ABSTRACT
The levels of metronidazole and pefloxacin in plasma and tissue penetration of both drugs were studied after prophylactic administration to 7 patients undergoing colorectal surgery. Metronidazole (1,500 mg) and pefloxacin (800 mg) were administered as an intravenous infusion 1 hour before surgery. Mean plasma levels of pefloxacin decreased from 12.92 +/- 4.10 microg/ml at the end of the infusion to 2.18 +/- 1.03 microg/ml at 36 h. These values were above the MIC90 for E. coli (0.125 microg/ml) and E. faecalis (0.5 microg/ml), microorganisms responsible for abdominal infections. Tissue pefloxacin levels were also measured with a range from 0.72 - 7.78 microg/g in subcutaneous cell tissue, from 1.94 - 17.55 microg/g in peritoneum and from 2.76 - 21.99 microg/g in colon wall. Mean plasma concentrations of metronidazole decreased from 39.89 +/- 17.08 microg/ml at the end of the infusion to 2.63 +/- 1.11 microg/ml at 36 h. During this period, concentrations were higher than 2 microg/ml, the MIC90 value for B. fragilis, the anaerobic pathogen more frequently involved in postoperative infections after rectal and colonic surgery. Tissue metronidazole levels ranged from 3.64 - 13.37 microg/g in subcutaneous cell tissue, from 3.26 - 41.66 microg/g in peritoneum and from 6.72 - 43.12 microg/g in colon wall. The AUC/MIC values (efficacy parameter for concentration-dependent killing antibiotics such as pefloxacin and metronidazole) obtained were the following: metronidazole AUC/MIC value for B. fragilis was 173; pefloxacin AUC/MIC values for E. coli and E. faecalis were 941 and 235, respectively. The values of these parameters are higher than the recommended values to ensure efficacy, which means good exposure of the antimicrobials to the microorganisms. In conclusion, the combination of pefloxacin and metronidazole as prophylactic agents to prevent infections in patients undergoing colorectal surgery produce plasma and tissue levels above the MIC values of the main pathogens responsible for this kind of infections.
