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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.

The risk of transfer of vancomycin resistance to staphylococci is a real possibility and has been achieved in the laboratory. Prolonged colonization occurs with vancomycin-resistant Enterococcus (VRE), and many more patients are colonized than infected. The failure to identify, isolate, and adhere to infection control measures when caring for VRE-colonized patients dooms to failure any means to control its spread. Control of vancomycin use alone is unlikely to greatly affect the number of patients at risk for VRE colonization. The global spread of VRE may be impossible to stop, but infection control measures are the most important line of defense inside hospitals.

Introduction: "Pharmacodynamics" refers to the relationship of drug concentrations in serum or tissues to effects on biologic systems. Concepts used to describe antimicrobial pharmacodynamics include the minimal inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), and serum bactericidal titers (SBT), as well as post-antibiotic effect., Methods: Pertinent published literature was identified through a MEDLINE search., Results: Aminoglycosides have a concentration-dependent effect on bacteria killing and possess a relatively long postantibiotic effect. Given these characteristics, single-daily dosing, where the total daily dose with a traditional aminoglycoside regimen is given as one dose, may be more efficacious compared with more frequent dosing. For beta-lactam antimicrobials, bacterial killing is related to the duration of time that the free drug concentration exceeds the bacterial MIC. Beta-lactam antimicrobials have been shown to have no, or a short postantibiotic effect. Beta-lactam antimicrobials may be more effective when administered as continuous intravenous infusions., Conclusions: Pharmacodynamic variation may result from differences in drug sensitivity among individuals and the nature of the interaction between antimicrobials and microorganisms. Proper use of pharmacokinetic and pharmacodynamic principles can result in more effective and less toxic antimicrobial regimens.

Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce the overall costs attributable to infections. Principles of prophylaxis include providing effective levels of antibiotics in the decisive interval, and, in most instances, limiting the course to intraoperative coverage only. Use in The National Research Council clean contaminated operations is appropriate and, in many instances, has been proven beneficial. Antibiotic prophylaxis is also indicated for clean operations, such as those involved with insertion of prosthetic devices, that are associated with low infection risk and high morbidity. Extension of antibiotic prophylaxis to other categories of clean wounds should be limited to patients with two or more risk factors established by criteria in the study of the efficacy of nosocomial infection control (SENIC) because the baseline infection rate in these patients is high enough to justify their use. Cefazolin (or cefoxitin when anaerobic coverage is necessary) remains the mainstay of prophylactic therapy. Selection of an alternate agent should be based on specific contraindications, local infection control surveillance data, and the results of clinical trials. Newer criteria for determining the risk of "site infection" (wound and intracavitary) are in evolution and may lead to modification of these recommendations over the next several years.

Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin-clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third-generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable.

When used appropriately, antimicrobial prophylaxis is highly beneficial and cost effective. Antibiotics are not indicated for "clean procedures" such as hernia and breast surgery. A single preoperative dose will suffice, followed by an intraoperative dose if the operation takes more than 3 hours. For vascular (prosthesis or groin wound), head and neck (pharynx entered), thoracic (gastrointestinal or respiratory entrance) and high-risk gastroduodenal and biliary procedures, cefazolin, 1 g intravenously, is indicated. For procedures involving small intestine, appendix or penetrating abdominal trauma, cefoxitin or cefotetan, 2 g intravenously, is indicated. For colorectal procedures, either oral neomycin plus erythromycin or intravenous aminoglycoside plus clindamycin (or metronidazole) are effective. If valvular heart disease is present, endocarditis prophylaxis should be administered.

The prophylactic use of antibiotics in elective surgery of the colon is accepted practice, but it has inherent risks. The authors report the case of a 70-year-old woman who had wound infection and severe, relapsing pseudomembranous colitis due to Clostridium difficile after a short course of antibiotics given orally and parenterally at the time of elective resection of the colon. Perioperatively, she received erythromycin base and neomycin orally, plus netilmicin and metronidazole intravenously. Although the concomitant administration of parenteral antibiotics may enhance the benefit of antibiotics given orally before operation, this does not entirely prevent wound infection. Until the relation between the number of drugs and risk of antibiotic-associated colitis is more clearly defined, caution should be exercised in the use of multiple antibiotics in elective colonic surgery.