Study on pharmacokinetics of prophylactic antibiotics for surgical site infection by ESBL-producing Escherichia coli after lower gastrointestinal surgery

JRCT ID: jRCTs061190025

Registered date:18/12/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: lower gastrointestinal disease with surgical indication (regardless of benign or malignant)
• Date of first enrollment: 09/01/2020
• Target sample size: 30
• Study type: Interventional

Intervention(s)

<Intervention; drug administration, intraoperative additional administration>
Cefmetazole, flomoxef or ceftolozane-tazobactam + metronidazole is administered intravenously as a prophylactic antibiotics for elective lower gastrointestinal surgery. Each drug is administered just before the surgery and during surgery.
1) cefmetazole administration case
Cefmetazole 1g is administered by a 30-minute intravenous infusion 30 minutes before the start of the surgery. Another infusion is repeated every 3 hours after the completion of the first administration.
2) flomoxef administration case
Flomoxef 1g is administered by a 30-minute intravenous infusion 30 minutes before the start of the surgery. Another infusion is repeated every 2 hours after the completion of the first administration.
3) ceftolozane-tazobactam + metronidazole administration case
First, metronidazole 500mg is administered by a 20-minute intravenous infusion 80 minutes before the start of the surgery. Followng that, ceftolozane-tazobactam 1.5g is administered by a 60-minute intravenous infusion. Every 3 hours after the completion of the first administration, another infusion of ceftolozane-tazobactam is repeated without additional metronidazole.
<Sample collection>
a) cefmetazole, or flomoxef administration case
Blood (approx. 2 ml), peritoneal fluid (approx. 2 ml), subcutaneous adipose tissue (approx. 4 mm square) and peritoneum (approx. 4 mm square) are collected 30 minutes after the start of the first drug administration and every hour thereafter till the end of the surgery.
b) ceftolozane-tazobactam plus metronidazole administration case
Blood (approx. 3 ml), peritoneal fluid (approx. 3 ml), subcutaneous adipose tissue (approx. 6 mm square) and peritoneum (approx. 6 mm square) are collected 60, 90 and 120 minutes after the start of the first drug administration and every hour thereafter, and just before the end of the surgery.
<Drug concentration measurement>
After collecting the samples, measure the drug concentration used for each sample.
Analyzing the results, drug concentration in plasma, peritoneal fluid, peritoneum, subcutaneous adipose tissue and pharmacokinetic parameters are compared and examined.

Outcome(s)

• Primary Outcome: Pharmacokinetic parameters (Cmax, AUC, T1/2, Tmax) of each drug in plasma, peritoneal fluid and abdominal tissues (peritoneum and subcutaneous adipose tissue)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1 Patients scheduled for elective lower gastrointestinal surgery (regardless of open surgery or laparoscopic surgery)
gastrointestinal surgery (limited to open surgery cases)
2 Inpatients over 20 years old (include 20 years old) who agree to participate in this study, regardless of gender
3 Patients who can give written informed consent to participate in this study

Exclude criteria

1 Patients with a history of allergies to Cefmetazole, Flomoxef, Ceftolozane/Tazobactam or Metronidazole
2 Patients with a history of allergies to cephems
3 Combined use of
4 Patients who are pregnant or nursing
5 Patients with organic diseases in the brain and spinal cord
6 Patients with renal dysfunction who have creatinine clearance less than 50 ml / min estimated by Cockloft-Gault equation
7 Patients judged inappropriate for this study by the researcher

Related Information

• Primary Sponsor: Ohge Hiroki
• Secondary Sponsor: Yoshimura Kosuke