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Abdominal infections are treated by resuscitation, abdominal drainage, control of the source of infection, and antimicrobial agents. Ideally, antimicrobial therapy is active against expected pathogens, safe and effective in clinical trials, inexpensive, and unlikely to promote drug resistance. Numerous single-agent and combination-drug regimens have been efficacious in clinical trials, based on coverage of Escherichia coli and Bacteroides species, the predominant pathogens isolated. Whether expanded antimicrobial coverage is required, especially in hospital-acquired infections, is controversial. Candida infections should be treated with antifungal therapy in patients with recurrent abdominal infections, immunosuppressed patients, and those with candidal abscesses. Most agents have few serious adverse effects; aminoglycosides are the least expensive agents but cause nephro- and ototoxicity. There is little information on the promotion of drug resistance in this condition. Recent developments include the introduction of ticarcillin/clavulanic acid, ampicillin/ sulbactam, piperacillin/tazobactam, meropenem, aztreonam/clindamycin, and ciprofloxacin/metronidazole; success with once-daily aminoglycosides; evidence that antibiotics limit infectious complications of pancreatitis; controversy over the value of diagnostic cultures; the use of oral therapy; evidence in favor of shorter courses of treatment; and the introduction of pharmacoeconomic studies. Clinical investigators are challenged to improve drug trials by stratifying and controlling for the adequacy of surgical intervention.

Postoperative peritonitis is potentially lethal and is usually caused by leakage of gut contents. Successful management depends on early diagnosis and treatment which require clinical suspicion and aggressive diagnostic imaging. Treatment consists of fluid and nutritional resuscitation, peritoneal toilet, control of gut leakage and initiation of antimicrobial therapy. Since delay in diagnosis is common, antimicrobial treatment is usually begun when the infection has become well developed. Experimental evidence has shown that in some settings antimicrobial agents do not perform as well in later stages of infection but whether this applies to peritonitis is not known. The optimal duration of antimicrobial therapy has not been studied specifically in postoperative peritonitis. Arguments for prolonged treatment include the potential for greater killing of bacteria in patients who have severe infections. Arguments against prolongation of therapy include the lesser role of antibiotics compared with operative management, doubt about the value of antibiotics' ability to kill bacteria at later stages of infection and the significant number of infective and non-infective complications of drug therapy. Limitation of antimicrobial treatment to no more than seven days is advocated. Persistent clinical signs, fever, or leucocytosis should prompt a search for a drainable focus of infection in the abdomen or treatable site elsewhere.

Background: The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial., Methods: A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America., Results: In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation., Conclusions: This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

Scheduled relaparotomy is attracting interest as a means of treating intra-abdominal sepsis. It is the subject of several studies to evaluate its role in the management of peritoneal infection. However, indications for this procedure are not clear and current knowledge does not allow for adequate scientific evaluation. Many trials lack control groups and historical control groups cannot be evaluated on criteria, such as illness severity, concomitant health problems or even surgical technique. Indicators of outcome are generally described in insufficient detail; only death or survival are reported and important morbidity and resource utilization data are not included. A randomized, prospective, multicenter clinical trial using standardized techniques is necessary to determine the usefulness of scheduled relaparotomy performed on different patients.

Twenty-three surgeons at three McGill University hospitals were interviewed about their treatment of intra-abdominal sepsis. They described their use of antibiotics, operative practices and other treatment of generalized peritonitis and intra-abdominal abscesses. If more than 75% of respondents used a given method, its use was considered "uniform" unless substantial interhospital variation existed for that method. Treatment was variable in 18 situations. Only four of these involved systemic antibiotic use--drug regimens in appendicitis and intra-abdominal abscess, and duration of antibiotic therapy following appendicitis and perforated duodenal ulcer. The other 14 examples of variation were in operative management. In generalized peritonitis, they were: use of diagnostic paracentesis; abdominal lavage with saline alone versus saline plus antibiotic use; whether the peritoneum should ever be left open; the use or avoidance of drains; primary versus delayed wound closure in appendicitis, bowel perforation and trauma with gastrointestinal perforation and, finally, wound lavage with saline alone or with antibiotics. Treatment of intra-abdominal abscesses varied in regard to the diagnostic and therapeutic roles of percutaneous needle aspiration, the preferred route of drainage of a pelvic abscess, the use of an extra- or trans-serosal approach to a subphrenic abscess, local versus full abdominal exploration for a single abscess and the type of drain used. The authors conclude that operative management of intra-abdominal sepsis varies widely among surgeons. This fact invalidates many "controlled" trials of antibiotics and should focus attention less on drugs and more on surgical treatment.

We present preliminary data on the role of antibiotics in intraabdominal sepsis using a new, clinically relevant animal model. Peritoneal cavity infection was induced by ligation and perforation of the cecum in adult rats. Surviving rats were randomized to receive either saline or cefoxitin at the time of cecal excision and peritoneal lavage, 18 h after the onset of infection. This is different from previous models of abdominal sepsis (in which antibiotics are given within 4 h of peritoneal contamination) and mimics the clinical setting in which antibiotics are initiated much later, at the time of operation. Antibiotic-treated rats received 20 mg cefoxitin i.m. every 8 h for 7 days; controls received saline at similar times. Thirty-nine of 67 control rats died (58%) versus 20 of 64 (31%) that received cefoxitin (p less than 0.005). We conclude that even with delayed administration, antibiotics appear to improve the outcome of intraabdominal sepsis. With further characterization of this model we plan to use it as an in vivo assay to compare the efficacy of different antimicrobial agents in intraabdominal sepsis.

We have previously shown that experimental peritonitis secondary to fecal bacteria plus barium sulfate suppresses delayed cutaneous hypersensitivity (DCH) in rats. We examined herein the role of barium sulfate. In a series of experiments presensitized rats were simultaneously skin tested with intradermal keyhole limpet hemocyanin and given an intraperitoneal injection of either (1) a mixture of four fecal bacteria in their nutrient broths, (2) bacteria and broths plus barium sulfate, (3) sterile broths plus barium, (4) sterile barium alone, (5) nutrient broths, or (6) saline. In rats given sterile barium we measured phagocyte delivery to subcutaneous polyvinyl alcohol sponges. We found that (1) the coadministration of barium sulfate was necessary for rats given bacteria to die (P = 0.03) or develop abdominal abscesses (P less than 0.005), (2) suppression of DCH occurred in 70% of rats receiving sterile barium sulfate vs 0% in saline controls (P = 0.0001), (3) early suppression of DCH was associated with subsequent death and abscess formation in rats given bacteria plus barium (P = 0.00002) and with intraabdominal barium collections in rats given barium alone (P less than 0.02), (4) barium sulfate administration caused suppression of phagocyte delivery to subcutaneous sponges: 23.2 X 10(6) cells/site vs 43.1 X 10(6) cells/site in saline controls (P less than 0.005). We conclude that barium sulfate itself has profound systemic effects in the rat model of intraabdominal sepsis. Early suppression of DCH is associated with a poor outcome in septic rats.

Generalized peritonitis was assessed in 176 patients, 67 (38%) of whom died. Cases were divided into causative groups: (1) appendicitis and perforated duodenal ulcer, (2) intraperitoneal origin other than appendix or duodenum, and (3) postoperative peritonitis. Mortalities were 10%, 50%, and 60%, respectively. Postoperative peritonitis was characterized by lack of influence of age on outcome, late operation, and more frequent organ failure. Delayed surgery carried a worse prognosis. Organ failure was a risk factor with 76% mortality, and was associated with late operation. Early surgery in organ failure improved survival. More sensitive indicators of early organ dysfunction might improve survival.

The pathogenicity of enterococci in intraabdominal sepsis has not been clarified. Therefore, fecal-type peritonitis was induced in rats by intraperitoneal injection of barium sulfate along with a bacterial inoculum consisting of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens with or without Streptococcus faecalis. Mortality at 19 d and characteristics of intraabdominal abscesses in survivors at 19 d were analyzed. The presence of S. faecalis in the original inoculum was significantly associated with death or large (greater than 20 mm) abscess formation when these two end points were examined together. S. faecalis may synergize with other bacteria in intraabdominal sepsis to augment morbidity and possibly mortality.

Therapeutic trials for intra-abdominal sepsis require pretreatment stratification; physiologic scoring has been recently proposed for this purpose. We have prospectively tested the validity of one such scoring system, namely, the Acute Physiology and Chronic Health Evaluation (APACHE II). As part of a larger database, we correlated APACHE II scores with mortality in 100 patients hospitalized for generalized peritonitis or abdominal abscess. Use of steroids was recorded because of our suspicion that steroids increase mortality but blunt the physiologic response to sepsis. Thirty-one patients died, including 12 of 19 patients receiving steroids. Stepwise discriminant analysis revealed that the APACHE II score and steroid use were each independently associated with the rate of mortality. We report a prospective validation of pretreatment APACHE II scoring in abdominal sepsis. Steroid use is an independent risk factor.