Understanding persistent bacterial lung infections: clinical implications informed by the biology of the microbiota and biofilms

Abstract

The infections found in chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis share a number of clinical similarities, the most striking of which is bacterial persistence despite the use of antibiotics. These infections have been clinically described using culture-based methods usually performed on sputum samples, and treatment has been directed towards the bacteria found in this manner. Unfortunately the clinical response to antibiotics is frequently not predictable based on these cultures, and the role of these cultured organisms in disease progression has been debated. The past 20 years have seen a revolution in the techniques used to describe bacterial populations and their growth patterns. These techniques have revealed these persistent lung infections are vastly more complicated than described by traditional, and still widely relied upon, sputum cultures. A better understanding of the initiation and evolution of these infections, and better clinical tools to describe them, will dramatically alter the way patients are cared for. While clinical tests to more accurately describe these infections are not yet available, the better appreciation of these infections afforded by current science should enlighten practitioners as to the care of their patients with these diseases.

Keywords: Chronic obstructive pulmonary disease; bronchiectasis; cystic fibrosis; microbiota; sputum culture.

Figure 1. The inherent challenge in morphotype selection for further testing and clinical report

All of the colonies on this image are various morphotypes of P. aeruginosa, and each patient with persistent lung disease may harbor dozens of these morphotypes if carefully screened. Typically one or two are subjectively chosen for MIC testing and clinical report. Bacterial medium is a Congo red agar, image and background discussion kindly provided by H. Kulasekara and L. Hoffman.

Figure 2. Diversity of the microbiota is correlated with lung function

In this study by Zemanick, bacterial diversity was determined in patients undergoing an exacerbation. The Shannon Diversity score is a measure of the richness and eveness of populations. Patients with lower FEV1% predicted scores typically contain less diversity. The size of the circle represents the relative abundance of P. aeruginosa with larger circles indicating patients dominated by P. aeruginosa. Reproduced with permission from the authors, obtained via open access from PLOS one.

Figure 3

An updated model of persistent lung infection informed by knowledge of microbiota and biofilms