Developing molecular amplification methods for rapid diagnosis of respiratory tract infections caused by bacterial pathogens.

Current diagnostic methods for bacterial respiratory tract infections are slow and often of marginal value for patient management if the adequacy of the specimen is not confirmed before culture. Molecular amplification tests, which are highly sensitive, can provide results in hours rather than days but may not distinguish colonization from infection unless a quantification step is included. Defining the reference method to be used for evaluating a novel molecular assay, with input from the US Food and Drug Administration (FDA), is critical before initiating development of a potential product. Although expectorated sputum may be the clinician's specimen of choice for testing because of ease of collection, the poor quality of such specimens may pose problems for clinical trials of novel amplification tests. There are still many gaps in our understanding of the interplay between colonization and infection and of the role that amplification tests may play in guiding anti-infective therapy. Thus, the performance parameters of a new diagnostic method should be closely matched to a precisely defined intended use statement.