The therapeutic ratio for an antibiotic is the serum level of the bactericidal antibiotic divided by the minimal inhibitory concentration (MIC) of the organism being treated.
antibiotic serum level-to-MIC ratio =
= (serum level of antibiotic after a dose) / (MIC)
For bloodstream or soft tissue infections, a therapeutic ratio of 4 :1 to 8 :1 is usually sufficient, whereas for pulmonary infection, a ratio of 16: 1 may be required to provide adequate tissue levels, since there is poor penetration of antibiotics into sputum.
For penicillin, this ratio is typically high and easy to achieve. For example, the average MIC for penicillin against Streptococcus group A or S. pneumoniae is 0.015-0.020 µg/mL. With low?dose penicillin,
therapeutic ratio =
= approximately (6.0 µg/mL) / (0.02 µg/mL)
= 300:1 therapeutic ratio.
For aminoglycosides, it is often a problem to achieve adequate therapeutic ratios. If K. pneumoniae's MIC for gentamicin is approximately 1.56 µg/mL
The therapeutic ratio with average serum levels =
= (6 µg/mL) / (1.56 µg/mL)
= about a fourfold ratio
This therapeutic ratio of 4:1 is adequate, in theory, for bloodstream infections. However, this peak is maintained for less than 1?2 hours, and suboptimal dosing is not uncommon with aminoglycosides. Even lower concentrations of the antibiotic are found at tissue levels.
A related problem with the use of aminoglycosides is the narrow margin between effective and toxic concentrations - See [Therapeutic Index]
