Eagle effect

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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, [1] [2] though recent usage generally refers to the relative lack of efficacy of beta lactam antibacterial drugs on infections having large numbers of bacteria. [3] The former effect is paradoxical because the effectiveness of an antibiotic generally rises with increasing drug concentration.

Mechanism

Proposed mechanisms:

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. [7]

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References

  1. 1 2 Eagle, Harry; Musselman, A. D. (July 1948). "The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms". The Journal of Experimental Medicine. 88 (1): 99–131. doi:10.1084/jem.88.1.99. PMC   2135799 . PMID   18871882.
  2. Yourassowsky, E; Vander Linden, MP; Lismont, MJ; Schoutens, E (1978). "Qualitative study of paradoxical zone phenomenon of penicillins against 17 bacterial species of clinical importance". Chemotherapy. 24 (2): 92–6. doi:10.1159/000237766. PMID   340171.
  3. Stevens, DL; Gibbons, AE; Bergstrom, R; Winn, V (July 1988). "The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis". The Journal of Infectious Diseases. 158 (1): 23–8. doi:10.1093/infdis/158.1.23. PMID   3292661.
  4. Pollard, Andrew J.; McCracken, George H.; Finn, Adam (2004). Hot Topics in Infection and Immunity in Children. Springer. p. 187. ISBN   9780306483448.
  5. Ikeda, Y; Fukuoka, Y; Motomura, K; Yasuda, T; Nishino, T (January 1990). "Paradoxical activity of beta-lactam antibiotics against Proteus vulgaris in experimental infection in mice". Antimicrobial Agents and Chemotherapy. 34 (1): 94–7. doi:10.1128/AAC.34.1.94. PMC   171526 . PMID   2183712.
  6. Pharmaceutical Microbiology, pg188, 7th Edition, Denyer, Hodges, Gorman
  7. Hasan, Nurhasni; Cao, Jiafu; Lee, Juho; Hlaing, Shwe Phyu; Oshi, Murtada A.; Naeem, Muhammad; Ki, Min-Hyo; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook (2021-06-02). "Bacteria-Targeted Clindamycin Loaded Polymeric Nanoparticles: Effect of Surface Charge on Nanoparticle Adhesion to MRSA, Antibacterial Activity, and Wound Healing". Pharmaceutics. 11 (5): 236. doi: 10.3390/pharmaceutics11050236 . PMC   6571677 . PMID   31096709.