Inappropriate use of metronidazole in gastrointestinal surgery

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.