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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Antibiotics in surgery: evidence of anecdote?

, M.D.

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In surgical practice, antimicrobial agents are administered in three types of situation: as prophylaxis, as an adjunct to operative treatment, and as therapy. Prophylactic antibiotics are given preoperatively to reduce the incidence of surgical site infection; adjunctive therapeutic antimicrobial agents are given in the setting of operative management of infections such as secondary peritonitis or necrotizing fasciitis; and antibiotics are used as primary therapy when operation is not performed, such as for cellulitis, or postoperative pneumonia. In the latter situation, antimicrobial actions and effects do not differ from those of other “medically treated” infections such as meningitis or uncomplicated urinary infection. Such antibiotic use as primary therapy will not be considered further. This chapter will discuss “surgical infections”, in which antimicrobial agents are given in association with operation or other types of drainage.

The clinical value of antimicrobial agents cannot be assumed simply because they inhibit or kill microbial pathogens in vitro. Pharmacodynamic studies, which show how pharmaceutical agents interact with their therapeutic targets, have found that the success of antimicrobial agents at eliminating bacterial pathogens is affected by the local milieu of infection (1). Pharmacodynamic principles are demonstrated by studies in animal models, in which the local milieu of infection is controlled by adjusting the inoculum density, duration of infection before treatment, and other factors. The most important animal research in surgical infections is the seminal study of Burke (2). Burke showed that the duration of skin wound contamination affects the efficacy of antimicrobial agents in preventing infection. Antibiotics work best when given before contamination; after three to four hours following bacterial inoculation, the value of antibiotics is greatly diminished.

Burke's study changed antibiotic science and practice in surgery by establishing in animals that antimicrobial agents prevent subcutaneous infection when administered before incision and contamination. The efficacy of antimicrobial prophylaxis was soon confirmed in patients in clinical trials (3, 4). The first definitive prospective randomized study of Polk et al. in 1969 began a wave of clinical trials in prophylaxis that continues presently. These prophylaxis studies have answered numerous questions about indications for prophylaxis, the optimal spectrum of antibacterial coverage and timing and duration of drug administration (5). Clinical trials in prophylaxis continue to address controversial issues that need further study: the value of prophylaxis in clean operations (6), the most appropriate duration of antimicrobial administration in cardiovascular procedures (7), the role of certain drugs such as aminoglycosides and vancomycin (8), implementation issues (9, 10) and the value of oral v systemic drug administration in colorectal procedures (11). Overall, antimicrobial prophylaxis has achieved a solid scientific footing based on numerous prospective randomized trials, and evidence of cost-efficacy (12). Perusal of the chapter on antibiotic prophylaxis in this book reveals numerous examples of level I evidence.

In contrast to prophylaxis, clinical trials of antimicrobial agents as therapeutic adjuncts in surgery have not yielded evidence of high quality. There are several reasons for this, best illustrated by studies in abdominal infection: a quick look at the chapter on abdominal infection reveals few examples of level I evidence. As abdominal infection is the most common, life-threatening surgical infection, its importance is obvious. Numerous clinical trials of treatment of abdominal infections have appeared in the published literature over the last decades. Some of these reports have assessed the outcomes of operative management, but most have dealt with the efficacy of antimicrobial therapy. To date, these studies have culminated in few evidence-based conclusions other than the need to cover aerobic/facultative and anaerobic pathogens (13, 14). At present, randomized trials have told us that as long as Escherichia coli and Bacteroides spp. are covered, it does not appear to matter what antimicrobial regimen is used. This bland conclusion from so much data does not help us answer important questions such whether patients with hospital-acquired abdominal infections require broader coverage (as has been suggested by observational studies (15, 16)) and how long patients should be treated.

The lack of conclusive evidence from abdominal infection studies is related to the causes of treatment failure. Antimicrobial therapy, the object of clinical trials, is one of many determinants of outcome after treatment for abdominal infections. The most important determiant of outcome is operative management: inadequate surgical treatment will lead to treatment failure despite optimal antibiotic use (14). The primacy of surgical management explains why antimicrobial therapy is only an adjunct. Other determinants of outcome include adequacy of resuscitation and other supportive therapies, degree of peritoneal contamination, duration of infection before treatment, and pre-existing medical conditions. Currently, there is no validated method to stratify, standardize or control for these determinants, although severity of illness is addressed by physiologybased scoring systems (17). In clinical trials as in clinical practice, the effects of antimicrobial therapy are obscured potentially by one or more of these confounding variables. The U.S. Food and Drug Administration and the Surgical Infection Society (SIS) both have attempted to improve the quality of clinical trials in abdominal infection with efforts to define, stratify, and where possible, standardize determinants of outcome other than antimicrobial therapy (18, 19). Recently, the SIS has sponsored efforts to define and standardize source control, without which treatment generally will fail (20). Until such foundational work has developed valid methods to control for multiple outcome determinants, evidence-based practice will remain elusive. Other examples of adjunctive antibiotic administration in which the role of antibiotics has not been clarified are necrotizing soft tissue infections and infected prosthetic implants.

Conclusion

Numerous prospective randomized clinical trials have studied the efficacy of antimicrobial agents in surgical infections. The efficacy of prophylactic antibiotics is well established, with level I evidence available for numerous indications. The role of antimicrobial agents as adjunctive therapy for surgically treated conditions such as abdominal infections is less clear. Evidence from clinical trials of adjunctive antibiotic treatment is obscured by confounding determinants of treatment failure. Until clinical investigators have developed methods to define and control for such variables, level I evidence will be difficult to attain.

References

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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK7006

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