Antimicrobial pharmacodynamics is the relationship between the concentration of anantibiotic and its ability to inhibit vital processes ofendo- or ectoparasites andmicrobial organisms.[1] This branch ofpharmacodynamics relates the concentration of an anti-infective agent to its effect, specifically to its antimicrobial effect.[2]
Theminimum inhibitory concentration (MIC) andminimum bactericidal concentration are used to measurein vitro activity ofantimicrobial agents. They are good indicators of antimicrobial potency, but don't give any information relating to time-dependent antimicrobial killing (the so-called post antibiotic effect).[1]
The post-antibiotic effect (PAE) is defined as persistent suppression ofbacterial growth after a brief exposure (1 or 2 hours) of bacteria to anantibiotic even in the absence ofhost defense mechanisms.[3] Factors that affect the duration of the post-antibiotic effect include duration of antibiotic exposure, bacterial species, culture medium and class of antibiotic. It has been suggested that an alteration of DNA function is possibly responsible for the post-antibiotic effect following the observation that most inhibitors of protein and nucleic acid synthesis (aminoglycosides,fluoroquinolones,tetracyclines,clindamycin, certain newermacrolides/ketolides, andrifampicin andrifabutin) induce long-term PAE against susceptible bacteria.[3][4] Theoretically, the ability of an antibiotic to induce a PAE is an attractive property since antibiotic concentrations could fall below the MIC for the bacterium yet retain their effectiveness in their ability to suppress the growth. Therefore, an antibiotic with PAE would require less frequent administration and it could improve patient adherence with regard to pharmacotherapy.[3][5] Proposed mechanisms include (1) slow recovery after reversible nonlethal damage to cell structures; (2) persistence of the drug at a binding site or within theperiplasmic space; and (3) the need to synthesize new enzymes before growth can resume. Most antimicrobials possess significant in vitro PAEs (≥ 1.5 hours) against susceptible gram-positivecocci. Antimicrobials with significant PAEs against susceptible gram-negative bacilli are limited tocarbapenems and agents that inhibit protein or DNA synthesis.[6]
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