Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management

Abstract

Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data.