The Effect of Metronidazole on the Incidence of Postoperative Wound Infection in Elective Colon Surgery C. Brass, MD, Montreal, Quebec, Canada G. K. Richards, MB, MRC (Path), Montreal, Quebec, Canada J. Ruedy, MD, Montreal, Quebec, Canada J. Prentis, FIMLT, Montreal, Quebec, Canada E. John Hinchey, MD, FACS, Montreal, Quebec, Canada
wound infection after colon surgery remains a problem in spite of the introduction of prophylactic antibiotics. Although published series have shown a dramatic reduction of wound infections with a variety of antibiotics [I-4], it has been the experience of the surgical service of the Montreal General Hospital that the rate of postoperative wound infection has remained high (10 to 16 per cent). It is remarkable that there have been few controlled studies that have reproduced the results on which many of the recommendations for selection of prophylactic antibiotics are based. In earlier studies, prophylactic antibiotics were chosen for their effect on the aerobic flora. It has been recognized in recent years that anaerobic organisms are the predominant flora of the colon and these organisms can be cultured from many of the wound infections and abscesses that occur after colon surgery [5]. In some cases anaerobes are the only organism isolated. The pathogenicity of these organisms has been demonstrated experimentally in animals [6] and they have been incriminated in clinical situations in man. The role of the anaerobes in the development of wound infection at present is speculative, but there are considerable data to suggest that they may play a major role in these infections. Three studies have shown a reduction in the incidence of wound infection after the reduction of the anaerobic flora from the colon at the time of operation [3,7,8]. None of these studies provided quantitative data concerning the reduction of the flora nor correlation of the presence of anaerobic flora at the time of operation with the incidence of wound infection. Postoperative
From the DepMnw& of Clinical Phsmwology. Microbblogy, and Surgery, McGill University and the Montreal General Hospital, Montreal, Quebec, Canada. Reprint requests should be addressed to E. John Hinchey. MD, Montreal General Hospital, 1650 Cedar Avenue, Room 947, Montreal, Quebec H3G lA4. Canada. Presented at the Eighteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, Toronto, Ontario, Canada, May 24-25, 1977.
Volume 135, January 1978
The present study was planned to further examine the hypothesis that the anaerobic flora of the gut play an important role in the development of wound infection and that suppression of these organisms in the bowel at the time of surgery will result in a significant reduction in infection rates. A series of in vitro studies were carried out to determine a suitable antimicrobial agent for this purpose. Metronidazole (FlagyP) was chosen for its bactericidal activity specific for anaerobes (especially bacteroides spp.) coupled with its freedom from side effects. It is found effective at low concentrations even in the presence of mixed fecal flora in high density ( lo7 organisms/ ml) approximating the conditions found in the bowel. In this respect it was superior to other antimicrobial agents tested, including erythromycin. Material and Methods Clinical Study
The study population consisted of eighty consecutive patients admitted to the surgical services of the Montreal General Hospital for elective colon surgery. Patients were included in the study if the bowel was incised at operation. Patients were excluded if they had received antibiotics during the two weeks before surgery or if there was evidence of infection before the operation. Patients with leukopenia (white blood cell count O.l
Bacteroides Control Trial Patients Patients 6 0 1 4 1 1 1 1 2
14 1 3 1 0 1 0 0 0
Nil 104 5.6 X lo8 2.7 X lo5 p O.l
0 0 0 1 2 3 5 3 3 1
10-s 10-e 8.6 x 10-l 4.3 x 10-s p
wound infection after colon surgery remains a problem in spite of the introduction of prophylactic antibiotics. Although published series have shown a dramatic reduction of wound infections with a variety of antibiotics [I-4], it has been the experience of the surgical service of the Montreal General Hospital that the rate of postoperative wound infection has remained high (10 to 16 per cent). It is remarkable that there have been few controlled studies that have reproduced the results on which many of the recommendations for selection of prophylactic antibiotics are based. In earlier studies, prophylactic antibiotics were chosen for their effect on the aerobic flora. It has been recognized in recent years that anaerobic organisms are the predominant flora of the colon and these organisms can be cultured from many of the wound infections and abscesses that occur after colon surgery [5]. In some cases anaerobes are the only organism isolated. The pathogenicity of these organisms has been demonstrated experimentally in animals [6] and they have been incriminated in clinical situations in man. The role of the anaerobes in the development of wound infection at present is speculative, but there are considerable data to suggest that they may play a major role in these infections. Three studies have shown a reduction in the incidence of wound infection after the reduction of the anaerobic flora from the colon at the time of operation [3,7,8]. None of these studies provided quantitative data concerning the reduction of the flora nor correlation of the presence of anaerobic flora at the time of operation with the incidence of wound infection. Postoperative
From the DepMnw& of Clinical Phsmwology. Microbblogy, and Surgery, McGill University and the Montreal General Hospital, Montreal, Quebec, Canada. Reprint requests should be addressed to E. John Hinchey. MD, Montreal General Hospital, 1650 Cedar Avenue, Room 947, Montreal, Quebec H3G lA4. Canada. Presented at the Eighteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, Toronto, Ontario, Canada, May 24-25, 1977.
Volume 135, January 1978
The present study was planned to further examine the hypothesis that the anaerobic flora of the gut play an important role in the development of wound infection and that suppression of these organisms in the bowel at the time of surgery will result in a significant reduction in infection rates. A series of in vitro studies were carried out to determine a suitable antimicrobial agent for this purpose. Metronidazole (FlagyP) was chosen for its bactericidal activity specific for anaerobes (especially bacteroides spp.) coupled with its freedom from side effects. It is found effective at low concentrations even in the presence of mixed fecal flora in high density ( lo7 organisms/ ml) approximating the conditions found in the bowel. In this respect it was superior to other antimicrobial agents tested, including erythromycin. Material and Methods Clinical Study
The study population consisted of eighty consecutive patients admitted to the surgical services of the Montreal General Hospital for elective colon surgery. Patients were included in the study if the bowel was incised at operation. Patients were excluded if they had received antibiotics during the two weeks before surgery or if there was evidence of infection before the operation. Patients with leukopenia (white blood cell count O.l
Bacteroides Control Trial Patients Patients 6 0 1 4 1 1 1 1 2
14 1 3 1 0 1 0 0 0
Nil 104 5.6 X lo8 2.7 X lo5 p O.l
0 0 0 1 2 3 5 3 3 1
10-s 10-e 8.6 x 10-l 4.3 x 10-s p
