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Postantibiotic effect in vitro

The interaction between a microorganism and various physical and chemical treatments is complex in nature. In many cases, bacterial killing seems to be a gradual process, and if the process has not progressed too far the surviving bacteria do not immediately resume multiplication. However, after incubation in a suitable environment, they regain the ability to multiply after a longer lag period as compared with non-treated bacteria. Treatments demonstrated to induce an extended lag before bacterial regrowth include heating, freezing, drying, radiation (Mackey & Derrick, 1982), exposure to the platelet-microbicidal protein (Yeaman et al. 1992) and amiloride, an inhibitor of potassium electrolyte transport (Giunta et al. 1986). The phenomenon with delayed regrowth following short-term exposure to an antimicrobial agent has been termed postantibiotic effect (PAE). Awareness of PAE as a biological phenomenon is not new. In 1944, Bigger noted delayed development in turbidity after adding penicillinase to cultures of staphylococci previously exposed to penicillin (Bigger, 1944). A few years later Parker (Parker & Luse, 1948; Parker & Marsh, 1946) demonstrated that staphylococci briefly exposed to penicillin and transferred to a drug free medium did not resume normal growth for up to three hours. Eagle confirmed and extended these observations with penicillin to staphylococci and streptococci both in vitvu and in vivu (Eagle et al. 1950b; Eagle et al. 1950b; Eagle & Musselman, 1949b; Eagle et al. 1950b). For the next decades PAE was studied by researchers in mycobacteriology. It was observed that most antimycobacterial drugs induced an extended bacterial lag of regrowth (Beggs & Jenne, 1969; Mitchison & Dickinson, 1971; Dickinson, 1968; Dickinson et al. 1968; Dickinson & Mitchison, 1966; Armstrong, 1960). In the 1970’s PAE was “rediscovered” in non-mycobacterial microorganisms (Wilson & Rolinson, 1979; Rolinson et al. 1977; Hunter et al. 1976; McDonald et al. 1977; McDonald et al. 1976) and during the past two decades PAE has been proved in almost every bacteria-drug combination tested. The intention of this review is to present data contributed by the author on PAE in vitro, which will include: methods used for determination of PAE, factors of importance for the presence and duration of PAE, the mechanism of action behind the PAE, and other postexposure events. Finally, considerations are given to the potential clinical significance of PAE.