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Chapter 36. Antibiotic Therapy in Critical Illness

Michael S Niederman, MD, FCCP
DOI: 10.1378/critcare.21.36
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Sections

Objectives 
  • Review the mechanism of action of commonly used antibiotics.

  • Review principles of pharmacokinetics and pharmacodynamics of antibiotic use to define how to optimize antibiotic dosing.

  • Define strategies for antibiotic stewardship in the critically ill that could minimize the development of antibiotic resistance.

  • Illustrate the principles of antibiotic use by examining the treatment of pneumonia.

  • Review mechanisms of antibiotic resistance.

Synopsis 

Antibiotic therapy must be optimized in critically ill patients to lead to the greatest likelihood of success to treat severe infection. To effectively treat patients, it is necessary to give appropriate therapy (matching the pathogen to the drug), but also adequate therapy, which requires proper dosing. Some critically ill patients with sepsis have hyperdynamic circulation and require higher than normal doses of antibiotics to achieve effective serum levels. When dosing antibiotics, especially if infection with a potentially drug resistant pathogen is present, it is necessary to optimize bacterial killing by being aware of antimicrobial bactericidal mechanisms. Drugs such as aminoglycosides and quinolones kill in a concentration-dependent fashion, and maximizing the peak serum concentrations by once daily dosing may be most effective. Other agents, such as the β-lactams, kill in a time-dependent fashion and therapy can be optimized by prolonged or continuous infusion. Some older antimicrobials are not as effective as in the past, including third generation cephalosporins which can induce bacterial β-lactamase production, and quinolones which are not as effective against resistant gram-negatives as in the past. To preserve antibiotics for the future, it is necessary to understand mechanisms of antibiotic resistance and to practice antimicrobial stewardship by focusing on proper antibiotic dosing, de-escalation therapy, the development of local protocols for antibiotic choice, but not by restricting access to potentially effective broad-spectrum agents.

Antibiotic therapy must be optimized in critically ill patients to lead to the greatest likelihood of success to treat severe infection. To effectively treat patients, it is necessary to give appropriate therapy (matching the pathogen to the drug), but also adequate therapy, which requires proper dosing. Some critically ill patients with sepsis have hyperdynamic circulation and require higher than normal doses of antibiotics to achieve effective serum levels. When dosing antibiotics, especially if infection with a potentially drug resistant pathogen is present, it is necessary to optimize bacterial killing by being aware of antimicrobial bactericidal mechanisms. Drugs such as aminoglycosides and quinolones kill in a concentration-dependent fashion, and maximizing the peak serum concentrations by once-daily dosing may be most effective. Other agents, such as the β-lactams, kill in a time-dependent fashion, and therapy can be optimized by prolonged or continuous infusion. Some older antimicrobials are not as effective as in the past, including third-generation cephalosporins, which can induce bacterial β-lactamase production, and quinolones, which are not as effective against resistant gram-negative organisms as in the past. To preserve antibiotics for the future, it is necessary to understand mechanisms of antibiotic resistance and to practice antimicrobial stewardship by focusing on proper antibiotic dosing, de-escalation therapy, and the development of local protocols for antibiotic choice, but not by restricting access to potentially effective broad-spectrum agents.

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