New criteria for selecting the proper antimicrobial chemotherapy for severe sepsis and septic shock.
The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care. Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy even if it is administered rationally. Not all antimicrobial agents are equally capable of inducing septic shock; this is dependant on their mechanism of action rather than on the causative pathogen species. The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominates. Some antibiotics such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones do not have the propensity to provoke septic shock because their rapid bactericidal activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.
Department of Preclinical and Clinical Pharmacology, Università di Firenze, Italy.
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D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D019446:Endotoxemia / Q000139:chemically induced*; D004731:Endotoxins / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000188:drug therapy*; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007769:Lactams; D012307:Risk Factors; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D007769:Lactams