Pharmacokinetics of vancomycin in sputum of intubated patients: Optimized intravenous delivery vs. inhaled therapy.

ABSTRACT

AIMS: Intubated patients with methicillin-resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15-20 µg/mL) in 38-79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit. METHODS: Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15-20 µg/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re-assessed after 4 treatments of inhaled vancomycin (120 mg/2 mL) via a previously characterized nebulizing system that deposited 18 ± 2 mg in the lungs. Vancomycin post-distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin. RESULTS: Mean serum trough concentration was 18.4 ± 6.5 µg/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to therapeutic (15.7-17 µg/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199 ± 37.0 µg/mL (P = .002) exceeding minimum inhibitory concentration by 2 orders of magnitude. CONCLUSION: Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator-associated methicillin-resistant Staphylococcus aureus infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator-associated pneumonia and as single therapy in tracheobronchitis.