Antibiotic management of lung infections in cystic fibrosis. I. The microbiome, methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and multiple infections

Abstract

Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, but many other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.

Keywords: Burkholderia cepacia; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; methicillin-resistant Staphylococcus aureus; microbiome.

Figure 1.

Schematic representation of airway bacterial community diversity versus patient age or lung disease severity. Available data suggest that after an initial increase during childhood, airway bacterial diversity peaks in young adulthood and then declines with advancing age and lung disease progression. At end-stage disease, bacterial communities may be dominated by a single species, most often a “typical” cystic fibrosis opportunistic pathogen. H. influenza = Haemophilus influenzae; P. aeruginosa = Pseudomonas aeruginosa; S. aureus = Staphylococcus aureus.