Pharmacokinetics of intermittent dosed intravenous vancomycin in adult persons with cystic fibrosis

Abstract

Background Antibiotics have altered pharmacokinetics (PK) in persons with cystic fibrosis (PwCF) during treatment for an acute pulmonary exacerbation (APE). The Cystic Fibrosis Foundation Pulmonary Guidelines–Treatment of Pulmonary Exacerbations do not provide specific recommendations for treatment of methicillin‐resistant Staphylococcus aureus (MRSA) lung infections. However, the American Thoracic Society Guidelines recommend vancomycin as the first‐line therapy. Only one study has previously described a single dose of intravenous (IV) vancomycin PK in adult PwCF. Our study aimed to describe intermittent IV vancomycin PK at steady‐state in adult PwCF. Methods Adult PwCF who were admitted to University of Utah Hospital between May 11, 2014 and August 31, 2020, and received intermittent IV vancomycin for the treatment of an APE were included in this study. The primary outcome was to describe the drug volume of distribution (Vd), drug clearance, elimination half‐life, and total daily dose of vancomycin. Secondary outcomes were rates of acute kidney injury (AKI), liver injury, and infusion‐related reactions. Results Thirteen patients were included. The mean Vd was 0.54 L/kg on Day 3 and 0.53L/kg on Day 7. CLvanco was 5.11L/h on Day 3 and 4.69 L/h on Day 7. Zero patients experienced an AKI, two patients experienced liver injury, and no patients experienced infusion‐related reactions. Conclusions Our results demonstrate that in PwCF intermittent IV vancomycin steady‐state PK are similar to previously reported single‐dose IV vancomycin. Additionally, CLvanco minimally changes from Day 3 to Day 7, although this study was not powered to detect a difference.

The pharmacokinetics and pharmacodynamics of continuous infusion vancomycin in adult people with cystic fibrosis

“…We utilized TDM to calculate CL vanco and AUC:MIC for each patient. The CL vanco was similar to a previous study by Lindley et al, 15 which reported a mean CL vanco of 5.11 L/h for intermittent dosed IV vancomycin in adult PwCF.…”

“…Pleasants et al 14 examined the PK of a single dose of IV vancomycin in a small group of adult PwCF and found similar volume of distribution (V d ) and vancomycin clearance (CL vanco ) to adults without CF. Lindley et al 15 described the PK of intermittent IV vancomycin at steady state in 13 adult PwCF and found similar results to that of Pleasants et al 14 We aimed to describe the PK of continuous infusion vancomycin in the adult PwCF being treated for a PEx at the University of Utah Adult Cystic Fibrosis Center. AKI was defined by the Risk, Injury, Failure, Loss, ESRD criteria and liver injury was defined as elevations of alanine transaminase, aspartate aminotransferase, or alkaline phosphatase that exceeded three times the upper limit of normal.…”

“…Most patients (19 patients) had an MRSA vancomycin MIC < 2. Thirteen patients were coinfected with P. previous study by Lindley et al, 15…”

“…These studies found lower incidence of kidney injury and improved clinical outcomes 11–13 . Currently, only two studies have been published on the PK of intermittent IV vancomycin in adult PwCF, but no studies have described the PK of continuous infusion vancomycin in this patient population 14,15 …”

“…[11][12][13] Currently, only two studies have been published on the PK of intermittent IV vancomycin in adult PwCF, but no studies have described the PK of continuous infusion vancomycin in this patient population. 14,15 Two small descriptive studies have described the PK of IV vancomycin in PwCF. Pleasants et al 14 examined the PK of a single dose of IV vancomycin in a small group of adult PwCF and found similar volume of distribution (V d ) and vancomycin clearance (CL vanco ) to adults without CF.…”