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.

Abstract

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 (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)-alpha , 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 < or = 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 > or = 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF- alpha , 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.

• Authors: Anand Kumar, Cameron Haery, Bhanu Paladugu, Aseem Kumar, Simon Symeoneides, Leo Taiberg, Jailan Osman, Gordon Trenholme, Steven M Opal, Roy Goldfarb, Joseph E Parrillo
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 193 Issue 2 Pg. 251-8 (Jan 15 2006) ISSN: 0022-1899 [Print] United States
• PMID: 16362889 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Lactic Acid

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Cardiac Output
• Disease Models, Animal
• Escherichia coli Infections (drug therapy, mortality, physiopathology)
• Heart Rate
• Hypotension (physiopathology)
• Interleukin-6 (blood)
• Lactic Acid (blood)
• Male
• Mice
• Shock, Septic (drug therapy, microbiology, mortality, physiopathology)
• Statistics as Topic
• Stroke Volume
• Survival Analysis
• Time Factors
• Tumor Necrosis Factor-alpha (analysis)