caa a22 4500 397592353 CHVBK 20180308164942.0 cr unu---uuuuu 161202e199606 xx s 000 0 eng 10.1093/jac/37.suppl_C.9 doi (NATIONALLICENCE)oxford-10.1093/jac/37.suppl_C.9 Correlation of increased azithromycin concentrations with phagocyte infiltration into sites of localized infection [Elektronische Daten] [A. E. Girard, C. R. Cimochowski, J. A. Faiella] Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 μg compared with ≤ 0.01-0.03 fig at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection. © 1996 The British Society for Antimicrobial Chemotherapy Articles nationallicence Girard A. E. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut Cimochowski C. R. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut Faiella J. A. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-06), 9-19 0305-7453 37<9 1996 37 jac https://doi.org/10.1093/jac/37.suppl_C.9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.suppl_C.9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Girard A. E. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut NATIONALLICENCE 700 1- Cimochowski C. R. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut NATIONALLICENCE 700 1- Faiella J. A. Central Research Division, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-06), 9-19 0305-7453 37<9 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