The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model ofEscherichia coliSeptic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
| Autor: | Gordon M. Trenholme, Bhanu P Paladugu, Jailan Osman, Aseem Kumar, Roy D. Goldfarb, Cameron Haery, Steven M. Opal, Joseph E. Parrillo, Anand Kumar, Leo Taiberg, Simon Symeoneides |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Time Factors medicine.drug_class Statistics as Topic Antibiotics Fibrinogen Gastroenterology Mice Heart Rate Internal medicine Animals Immunology and Allergy Medicine Lactic Acid Cardiac Output Interleukin 6 Escherichia coli Infections Survival analysis biology Interleukin-6 Tumor Necrosis Factor-alpha business.industry Septic shock Interleukin Stroke Volume medicine.disease Shock Septic Survival Analysis Anti-Bacterial Agents Disease Models Animal Infectious Diseases Shock (circulatory) Immunology biology.protein Tumor necrosis factor alpha Hypotension medicine.symptom business medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 193:251-258 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/498909 |
| Popis: | Background. This 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. Methods. Surgical implantation of an E. coli (018:Kl: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. Results. A 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-a, and IL-6 levels. Conclusions. The 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. |
| Databáze: | OpenAIRE |
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