Safety and effectiveness of a risk-stratified venous thromboembolism prophylaxis algorithm in young people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) have an increased risk of thrombosis due to acquired thrombophilia secondary to chronic systemic inflammation and central venous catheter use for treatment of pulmonary infections. The objective of this study is to determine the safety and effectiveness of a risk-stratified, venous thromboembolism (VTE) prophylaxis intervention. METHODS: This single-center, IRB-approved, retrospective study assessed patients with CF admitted to our institution for treatment of a pulmonary exacerbation from 2017 to 2019. Data and outcomes were manually extracted from the electronic medical record and internal CF clinical database. Subject characteristics, calculated VTE risk, prophylaxis interventions prescribed, VTE incidence, and adverse events were captured. RESULTS: A total of 135 CF patients had 354 admissions for pulmonary exacerbations in the time frame of the study. The majority of admissions (88.7%) were classified as moderate or high risk for VTE using the algorithm. Overall, VTE prophylaxis intervention determined by the algorithm was initiated in 36.2% of admissions. During the study period, no VTE events occurred. Four minor bleeding adverse effects were reported in patients receiving VTE chemical prophylaxis with enoxaparin (4.2%). CONCLUSIONS: This study provides the first reported outcomes following implementation of a risk-stratified VTE prophylaxis algorithm in hospitalized young people with CF. In this population at increased risk, use of risk-stratified prophylaxis was safe and effective in preventing VTE. Additional work to improve and maintain adherence to the algorithm and VTE prophylaxis interventions at our institution is planned and similar care should be considered at other pediatric CF care centers.

Pharmacokinetics of oral antimycobacterials and dosing guidance for Mycobacterium avium complex treatment in cystic fibrosis.

BACKGROUND: Treatment failure of Mycobacterium avium complex (MAC) pulmonary disease occurs in about 30% of people with cystic fibrosis (CF) and may be a result of abnormal drug concentrations. METHODS: Prospective, cross-over, single-dose PK study of 20 pancreatic insufficient individuals with CF and 10 healthy controls (HC). CF subjects received simultaneous doses of oral azithromycin, ethambutol, and rifampin in the fasting state and with food and pancreatic enzymes, separated by two weeks. HC received fasting doses only. A non-compartmental model was used to estimate PK parameters of drugs and metabolites. RESULTS: Azithromycin maximum concentration (Cmax ) was higher and rifampin Cmax was lower in fasting CF subjects compared to HC, while other PK measures, including those for ethambutol, were similar. Addition of food and enzymes did not improve the Cmax of the antimycobacterial drugs. Nineteen of 20 CF subjects had one or more abnormal Cmax z-scores in either the fasting or fed state (or both), when compared to HC. CONCLUSION: PK profiles of azithromycin and ethambutol were similar between CF and HC, except azithromycin Cmax was slightly higher in people with CF after a single dose. Rifampin PK parameters were altered in persons with CF. Addition of food and enzymes in CF subjects did not improve PK parameters. Standard dosing guidelines should be used as a starting point for people with CF initiating MAC therapy and therapeutic drug monitoring should be routinely performed to prevent the possibility of treatment failure due to abnormal drug concentrations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372383 Prior abstract publication: 1. Martiniano S, Wagner B, Brennan L, Wempe M, Anderson P, Nick J, Sagel S. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. Am J Resp Crit Care Med A4842-A4842, 2017. 2. Martiniano SL, Wagner BD, Brennan L, Wempe MF, Anderson PL, Nick JA, Sagel SD. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. J Cyst Fibros 16: S52-53, 2017.

Therapeutic antibiotic serum concentrations by two blood collection methods within the pediatric patient: A comparative effectiveness trial.

Repeated venipunctures and fingersticks to confirm serum drug concentrations cause pain and dissatisfaction for pediatric patients and their families. In many organizations, the standard of care to obtain therapeutic serum drug concentrations by peripheral venipuncture or capillary fingerstick, even when the patient has an existing peripheral intravenous catheter (PIV) or central venous catheter (CVC). The primary objective of this study was to assess agreement between serum tobramycin/vancomycin concentrations collected from a CVC or PIV, versus venipuncture or fingerstick. Among hospitalized pediatric patients (age 3 months to 22 years), 36 paired blood samples were collected. Serum trough vancomycin and random tobramycin concentrations were compared between peripheral intravenous or CVC samples, and venipuncture or fingerstick samples within the same patient. A strict sampling protocol for obtaining the samples was followed, that included collection of the CVC/PIV sample before the venipuncture or fingerstick, less than 2 min between collections of samples from the different sites, and a strict volume-based flush and waste protocol. Concordant correlation coefficients demonstrated substantial agreement between CVC/PIV and venipuncture/fingerstick concentrations for vancomycin (n = 17) and tobramycin (n = 19) (Rc = 0.982 for both). Bland-Altman analyses demonstrated good overall between-method agreement within subjects and minimal bias. Consequently, using a lumen volume-based flush and waste protocol, children with indwelling catheters may not require additional venipunctures and/or fingersticks for confirmation of drug concentrations while hospitalized, improving the quality of care and patient satisfaction.