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Pharm Res ; 35(6): 116, 2018 Apr 11.
Article in English | MEDLINE | ID: mdl-29644481

ABSTRACT

PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%). CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.


Subject(s)
Antibiotic Prophylaxis/methods , Bariatric Surgery/adverse effects , Cefazolin/administration & dosage , Models, Biological , Surgical Wound Infection/prevention & control , Adult , Bariatric Surgery/methods , Cefazolin/pharmacokinetics , Dose-Response Relationship, Drug , Female , Humans , Microbial Sensitivity Tests , Microdialysis , Middle Aged , Obesity, Morbid/surgery , Subcutaneous Tissue/metabolism , Surgical Wound Infection/etiology , Surgical Wound Infection/microbiology , Young Adult
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