Correspondence

Antibiotic Prophylaxis in Colorectal Surgery

N Engl J Med 2007; 356:1684-1685April 19, 2007

Article

To the Editor:

Fifteen years ago, Martin et al. showed that when a single intravenous dose of 2 g of cefotetan was administered to patients immediately before colorectal surgery, adequate concentrations of cefotetan in both the blood and colonic wall were maintained during surgical anastomosis (for a mean [±SD] period of 151±54 minutes) and throughout surgery.1 These concentrations of cefotetan remained superior to the minimum inhibitory concentrations of the drug for 90% of Staphylococcus aureus (16.0 mg per liter), Escherichia coli (0.05 mg per liter), and Bacteroides fragilis (8.0 mg per liter). However, concentrations of cefotetan in the abdominal wall and epiploic fat were no longer sufficient to provide protection against S. aureus and B. fragilis on surgical closure (216±76 minutes).1 Thus, Martin and colleagues suggested an additional dose of 1 g of cefotetan before closure to achieve adequate protection.1

In the study by Itani and colleagues (Dec. 21 issue),2 low concentrations of cefotetan at closure3 due to inappropriate timing of preoperative antibiotic administration (60 to 119 minutes before incision in many patients),4 prolonged surgery (up to 313 minutes),4 and obesity (in 27% of the patients for whom doses were not adjusted),4 as well as increased minimum inhibitory concentrations of cefotetan5 may have contributed to the differences between the study groups in the incidence of superficial incisional infection and cefotetan failure.

Pierre Moine, M.D., Ph.D.
University of Colorado Health Sciences Center, Denver, CO 80262
pierre.moine@uchsc.edu

Karim Asehnoune, M.D.
Centre Hospitalier Universitaire de Nantes, 44093 Nantes, France

5 References

1. 1

   Martin C, Portet C, Lambert D, et al. Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery. Antimicrob Agents Chemother 1992;36:1115-1118
   Web of Science | Medline

2. 2

   Itani KMF, Wilson SE, Awad SS, Jensen EH, Finn TS, Abramson MA. Ertapenem versus cefotetan prophylaxis in elective colorectal surgery. N Engl J Med 2006;355:2640-2651
   Full Text | Web of Science | Medline

3. 3

   Zelenitsky SA, Ariano RE, Harding GKM, Silverman RE. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother 2002;46:3026-3030
   CrossRef | Web of Science | Medline

4. 4

   Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis 2004;38:1706-1715
   CrossRef | Web of Science | Medline

5. 5

   Hoellman DB, Spangler SK, Jacobs MR, Appelbaum PC. In vitro activities of cefminox against anaerobic bacteria compared with those of nine other compounds. Antimicrob Agents Chemother 1998;42:495-501
   Web of Science | Medline

To the Editor:

The incidence of postoperative infection in the study reported by Itani and colleagues was extraordinarily high. The search for a new antibiotic to reduce this rate of infection not only does not bring the rate of infection into an acceptable range but also ignores a critical cause of surgical-site infection — the surgical technique. In the prevention of wound infections, more antimicrobial agents for use as prophylaxis will never overcome errors in surgical technique.

Alan R. Spievack, M.D.
Harvard Medical School, Boston, MA 02115
arspievack@comcast.net

Author/Editor Response

Moine and Asehnoune note that the timing of the administration of antimicrobial agents, the dose, and the possible need for additional administration are important factors in the success of prophylaxis against surgical-site infection. The longer half-life of ertapenem, as compared with that of cefotetan, permits simpler dosing in longer procedures and in patients in whom the 60-minute window of administration is missed. In our analysis, a lower body-mass index, the use of ertapenem, and a shorter duration of surgery were independent predictors of a better outcome, but the timing of prophylaxis was not.

Spievack points out that surgical technique is another important factor in the prevention of surgical-site infection. In our prospective study, patients were randomly assigned to receive either ertapenem or cefotetan and were operated on by the same groups of surgeons in 51 institutions. The rate of surgical-site infection in this study was similar to that in other studies1 in which the proper definition of surgical-site infection and follow-up were instituted. This high rate of surgical-site infection reflects a problem in elective colorectal surgery that surgeons need to acknowledge and address. Although more antibiotics are not the solution, better antibiotics can help.

Kamal M.F. Itani, M.D.
Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132
kitani@med.va.gov

Murray A. Abramson, M.D., M.P.H.
Merck, Rahway, NJ 07065

1 References

1. 1

   Smith RL, Bohl JK, McElearney ST, et al. Wound infection after elective colorectal resection. Ann Surg 2004;239:599-607
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Shaojun Shi, Yani Liu, Zhongfang Li, Heng Zheng, Yongning Lv, Hui Chen. (2010) Pharmacokinetics and tolerability of intravenous cefotetan disodium for injection in healthy Chinese volunteers: A randomized, open-label, single- and multiple-dose study. Clinical Therapeutics 32:10, 1832-1841
   CrossRef