Impact of elexacaftor/tezacaftor/ivacaftor on bacterial cultures from people with cystic fibrosis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have shown beneficial effects on both forced expiratory volume in 1 s (FEV1 ) and frequency of pulmonary exacerbations in people with cystic fibrosis (CF). These positive outcomes may be related to changes in bacterial colonization within the lungs. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the first triple therapy CFTR modulator approved for use in people with CF 6 years and older. This study aimed to determine the impact of ELX/TEZ/IVA on the isolation of Pseudomonas aeruginosa (Pa), methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA, respectively) in respiratory cultures. METHODS: A retrospective chart review of the electronic medical record at the University of Iowa was completed for individuals 12 years and older taking ELX/TEZ/IVA for at least 12 months. The primary outcome was determined by assessing bacterial cultures pre- and postinitiation of ELX/TEZ/IVA. Baseline demographic and clinical characteristics were summarized using mean and standard deviation for continuous outcomes and count and percentage for categorical outcomes. Culture positivity for Pa, MSSA, and MRSA was compared among enrolled subjects between pre- and posttriple combination therapy periods using an exact McNemar's test. RESULTS: One hundred and twenty-four subjects prescribed ELX/TEZ/IVA for at least 12 months met the requirements for inclusion within our analysis. Culture positivity for Pa, MSSA, and MRSA was approximately 54%, 33%, and 31%, respectively, for the pre-ELX/TEZ/IVA period. Prevalence decreased to approximately 30%, 32%, and 24% (-24.2% [p < 0.0001], -0.7% [p = 1.00], and -6.5% [p = 0.0963], respectively) post-ELX/TEZ/IVA. The source of bacterial culture was predominantly sputum (70.2%) in the pre-ELX/TEZ/IVA group, whereas a throat source (66.1%) was more common post-ELX/TEZ/IVA. CONCLUSIONS: ELX/TEZ/IVA treatment has an appreciable impact on the detection of common bacterial pathogens in CF respiratory cultures. While previous studies have found a similar effect with single and double CFTR modulator therapies, this is the first single-center study to show the impact of triple therapy, ELX/TEZ/IVA, on bacterial isolation from airway secretions.

Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder that results in the buildup of mucus in various organs. Ninety percent of CF patients are classified as pancreatic insufficient, leading to malabsorption of nutrients and fat-soluble vitamins without the assistance of exogenous pancreatic enzymes. This study was designed to determine if serum 25-hydroxyvitamin D concentrations were impacted by initiation of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). METHODS: Serum 25-hydroxyvitamin D concentrations were measured before and 1 year post-ELX/TEZ/IVA initiation. A Wilcoxon signed-rank test was used to compare values. RESULTS: Seventy-six patients were included in the final analysis. The average age of our population was 25.8 years (SD = 13.2 years) with a majority being male, homozygous F508del, pancreatic insufficient, and not modulator-naive. The median increase of serum vitamin D concentration after initiating ELX/TEZ/IVA was 5 ng/ml (interquartile range = -4, 13; p = .0035). CONCLUSIONS: We suggest that ELX/TEZ/IVA may improve fat-soluble vitamin absorption, specifically serum 25-hydroxyvitamin D. These results may lead to adjustments in vitamin supplementation in patients receiving cystic fibrosis transmembrane conductance regulator modulator therapy.

Off-label use of intravenous antimicrobials for inhalation in patients with cystic fibrosis.

Management of infections in patients with cystic fibrosis (CF) presents challenges for healthcare providers, including the eradication of initial acquisition, treatment of acute exacerbations, and chronic infection with suppressive therapy. Inhaled antimicrobial therapy for infections in patients with CF has been used in these capacities, often in an effort to achieve optimal concentrations in sputum for antimicrobial efficacy while mitigating potential toxicities associated with systemic therapy. Unfortunately, there are few commercially available products formulated for inhalation, resulting in the off-label use of other formulations, such as intravenous products, administered via nebulization. This review aims to examine the evidence supporting the efficacy of these off-label formulations for management of acute and chronic infections associated with CF, as well as adverse effects associated with their use.

Impact of pharmacy services on cystic fibrosis transmembrane conductance regulator modulator prescribing at a pediatric cystic fibrosis center.

BACKGROUND: This study was undertaken to determine if the presence of a clinical pharmacy team impacted patients' access to cystic fibrosis transmembrane conductance regulator (CFTR) modulators. METHODS: A retrospective chart review of electronic medical records from the University of Iowa Hospitals and Clinics (UIHC) was conducted. Data were collected regarding the timing of prior authorization (PA) submissions and approvals from 2012 to 2018. The Wilcoxon rank-sum test was used to compare the meantime (days) between prescription and PA submission dates, and PA submission and approval date for all patients included in the analysis. Comparisons were made for pre- and postpharmacy services eras as well as the UIHC Specialty Pharmacy versus a non-UIHC Specialty Pharmacy. RESULTS: Sixty-three patients were included in the final analysis. The average time between prescription date and PA submission was 12.5 days (standard deviation [SD] = 17.4 days) in the preclinical pharmacy services era and 3.5 days (SD = 5.8 days; P = .028) in the postclinical pharmacy services era. The average time to PA submission significantly decreased from 9.8 days (SD = 13.1 days) to 1.3 days (SD = 4.2 days; P < .0001) when prescriptions were filled by the UIHC Specialty Pharmacy vs a non-UIHC Specialty Pharmacy. CONCLUSIONS: There was a significant benefit to CFTR modulator prescribing when clinical pharmacy services were incorporated in our cystic fibrosis (CF) care team, which will become increasingly important with the anticipation of new CF medications in the near future.