This article focuses on the selection of appropriate antibiotics in the early stages of sepsis management. The likely microbial causes of the sepsis syndrome include Staphylococcus aureus, Gram-negative bacilli of the family Enterobacteriaceae, Pseudomonas aeruginosa, anaerobic Gram-negative bacilli, and Neisseria meningitidis. Staphylococcus aureus may be methicillin-resistant; vancomycin is the treatment of choice when these are suspected. Methicillin-susceptible S. aureus are optimally treated with anti-staphylococcal penicillins (e.g., nafcillin), first-generation cephalosporins (e.g., cefazolin), cefamandole, cefuroxime, or imipenem, and perhaps ampicillin-sulbactam, ticarcillin-clavulanic acid, or piperacillin-tazobactam. When Gram-negative bacilli are suspected, the more resistant species, such as P. aeruginosa and Enterobacter cloacae, should be targeted if likely to be present. Imipenem is predictably active against all the Enterobacteriaceae but P. aeruginosa strains may be resistant. Ceftazidime, cefoperazone, piperacillin-tazobactam, and ticarcillin-clavulanic acid are often, but not always, active against P. aeruginosa and E. cloacae. Thus, when these species are reasonably likely, an aminoglycoside or quinolone should be added to the beta-lactam chosen. Bacteroides fragilis group strains are very likely to be susceptible to metronidazole, ticarcillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, imipenem, and (often) chloramphenicol. The antibiotic choice should be based on the likely microbiology as predicted from the probable site of origin on the sepsis. These correlations are discussed in the article. Imipenem plus an aminoglycoside or quinolone will cover the majority of pathogens likely to cause sepsis, but vancomycin must be added if methicillin-resistant S. aureus is possible. Anti-lymphokine and anti-endotoxin drugs have yielded promising results. Alleged imperfections in design, execution, and/or analysis of some studies reported to date have delayed formal approval of the anti-endotoxin drugs in the USA. Definitive evaluations of other similar drugs are underway.
