Decrease in intravenous antibiotic use with adjunctive aerosolized amikacin treatment in intubated mechanically ventilated patients with Gram-negative pneumonia

Introduction

Aerosolized antibiotics may increase lung concentration, reducing the need for i.v. antibiotics. We evaluated safety and i.v. antibiotic use with inhaled amikacin (AMK) during adjunctive treatment of intubated patients with Gram-negative pneumonia.

Methods

A double-blind, placebo-controlled, study of aerosol AMK delivered via the Pulmonary Drug Delivery System (PDDS^®; Nektar Therapeutics) in ventilated patients with Gram-negative pneumonia as an adjunctive to i.v. therapy per ATS guidelines. Patients were randomized to receive aerosol containing 400 mg AMK daily with placebo (normal saline) 12 hours later, 400 mg AMK twice daily or placebo twice daily. The i.v. antibiotics (agent and duration) were determined by the attending physician. The AMK peak serum concentration, trough concentrations and tracheal aspirates were drawn.

Results

The mean number of i.v. antibiotics at the end of the study (mean 7 days) were two times greater with placebo than with twice-daily AMK (P < 0.02) (Figure 1). For daily and twice-daily AMK, the serum C_max were 1.3 and 1.8 μg/ml (respectively) on day 1, and 2.3 and 3.2 μg/ml on day 3. Mean trough levels were 0.87 and 1.49 μg/ml. Tracheal aspirate levels (mean) on day 3 were 6.9 mg/ml (daily) and 16.2 mg/ml (twice daily). Aerosol AMK was well tolerated with no difference in adverse events across treatment groups.

Figure 1

Conclusion

Repeated doses of adjunctive inhaled AMK to mechanically ventilated patients with Gram-negative pneumonia was safe, well tolerated, and associated with less i.v. antibiotic use than placebo.