Resistance to macrolides in vitro is increasingly being reported. However, there has been no corresponding increase in clinical failures noted. Lack of clinical failures due to resistance is most likely the result of the high intracellular concentrations that these drugs achieve in phagocytes. In the case of clarithromycin, concentrations in both monocytes and granulocytes fluctuate between peaks of approximate to 22-25 mg/l and troughs of approximate to 5 mg/l during a standard dosing interval. In contrast, azithromycin attains concentrations of over 60 mg/l in granulocytes and at least 100 mg/l in monocytes. After 7 days, azithromycin concentrations of > 32 mg/l are still observed. These data also imply that against pathogens with increasing minimum inhibitory concentrations (MICs), macrolides with relatively lower or less sustained intracellular concentrations will become ineffective clinically much sooner than compounds, such as azithromycin, that concentrate to a high degree and are retained in white blood cells for prolonged periods. (C) 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.
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Bermudez, LE
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Petrofsky, M
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Petrofsky, M
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Kolonoski, P
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Calif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USACalif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA
Kolonoski, P
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Young, LS
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Calif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USACalif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA
Bermudez, LE
;
Petrofsky, M
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Calif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USACalif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA
Petrofsky, M
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Kolonoski, P
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Calif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USACalif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA
Kolonoski, P
;
Young, LS
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