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Query: UMLS:C0026916 (MAC)
 5,226 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 is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.
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PMID:Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications. 131 48

The comparative activities of azithromycin and clarithromycin and the activities of azithromycin alone and in combination with other antimycobacterial agents were evaluated in the beige mouse model of disseminated Mycobacterium avium complex infection. Azithromycin was similar in activity to clarithromycin. Azithromycin plus clofazimine plus ethambutol reduced the number of splenic organisms more than azithromycin alone, while the combination was less active than azithromycin alone for bacteria in lungs. Rifabutin had activity similar to that of azithromycin for organisms in spleens and lungs. Rifabutin plus azithromycin was more active than either agent alone for organisms in spleens, but the combination's activity was not significantly different from that of rifabutin for organisms in lungs. The activity of azithromycin against several M. avium complex isolates was evaluated. The reduction of viable cell counts in spleens ranged from 1.7 to 0.8 log units. For the three isolates studied, there was little correlation between the in vitro MIC and the in vivo activity.
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PMID:Activity of azithromycin against Mycobacterium avium infection in beige mice. 132 22

The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection.
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PMID:Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages. 165 60

Mycobacterium avium complex infection is common in patients with AIDS. Experimentally infected mice have been treated successfully with azithromycin, a macrolide antibiotic. We report an uncontrolled phase I study in which male homosexuals with AIDS and M avium complex disease were given 500 mg azithromycin per day orally for 10, 20, or 30 days. Quantitative blood cultures showed a mean reduction in mycobacteraemia from 118 colony forming units (cfu)/ml to 43 cfu/ml in 3 patients treated for 10 days, and from 2028 cfu/ml to 136 cfu/ml in 21 patients treated for 20 or 30 days. Of the patients treated for 20 or 30 days, 15 of 21 with fever pretreatment and 12 of 18 with night sweats pretreatment reported resolution of these symptoms. The principal side-effects were loose stools or diarrhoea, but these did not result in cessation of therapy. Azithromycin, as a single oral agent, safely reduced M avium complex bacteraemia and associated symptoms in almost 75% of patients treated for at least 20 days. Further studies are needed to assess emergence of resistance.
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PMID:Azithromycin for treatment of Mycobacterium avium-intracellulare complex infection in patients with AIDS. 168 44

Azithromycin and clarithromycin are structural analogues of erythromycin that have similar mechanisms of action. The newer macrolides have several distinct advantages over erythromycin, including improved oral bioavailability; longer half-life, allowing once or twice daily administration; higher tissue concentrations; and fewer gastrointestinal adverse effects. Clarithromycin and azithromycin also have enhanced antimicrobial activity. The clinical efficacy of the newer macrolides has been similar to erythromycin for the treatment of upper and lower respiratory tract and skin and soft tissue infections. New therapeutic roles include the use of azithromycin for C. trachomatis infections and the inclusion of clarithromycin or azithromycin as part of therapeutic regimens for disseminated MAC infections in HIV-infected patients. Further clinical trials are needed to determine the optimal roles for and uses of these new macrolides.
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PMID:The newer macrolides. Azithromycin and clarithromycin. 749 Apr 41

In June 1993, the United States Public Health Service (USPHS) made recommendations for treatment of disseminated Mycobacterium avium complex (MAC) in patients infected with the human immunodeficiency syndrome (HIV). It was suggested that every treatment regimen include either azithromycin or clarithromycin plus one or more of the following drugs: ethambutol, clofazimine, rifabutin, rifampin, ciprofloxacin, or amikacin. This study compares the effect of multiple drug therapy regimens on the survival of patients of the HIV outpatient department of the Medical Center of New Orleans, Louisiana. A retrospective chart review of 122 confirmed cases of MAC was conducted. Three treatment groups were considered: no/monotreatment (n = 40), multitreatment without clarithromycin (n = 32), and multitreatment with clarithromycin (n = 50). Azithromycin, amikacin, and rifabutin were not used in this clinic during the study period. Both multitreatment without clarithromycin (p < 0.03) and multitreatment with clarithromycin (p < 0.005) were significantly protective for survival after adjusting for CD4 cell count at time of diagnosis, nonadherence to treatment, number of concomitant opportunistic infections at diagnosis, and weight loss > 10%. Neither of the groups that received multidrug therapy were significantly less likely to have MAC-related symptoms than the no/mono group at 3 and 6 months postdiagnosis. These findings support the USPHS recommendation for multiple drug treatment either with or without clarithromycin. Prospective controlled clinical trials will clarify the optimal regimen for disseminated MAC disease.
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PMID:Comparison of multiple drug therapy regimens for HIV-related disseminated Mycobacterium avium complex disease. 774 89

Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections. In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient. This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once-daily dosing to 58% with four-times-a-day dosing. Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous. In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H. influenzae, MAC in AIDS, MOTT, and leprosy. Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis.
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PMID:Azithromycin and clarithromycin. 779 24

Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointestinal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory concentrations of antibiotics which have anti-MAC activity in vitro affect the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MIC, 2.6 micrograms/ml), sparfloxacin (MIC, 8.4 micrograms/ml), or azithromycin (MIC, 32 micrograms/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then washed to remove unbound bacteria and were subsequently lysed. The number of MAC isolates that bound to the HT-29 cells was determined by plating the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 micrograms/ml reduced MAC binding to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 micrograms/ml inhibited binding by 77 to 93%. Azithromycin at concentrations of 2, 10, and 30 micrograms/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin and quinolones.
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PMID:Rifabutin and sparfloxacin but not azithromycin inhibit binding of Mycobacterium avium complex to HT-29 intestinal mucosal cells. 806 66

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.
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PMID:Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine. 838 9


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