Overview
The goal of this study is to measure how well commonly used antibiotics reach the tissue in the head and neck region in adults with a postoperative neck infection or undergoing reconstructive nasal surgery with an inferior turbinate flap. The study also describes markers of ischemia and inflammation in the newly created flap during the first days after surgery.
The main question it aims to answer is: For how long do the free concentrations of cefuroxime, cloxacillin, dicloxacillin, and amoxicillin/clavulanic acid stay above the minimal inhibitory concentration (T\>MIC) in infected tissue, non-infected tissue, the flap, and plasma?
Participants will receive the antibiotics on a fixed, protocol-defined schedule for about two days. Small microdialysis catheters will be placed in the tissue to collect fluid continuously, and serial blood samples will be drawn. Participation ends when the last sample is collected and the catheters are removed.
Description
Infections in the head and neck region and reconstructive surgery in the nasal and sinus area are associated with considerable morbidity and require effective antibiotic treatment. Treatment is based mainly on systemic antibiotic concentrations, but little is known about actual tissue penetration in infected tissue and in reconstructed flaps, where perfusion, edema, ischemia, and inflammation may alter drug distribution. Microdialysis is a minimally invasive method for continuous sampling of free, pharmacologically active drug concentrations and metabolic and inflammatory markers in the extracellular fluid.
This is a prospective, non-randomized, open-label, exploratory interventional study with two sub-studies and a total of 16 participants. All study drugs are marketed antibiotics used in routine clinical practice; they are administered in a protocol-defined regimen to allow pharmacokinetic sampling.
Sub-study 1 (n=8): Adults admitted with a postoperative infection in the neck. Treatment is started on day 1 with cefuroxime 750 mg IV four times daily and dicloxacillin 1000 mg orally four times daily. On day 2, microdialysis catheters are placed in infected and non-infected subcutaneous tissue of the neck, and sampling is performed over two consecutive dosing intervals: (1) cefuroxime 750 mg IV plus dicloxacillin 1000 mg orally, sampled for 6 hours; and (2) cefuroxime 1500 mg IV plus cloxacillin 1000 mg IV, sampled for 8 hours. This allows comparison of two cefuroxime doses and of oral dicloxacillin versus intravenous cloxacillin.
Sub-study 2 (n=8): Adults undergoing reconstructive surgery with an inferior turbinate flap (IFT flap). Postoperatively, amoxicillin/clavulanic acid 500/125 mg and dicloxacillin 1000 mg are given orally three times daily. Microdialysis catheters are placed in the flap and in the nasal septal mucosa (reference tissue). Ischemia markers (glucose, lactate, pyruvate, glycerol) and inflammatory proteins are sampled hourly during the first 6 postoperative hours and in the morning and evening of day 2. Antibiotic concentrations are measured over one dosing interval after the morning dose on day 2.
In both sub-studies, dialysate is collected in 30-60 minute intervals and serial blood samples are drawn for plasma concentrations. Catheters are calibrated in vivo at the end of sampling. Drug concentrations are analysed by LC-MS. Clinically indicated treatment can be changed by the treating physician at any time.
Eligibility
Inclusion Criteria:
- Signed informed consent
- Either a postoperative infection in the neck (sub-study 1) or planned reconstruction with an inferior turbinate flap (sub-study 2)
- Age 18 years or older
Exclusion Criteria:
- Known allergy or hypersensitivity to any of the study antibiotics (cefuroxime, cloxacillin, dicloxacillin, or amoxicillin/clavulanic acid)
- eGFR below 30 mL/min/1.73 m2
- Pregnancy or planned pregnancy
