Short summary

Piperacillin/tazobactam and cefuroxime are the two most widely used antibiotics in the field of abdominal surgery. In order to determine optimal dosage and minimize antibiotic resistance, it is important to be familiar with the pharmacokinetic profile of the antibiotic in the blood, as well as in the affected tissue. In two clinical studies, the antibiotic concentration is measured in blood and bile in patients undergoing an endoscopic procedure of the common bile duct.

Rationale

The aim of this project is to evaluate whether current dosages used in the clinic of piperacillin and cefuroxime are sufficient in providing optimal treatment of infections in the biliary system while minimizing the risk of resistance developing.

In 2019, it was estimated that bacterial antimicrobial resistance resulted in 1.27 million deaths worldwide. The third most common infectious syndrome site was intra-abdominal infections. WHO have arrived at an action plan with five topics that address the issue of how to prevent the problem from escalating further. One of the topics is how to optimize the most effective dosage of antibiotics.

The use of broad-spectrum penicillin in Danish hospitals including piperacillin/tazobactam, has risen by 197% from 2011 to 2020. Within the field of abdominal surgery, piperacillin/tazobactam and cefuroxime are the two most common antibiotics utilized in the treatment of acute infections as well prophylaxis prior to surgical procedures. The dosage of the two antibiotics is primarily based on the pharmacokinetic properties measured in the blood but not in the tissue sites where the infections occur. Piperacillin and cefuroxime are both broad-spectrum penicillins that are effective in eradicating the harmful bacteria over time. The best measure of efficacy is the lowest inhibitory concentration of an antibiotic to a given bacteria over time (T>MIC). It is crucial to optimally treat and prevent infection while at the same time assuring that the antibiotic concentrations are not sub-lethal to the bacteria. Current studies used to evaluate antibiotic concentrations in the abdomen are outdated and mainly focus on tissue penetration using the biopsy-method, rather than focusing on the pharmacokinetic profile.

No prior study has measured the concentration of antibiotic in bile over specific time periods. The project will be unique in order to provide extensive understanding of the pharmacokinetic profile of piperacillin and cefuroxime in bile compared to plasma. By identifying optimal treatment parameters, the use of dosages that are sub-lethal to bacteria is substantially reduced resulting in a much lower opportunity for the microorganisms to survive and develop resistance.

This will help optimize the prophylactic dosage given to patients prior to procedures performed on the gallbladder, the common bile duct, the liver and the pancreas, and can potentially reduce the risk of postoperative infections.

Description of the cohort

Patients planned for endoscopic retrograde cholangiopancreticography (ERCP) at the Department of Surgery, Lillebælt Hospital and at the Department of Surgery, Aalborg University Hospital will be included.

Data and biological material

Data from the medical records will be collected regarding alcohol, smoking, bloodtests, height, weight, BMI, gender and age. Biological material from the patients consists of a bile and blood sample. Samples will also be collected and stored in a biobank, which will consist of bile, EDTA-plasma, lithium-heparin plasma, full blood and serum.

Collaborating researchers and departments

Department of Surgery, Aalborg University Hospital

• Jan Bech Pedersen, MD Consultant, PhD, Associate Professor

Department of Surgery, Aarhus University Hospital

• Anders Riegels Knudsen, MD Consultant, PhD, Associate Professor

Department of Vascular Surgery, Lillebaelt Hospital

• Kim Christian Houlind, MD Consultant, PhD, M.M.Sc

The Orthopedic Research Unit, Aarhus University Hospital

• Mats Bue, MD, PhD, Assistant Professor
• Pelle Emil Hanberg, MD, PhD, Assistant Professor

Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital