The Eagle effect, Eagle phenomenon, or paradoxical zone phenomenon, named after
Harry Eagle who first described it, originally referred to the
paradoxically reduced antibacterial effect of penicillin at high doses,
though recent usage generally refers to the relative lack of efficacy of beta lactam antibacterial drugs on infections having large numbers of bacteria.
The former effect is paradoxical because the effectiveness of an antibiotic generally rises with increasing drug concentration.
Mechanism
Proposed mechanisms:
*Reduced expression of
penicillin binding proteins
Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discov ...
during stationary growth phase
*Induction of microbial resistance mechanisms (such as beta lactamases with short half-lives) by high drug concentrations
*Precipitation of antimicrobial drug in vitro,
[ possibly also leading to the crystallized drug being mis-detected as colonies of the microbe.
*Self- antagonising the receptor with which it binds (]penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
binding proteins, for example, in the case of a penicillin).[''Pharmaceutical Microbiology'', pg188, 7th Edition, Denyer, Hodges, Gorman]
Penicillin is a bactericidal antibiotic that works by inhibiting cell wall synthesis but this synthesis only occurs when bacteria are actively replicating (or in the log phase of growth). In cases of extremely high bacterial burden (such as with Group A Strep), bacteria may be in the stationary phase of growth. In this instance since no bacteria are actively replicating (presumably due to nutrient restriction) penicillin has no activity. This is why adding an antibiotic like clindamycin, which acts ribosomally, kills some of the bacteria and returns them to the log phase of growth.
References
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Antimicrobial resistance