1. Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis
- Author
-
Tadakazu Hisamatsu, Shunsuke Watanabe, Masao Toki, Koichi Gondo, Kazushige Ochiai, Tsubasa Yoshida, Tomoyuki Goto, Hirotaka Ota, Isamu Kurata, and Yasuharu Yamaguchi
- Subjects
0301 basic medicine ,Microbiology (medical) ,Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Cholangitis ,030106 microbiology ,Antibiotics ,Microbial Sensitivity Tests ,Group A ,Gastroenterology ,Severity of Illness Index ,Group B ,Drug Administration Schedule ,03 medical and health sciences ,Minimum inhibitory concentration ,Leukocyte Count ,0302 clinical medicine ,Internal medicine ,White blood cell ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Clinical efficacy ,Endoscopy, Digestive System ,Aged ,Retrospective Studies ,Aged, 80 and over ,Bacteria ,Dose-Response Relationship, Drug ,Pharmacokinetic pharmacodynamic ,business.industry ,Ceftriaxone ,Bacterial Infections ,Middle Aged ,Prognosis ,Anti-Bacterial Agents ,Infectious Diseases ,medicine.anatomical_structure ,C-Reactive Protein ,Treatment Outcome ,Acute Disease ,Drainage ,Female ,business ,medicine.drug - Abstract
The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.
- Published
- 2019