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Inappropriate use of metronidazole in gastrointestinal surgery
C J Ingoldby1, P H Dean, P Vowden
1Department of Surgery, St James's University Hospital, Leeds, UK.
Abstract:
Pharmacokinetic data suggest that current treatment regimens of metronidazole in abdominal surgery are not always appropriate. We have examined antibiotic concentrations during emergency and elective surgery using a specific and sensitive high pressure liquid chromatography assay. Serum and tissue concentrations were measured after intravenous infusion during intra-abdominal surgery and after suppositories given before appendicectomy. After intravenous dosage, bactericidal concentrations were reached in serum (13.6 +/- 7.8 micrograms/ml), bowel (9.0 +/- 6.6 micrograms/g), tumour (9.9 +/- 7.1 micrograms/g) and subcutaneous fat (4.9 +/- 3.2 micrograms/g). After suppositories the concentrations were: serum 4.6 +/- 2.7 micrograms/ml, appendix 1.1 +/- 0.6 micrograms/g, fat 1.5 +/- 0.9 micrograms/g and peritoneal fluid 4.7 +/- 4.3 micrograms/g. These values were obtained at a mean interval of 86.9 +/- 27.5 min following administration of the drug. Serum concentrations were measured during post-surgical infusion of 500 mg i.v. 8 or 12 hourly. Mean concentrations after 8 hourly doses were 16.3 +/- 4.85 micrograms/ml pre-dose and 28.7 +/- 6.76 micrograms/ml post-dose, with evidence of drug accumulation by detection of metabolites. Twelve hourly infusions gave pre-dose levels of 7.4 +/- 3.86 micrograms/ml and post-dose levels of 17.1 +/- 3.69 micrograms/ml. Metronidazole (500 mg) intravenously at induction of anaesthetic gives effective prophylactic concentrations in all tissues including tumour, but a metronidazole 1 g suppository before appendicectomy does not provide reliable tissue concentrations. Metronidazole (500 mg) i.v. 12 hourly gives effective bactericidal concentrations of the drug and is more economical.
Insights
Intravenous metronidazole (500 mg) at anesthesia induction provides effective surgical prophylaxis. However, 1g suppositories before appendicectomy do not ensure reliable tissue concentrations for abdominal surgery.
Area of Science:
- Pharmacology
- Surgical Infectious Diseases
Background:
- Current metronidazole treatment regimens for abdominal surgery may be suboptimal.
- Accurate pharmacokinetic data are crucial for optimizing antibiotic therapy in surgical settings.
Purpose of the Study:
- To evaluate serum and tissue concentrations of metronidazole following intravenous and suppository administration during abdominal surgery.
- To determine the appropriateness of current metronidazole dosing strategies in surgical patients.
Main Methods:
- Utilized a specific and sensitive high-pressure liquid chromatography assay to measure antibiotic concentrations.
- Measured serum and tissue concentrations (bowel, tumor, fat, appendix, peritoneal fluid) after intravenous infusion and suppository administration.
- Monitored serum concentrations during post-surgical intravenous infusions (8 or 12 hourly).
Main Results:
- Intravenous metronidazole (500 mg) achieved bactericidal concentrations in serum, bowel, tumor, and subcutaneous fat.
- Metronidazole suppositories (1 g) resulted in lower concentrations in serum, appendix, fat, and peritoneal fluid.
- Post-surgical intravenous infusions (500 mg) every 12 hours maintained effective bactericidal concentrations and showed less accumulation than 8-hourly dosing.
Conclusions:
- Intravenous metronidazole (500 mg) at anesthetic induction is effective for surgical prophylaxis in abdominal procedures.
- Metronidazole suppositories (1 g) before appendicectomy do not reliably achieve therapeutic tissue concentrations.
- A 12-hourly intravenous regimen of metronidazole (500 mg) is effective, bactericidal, and more economical for post-operative care.