Pharmacokinetics of ampicillin-sulbactam and the renal function-based optimization of dosing regimens for prophylaxis in patients undergoing cardiovascular surgery.
Surgical site infections are a major cause of postoperative morbidity and mortality in cardiovascular surgery. Proper antibiotic prophylaxis can reduce the rate of such infections, but the concentration of antibiotic must be maintained at an adequate level throughout the operation. This study aimed to use renal function to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used prophylactic antibiotic, to maintain adequate concentrations throughout the course of surgery. The mean volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 13.2 l, 0.652 h⁻¹, 1.32 h, and 8.45 l/h, respectively. A statistically significant (P < 0.0001) correlation (r = 0.771) was observed between the total clearance of ampicillin and creatinine clearance of the patients. Plasma concentrations of ampicillin were simulated with the pharmacokinetic parameters obtained. We developed a nomogram for adjusting the dosing interval according to renal function and predicted ampicillin trough concentrations. We revealed the best dosage and dosing interval for cardiovascular surgery by analyzing the perioperative pharmacokinetics of ampicillin-sulbactam administered prophylactically. We suggest that the dosage and dosing interval for ampicillin-sulbactam should be adjusted to optimize treatment efficacy and safety, on the basis of the MIC₉₀ of methicillin-sensitive Staphylococcus aureus (MSSA) in each institution.


BACKGROUND
UMIN000007356.
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Yuta
Y
Yokoyama
Kazuaki
K
Matsumoto
Hiroyuki
H
Yamamoto
Yoshifumi
Y
Iguro
Yutaka
Y
Imoto
Kazuro
K
Ikawa
Norifumi
N
Morikawa
Shiro
S
Ishida
Yoshiro
Y
Okano
Erika
E
Watanabe
Yoshihiro
Y
Shimodozono
Katsushi
K
Yamada
Yasuo
Y
Takeda
D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000379:methods; D006348:Cardiac Surgical Procedures / Q000379:methods; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D013407:Sulbactam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013530:Surgical Wound Infection / Q000517:prevention & control
D000900:Anti-Bacterial Agents; C035444:sultamicillin; D000667:Ampicillin; D003404:Creatinine; D013407:Sulbactam