Background and objectives: Penicillin/beta-lactamase inhibitors are often used to treat aspiration pneumonia in patients resuscitated after cardiac arrest (CA). The impact of hypothermic temperature control on the pharmacokinetics of amoxicillin/clavulanate (AMO/CLAV) and ampicillin/sulbactam (AMP/SULB) has not been studied. Our objective was to evaluate the effects of hypothermic temperature control on the plasma and soft tissue pharmacokinetics of AMO/CLAV and AMP/SULB, including pulmonary concentrations of AMP/SULB, in patients resuscitated after CA.

Methods: This prospective clinical study involved ten adult patients after CA receiving either AMO/CLAV 2 g/0.2 g or AMP/SULB 2 g/1 g intravenously every 8 h. Patients underwent hypothermic temperature control (33 ± 1 °C) for 24 h, followed by normothermia. Plasma, urine, muscle, and subcutaneous pharmacokinetics were measured and plasma protein-binding assessed for each subject. Microdialysis determined unbound drug concentrations in soft tissues. The pulmonary concentration of AMP/SULB was analyzed in the epithelial lining fluid.

Results: No significant differences in plasma pharmacokinetics or renal excretion of AMO/CLAV and AMP/SULB were observed between the two temperature conditions. Soft tissue concentrations showed no consistent trend. Pharmacokinetic/pharmacodynamic targets (time that the unbound plasma concentrations were above the minimal inhibitory concentration [MIC] for MIC up to 8 mg/L) were met but not for 16 mg/L. Pulmonary concentrations of AMP/SULB in the epithelial lining fluid showed no clear trend.

Conclusion: This study indicates that hypothermic temperature control does not significantly affect plasma concentrations, soft tissue concentrations, or renal excretion of AMO/CLAV and AMP/SULB in patients resuscitated after CA. However, pulmonary concentrations of AMP/SULB exhibited interindividual variability.