Table 3.

Features to consider in the design of future trials of inhaled antibiotics.

Trial design

Clinical endpoint

Mortality

Clinical cure

Microbiologic eradication

Change in CPIS over time

Reduction in use of systemic antibiotics and antibiotic side effects

Other endpoints: Monitor for emergence of resistance during therapy

Design features

Adjunctive to systemic therapy routinely, or only as salvage therapy?

Limit prior systemic antibiotics

Define duration of systemic therapy for pneumonia: 7–10 days maximum

Define duration of inhaled antibiotics: to parallel intravenous antibiotics

Antibiotic choice

Only gram–negatives or also include therapy for gram-positives (use more than one drug)?

Define dose of inhaled antibiotic

Specify which systemic therapy is used.

Patient population

Ventilated only, or also include non-ventilated?

At risk for MDR pathogens or proven MDR pathogens?

Only MDR gram–negatives or also MDR gram–positives?

APACHE II of 10–25

Technical considerations

Define aerosol delivery device

Define how to coordinate device with ventilator

Define ventilator settings, sedation, humidification

Measure drug levels in tracheal secretions and in distal lung lavage from pneumonic and non-pneumonic areas