Lisa T Hong1, Theodore G Liou2, Rishi Deka3, Jordan B King4, Vanessa Stevens2, David C Young5. 1. Loma Linda University School of Pharmacy, Loma Linda, CA. Electronic address: lhong@llu.edu. 2. University of Utah School of Medicine, Salt Lake City, UT. 3. Department of Radiation Medicine and Applied Sciences, University of California San Diego, San Diego, CA. 4. Kaiser Permanente Colorado, Aurora, CO. 5. University of Utah College of Pharmacy, Salt Lake City, UT; University of Utah Health Care, Salt Lake City, UT.
Abstract
BACKGROUND: Several clinical trials have shown the efficacy of continuous infusion beta-lactam (BL) antibiotics in patients with cystic fibrosis (CF); however, little is known about pharmacokinetic changes during the treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. METHODS: This study was a retrospective cohort study of 162 adult patients with CF admitted to the University of Utah Hospital between January 1, 2008, and May 15, 2014, for treatment of an APE with both a continuous infusion BL and IV tobramycin. We extracted the administered doses of continuous infusion BLs and tobramycin along with serum drug concentrations and calculated medication clearance rates. The primary outcome was change in clearance rates of continuous infusion BLs between day 2 and day 7 of APE treatment. RESULTS: The BL clearance rate increased 20.7% (95% CI, 11.42 to 32.49; P < .001), whereas the tobramycin clearance rate decreased 6.3% (95% CI, -12.29 to -4.45; P < .001). The mean percent predicted FEV1 increased between admission and discharge by 12.2% (95% CI, -13.81 to -10.55; P < .001). CONCLUSIONS: Clinicians should monitor BL levels along with aminoglycoside levels and make dose adjustments to maximize the chance of optimal antibiotic treatment. Continuous infusion BL and tobramycin clearance can change dramatically during the treatment of an APE, which may necessitate significant changes in dosing to achieve optimal antibiotic levels. Clearance rates of these antibiotics may change in opposite directions, requiring specific monitoring of each medication.
BACKGROUND: Several clinical trials have shown the efficacy of continuous infusion beta-lactam (BL) antibiotics in patients with cystic fibrosis (CF); however, little is known about pharmacokinetic changes during the treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. METHODS: This study was a retrospective cohort study of 162 adult patients with CF admitted to the University of Utah Hospital between January 1, 2008, and May 15, 2014, for treatment of an APE with both a continuous infusion BL and IV tobramycin. We extracted the administered doses of continuous infusion BLs and tobramycin along with serum drug concentrations and calculated medication clearance rates. The primary outcome was change in clearance rates of continuous infusion BLs between day 2 and day 7 of APE treatment. RESULTS: The BL clearance rate increased 20.7% (95% CI, 11.42 to 32.49; P < .001), whereas the tobramycin clearance rate decreased 6.3% (95% CI, -12.29 to -4.45; P < .001). The mean percent predicted FEV1 increased between admission and discharge by 12.2% (95% CI, -13.81 to -10.55; P < .001). CONCLUSIONS: Clinicians should monitor BL levels along with aminoglycoside levels and make dose adjustments to maximize the chance of optimal antibiotic treatment. Continuous infusion BL and tobramycin clearance can change dramatically during the treatment of an APE, which may necessitate significant changes in dosing to achieve optimal antibiotic levels. Clearance rates of these antibiotics may change in opposite directions, requiring specific monitoring of each medication.
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