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Inadequate levels of metronidazole in subcutaneous fat after standard prophylaxis
J M Badia1, R de la Torre, M Farré
1Department of Surgery, Hospital Universitari del Mar, Barcelona, Spain.
Abstract:
The efficacy of antibiotic prophylaxis depends on appropriate tissue levels of the drug being present at the time of potential wound contamination. Metronidazole concentrations in serum, muscle and subcutaneous fat were measured after a single intravenous dose given at two different intervals before operation. Twenty-six patients undergoing abdominal wall procedures were divided into two groups. Patients in group 1 received metronidazole 500 mg intravenously 2 h before surgery, and those in group 2 were given the drug during induction of anaesthesia. Mean plasma levels of metronidazole at the beginning of the procedure were significantly lower (P = 0.01) in group 1 (7.3 (95 per cent confidence interval 5.7-8.9)) micrograms/ml than in group 2 (12.3 (8.9-15.7)) micrograms/ml although in both cases were above the minimum inhibitory concentration for 90 per cent of Bacteroides fragilis. Similar therapeutic concentrations of metronidazole were achieved in plasma and muscle in both groups at the end of the operation. However, patients in both groups had non-therapeutic concentrations of metronidazole in subcutaneous fat: group 1 0.9 (0.6-1.2) micrograms/mg, group 2 1.2 (0.7-1.7) micrograms/mg at the beginning of operation, and 1.2 (0.8-1.6) and 1.5 (0.9-2.1) micrograms/mg respectively at the end of the procedure. It is concluded that infusion of metronidazole 2 h before surgery or during induction of anaesthesia achieved adequate plasma and muscle levels but failed to achieve therapeutic levels in subcutaneous fat.
Insights
Antibiotic prophylaxis with metronidazole achieved adequate plasma and muscle drug levels for abdominal surgery. However, subcutaneous fat concentrations remained below therapeutic levels, potentially impacting wound infection prevention.
Area of Science:
- Surgical Infection Prevention
- Pharmacokinetics
- Antimicrobial Therapy
Background:
- Effective antibiotic prophylaxis requires optimal drug concentrations at the surgical site.
- Metronidazole is commonly used for anaerobic bacterial infections and prophylaxis.
Purpose of the Study:
- To compare metronidazole tissue concentrations after administration at two different pre-operative intervals.
- To assess the adequacy of metronidazole levels in serum, muscle, and subcutaneous fat for surgical prophylaxis.
Main Methods:
- Twenty-six patients undergoing abdominal wall procedures received a single intravenous dose of metronidazole.
- Group 1 received 500 mg 2 hours before surgery; Group 2 received the dose during anesthesia induction.
- Drug concentrations were measured in plasma, muscle, and subcutaneous fat at the start and end of surgery.
Main Results:
- Plasma metronidazole levels were significantly lower in Group 1 (given 2h pre-op) compared to Group 2 (given during anesthesia induction).
- Both groups achieved therapeutic plasma and muscle concentrations of metronidazole.
- Subcutaneous fat concentrations of metronidazole were sub-therapeutic in both groups throughout the procedure.
Conclusions:
- Intravenous metronidazole administration 2 hours before surgery or during anesthesia induction provides adequate plasma and muscle levels.
- Current dosing regimens may not achieve therapeutic metronidazole concentrations in subcutaneous fat, potentially compromising prophylaxis efficacy.
- Further research is needed to optimize metronidazole dosing for effective surgical site infection prevention.