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)

Animal lung macrophages or human peripheral blood mononuclear cells have been used for testing intracellular activity of anti-Legionella antibiotics; such studies are labor intensive such that comparative antibiotic studies for the many Legionella species are few. We evaluated a human monocyte cell line (HL-60) as an alternative model. HL-60 (1.5 x 10(6) cells/well) was differentiated into adherent cell and infected with 1.5 x 10(7) CFU of Legionella pneumophilia (L. pneumophilia). Erythromycin and quinolones, ciprofloxacin, ofloxacin, and levofloxacin were added to cells at 1 and 8 x MIC. Percent (%) inhibition ratios equal to total L. pneumophila with agent divided by L. pneumophila without agent x 100 were determined at 48 h; lower ratios implied greater potency. By broth dilution in buffered yeast extract broth, the most potent agents against L. pneumophila were (MIC): ciprofloxacin (0.015-0.03), ofloxacin (0.015-0.03), levofloxacin (0.015-0.03), erythromycin (0.125-1.0 microgram/mL). In the intracellular model, the most potent inhibitors of L. pneumophila multiplication at 8 x MIC were (in order of potency) levofloxacin (24.2%), ciprofloxacin (30.6%), ofloxacin (37.1%), and erythromycin (55.0%). All the quinolones were highly active and significantly more potent against L. micdadei and L. bozemanii when compared to L. pneumophila.
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PMID:Comparative activity of ciprofloxacin, ofloxacin, levofloxacin, and erythromycin against Legionella species by broth microdilution and intracellular susceptibility testing in HL-60 cells. 948 30

Quinupristin/dalfopristin displays in-vitro bacteriostatic activity against all Legionella spp. (MICs = 0.06-2 mg/L), with Legionella pneumophila usually being at least two-fold more sensitive to quinupristin/dalfopristin than Legionella bozemanii, Legionella dumoffii, Legionella gormanii and Legionella micdadei (MIC = 0.06-2 vs 1-2 mg/L, respectively). Against Legionella spp., quinupristin/dalfopristin was at least as active as erythromycin. Quinupristin/dalfopristin was active in vitro against all Mycoplasma spp. tested (MIC = 0.05-2 mg/L), with Mycoplasma hominis being less susceptible than other species. Quinupristin/dalfopristin was active against erythromycin-resistant strains of Mycoplasma fermentans and M. hominis (MIC90 = 0.5 and 2 mg/L, respectively), and doxycycline-resistant strains of Ureaplasma urealyticum (MIC90 = 1 mg/L). The in-vitro bacteriostatic activity against Mycoplasma pneumoniae and Mycoplasma genitalium (MIC90 = 0.1 and 0.05 mg/L, respectively) was similar to that of erythromycin and doxycycline. Quinupristin/dalfopristin was actively taken up by murine macrophages, and incubation of the drug (2.5 mg/L) with macrophages containing ingested Staphylococcus aureus resulted in the death of 70% of intracellular bacteria within 120 min. Intracellular concentrations of quinupristin/dalfopristin reached 50 and 30 times the extracellular concentration, respectively, showing that these compounds readily penetrate into cells. The intracellular activity of quinupristin/dalfopristin may make it suitable for use in some, presently difficult-to-treat, infections caused by intracellular organisms.
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PMID:A review of the in-vitro activity of quinupristin/dalfopristin against intracellular pathogens and mycoplasmas. 951 Oct 64

We determined the MICs of ampicillin, ciprofloxacin, erythromycin, imipenem, and rifampin for two clinical isolates of Legionella pneumophila serogroup 1 by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction assay and by quantitative culture. To test the influence of subinhibitory concentrations (sub-MICs) of antimicrobial agents on Legionella uptake into Acanthamoeba castellanii and U937 macrophage-like cells, both strains were pretreated with 0.25 MICs of the antibiotics for 24 h. In comparison to that for the untreated control, subinhibitory concentrations of antibiotics significantly reduced Legionella uptake into the host cells. Measurement of the binding of monoclonal antibodies against several Legionella antigens by enzyme-linked immunoassays indicated that sub-MIC antibiotic treatment reduced the expression of the macrophage infectivity potentiator protein (Mip), the Hsp 60 protein, the outer membrane protein (OmpM), an as-yet-uncharacterized protein of 55 kDa, and a few lipopolysaccharide (LPS) epitopes. In contrast, the expression of some LPS epitopes recognized by monoclonal antibodies 8/5 and 30/4 as well as a 45-kDa protein, a 58-kDa protein, and the major outer membrane protein (OmpS) remained unaffected.
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PMID:Subinhibitory concentrations of antimicrobial agents reduce the uptake of Legionella pneumophila into Acanthamoeba castellanii and U937 cells by altering the expression of virulence-associated antigens. 979 18

In France the current consensus for the treatment of community-acquired pneumonia is based on the French Society for Infectious Diseases 1991 guidelines. In healthy adults without signs of severe disease, oral amoxicillin is recommended at the dose of 3 g per day for 8 to 10 days. This empirical choice is warranted by the prevalence of pneumococcal infections, found as causal agents in half to two-thirds of the bacteriologically proven cases. The 3 g dose is recommended due to the increasing risk of penicillin-resistant S. pneumoniae with MIC > 1 microgram/ml and exceptionally > 2 micrograms/ml. Clinical experience has shown that with a threshold at 2 micrograms/ml, 3 g of amoxicillin is a safe and sure choice. The duration is undoubtedly too long for most patients, but is a prudent measure due to the lack of clinical signs distinguishing between patent infection and its prolongation by inflammatory processes. Indiscriminate prescription of amoxicillin alone is however unacceptable as aminopenicillin is not effective against all microbial agents responsible for community-acquired pneumonia. The risk of selecting resistant strains is very real. Use of a large spectrum antibiotic could be indicated as first line treatment in patients with risk factors (underlying chronic disease, institutionalization, exposure to Gram negatives or S. aureus). For such patients, combination with a beta-lactamase inhibitor (coamoxiclav) or a cephalosporin with a MIC similar to that for penicillin G (cefpodoxime proxetil, cefuroxime axetil) could be recommended. In case of severe disease, Legionella pneumophila must be taken into consideration, implicating adjuction of a macrolide. Wide spectrum fluoroquinolones such as the soon to be available trovafloxacin offer a safe alternative, covering the main microorganisms responsible for community acquired pneumonia. Widespread use would however increase the risk of microbial resistance. In the current epidemiological situation in France, prescription of an aminopenicillin alone for alveolar community-acquired pneumonia in healthy adults remains the gold standard for first line therapy.
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PMID:[Can aminopenicillin be prescribed as monotherapy in case of community-acquired pneumonia?]. 981 92

The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular Legionella pneumophila L-1033, serogroup 1, were studied. In an in vitro system utilizing adherent human monocytes, L. pneumophila L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods. The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (P < 0.01). The decrease in CFU with rifampin was first observed at 48 h (P < 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin. Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (P < 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not. Removal of levofloxacin after 24 h of incubation resulted in regrowth of L. pneumophila L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin. At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin. Levofloxacin had a significantly higher bactericidal activity against L. pneumophila L-1033 than erythromycin or rifampin. In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin.
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PMID:Antibacterial effects of levofloxacin, erythromycin, and rifampin in a human monocyte system against Legionella pneumophila. 983 7

The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds. Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results. Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin. This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class. Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest [AB BIODISK, Solna, Sweden] broth microdilution, and disk diffusion). Variations in inoculum concentration had minimal effect on dirithromycin potency. In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant. Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M. catarrhalis, and also possesses a modest in vitro potency versus H. influenzae coupled with excellent pharmacokinetic properties. In vitro tests with dirithromycin will continue to be problematic for H. influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest).
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PMID:Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results. 1021 55

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.
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PMID:In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. 1022 17

TWO-PHASE ACTION: Pristinamycin is composed of two active substances A and B. Pristinamycin A (SA) first binds to the ribosome subunit 50s. Pristinamycin B (SB) then locks onto SA causing irreversible inhibition of bacterial protein production. WELL-ADAPTED ACTIVITY SPECTRUM: A member of the streptogramin family of antibiotics, pristinamycin is active against the main bacteria causing respiratory tract infections (pneumococci, S. aureus, H. influenzae) as well as against mycoplasma and anaerobic pathogens. ANTI-PNEUMOCOCCI ACTIVITY: Minimal inhibitory concentrations measured over the last 5 years have confirmed that the antibacterial activity of pristinamycin against pneumococci remains unchanged even for strains which develop resistance to other antibiotics, particularly to penicillin or erythromycin. OTHER BACTERIA: The activity of pristinamycin against H. influenzae is a constant finding (unimodal distribution of MIC). The persistent of pristinamycin activity against S. aureus strains, excepting a few SA- resistant strains and SA + SB- resistant strains, is remarkable. MIC studies have also demonstrated the constant susceptibility of Moraxella catarrhalis, non-groupable streptococci, anaerobic bacteria, and Legionella pneumophila.
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PMID:[In vitro activity of pristinamycin on respiratory bacteria]. 1050 76

Although most respiratory tract infections (RTI) are caused by viruses, various bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, are common causes of community-acquired pneumonia, acute exacerbations of chronic bronchitis, otitis media and sinusitis. Empirical antibiotic therapy of patients with RTI must take account of the increasing prevalence of resistance among the predominant pathogens. Europe-wide susceptibility surveillance studies have revealed that resistance to penicillin and macrolides is highly prevalent among isolates of S. pneumoniae from France and Spain. Uniquely, in Italy, macrolide resistance is highly prevalent while the prevalence of penicillin resistance is low. Resistance to other antibiotic classes, including chloramphenicol, doxycycline and, in particular, co-trimoxazole, is associated with penicillin resistance in pneumococci, but resistance to the fluoroquinolones is rare. beta-Lactamase production is the principal mechanism of resistance in isolates of H. influenzae and M. catarrhalis, with fluoroquinolone resistance being detected rarely in these pathogens. In 1998 a surveillance study involving 15 European countries determined the susceptibilities of many respiratory pathogens to a range of antimicrobials, including grepafloxacin. The MIC(90) of grepafloxacin for 1251 isolates of S. pneumoniae was 0.25 mg/L, the MICs for only five strains being >2 mg/L, and 99.4% of all of the isolates tested were inhibited by concentrations </=0.5 mg/L. The MIC(90)s of grepafloxacin for 587 isolates of H. influenzae and 323 of Haemophilus parainfluenzae were 0.015 and 0.06 mg/L, respectively, while that for 509 isolates of M. catarrhalis was 0.03 mg/L. The MIC(90)s for 1164 isolates of methicillin-susceptible Staphylococcus aureus and 435 isolates of Klebsiella pneumoniae were 0.12 and 0.25 mg/L, respectively. Other studies have shown grepafloxacin to be highly active against clinical isolates of Legionella pneumophila (MIC(90) 0.015 mg/L), Mycoplasma pneumoniae (MIC(90) 0.5 mg/L) and Chlamydia pneumoniae (MICs 0.06-0.12 mg/L). Current susceptibility data indicate that fluoroquinolone resistance rates among bacterial respiratory tract pathogens are low in European countries. The enhanced potency and activity of grepafloxacin against isolates of S. pneumoniae, including those exhibiting resistance to unrelated classes of antibiotics, together with its activity against other respiratory tract pathogens, suggest that this drug has considerable potential as empirical therapy of patients with a wide range of RTI.
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PMID:Respiratory pathogens: assessing resistance patterns in Europe and the potential role of grepafloxacin as treatment of patients with infections caused by these organisms. 1071 6

Moxifloxacin (BAY 12-8039) is a new 8-methoxy-fluoroquinolone antibacterial agent. The minimum inhibitory concentration for 90% of organisms (MIC90) is less than 0.25 mg/L for commonly isolated community-acquired respiratory tract pathogens including penicillin-susceptible and -resistant Streptococcus pneumoniae, Haemophilus sp, and Moraxella catarrhalis, and less than 1.0 mg/L for atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. To date, emergence of resistance to moxifloxacin has been uncommon, including selection of resistance under experimental conditions (methicillin-sensitive Staphylococcus aureus, S. pneumoniae). A postantibiotic effect is observed for both gram-positive and gram-negative bacteria. Human pharmacokinetics in healthy volunteers after a single 400-mg oral dose were mean maximum concentration (Cmax) 3.2 mg/L, area under the curve (AUC) 37 mg x hour/L, and terminal elimination half-life 12.0 hours. At steady-state, Cmax and AUC were approximately 4.5 mg/L and 48 mg x hour/L, respectively. Because of a balanced system of excretion, no dosage adjustments are required in patients with renal or hepatic impairment. Moxifloxacin also has excellent penetration into upper and lower respiratory tissues. Laboratory pharmacodynamic models suggest that MIC and AUC values predict therapeutic response. Notably, the drug can be administered once/day and is not associated with drug interactions secondary to altered hepatic metabolism. In addition, since its metabolism does not involve the cytochrome P450 system, many common drug interactions are absent. The agent is being investigated in clinical trials and shows promise as a safe and effective once-daily treatment of respiratory infections. In addition, its chemical structure and pharmacokinetic and pharmacodynamic properties indicate that it has enhanced potential to minimize emergence of bacterial resistance, which should make it an excellent choice for treating respiratory tract infections now and in the future.
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PMID:Moxifloxacin, a new antibiotic designed to treat community-acquired respiratory tract infections: a review of microbiologic and pharmacokinetic-pharmacodynamic characteristics. 1073 Jun 81


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