CORRELATION BETWEEN BACTERICIDAL ACTIVITY AND POSTANTIBIOTIC EFFECT FOR 5 ANTIBIOTICS WITH DIFFERENT MECHANISMS OF ACTION

Theoretically, if the postantibiotic effect (PAE) reflects the duratio n of cellular recovery, then the extent of cellular damage inflicted o n bacteria by an antibiotic, as suggested by the degree of bactericida l activity, should reflect the length of PAE; this is especially true if binding of the antibiotic to bacterial receptors is irreversible. T o test this hypothesis, correlation between PAEs and bactericidal rate constants measured simultaneously at various antibiotic concentration s 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: t he first three bind irreversibly to bacterial receptors, while trimeth oprim and tetracycline bind reversibly. Both PAE and bactericidal acti vity increased nonlinearly with concentrations in a saturable manner f or all the combinations studied. Linear least-square regression analys es showed strong correlations (P < 0.01) between the two responses for individual combinations. Such a linear relationship also extended, wi th good correlation (P < 0.05), across the five combinations when indi vidual maximal bactericidal rate constants and PAEs were considered se parately. These observations suggest that cellular recovery from nonle thal damage following antibiotic exposure may be a major determinant o f PAE.