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Published on: July 21, 2023
Perioperative penetration of metronidazole into muscle tissue: a microdialysis study
Juri Karjagin1, Rein Pähkla, Joel Starkopf
1Anaesthesiology and Intensive Care Clinic, University of Tartu, Puusepa Street 8, 51014 Tartu, Estonia. jyrika@kliinikum.ee
Objective:
To evaluate the concentration of metronidazole in muscle tissue using microdialysis and to compare it with plasma concentration and in vitro-defined MIC(90) (minimal inhibiting concentration) for the most frequent anaerobic bacteria isolated in our hospital.
Materials And Methods:
Six female patients scheduled for elective gynaecological surgery were included. Exclusion criteria were active inflammatory process and being overweight (BMI more than 30). Microdialysis catheters (CMA 60 catheters with 20 kDa cut-off membrane) were placed into the m. vastus lateralis. The microdialysis perfusion rate was 2 microl/min. To assess in vivo recovery of the drug, retrodialysis with a 5-mg/l solution of metronidazole was performed. Microdialysis and blood samples were collected simultaneously 10 h after metronidazole administration. MIC(90) data were obtained from the database of the microbiology laboratory of the local hospital.
Results:
Data from five patients were included in analysis. The metronidazole concentration in blood achieved a value of 16.5+/-4.6 mg/l at 30 min (first available data), while in muscle a maximum level of 7.8+/-1.5 mg/l was achieved at 114 min. The mean MIC(90) for the Bacteroides fragilis group was 0.25+/-0.26 mg/l. Data from mean plasma concentrations were fitted into the two-compartmental model and time over MIC(90) and time over four times MIC(90) were calculated, which were 52.1+/-13.5 h and 33.2+/-8.7 h, respectively. The C(max)/MIC(90) ratio was 65.8+/-18.5 for plasma and 31.1+/-6.2 for muscle.
Conclusion:
The present data demonstrate that metronidazole penetrates well into muscle tissue. Muscle tissue concentrations reach values far greater than MIC(90) for the Bacteroides fragilis group and persist at such high levels for at least 10 h.
Insights
Metronidazole effectively penetrates muscle tissue, reaching concentrations significantly higher than the minimal inhibiting concentration (MIC(90)) for common anaerobic bacteria. These elevated muscle levels persist for at least 10 hours post-administration.
Area of Science:
- Pharmacology
- Infectious Diseases
- Surgical Research
Background:
- Metronidazole is a crucial antibiotic for anaerobic bacterial infections.
- Understanding its tissue penetration is vital for optimizing treatment efficacy.
- Muscle tissue drug concentrations are not well-characterized for metronidazole.
Purpose of the Study:
- To quantify metronidazole concentration in muscle tissue via microdialysis.
- To compare muscle concentrations with plasma levels and in vitro MIC(90) values.
- To assess metronidazole's efficacy against common anaerobic bacteria.
Main Methods:
- Microdialysis catheters inserted into vastus lateralis muscle in six female patients.
- Simultaneous collection of microdialysis and blood samples 10 hours post-metronidazole administration.
- Comparison of measured concentrations with hospital microbiology laboratory MIC(90) data.
Main Results:
- Muscle metronidazole concentration reached a maximum of 7.8±1.5 mg/l at 114 minutes.
- Plasma concentration peaked at 16.5±4.6 mg/l at 30 minutes.
- Muscle concentrations were significantly higher than the mean MIC(90) of 0.25±0.26 mg/l for Bacteroides fragilis group.
Conclusions:
- Metronidazole demonstrates excellent penetration into human muscle tissue.
- Achieved muscle concentrations exceed the MIC(90) for key anaerobic pathogens.
- Sustained high concentrations in muscle suggest effective therapeutic levels for at least 10 hours.
