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Journal of Antimicrobial Chemotherapy (1992) 30, 497-507
© 1992 The British Society for Antimicrobial Chemotherapy

research-article

Potentiation of azithromycin activity against Escherichia coli by human serum ultrafiltrate

H. Pruum and P. J. McDonald

Department of Microbiology and Infectious Diseases. Flinders Medical Centre Bedford Park, Australia 5042

Received 11 December 1991; returned 13 May 1992; accepted 13 May 1992

In this study we investigated the influence of serum ultrafiltrate on the activities of azithromycin, other macrolides and unrelated antibiotics against Escherlchia 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.


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