Understanding pharmacokinetics/pharmacodynamics in managing neonatal sepsis

This review describes recent pharmacokinetic and/or pharmacodynamic studies of antimicrobial agents used for treatment of neonatal sepsis.

Pharmacodynamic targets in adults and neonates with sepsis are likely similar; thus, extrapolations are possible. When using beta-lactams, the free-drug concentration should be maintained above the minimum inhibitory concentration (MIC) level for the entire dosing interval, but thus far clinical studies have failed to demonstrate that continuous infusion should be preferred over bolus administration. In aminoglycosides, peak concentration (Cmax)/MIC ratio of 8 or even higher, if possible, should be targeted. For vancomycin, the pharmacokinetic/pharmacodynamic target area under the serum concentration curve (AUC)/MIC ratio of more than 400 is advocated for clinical effectiveness in adults, but with current dosing this will be achieved only if MIC is less than 2 mg/l. In other situations alternative agents are recommended. Neonatal dosing regimens of echinocandins have not been established; preliminary data indicate a dose of 25 mg/m for caspofungin and 7 mg/kg q24h (patients with birth weight >or=1000 g) or 10 mg/kg q24 h (patients with birth weight <1000 g) for micafungin ensure exposure similar to currently recommended adult doses.

The targets proposed, mainly for adults with sepsis, are likely applicable also to neonates, but prior to recommending them for clinical application more studies in septic neonates are required.