A new paradigm for treating infections: "go hard and go home"

Lipman, Jeffrey and Boots, Rob (2009) A new paradigm for treating infections: "go hard and go home". Critical Care and Resuscitation, 11 4: 276-281.


Author Lipman, Jeffrey
Boots, Rob
Title A new paradigm for treating infections: "go hard and go home"
Formatted title
A new paradigm for treating infections: "go hard and go home"
Journal name Critical Care and Resuscitation   Check publisher's open access policy
ISSN 1441-2772
Publication date 2009-12-01
Year available 2009
Sub-type Article (original research)
Volume 11
Issue 4
Start page 276
End page 281
Total pages 6
Editor Peter V van Heerden
Rinaldo Bellomo
Place of publication Australia
Publisher Australasian Academy of Critical Care Medicine
Collection year 2010
Language eng
Subject C1
Abstract Abstract: There is now significant evidence that initial use of the correct antibiotic saves more lives than virtually all other intensive care therapy. This means covering all possible causative organisms with the initial empirical choice. For nosocomial sepsis, broad-spectrum antibiotics must be started as soon as the relevant samples have been taken for culture, with deescalation of therapy targeted to the causative organisms when results and susceptibilities are available. There is an international trend to use shorter antibiotic courses. Pseudomonas pneumonia probably needs a 7-10 day course. In our ICU, provided the infection source is controlled, we seldom use antibiotic courses longer than 7 days. Evaluation of the kill characteristics of antibiotics in experimental models suggests that different classes of antibiotics should have different dosing regimens. For β- lactam antibiotics, the kill characteristic is almost entirely related to the time that tissue and plasma levels exceed a certain threshold, with no significant post-antibiotic effect, particularly against gram-negative organisms. Kill characteristics of other antibiotics, such as aminoglycosides, relate to adequate peak concentrations and a significant post-antibiotic effect. Clinically, these kill characteristics translate into the need for appropriate doses of the various antibiotics in patients with sepsis. We have shown that some patients with normal serum creatinine levels have very high creatinine clearance rates; in ICU patients with sepsis, blood pressure and tissue perfusion are maintained with large fluid loads and inotropic agents, thereby raising creatinine clearance. High clearances produce low trough concentrations of antibiotic, with important implications for underdosing and the development of antibiotic resistance. The new paradigm for treating sepsis, particularly nosocomial sepsis, is: get it right the first time, hit hard up front, and use large doses of broad-spectrum antibiotics for a short period.
Formatted abstract
Abstract: There is now significant evidence that initial use of the correct antibiotic saves more lives than virtually all other intensive care therapy. This means covering all possible causative organisms with the initial empirical choice. For nosocomial sepsis, broad-spectrum antibiotics must be started as soon as the relevant samples have been taken for culture, with deescalation of therapy targeted to the causative organisms when results and susceptibilities are available.

There is an international trend to use shorter antibiotic courses. Pseudomonas pneumonia probably needs a 7-10 day course. In our ICU, provided the infection source is controlled, we seldom use antibiotic courses longer than 7 days.

Evaluation of the kill characteristics of antibiotics in experimental models suggests that different classes of antibiotics should have different dosing regimens. For β- lactam antibiotics, the kill characteristic is almost entirely related to the time that tissue and plasma levels exceed a certain threshold, with no significant post-antibiotic effect, particularly against gram-negative organisms. Kill characteristics of other antibiotics, such as aminoglycosides, relate to adequate peak concentrations and a significant post-antibiotic effect.

Clinically, these kill characteristics translate into the need for appropriate doses of the various antibiotics in patients with sepsis. We have shown that some patients with normal serum creatinine levels have very high creatinine clearance rates; in ICU patients with sepsis, blood pressure and tissue perfusion are maintained with large fluid loads and inotropic agents, thereby raising creatinine clearance. High clearances produce low trough concentrations of antibiotic, with important implications for underdosing and the development of antibiotic resistance.

The new paradigm for treating sepsis, particularly nosocomial sepsis, is: get it right the first time, hit hard up front, and use large doses of broad-spectrum antibiotics for a short period.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Thu, 22 Apr 2010, 03:31:33 EST by Amanda Jones on behalf of Anaesthesiology and Critical Care - RBWH