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Antibiotic Tissue Penetration and Tissue Response in Head and Neck Infection and Reconstructive Surgery (ANTIBIOTIKA)

1. november 2026 opdateret af: Tejs Ehlers Klug

Antibiotic Penetration and Tissue Response in Infection and Reconstructive Surgery of the Head and Neck Region: A Microdialysis Study of Cefuroxime, Cloxacillin, Dicloxacillin, and Amoxicillin/Clavulanic Acid

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

16

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

  • Navn: Tejs Ehlers Klug, MD, DMSc
  • Telefonnummer: +45 51604046
  • E-mail: tejsklug@rm.dk

Studiesteder

  • Danmark
      • Aarhus N, Danmark, 8200
        • Rekruttering
        • Aarhus University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Sub-study 1: Postoperative Neck Infection

Adults with a postoperative infection in the neck (n=8). Cefuroxime 750 mg IV four times daily and dicloxacillin 1000 mg orally four times daily from day 1. On day 2, microdialysis in infected and non-infected subcutaneous tissue over two consecutive dosing intervals: (1) cefuroxime 750 mg IV + dicloxacillin 1000 mg orally (6 hours); (2) cefuroxime 1500 mg IV + cloxacillin 1000 mg IV (8 hours), with serial plasma samples.
Medicin: Cefuroxime

Sub-study 1: Cefuroxime 750 mg intravenously four times daily from day 1. On day 2, one dosing interval of cefuroxime 750 mg IV (sampled over 6 hours) followed by one dosing interval of cefuroxime 1500 mg IV (sampled over 8 hours), to compare tissue penetration of the two doses.

Medicin: Dicloxacillin

Dicloxacillin 1000 mg orally. Sub-study 1: four times daily from day 1, with tissue and plasma sampling during the first dosing interval on day 2 (6 hours). Sub-study 2: three times daily postoperatively from day 1, with tissue and plasma sampling over one dosing interval after the morning dose on day 2.

Medicin: Cloxacillin

Sub-study 1: Cloxacillin 1000 mg intravenously as a single dose in the second dosing interval on day 2 (given together with cefuroxime 1500 mg IV), with tissue and plasma sampling over 8 hours, to compare with oral dicloxacillin.

Procedure: Microdialysis and serial blood sampling

CE-marked microdialysis catheters perfused with isotonic saline (0.5-1 microL/min) are placed in the target tissues: infected and non-infected subcutaneous neck tissue (sub-study 1), or the inferior turbinate flap and nasal septal mucosa as reference tissue (sub-study 2). Dialysate is collected in 30-60 minute intervals, with serial blood samples drawn for plasma concentrations. Catheters are calibrated in vivo at the end of sampling and then removed.
Eksperimentel: Sub-study 2: Inferior Turbinate Flap Reconstruction

Adults undergoing reconstructive surgery with an inferior turbinate flap (n=8). Amoxicillin/clavulanic acid 500/125 mg and dicloxacillin 1000 mg orally three times daily postoperatively from day 1. Microdialysis in the flap and in nasal septal mucosa (reference tissue): ischemia markers and inflammatory proteins hourly for the first 6 postoperative hours and morning/evening on day 2; amoxicillin and dicloxacillin concentrations over one dosing interval after the morning dose on day 2, with serial plasma samples.
Medicin: Dicloxacillin

Dicloxacillin 1000 mg orally. Sub-study 1: four times daily from day 1, with tissue and plasma sampling during the first dosing interval on day 2 (6 hours). Sub-study 2: three times daily postoperatively from day 1, with tissue and plasma sampling over one dosing interval after the morning dose on day 2.

Procedure: Microdialysis and serial blood sampling

CE-marked microdialysis catheters perfused with isotonic saline (0.5-1 microL/min) are placed in the target tissues: infected and non-infected subcutaneous neck tissue (sub-study 1), or the inferior turbinate flap and nasal septal mucosa as reference tissue (sub-study 2). Dialysate is collected in 30-60 minute intervals, with serial blood samples drawn for plasma concentrations. Catheters are calibrated in vivo at the end of sampling and then removed.

Medicin: Amoxicillin/Clavulanic Acid

Sub-study 2: Amoxicillin/clavulanic acid 500/125 mg orally three times daily postoperatively from day 1 (together with dicloxacillin), with tissue and plasma sampling of amoxicillin over one dosing interval after the morning dose on day 2.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Time Above the Minimal Inhibitory Concentration (T>MIC) in Tissue and Plasma
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Time during which the free concentration of each study antibiotic (cefuroxime, cloxacillin, dicloxacillin, and amoxicillin/clavulanic acid) exceeds the minimal inhibitory concentration in each measured tissue (microdialysis) and in plasma (serial blood samples), calculated from concentration-time profiles. Pre-specified MIC targets: cefuroxime 4 mg/L; cloxacillin 2 mg/L; dicloxacillin 2 mg/L; amoxicillin/clavulanic acid 2 mg/L (amoxicillin component). Reported as time (hours) and as percentage of the dosing interval.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Area Under the Concentration-Time Curve (AUC) in Tissue and Plasma
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

AUC of the free concentration of each study antibiotic in each measured tissue compartment (microdialysis) and in plasma.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.
Tissue Penetration Ratio (AUC Tissue / AUC Plasma)
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Ratio of the AUC of the free antibiotic concentration in each tissue compartment to the AUC in plasma, for each study antibiotic.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.
Maximum Concentration (Cmax) in Tissue and Plasma
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Peak free concentration of each study antibiotic in each measured tissue compartment and in plasma.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.
Time to Maximum Concentration (Tmax) in Tissue and Plasma
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Time from dose administration to peak free concentration of each study antibiotic in each measured tissue compartment and in plasma.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.
Elimination Half-Life (T1/2) in Tissue and Plasma
Tidsramme: Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.

Elimination half-life of each study antibiotic in each measured tissue compartment and in plasma, derived from the concentration-time profiles.
Sub-study 1: two consecutive dosing intervals on day 2 (0-6 hours and 0-8 hours after dosing). Sub-study 2: one dosing interval (approximately 8 hours) after the morning dose on postoperative day 2.
Lactate/Pyruvate Ratio in the Inferior Turbinate Flap
Tidsramme: Hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2.

Lactate/pyruvate ratio measured in microdialysate from the inferior turbinate flap and the nasal septal reference tissue, as a marker of tissue ischemia (sub-study 2).
Hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2.
Tissue Ischemia Markers (Glucose, Lactate, Pyruvate, and Glycerol)
Tidsramme: Sub-study 2: hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2. Sub-study 1: during the sampling period on day 2 (up to approximately 14 hours).

Concentrations of glucose, lactate, pyruvate, and glycerol in microdialysate from the measured tissue compartments.
Sub-study 2: hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2. Sub-study 1: during the sampling period on day 2 (up to approximately 14 hours).
Inflammatory Proteins in Microdialysate
Tidsramme: Hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2.

Levels of inflammatory proteins measured in microdialysate from the inferior turbinate flap and the nasal septal reference tissue, to characterize the early postoperative inflammatory tissue response (sub-study 2).
Hourly during the first 6 postoperative hours (day 1), and in the morning and evening of postoperative day 2.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Tejs Ehlers Klug

Samarbejdspartnere

Danish Cancer Society

Efterforskere

  • Ledende efterforsker: Tejs Ehlers Klug, MD, DMSc, Aarhus University Hospital

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. november 2026

Primær færdiggørelse (Anslået)

1. september 2028

Studieafslutning (Anslået)

1. december 2028

Datoer for studieregistrering

Først indsendt

20. oktober 2026

Først indsendt, der opfyldte QC-kriterier

20. oktober 2026

Først opslået (Faktiske)

26. oktober 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2026-526995-22-00
  • 2026-526995-22-00 (Ctis)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

IPD-planbeskrivelse

Individual participant data will not be shared publicly due to Danish and EU data protection legislation (GDPR). Aggregated results will be published in peer-reviewed journals and reported in CTIS.

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