Eagle and Musselman first reported an unexpected concentration-dependent change in bactericidal activity of beta-lactam antibiotics.
Expectation: The bactericidal activity of an antibiotic increases along with an increase in its concentration (dose dependent activity), i.e., the more the better.
Paradoxical finding: The bactericidal activity of an antibiotic is greater at a lower concentration than it is at a higher concentration, i.e., the less then better.
The precise cause for this is uncertain. A favored hypothesis is that the antibiotic suppresses synthesis of autolytic proteins that terminate the organism.
While first demonstrated in vitro, it has been seen in vivo in experimental animals.
When prescribing an antibiotic it is best to adhere to the dosage recommendations based on clinical studies, and not to assume that giving more will be beneficial.
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