Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness

Many factors over which there may be little control may influence the response of a patient to therapy. However, therapy with antibiotics can be readily optimised.

Concentration-dependent agents such as aminoglycosides appear effective and to entail fewer side effects when given in large, infrequent doses. There is also evidence that time-dependent antibiotics often fail to reach adequate concentrations throughout the treatment period. To date no randomised controlled prospective trial has demonstrated improvement in clinical outcome following infusion rather than intermittent boluses of time-dependent antibiotics. Critical illness alters antibiotic pharmacokinetics principally through increases in volume of distribution. Other than glycopeptides and aminoglycosides, antibiotic blood concentrations are rarely monitored and therefore adequate concentrations can only be inferred from clinical response.

Failure to respond within the first few days of empirical treatment may be due to antibiotic resistance or inadequate doses. Therefore the same rigor should be applied to achieving adequate antibiotic concentrations as is applied to inotropes, which are titrated to achieve predetermined physiological targets.