Diagnostic Techniques and Procedures for Establishing the Microbial Etiology of Ventilator-Associated Pneumonia for Clinical Trials: The Pros for Quantitative Cultures

Use of only clinical criteria for enrolling patients in clinical trials leads to inclusion of many patients who have no pulmonary infection, which can make the evaluation of new treatment modalities difficult. Quantitative cultures of specimens obtained using bronchoscopic or nonbronchoscopic techniques, such as bronchoalveolar lavage and/or protected specimen brush, are much more specific and could improve identification of patients with ventilator-associated pneumonia. Microscopic examination of distal respiratory secretions with use of Gram staining permits randomizing only patients with a high probability of ventilator-associated pneumonia and, thus, avoids the potential bias that can result from secondary exclusions. Invasive techniques also offer a sensitive and specific approach for identifying the responsible microorganisms, which is particularly important when evaluating antimicrobial agents for which bactericidal activity can be highly variable from one pathogen to another. Follow-up evaluation of the infected site with use of the same techniques permits determination of the pharmacokinetic and/or pharmacodynamic parameters of the new agents and their microbiological efficacy, compared with current antibiotics.