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)

In addition to erythromycin, macrolides now available in the United States include azithromycin and clarithromycin. These two new macrolides are more chemically stable and better tolerated than erythromycin, and they have a broader antimicrobial spectrum than erythromycin against Mycobacterium avium complex (MAC), Haemophilus influenzae, nontuberculous mycobacteria, and Chlamydia trachomatis. All three macrolides have excellent activity against the atypical respiratory pathogens (C. pneumoniae and Mycoplasma species) and the Legionella species. Azithromycin and clarithromycin have pharmacokinetics that allow shorter dosing schedules because of prolonged tissue levels. Both azithromycin and clarithromycin are active agents for MAC prophylaxis in patients with late-stage acquired immunodeficiency syndrome (AIDS), although azithromycin may be the preferable agent because of fewer drug-drug interactions. Clarithromycin is the most active MAC antimicrobial agent and should be part of any drug regimen for treating active MAC disease in patients with or without AIDS. Although both azithromycin and clarithromycin are well tolerated by children, azithromycin has the advantage of shorter treatment regimens and improved tolerance, potentially improving compliance in the treatment of respiratory tract and skin or soft tissue infections. Intravenously administered azithromycin has been approved for treatment of adults with mild to moderate community-acquired pneumonia or pelvic inflammatory diseases. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens, particularly Streptococcus pneumoniae, group A streptococci, and H. influenzae. The emergence of macrolide resistance with these common pathogens may limit the clinical usefulness of this class of antimicrobial agents in the future.
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PMID:The macrolides: erythromycin, clarithromycin, and azithromycin. 1037 39

The comparative in vitro potency and post-antibiotic effect (PAE) of gemifloxacin (SB-265805), moxifloxacin, trovafloxacin, grepafloxacin, levofloxacin, ofloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin and rifampicin were evaluated against Legionella pneumophila serogroups 1-9 and 12 (n = 204) and other Legionella spp. (n = 34). MICs were determined by standard two-fold agar dilution. PAE was determined by exposing the isolates to the test agents at 4 x MIC for 1 h. Trovafloxacin was the most potent agent overall (MIC range < or =0.004-0.016 mg/L, MIC(90) < or =0.008 mg/L). Of the other quinolones tested, gemifloxacin, moxifloxacin, grepafloxacin and levofloxacin were more potent (MIC(90) 0.016 mg/L) against L. pneumophila than ciprofloxacin and ofloxacin (MIC(90) 0. 03 mg/L). Against Legionella spp., the test quinolones were more potent (MIC range < or =0.004-0.06 mg/L) than either erythromycin or azithromycin (MIC(90) 0.5 and 0.25 mg/L, respectively). Gemifloxacin had the longest PAE (4.65 h) of the agents tested against erythromycin-resistant L. pneumophila. Of the quinolones, only gemifloxacin, grepafloxacin, levofloxacin and ofloxacin had PAEs of >3 h against erythromycin-resistant Legionella spp. Azithromycin, erythromycin and clarithromycin had PAEs of <3 h against all erythromycin-resistant strains. Against erythromycin-susceptible L. pneumophila, only gemifloxacin, moxifloxacin, ofloxacin and ciprofloxacin had PAEs of >3 h, and only rifampicin, ofloxacin, gemifloxacin and erythromycin had PAEs of >2 h against erythromycin-susceptible Legionella spp. The superior potency of gemifloxacin compared with erythromycin indicates that it may be of use in the treatment of legionellosis. The significant PAE described here, combined with favourable pharmacokinetics, supports once-daily dosing for gemifloxacin in the treatment of legionella infections.
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PMID:Comparative in vitro activity and post-antibiotic effect of gemifloxacin against Legionella spp. 1082 31

We investigated the antimicrobial efficacy of clinically meaningful, low concentrations of azithromycin against intracellular growth of two clinical isolates of Legionella pneumophila. The mature monocytic cell line Mono Mac 6 was used as a model to investigate the effects of antimicrobial agents on L. pneumophila. Extracellular susceptibility was determined by microdilution susceptibility testing in BYEalpha broth after 48 h of incubation. Mono Mac 6 cells infected with L. pneumophila were incubated with various concentrations of azithromycin. After 2 days of incubation, intracellular bacteria were released from the phagocytes and plated on to BCYEalpha agar. Addition of the intracellular-acting antibiotics azithromycin or ciprofloxacin at their MICs (0.5 and 0. 015 mg/L, respectively) resulted in a significant decrease in cfu, of up to approximately 1 log(10) after 48 h of incubation. In contrast, incubation of intraphagocytic L. pneumophila in the presence of antibiotics without intracellular activity (ceftizoxime, imipenem or amoxycillin-clavulanic acid) did not have any effect. Azithromycin inhibited intracellular replication at concentrations as low as 0.125 mg/L, approximately one-quarter of the extracellular MIC. The Mono Mac 6 cell line is a useful infection model for investigating the intracellular activity of antimicrobial agents in vitro. In accordance with clinical data and animal experiments, azithromycin and ciprofloxacin inhibited the intraphagocytic replication of L. pneumophila. In particular, azithromycin killed ingested legionellae in vitro at concentrations below the peak serum concentrations and below the MIC.
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PMID:The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo. 1122 73

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

Azithromycin is highly active against Legionella pneumophila and has been shown to be efficacious in animal models and in clinical studies of patients with legionnaires disease. This open, prospective, multicenter trial evaluated azithromycin for the treatment of legionnaires disease. Twenty-five hospitalized patients with community-acquired pneumonia and a positive result of a L. pneumophila serogroup 1 urinary antigen assay received monotherapy with intravenous azithromycin (500 mg/day) for 2-7 days, followed by oral azithromycin (1500 mg administered over the course of 3 or 5 days). The mean total duration of intravenous plus oral therapy was 7.92 days. The overall cure rate among clinically evaluable patients was 95% (20 of 21 patients) at 10-14 days after therapy and 96% (22 of 23 patients) at 4-6 weeks after therapy. The results of this study support previously reported data demonstrating that azithromycin is both safe and efficacious for the treatment of hospitalized patients with legionnaires disease.
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PMID:Azithromycin in the treatment of Legionella pneumonia requiring hospitalization. 1461 70

Macrolides, fluoroquinolones, doxycycline, and ketolides show a good intrinsic activity against intracellular pathogens which are responsible for a variable percentage of community-acquired pneumonia (CAP). These therapeutic agents all seem effective in treating most cases of CAP caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella spp. Among quinolones, the more recent fluoroquinolones, such as gemifloxacin or moxifloxacin, generally show a better intrinsic activity than the older ones. Among macrolides, azithromycin, and clarithromycin show a better pharmacokinetic profile. Both of them are available in intravenous form. It is quite common for M. pneumoniae and C. pneumoniae to continue to be shed in respiratory secretions, weeks after an effective therapy. The clinical relevance of this finding is not clear since most of these patients have a good outcome. Azithromycin, due to its advantageous pharmacokinetic profile, seems the best option when antibiotic prophylaxis is considered in some epidemiological settings. It has been proved effective in closed M. pneumoniae outbreaks.
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PMID:13--Antibiotic therapy of community-acquired pneumonia (CAP) caused by atypical agents. 1709 77

Given the nonspecific clinical manifestations of Legionnaires' disease and the high mortality of untreated Legionnaires' disease, we recommend routine use of Legionella testing, especially the Legionella urinary antigen test, for all patients with community-acquired pneumonia. This includes patients with ambulatory pneumonia and hospitalized children. Legionella cultures should be more widely available, especially in hospitals where the drinking water is colonized with Legionella. Azithromycin or levofloxacin can be considered as first-line therapy. Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones and other macrolides (especially clarithromycin) are also effective. The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar. If the Legionnaires' disease is hospital-acquired, culturing of the hospital drinking water for Legionella is indicated.
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PMID:Treatment strategies for Legionella infection. 1940 87

Legionella species are important causative pathogens for severe community-acquired pneumonia (CAP). Most cases of Legionella pneumonia are due to Legionella pneumophila serogroup 1, and CAP due to L. pneumophila serogroup 9 is rare. A fourth case of CAP due to L. pneumophila serogroup 9 has been reported, and initial treatment using single-dose oral azithromycin appeared useful. Azithromycin or fluoroquinolone injection is usually recommended for the treatment of Legionella pneumonia, and no previous reports have shown the effectiveness of single-dose oral azithromycin. This case report is therefore valuable from the perspective of possible treatment for mild to moderate Legionella pneumonia using single-dose oral azithromycin.
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PMID:A Case of Community-Acquired Pneumonia Due to Legionella pneumophila Serogroup 9 Wherein Initial Treatment with Single-Dose Oral Azithromycin Appeared Useful. 2889 May 5


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