Antimicrobial resistance and susceptibility testing in cystic fibrosis lung infections

Cystic fibrosis is an inherited, multi-system disease caused by malfunction of the Cystic Fibrosis Conductance Regulator (CFTR) gene/protein. The abnormal function of CFTR results in abnormalities of in sodium and water transport with abnormally viscous secretions. Lung disease, the main morbidity and mortality, is characterized by chronic bacterial endobronchial infection. The endobronchial microenvironment further shows neutrophilic inflammation, high protease activity and anaerobic conditions.

Key bacteria in CF include Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and also other gram-negatives e.g. Achromobacter and Stenotrophomonas. SA is the earliest organism and in the U.S. 25% of the infections are due to methicillin resistant SA (MRSA). Chronic infection of MRSA and PA is associated with worse clinical outcomes. Bacterial adaptations present for both organisms or in mixed infections include biofilm formation, mucoidity and slow growing phenotypes. Data is shown on details of these findings for each bacterium from studies using bacteria from sputum from people with CF.

Multi-drug resistance of PA is a clinical problem yet data from in vitro susceptibility is not accurate in predicting in vivo response. The adaptive bacterial growth modes and heterogeneity of isolates within the same sputum contribute to these discrepant findings.

In summary, in chronic bacterial CF lung infections in vitro testing is often not helpful and clinical acumen for selection of antibiotics is recommended.