Perioperative Antibiotic Dosage
Improved antibiotic dosing for surgical procedures
Before many surgical procedures, patients receive an antibiotic to prevent wound infections. Such infections prolong hospital stay, place a considerable burden on patients, and result in high costs. In Germany, a wound infection occurs in about one out of every twenty procedures. The most widely used agent worldwide in this indication is cefazolin. To ensure reliable protection, a sufficient level of the drug must be present in the blood throughout the entire surgery.
This is where an underestimated problem lies. Cefazolin is usually administered as a single, short infusion at the start of surgery. Afterwards, however, the blood level falls quickly and can drop below the protective threshold during longer procedures. Conversely, in cases of impaired kidney function and repeated dosing, the drug can accumulate and reach unnecessarily high concentrations. On top of this, only the unbound, "free" fraction of the antibiotic is actually effective. This fraction varies considerably from one person to another, depending for instance on body weight, kidney function or albumin level. During surgery, fluid shifts or the use of a heart-lung machine, alter drug levels even further. Reliable data on this subject are still entirely lacking, even though cefazolin is administered millions of times.
Prof. Dr. Alexander Brinkmann (left) and Dr. Otto Frey (right)
Our project closes this gap. Embedded in one of the largest studies of its kind worldwide – more than 700 cardiac and neurosurgical patients and around 4,000 blood samples – we are for the first time, systematically measuring both the total concentration and the free, pharmacologically active fraction of cefazolin. From these data we are developing a pharmacokinetic model that allows us to simulate different dosages on the computer. This enables us to determine which dose and which route of administration - single dose, repeated doses, or continuous infusion - offers the best protection against wound infections.
For patients, this means a tangible improvement in safety. More reliable protection against wound infections, fewer cases of under- and overdosing, and dosages tailored to the individual – for example in cases of severe obesity, impaired kidney function or procedures involving a heart-lung machine. At the same time, the project promotes the responsible use of antibiotics, helps to prevent resistance and supply shortages, and creates a scientific basis for future treatment recommendations. Clinical pharmacy and medicine are working hand in hand – for safer care and for the benefit of patients.