The indispensable role of pharmacy services and medication therapy management in cystic fibrosis.

Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)-specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate, and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF-specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF.

Vancomycin Dosing and Monitoring in the Treatment of Cystic Fibrosis: Results of a National Practice Survey.

OBJECTIVES: Vancomycin is commonly used in patients with cystic fibrosis (CF) to treat acute pulmonary exacerbations, but few guidelines exist to help dose and monitor patients. The objective of this study was to assess vancomycin use and monitoring strategies at Cystic Fibrosis Foundation (CFF)-accredited centers in hopes of developing and implementing vancomycin dosing and monitoring standards. METHODS: An anonymous national cross-sectional survey of pharmacists affiliated with CFF-accredited pediatric and/or adult centers was performed by using Surveymonkey.com. The survey consisted of 3 sections: (1) CF Center Demographic Information (10 questions); 2) vancomycin use in pediatric CF patients (31 questions); and 3) vancomycin use in adult CF patients (29 questions); it was administered from March 9, 2015, to April 13, 2015. RESULTS: The survey was completed by 31/69 (45%) pharmacists and 28 (90.3%) reported using vancomycin in the pediatric population. The most common initial starting dose for pediatric patients was 15 mg/kg/dose (57.1%) and every 6 hours was the most common dosing frequency (67.9%). The most common monitoring strategy was collection of a trough concentration (92.9%) with 57.7% of pharmacist targeting a range of 15 to 20 mg/L. The most common initial starting vancomycin dose in adults with CF was 15 mg/kg/dose (61.5%), and initial frequency of every 8 hours (73.1%). The most common monitoring strategy was a trough concentration (96.2%) with 83.3% of pharmacists reporting a goal trough range of 15 to 20 mg/L. CONCLUSIONS: The most common vancomycin dosing reported was 15 to 20 mg/kg/dose every 6 hours (pediatric) and 15 to 20 mg/kg/dose every 8 to 12 hours (adults). Serum concentrations measured to meet monitoring parameters of trough concentrations of 15 to 20 mg/L, or area under the curve to minimum inhibitory concentration ratio > 400, were the same in both pediatric and adult patients.

Outcomes in Postoperative Pediatric Cardiac Surgical Patients Who Received an Antiepileptic Drug.

BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical patients initiated on phenobarbital, phenytoin, and levetiracetam were queried. Patients were excluded if the AED was not initiated on the admission for surgery. Patients who received 1 AED were compared to patients who received 2 AED, and differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS: A total of 37 patients met the study criteria. Patients were initiated on an AED a median of 4 days following surgery and became seizure free a median of 1 day after initiation, with 65% remaining seizure free after the first dose. Half of all patients required 2 AEDs for seizure control, with a higher proportion of adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam. CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work is necessary to evaluate long-term neurodevelopmental outcomes in this population and whether outcomes are a result of the AED or of other clinical sequelae.

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach.

OBJECTIVES: Survey suggests that recommended doses and dosage regimens for antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations in cystic fibrosis (CF) patients are not used, and one way to address these disparities is the involvement of pharmacists who are dedicated to CF. This is the first survey specifically designed for pharmacists at Cystic Fibrosis Foundation (CFF)-accredited centers to identify how tobramycin and antipseudomonal beta-lactams are being used. The purpose of this survey is to quantify this information and to promote future study to allow for implementation of tobramycin and beta-lactam dosage and monitoring standardization. METHODS: An anonymous national cross-sectional survey of pharmacists that are affliated with CFF-accredited programs was performed using Qualtrics.com. RESULTS: The survey had a 48.5% response rate. Most pediatric pharmacists (78.6%) report using extended-interval tobramycin dosage. The most common reported starting dosage was 10 mg/kg every 24 hours; most centers aim for a maximum serum concentration (Cmax) between 20 and 40 mg/L (78.6%). A total of 26 adult pharmacists reported using extended-interval dosage (96%), using an initial dosage of 10 mg/kg/day. The most common parameters used to adjust dosage were Cmax and area under the curve (AUC; 31%); the Cmax goal was 20 to 40 mg/L (84.2%). Most respondents (79%) report using beta-lactams in combination with tobramycin. Extended-infusion and continuous-infusion beta-lactams were used more in adults than pediatric patients. CONCLUSIONS: Most CF pharmacists report using extended-interval tobramycin. With the information from this survey, the establishment of future consensus recommendations by pharmacists for optimal and consistent tobramycin and antipseudomonal beta-lactam dosage and monitoring strategies needs to be considered.

Evaluation of Vancomycin Dosing in Pediatric Cystic Fibrosis Patients.

OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15-20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 ± 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses.

Altered gentamicin serum concentrations in obese pediatric patients.

We performed a retrospective case-cohort study of 50 obese pediatric patients aged 2 to 18 years who received scheduled gentamicin therapy, with serum peak and trough concentrations measured. Obese pediatric patients had significantly higher gentamicin serum peak and trough concentrations despite receiving significantly lower mg/kg of actual body weight doses of gentamicin.

Once-daily gentamicin dosing in pediatric patients without cystic fibrosis.

STUDY OBJECTIVE: To estimate an appropriate once-daily gentamicin dose and dosing interval for non-critical care pediatric patients older than 3 months of age without cystic fibrosis. DESIGN: Pharmacokinetic analysis of data from a retrospective medical record review. SETTING: Large academic children's hospital. PATIENTS: One hundred fourteen non-critical care pediatric patients older than 3 months of age without cystic fibrosis who received multiple-daily dosing regimens of gentamicin between September 2007 and April 2008. MEASUREMENTS AND MAIN RESULTS: Patient-specific pharmacokinetic parameters were calculated using drug concentrations obtained at steady state. Once-daily doses were extrapolated for each patient to achieve goal peak and trough concentrations. Using the average of these doses and the patient-specific pharmacokinetic parameters, theoretical once-daily peak and trough concentrations were calculated for each patient. Patient characteristics were analyzed to determine differences between patients who did and those who did not achieve adequate peak concentrations. Mean +/- SD pharmacokinetic parameters were as follows: elimination rate constant 0.32 +/- 0.06 hour(-1), half-life 2.28 +/- 0.54 hours, and volume of distribution 0.24 +/- 0.08 L/kg. The only patient demographic characteristic found to have a significant effect on the extrapolated peak concentration was age. The following age-specific once-daily doses were calculated: 3 months to less than 2 years, 9.5 mg/kg; 2 years to less than 8 years, 8.5 mg/kg; and 8-18 years, 7 mg/kg. CONCLUSION: Age was the primary factor in determining the once-daily dose of gentamicin in our pediatric population. Further prospective research is necessary to determine the safety and efficacy of these age-based, once-daily doses for gentamicin.