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 chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.
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PMID:Clarithromycin and azithromycin: new macrolide antibiotics. 151 40

Azithromycin and clarithromycin are erythromycin analogues that have recently been approved by the FDA. These drugs inhibit protein synthesis in susceptible organisms by binding to the 50S ribosomal subunit. Alteration in this binding site confers simultaneous resistance to all macrolide antibiotics. Clarithromycin is several-fold more active in vitro than erythromycin against gram-positive organisms, while azithromycin is 2- to 4-fold less potent. Azithromycin has excellent in vitro activity against H influenzae (MIC90 0.5 microgram/ml), whereas clarithromycin, although less active against H influenzae (MIC90 4.0 micrograms/ml) by standard in vitro testing, is metabolized into an active compound with twice the in vitro activity of the parent drug. Both azithromycin and clarithromycin are equivalent to standard oral therapies against respiratory tract and soft tissue infections caused by susceptible organisms, including S aureus, S pneumoniae, S pyogenes, H influenzae, and M catarrhalis. Clarithromycin is more active in vitro against the atypical respiratory pathogens (e.g., Legionella), although insufficient in vivo data are available to demonstrate a clinical difference between azithromycin and clarithromycin. Superior pharmacodynamic properties separate the new macrolides from the prototype, erythromycin. Azithromycin has a large volume of distribution, and, although serum concentrations remain low, it concentrates readily within tissues, demonstrating a tissue half-life of approximately three days. These properties allow novel dosing schemes for azithromycin, because a five-day course will provide therapeutic tissue concentrations for at least ten days. Clarithromycin has a longer serum half-life and better tissue penetration than erythromycin, allowing twice-a-day dosing for most common infections. Azithromycin pharmacokinetics permit a five-day, single daily dose regimen for respiratory tract and soft tissue infections, and a single 1 g dose of azithromycin effectively treats C trachomatis genital infections; these more convenient dosing schedules improve patient compliance. Azithromycin and clarithromycin also are active against some unexpected pathogens (e.g., B burgdorferi, T gondii, M avium complex, and M leprae). Clarithromycin, thus far, appears the most active against atypical mycobacteria, giving new hope to what has become a difficult group of infections to treat. Gastrointestinal distress, a well known and major obstacle to patient compliance with erythromycin, is relatively uncommon with the new macrolides. Further clinical data and experiences may better define and expand the role of these new macrolides in the treatment of infectious diseases.
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PMID:Azithromycin and clarithromycin: overview and comparison with erythromycin. 132 67

Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species. In particular, it is more active against Haemophilus influenzae than other macrolides. In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life. The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies. Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections. Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.
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PMID:Azithromycin in lower respiratory tract infections. 133 93

After almost forty years of its introduction, erythromycin will not be the exclusive member of the macrolide group of antibiotic agents, but a new generation of its derivatives which surpass it in pharmacological properties and clinical efficacy will also be available. Clarithromycin, a 14-membered derivative, has shown acid stability, longer half-life, lower protein binding and higher lung tissue penetration. Its exceedingly high activity against erythromycin-susceptible gram-positive cocci, Mycoplasma pneumoniae, and Legionella pneumophila makes it and important alternative choice in the therapy of respiratory tract infections. Also, it has shown high activity against Chlamydia trachomatis, and high urinary clearance of this unmetabolized molecule, important properties which would render it a special role in the treatment of genitourinary tract infections. Azithromycin, a 15-membered derivative has shown enhanced basicity (due to the nitrogen atom in its lactone ring), longer half-life and lower protein bindings. Its exceptional activity against Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum and gram-negative bacteria, and its high concentration in tonsillar, pulmonary, prostatic and female reproductive tract tissues, assigns it an honorific place among the macrolides in the therapy against respiratory tract and genitourinary tract infections. Its role against T. gondii deserves further study, but points out this agent as a promise against this parasite.
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PMID:The new macrolides: expanding the ways in antibiotic treatment. 150 85

Azithromycin contains an aza-methyl substitution in the 15-membered aglycone ring and as such it is the prototype antibiotic of the azalide class, similar in mechanism of activity to the macrolides. It demonstrates a broad spectrum of activity against many aerobic and anaerobic Gram-positive species, and also inhibits a number of important aerobic and anaerobic Gram-negative bacteria. Significantly, azithromycin shows good activity against Haemophilus influenzae, an organism against which older macrolide antibiotics have proved disappointing. It is highly effective in inhibiting clinically significant intracellular pathogens such as Chlamydia trachomatis and Legionella. Bactericidal activity is seen for certain streptococci and for H. influenzae. Closely linked with azithromycin's microbiologic activity are its novel pharmacokinetics. Azithromycin moves rapidly from blood to tissue compartments where it remains for prolonged periods. Although serum concentrations remain low, the levels attained in the tissues (often greater than 2 mg/kg) are higher than the minimum inhibitory concentration for many common pathogens, and delivery of drug to infection sites by phagocytic cells contributes to these concentrations. This penetration into eukaryotic and prokaryotic cells may be responsible for azithromycin's expanded spectrum of activity, particularly against intracellular organisms. The use of antibiotic blood levels as breakpoints for susceptibility would appear to be inappropriate in the case of azalides. Rather, levels of drug at the tissue site of infection should be considered as guides to predicting efficacy. The in vitro activity of azithromycin, together with its unique tissue pharmacodynamics, define an agent that should demonstrate utility in infections of the respiratory tract, skin and skin structures, and certain sexually transmitted diseases.
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PMID:Clinical microbiology of azithromycin. 165 36

In recent years, a number of newer macrolides have been developed. One such antibiotic is azithromycin, which has a 15-membered ring structure and is classed as an azalide. The limitations of erythromycin and the discovery of pathogenic bacteria such as Campylobacter, Legionella and Chlamydia species provide incentives to study the usefulness of newer antibiotics of this class. Azithromycin has good activity against staphylococci, streptococci, Moraxella catarrhalis and other rapidly growing pyogenic bacteria. The good activity of azithromycin against Haemophilus influenzae (MIC90 0.5 mg/l) is particularly important as erythromycin has only marginal activity against this organism. Azithromycin has also been shown to be more potent than the macrolides against Enterobacteriaceae. In common with erythromycin and tetracycline, the agent has good activity against Legionella, Chlamydia and Campylobacter. Opportunistic infections involving Toxoplasma gondii and Pneumocystis carinii are an increasing problem and azithromycin is particularly interesting in view of its activity against these difficult-to-treat organisms.
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PMID:Spectrum of activity of azithromycin. 166 24

The activities of azithromycin, erythromycin, and ciprofloxacin against 21 Legionella isolates were measured by an agar dilution method and in macrophages. The MICs for 90% of strains tested were 2.0, 1.0, and 0.5 micrograms/ml for azithromycin, erythromycin, and ciprofloxacin, respectively. Azithromycin and ciprofloxacin were both bactericidal in the macrophage system, but erythromycin was bacteriostatic.
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PMID:In vitro activity of azithromycin against clinical isolates of Legionella species. 184 8

Azithromycin and erythromycin were compared for efficacy in guinea pigs infected with an aerosol containing Legionella pneumophila. When administered intraperitoneally, azithromycin was very effective in the treatment of experimental Legionnaires' disease. Even at the low dose of 3.6 mg/kg/day it gave 100% survival and eliminated lung infectivity two days following infection. In contrast, erythromycin at a much higher dose (96 mg/kg/day) gave only 83.3% survival and failed to eliminate organisms from the lung six days after infection. The histological findings confirmed the superiority of azithromycin. A single dose of azithromycin given intraperitoneally at 3.6 or 14.4 mg/kg gave survival rates of 83.3 and 100%, respectively. Azithromycin was also found to be superior to erythromycin in eliminating lung infectivity and reducing mortality, when administered orally. However, oral administration of azithromycin was not as effective as intraperitoneal when assessed by lung histopathology, although it was still superior to oral erythromycin treatment.
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PMID:Efficacy of azithromycin in the treatment of guinea pigs infected with Legionella pneumophila by aerosol. 215 27

The macrolide antibiotic azithromycin (CP-62,993; 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A; also designated XZ-450 [Pliva Pharmaceuticals, Zagreb, Yugoslavia]) showed a significant improvement in potency against gram-negative organisms compared with erythromycin while retaining the classic erythromycin spectrum. It was up to four times more potent than erythromycin against Haemophilus influenzae and Neisseria gonorrhoeae and twofold more potent against Branhamella catarrhalis, Campylobacter species, and Legionella species. It had activity similar to that of erythromycin against Chlamydia spp. Azithromycin was significantly more potent versus many genera of the family Enterobacteriaceae; its MIC for 90% of strains of Escherichia, Salmonella, Shigella, and Yersinia was less than or equal to 4 micrograms/ml, compared with 16 to 128 micrograms/ml for erythromycin. Azithromycin inhibited the majority of gram-positive organisms at less than or equal to 1 micrograms/ml. It displayed cross-resistance to erythromycin-resistant Staphylococcus and Streptococcus isolates. It had moderate activity against Bacteroides fragilis and was comparable to erythromycin against other anaerobic species. Azithromycin also demonstrated improved bactericidal activity in comparison with erythromycin. The mechanism of action of azithromycin was similar to that of erythromycin since azithromycin competed effectively for [14C]erythromycin ribosomebinding sites.
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PMID:Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms. 244 65

14C-labeled azithromycin, a new macrolide antibiotic, was accumulated by various phagocytic cells isolated from volunteers or patients. The concentration of the antibiotic in monocytes, polymorphonuclear leucocytes (PMNLs), and alveolar macrophages was greater than that in the surrounding medium by a factor of between 200 and 668. Azithromycin penetrated somewhat more rapidly into PMNLs and monocytes than into alveolar macrophages. On the other hand the final concentration in the alveolar macrophages was greater by a factor of about 3 than that in the other two phagocytic cells. Staphylococcus aureus, Legionella pneumophila and Haemophilus influenzae previously taken up by the phagocytes were rapidly inactivated by low (0.031-0.5 micrograms/ml) concentrations of the antibiotic, which in the presence of the cells were subinhibitory. There is thus a clear synergism between azithromycin and the phagocytic cells which leads to increased intracellular killing of the bacteria.
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PMID:Interaction of azithromycin and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes. 255 3


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