Sputum concentration of amikacin varies with nebulizer efficiency measured in vitro in patients on mechanical ventilators

Background

Evaluation of the clinical utility of aerosolized antibiotics in patients with ventilator-associated pneumonia has been hampered by the inefficiency of available nebulizers. The Aerogen pulmonary drug delivery system (APD) is in development for high-efficiency lung deposition of novel therapies in mechanically ventilated patients. We compared delivery of amikacin (AMIK) via APD vs the the Aeroneb Pro (AP), and vs the AirLife™ Misty Neb™ (MN), in mechanically ventilated patients. We wanted to determine how AMIK concentrations in the sputum relate to device efficiency previously determined in vitro [1].

Methods

Twelve patients on volume-cycled ventilation (various primary diagnoses and vent settings) were enrolled. All had purulent secretions, but no fever or X-ray evidence of pneumonia. On separate study days (≥ 2 days washout), patients received sulfite-free AMIK (125 mg/ml): 800 mg via MN, 800 mg via AP, or 400 mg via APD (in anticipation of higher efficiency), in randomized order. Tracheal aspirates were obtained at 15 min postdosing and amikacin concentrations were determined. Data were compared with in vitro measurements of lung dose using typical adult ventilator settings.

Results

All treatments were well tolerated. Table 1 presents the evaluable sputum AMIK concentrations from tracheal aspirates normalized to the starting dose (mg/ml/mg starting dose), and in vitro lung dose as the per cent of the total dose (means ± SD). Sputum concentrations were greater with AP and APD than with MN (P < 0.05). For the lung dose: APD > AP > MN (P < 0.05).

Table 1

Conclusions

APD delivered AMIK with greater efficiency than the marketed nebulizers. Concentrations of AMIK in the sputum were consistent with relative device efficiency measured in vitro. High efficiency delivery via APD may make aerosolized AMIK a viable part of treatment regimens for ventilator-associated pneumonia.