Time-dependent antimicrobials

• Beta-lactams (penicillins and cephalosporins) are considered to be time-dependent antimicrobials.
• In this case, the key factor that correlates with efficacy of the antimicrobial is the percentage of time within a dosing interval that the concentration of antimicrobial remains above the minimum inhibitory concentration (MIC) for the organism.

– For beta-lactams being used against Gram-negative organisms, the level of antimicrobial should ideally be above the MIC for at least 80% of the time.

• In other words, the dosing interval is critical and missed doses will impact on efficacy.

Concentration-dependent antimicrobials

• Fluoroquinolones and aminoglycosides are generally considered to be concentration-dependent.
• This means that the efficacy of the antimicrobial, in terms of bacterial killing, increases as the drug level increases above the MIC of the organism.
• In other words, a high concentration relative to the MIC is key and thus dose size is critical. It doesn’t seem to matter if the level of the antimicrobial dips below the MIC for part of the dosing interval, provided this high concentration has been achieved.

– This is reflected in the fact that aminoglycosides, despite having relatively short half-lives, are most often dosed at a relatively high dose rate but only once daily.