Correlation between bactericidal activity and postantibiotic effect for five antibiotics with different mechanisms of action

Abstract

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.