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Advanced-generation macrolides: tissue-directed antibiotics.
Int J Antimicrob Agents. 2001; 18 Suppl 1:S11-5.IJ

Abstract

The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts.

Authors+Show Affiliations

The Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394, USA. guy.amsden@bassett.org

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11574189

Citation

Amsden, G W.. "Advanced-generation Macrolides: Tissue-directed Antibiotics." International Journal of Antimicrobial Agents, vol. 18 Suppl 1, 2001, pp. S11-5.
Amsden GW. Advanced-generation macrolides: tissue-directed antibiotics. Int J Antimicrob Agents. 2001;18 Suppl 1:S11-5.
Amsden, G. W. (2001). Advanced-generation macrolides: tissue-directed antibiotics. International Journal of Antimicrobial Agents, 18 Suppl 1, S11-5.
Amsden GW. Advanced-generation Macrolides: Tissue-directed Antibiotics. Int J Antimicrob Agents. 2001;18 Suppl 1:S11-5. PubMed PMID: 11574189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Advanced-generation macrolides: tissue-directed antibiotics. A1 - Amsden,G W, PY - 2001/9/28/pubmed PY - 2002/4/19/medline PY - 2001/9/28/entrez SP - S11 EP - 5 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 18 Suppl 1 N2 - The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts. SN - 0924-8579 UR - https://www.unboundmedicine.com/medline/citation/11574189/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924857901004101 DB - PRIME DP - Unbound Medicine ER -