The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels

• Published in: The Journal of infectious diseases Vol. 193; no. 2; pp. 251 - 258
• Main Authors: Kumar, Anand, Haery, Cameron, Paladugu, Bhanu, Kumar, Aseem, Symeoneides, Simon, Taiberg, Leo, Osman, Jailan, Trenholme, Gordon, Opal, Steven M., Goldfarb, Roy, Parrillo, Joseph E.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.01.2006; University of Chicago Press; Oxford University Press
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacteria; Bacteriology; Biological and medical sciences; Cardiac Output; Cytokines; Disease Models, Animal; Escherichia coli; Escherichia coli Infections - drug therapy; Escherichia coli Infections - mortality; Escherichia coli Infections - physiopathology; Fundamental and applied biological sciences. Psychology; Heart Rate; Hemodynamics; Hypotension; Hypotension - physiopathology; Infectious diseases; Interleukin-6 - blood; Lactates; Lactic Acid - blood; Male; Medical sciences; Mice; Microbiology; Miscellaneous; Mortality; Septic shock; Shock, Septic - drug therapy; Shock, Septic - microbiology; Shock, Septic - mortality; Shock, Septic - physiopathology; Statistics as Topic; Stroke Volume; Survival Analysis; Survival rates; Time Factors; Tumor Necrosis Factor-alpha - analysis; Shock; Infection; Animal model; Antibiotic; Treatment; Microbiology; Escherichia coli; Cytokine; Bacteria; Serum; Enterobacteriaceae
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/498909

BackgroundThis study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock MethodsSurgical implantation of an E. coli (O18:K1:H7)–laced, gelatin capsule–encased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF)–α, interleukin (IL)–6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment ResultsA critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in ⩽20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 18–24 h after implantation. Antibiotic treatment initiated ⩾12 h after implantation was associated with persistence of increased circulating serum lactate, TNF-α, and IL-6 levels ConclusionsThe timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated