Potentiation of azithromycin activity against Escherichia coli by human serum ultrafiltrate.
In this study we investigated the influence of serum ultrafiltrate on the activities of azithromycin, other macrolides and unrelated antibiotics against Escherichia coli. In the presence of serum ultrafiltrate the MIC of azithromycin was decreased by 10-fold. The activities of erythromycin and roxithromycin were also enhanced, although to a lesser extent. The potentiation of activity was inhibited by divalent cations and by pre-treatment of the ultrafiltrate with trypsin. Potentiation of azithromycin activity was associated with a pH-independent, early increase in bactericidal activity and inhibition of bacterial metabolism. We postulate that low molecular weight proteinaceous components of normal human serum interact with azithromycin and other macrolides to alter the susceptibility of Gram-negative bacteria to the antibiotics, possibly through increased macrolide penetration across the bacterial cell membrane permeability barriers.
Pruul
H
H
Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, Australia.
McDonald
P J
PJ
D017963:Azithromycin; D001770:Blood Bactericidal Activity; D001790:Blood Physiological Phenomena; D001798:Blood Proteins / Q000502:physiology; D002250:Carbon Radioisotopes; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D013936:Thymidine / Q000378:metabolism
D001798:Blood Proteins; D002250:Carbon Radioisotopes; D004917:Erythromycin; D017963:Azithromycin; D013936:Thymidine