caa a22 4500 397591136 CHVBK 20180308164939.0 cr unu---uuuuu 161202e199606 xx s 000 0 eng 10.1093/jac/37.suppl_C.21 doi (NATIONALLICENCE)oxford-10.1093/jac/37.suppl_C.21 Influence of immunosuppression on the pharmacokinetics and pharmacodynamics of azithromycin in infected mouse tissues [Elektronische Daten] [D. Girard, P. A. Regan, W. B. Milisen, J. A. Retsema, A. C. Swindell] Azithromycin has been shown to preferentially distribute to infection loci. Due to the potential contribution of phagocytes as transporters of drug to these sites, there has been some concern that immunosuppression of the cellular arm of the host defence system would greatly reduce the delivery of azithromycin to sites of infection and hence impair efficacy. Therefore, we evaluated the phannacokinetics and pharmacodynamics of azithromycin in a Staphylococcus aureus intramuscular infection model in normal and immunosuppressed mice, employing therapeutic and prophylactic regimens. Immunosuppression was induced by daily doses of cyclophosphamide that culminated in leucopenia with an underlying granulocy-topenic condition, with circulating peripheral granulocytes numbering from ≤ 0.1-0.3 × 109/L. Azithromycin tissue levels were not reduced in infection loci in granulocytopenic mice but moderate increases in Cmax, and AUC values were observed, relative to similar tissues from normal mice. The tissue half-life of azithromycin in infected tissues in a therapeutic mode (75 h) was three-fold longer than in a prophylactic mode (25 h); this correlated with the degree of inflammation (therapy was withheld until inflammation was evident; i.e., prophylaxis reduced inflammation). Histological examination of infected tissues from normal and leucopenic mice was indistinguishable despite a 70%-85% reduction in circulating granulocytes. Compared with untreated infected controls, bactericidal activity was noted following prophylaxis with azithromycin and bacteraemia was suppressed in mice receiving azithromycin therapeutically. In summary, these data indicate that azithromycin delivery and efficacy in a moderately immunosuppressed animal model are unimpaired. © 1996 The British Society for Antimicrobial Chemotherapy Articles nationallicence Girard D. Central Research Division, Pfizer Inc Groton, CT06340 aut Regan P. A. Central Research Division, Pfizer Inc Groton, CT06340 aut Milisen W. B. Central Research Division, Pfizer Inc Groton, CT06340 aut Retsema J. A. Central Research Division, Pfizer Inc Groton, CT06340 aut Swindell A. C. A. C. Swindell Associates 192 Monument Street, Groton, CT 06340, USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-06), 21-35 0305-7453 37<21 1996 37 jac https://doi.org/10.1093/jac/37.suppl_C.21 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.suppl_C.21 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Girard D. Central Research Division, Pfizer Inc Groton, CT06340 aut NATIONALLICENCE 700 1- Regan P. A. Central Research Division, Pfizer Inc Groton, CT06340 aut NATIONALLICENCE 700 1- Milisen W. B. Central Research Division, Pfizer Inc Groton, CT06340 aut NATIONALLICENCE 700 1- Retsema J. A. Central Research Division, Pfizer Inc Groton, CT06340 aut NATIONALLICENCE 700 1- Swindell A. C. A. C. Swindell Associates 192 Monument Street, Groton, CT 06340, USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-06), 21-35 0305-7453 37<21 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford