title: Pharmacokinetics of Prophylactic Ampicillin-Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass.
abstract: Antibiotic concentrations must be maintained at an adequate level throughout cardiovascular surgery to prevent surgical site infection. This study aimed to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used antibiotic prophylaxis regimen, to maintain adequate concentrations throughout the course of cardiovascular surgery with cardiopulmonary bypass (CPB). The total plasma concentrations of ampicillin were monitored in 8 patients after ampicillin (1 g)-sulbactam (0.5 g) administration via initial intravenous infusion and subsequent CPB priming. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin. The mean values for the volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 15.8±4.1 L, 0.505±0.186 h(-1), 1.52±0.47 h, and 7.72±2.72 L/h, respectively. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered every 3, 4, 6, and 12 h after the start of CPB, the predicted free trough plasma concentrations of ampicillin were 15.20, 8.25, 2.74, and 0.13 µg/mL, respectively. Therefore, an every-6-h regimen was needed to maintain the free ampicillin concentration at more than 2 µg/mL during cardiovascular surgery with CPB. We suggest that the dose and dosing interval for ampicillin-sulbactam should be adjusted to optimize the efficacy and safety of treatment, according to the minimum inhibitory concentrations for methicillin-sensitive Staphylococcus aureus isolates at each institution.
  
  
  BACKGROUND
  UMIN000007356.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Erika
authors.initials: E
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imoto
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D000368:Aged; D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011183:Postoperative Complications / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013407:Sulbactam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam