Pharmacogenetic actionability and medication prescribing in people with cystic fibrosis.

Although major advancements have been made in the therapeutics for people with cystic fibrosis (PwCF), many still require the use of multiple medications to manage acute exacerbations of disease and maintain health. Iterative trial and error processes of pharmacotherapeutic management can be optimized by assessing and incorporating pharmacogenetics. For 82 PwCF, we reviewed 2 years of medication use and response history and interrogated metabolizer status for common pharmacogenes, revealing 3336 medication exposure events (MEEs) to 286 unique medications. As expected, the more frequent MEEs were those commonly used to treat cystic fibrosis (CF), such as antibiotics and respiratory medications. Antibiotics also comprised 56.7% of the undesirable drug responses. The impact of gene variants on drug responses was assessed using Pharmacogenomics Knowledgebase (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Thirty-three (11.5%) medications have strong evidence of genetic influence on response as evidenced by gene-based dosing guidelines. 110 (38.5%) unique medications had at least one association with a very important pharmacogene, whereas 143 (50%) were associated with at least one clinical or variant annotation. Over 97% of participants had at least one actionable genotype. Eleven (13.4%) patients with an actionable genotype, taking the impacted medication, had an undesirable drug response described in the CPIC guidelines that could potentially have been mitigated with a priori knowledge of the genotype. PwCF take many medications for disease management, with frequent dose changes to elicit a desired clinical effect. As CF care evolves, implementing pharmacogenetics testing can improve efficiency and safety of prescribing practices using precision selection and dosing at medication initiation.

Ceftaroline vs vancomycin for the treatment of acute pulmonary exacerbations in pediatric patients with cystic fibrosis.

INTRODUCTION: Respiratory infection with methicillin-resistant Staphylococcus aureus (MRSA) is an increasing complication in cystic fibrosis (CF) that results in accelerated lung function decline and mortality. Vancomycin is considered a first-line intravenous treatment agent for MRSA associated acute pulmonary exacerbations (APEs); however, rates of vancomycin intolerance and resistance have been observed. These factors have led to the exploration of additional treatment options for treating MRSA associated APEs. METHODS: This is a retrospective chart review conducted at a CF center including patients 0 to 21 years of age with CF admitted for an APE and treated with either vancomycin or ceftaroline between January 2016 and August 2018. The primary endpoint was to determine ceftaroline efficacy compared to vancomycin in the treatment of MRSA associated APEs. RESULTS: There were 180 patients included in the study with 90 patients in each antibiotic group. Admission to discharge forced expiratory volume in 1 second (FEV1 ) improved in the ceftaroline (66.5% vs 81.1%; P < .001) and vancomycin (65.5% vs 77.3%; P < .001) treatment groups. No difference existed in mean change in FEV1 (14.1% vs 13.5%; P = .25) or readmissions (15% vs 22; P = .27) between ceftaroline and vancomycin groups, respectively. DISCUSSION: In this retrospective study, no difference existed between ceftaroline and vancomycin with regard to observed improvement in lung function from admission to discharge. Additionally, no difference was observed in mean FEV1 or readmission rate between the two groups. Ceftaroline may represent an effective and safe intravenous antimicrobial option for targeting MRSA in pediatric CF patients with APEs.