Journal of Antimicrobial Chemotherapy, Vol 40, 39-45, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
RC Li, SW Lee and CH Kong
Theoretically, if the postantibiotic effect (PAE) reflects the duration of
cellular recovery, then the extent of cellular damage inflicted on bacteria
by an antibiotic, as suggested by the degree of bactericidal activity,
should reflect the length of PAE; this is especially true if binding of the
antibiotic to bacterial receptors is irreversible. To test this hypothesis,
correlation between PAEs and bactericidal rate constants measured
simultaneously at various antibiotic concentrations was examined for five
antibiotic-bacterium combinations. Each of the five antibiotics used, i.e.
tobramycin, ciprofloxacin, dicloxacillin, trimethoprim and tetracycline,
has a different mechanism of action: the first three bind irreversibly to
bacterial receptors, while trimethoprim and tetracycline bind reversibly.
Both PAE and bactericidal activity increased nonlinearly with
concentrations in a saturable manner for all the combinations studied.
Linear least-square regression analyses showed strong correlations (P <
0.01) between the two responses for individual combinations. Such a linear
relationship also extended, with good correlation (P < 0.05), across the
five combinations when individual maximal bactericidal rate constants and
PAEs were considered separately. These observations suggest that cellular
recovery from nonlethal damage following antibiotic exposure may be a major
determinant of PAE.
ORIGINAL ARTICLES
Correlation between bactericidal activity and postantibiotic effect for five antibiotics with different mechanisms of action
Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin. ronli@cuhk.edu.hk
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