ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015, ciprofloxacin 0.03 and azithromycin 0.03. At 48 h, the mean percentage inhibition was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773; 38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/- 9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin. In this study, all three agents were highly active, with ABT-773 demonstrating similar activity to azithromycin against L. pneumophila.
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PMID:Intracellular activity of ABT-773 and other antimicrobial agents against Legionella pneumophila. 1200 84

The influence of bacterial strain and antibiotic concentration on the time to achieve in vitro bactericidal activity was determined for gatifloxacin and ciprofloxacin using time-kill methodology. Killing rates were significantly affected by bacterial strain, antibiotic concentration, and type of fluoroquinolone. The most rapid bactericidal activity was seen against members of the Enterobacteriaceae and with fluoroquinolone concentrations of 8-16 X MIC. In general, gatifloxacin demonstrated faster killing against Acinetobacter baumanii, Legionella pneumophila, Staphylococcus aureus, and Streptococcus pneumoniae.
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PMID:Comparative killing rates of gatifloxacin and ciprofloxacin against 14 clinical isolates: impact of bacterial strain and antibiotic concentration. 1237 32

The activities of tigecycline (Wyeth Research) against extracellular and intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia were studied. The tigecycline MIC at which 50% of strains are inhibited for 101 different Legionella sp. strains was 4 micro g/ml versus 0.125 and 0.25 micro g/ml for azithromycin and erythromycin, respectively. Tigecycline was about as active as erythromycin (tested at 1 micro g/ml) against the F889 strain of L. pneumophila grown in guinea pig alveolar macrophages and more active than erythromycin against the F2111 strain. Azithromycin (0.25 micro g/ml) was more active than (F889) or as active as (F2111) tigecycline (1 micro g/ml) in the macrophage model. When tigecycline was given (7.5 mg/kg of body weight subcutaneously once) to guinea pigs with L. pneumophila pneumonia, the mean peak serum and lung levels were 2.3 and 1.8 micro g/ml (1.2 and 1.5 micro g/g) at 1 and 2 h postinjection, respectively. The serum and lung areas under the concentration time curve from 0 to 24 h were 13.7 and 15.8 micro g. h/ml, respectively. Thirteen of 16 guinea pigs with L. pneumophila pneumonia treated with tigecycline (7.5 mg/kg subcutaneously once daily for 5 days) survived for 7 days post-antimicrobial therapy, as did 11 of 12 guinea pigs treated with azithromycin (15 mg/kg intraperitoneally once daily for 2 days). None of 12 guinea pigs treated with saline survived. Tigecycline-treated guinea pigs had average end of therapy lung counts of 1 x 10(6) CFU/g (range, 2.5 x 10(4) to 3.2 x 10(6) CFU/g) versus <1 x 10(2) CFU/g for azithromycin (range, undetectable to 100 CFU/g). A second guinea pig study examined the ability of tigecycline to clear L. pneumophila from the lung after 5 to 9 days of therapy; bacterial concentrations 1 day posttherapy ranged from log(10) 4.2 to log(10) 5.5 CFU/g for four different dosing regimens. Tigecycline is about as effective as erythromycin against intracellular L. pneumophila, but tigecycline inactivation by the test media confounded the interpretation of susceptibility data. Tigecycline was effective at preventing death from pneumonia in an animal model of Legionnaires' disease, warranting human clinical trials of the drug for the disease.
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PMID:Activities of tigecycline (GAR-936) against Legionella pneumophila in vitro and in guinea pigs with L. pneumophila pneumonia. 1254 55

As part of an epidemiological study of legionellosis, we investigated the growth within Acanthamoeba sp. and antibiotic susceptibility of 62 strains of Legionella spp. isolated from surface soils nationwide in 2001. 1) All strains tested grew in Acanthamoeba sp., suggesting that the strains were pathogenic. The minimum bacterial number required for the growth in the amoeba was 10(3)-10(8) CFU/ml and there were differences between the strains. 2) Susceptibility to 10 drugs was investigated using the Etest. The MIC90 values of imipenem, as a beta-lactam, and rifampicin, as an antitubercular agent, were 0.047 microgram/ml and 0.064 microgram/ml, respectively, showing high sensitivity. In contrast, sensitivity to minocycline, as a tetracycline, and piperacillin, as a beta-lactam, was low and the MIC90 values were 12 micrograms/ml and 16 micrograms/ml, respectively. Sensitivity to minocycline was particularly low, with a MIC value of 32 micrograms/ml, in two strains. The above findings suggested that all soil-derived strains were pathogenic, and susceptibility of the strains tended to be slightly lower than that of clinical isolates.
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PMID:[Fundamental studies on legionellosis--the growth with in Acanthamoeba sp. and antibiotics susceptibility of Legionella spp. isolated from soil samples in Japan]. 1266 Oct 83

An understanding of the pharmacokinetic and pharmacodynamic properties of antimicrobial agents enables better choices to be made in the clinical situation. The fluoroquinolones share several useful pharmacokinetic properties, such as good bioavailability (in most cases >85%) and the ability to penetrate and concentrate intracellularly, giving them activity against pathogens such as Legionella pneumophila and Listeria monocytogenes. Nevertheless, there are some important differences between the fluoroquinolones, and even the newer fluoroquinolones demonstrate a range of pharmacodynamic properties. When considering the area under the inhibition curve (AUIC) and the Cmax/MIC, the comparative figures are: ciprofloxacin and ofloxacin (5-25, 1-5); levofloxacin, grepafloxacin and gatifloxacin (25-75, 5-10); trovafloxacin (75-250, 10-20) and moxifloxacin, clinafloxacin and gemifloxacin (>250, >20). The development of resistance is also a concern, and selecting an agent that reaches an adequate concentration above the MIC will reduce the opportunity for resistance to develop. These properties should be considered when selecting a fluoroquinolone either for inclusion in a formulary, or for use in an individual patient.
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PMID:Maximizing efficacy and reducing the emergence of resistance. 1270 2

Grepafloxacin potency and spectrum of activity were re-evaluated against contemporary pathogens collected from clinical infections in 2001-2002. A total of 995 isolates were tested for grepafloxacin by the reference agar dilution method and these results were compared to those of 25 other antimicrobial agents. Grepafloxacin activity remained comparable to that of ciprofloxacin, levofloxacin and gatifloxacin against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (MIC(90), 0.03-2 microg/ml; 0.0-7.7% resistance rates). For Pseudomonas aeruginosa, grepafloxacin was active against ciprofloxacin-susceptible (MIC(90), 2 microg/ml), but not against ciprofloxacin-resistant (MIC(90), >8 microg/ml) isolates. Against methicillin-susceptible Staphylococcus aureus, grepafloxacin susceptibility rate was 91.4%, equal to that of levofloxacin. None of the fluoroquinolones showed reasonable activity against methicillin-resistant staphylococci. Gatifloxacin and grepafloxacin had the same MIC(90) against beta-hemolytic streptococci (0.25 microg/ml) and penicillin-susceptible Streptococcus pneumoniae (0.25 microg/ml). Grepafloxacin and other fluoroquinolone activities were not influenced by penicillin resistance in S. pneumoniae. Grepafloxacin was very active against Haemophilus influenzae (MIC(90), 0.03 microg/ml), Moraxella catarrhalis (MIC(90), 0.03 microg/ml) and Legionella spp. (MIC(90), 0.5 microg/ml). These results on recently isolated organisms indicate that grepafloxacin has a sustained potency and spectrum against most clinically important and indicated pathogens.
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PMID:Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States. 1296 54

The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.
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PMID:In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp. 1461 52

Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.
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PMID:Gemifloxacin: a new fluoroquinolone. 1515 13

Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial's antibacterial spectrum must include the most likely pathogens: Streptococcus pneumoniae, the most frequent cause of community-acquired pneumonia (CAP), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, as well as atypicals such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila (Chlamydia) pneumoniae. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC > or =2 mg/l) among isolates of S. pneumoniae varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility--including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12-1 mg/l)--is frequently found in association with macrolide resistance, which is found at a prevalence of 70-80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is beta-lactamase production among isolates of H. influenzae and M. catarrhalis. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.
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PMID:Comparative antimicrobial susceptibility of respiratory tract pathogens. 1531 48

LBM415 (NVP PDF-713) is the first member of the peptide deformylase (PDF) inhibitor class being developed for clinical trials as a parenteral and oral agent for treatment of community-acquired respiratory tract disease and serious infections caused by antimicrobial-resistant gram-positive cocci. In this study susceptibility testing results from 1,306 recent clinical isolates selected to over-represent resistance trends among the species were summarized. All staphylococci (153 strains; MIC at which 90% of isolates were inhibited [MIC90], 2 microg/ml), Streptococcus pneumoniae (170 strains; MIC90, 1 microg/ml), other streptococci (150 strains; MIC90, 1 microg/ml), enterococci (104 strains; MIC90, 4 microg/ml), Moraxella catarrhalis (103 strains; MIC90, 0.5 microg/ml), and Legionella pneumophila (50 strains; MIC90, 0.12 microg/ml) were inhibited at < or = 8 microg of LBM415/ml, as were 97% of Haemophilus influenzae isolates (300 strains; MIC90, 4 to 8 microg/ml). Among other bacterial groups, 100% of gram-positive and -negative anaerobes, including 22 Bacteroides spp. strains (31 strains total; MIC90, 1 microg/ml), were inhibited by < or = 4 microg/ml, whereas Enterobacteriaceae (112 strains) and most nonfermentative bacilli (107 strains) were not inhibited at readily achievable concentrations. The compound was found to have a dominantly bacteriostatic action, and spontaneous single-step mutational rates occurred at low levels (10(-6) to <10(-8)). Drug interaction studies failed to identify any class-specific synergistic interactions, nor were antagonistic interactions observed. Variations in broth and agar MIC test conditions demonstrated that, whereas the agar-based method trended towards a 1-log2 dilution-higher MIC than the broth method and was inoculum dependent, other variations in incubation environment, medium supplements, pH, or calcium concentration had little influence on LBM415 MIC results. Use of the efflux inhibitor phe-arg-beta-naphthylamide showed an average of 1 log2 dilution decrease in H. influenzae MICs, demonstrating the contribution of efflux pumps in influencing susceptibility to PDF inhibitors. The in vitro activity of LBM415 against targeted bacterial species, including resistant subsets, and other laboratory characteristics of this novel compound demonstrate the potential of PDF inhibitors as a new class of antimicrobial agents.
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PMID:Comparative antimicrobial characterization of LBM415 (NVP PDF-713), a new peptide deformylase inhibitor of clinical importance. 1579 28


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