| Autor: |
Reeder JA; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA., O'Sullivan CT; College of Nursing, University of Iowa Hospital and Clinics, Iowa City, Iowa, USA., Xu M; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA., Wu N; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA., Ince D; Department of Internal Medicine, Division of Infectious Diseases, Carver College of Medicine, University of Iowa Hospital and Clinics, Iowa City, Iowa, USA., Rogers WK; Department of Anesthesia, University of Minnesota Medical School, Minneapolis, Minnesota, USA., An G; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA. |
| Abstrakt: |
In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam. Comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 24 different redosing scenarios. Simulation results indicated that the ampicillin-sulbactam 2-h redosing scheme recommended by ASHP guidelines is likely too conservative given that 3-g dose (2-g ampicillin/1-g sulbactam) with 4-h redosing interval can reach the breakpoint of 2 mg/L for ampicillin in all populations even with the aggressive pharmacokinetic/pharmacodynamic (PK/PD) target of 100% f T > MIC. With the target 50% fT > MIC, all redosing schemes evaluated, including the 8-h redosing scenario, are predicted to be able to reach the breakpoint of 64 mg/L in all patients. According to our findings, redosing of ampicillin-sulbactam should be every 4 h instead of the currently recommended 2-h redosing schedule. Our PTA results should inform future updates to existing general antibiotic redosing guidelines; and, when used in combination with the availability of institution- and/or unit-specific ampicillin susceptibility patterns, our PTA results may be used to customize SSI prophylaxis redosing recommendations for ampicillin-sulbactam at individual hospitals. |
