Towards better ICU antibiotic dosing.

OBJECTIVE

To review the recent pharmacokinetic and pharmacodynamic reports of some of the commonly used antibiotics in critically ill patients and recommend alterations in their administration to improve their efficacy.

DATA SOURCES

Relevant articles and published reviews on aminoglycoside, third and fourth generation cephalosporins, vancomycin and ciprofloxacin dosing in critically ill patients.

SUMMARY OF REVIEW

Antibiotic regimens are derived from non-critically ill volunteers. To optimise antibiotic administration in the intensive care unit, the different 'kill-characteristics' of the antibiotic classes and the altered drug pharmacokinetics in critically ill patients should be considered together to re-evaluate the currently recommended regimens. Aminoglycosides require high peak levels to be most effective, hence large single daily doses are important. With the increased clearances in the critically ill patient, particularly those who have normal renal function, a more frequent administration than single daily dosing may be optimal (e.g. 18-hourly). Increased clearances of beta-lactam antibiotics result in low troughs causing a reduced duration of antibiotic levels above the minimum inhibitory concentration (i.e. the suggested pharmacological target for these drugs). In critically ill patients frequent dosing or even continuous infusions of the beta-lactam antibiotics may increase their effectiveness by maintaining blood levels above the minimum inhibitory concentration (MIC) for longer periods. Vancomycin has a high volume of distribution in the critically ill patient, thus the currently recommended maximum daily dose may lead to inadequate serum levels. Suggested targets for quinolone therapy involve more than just high peak levels. A ratio of Area Under (serum) Concentration (AUC) time curve to MIC of >125 has been shown to correlate with better clinical outcomes. Ciprofloxacin when given intravenously at 400 mg 8-hourly should achieve this, which is a regimen that has been shown to be safe.

CONCLUSIONS

Applying pharmacokinetic and pharmacodynamic principles to critically ill patients will lead to better antibiotic use and hopefully a better outcome.