DOI: 10.1097/01.CCM.0000050283.70684.EA

,  

,  

PMID: 12576985

Issn Print: 0090-3493

Publication Date: 2003/02/01


Print

How do we achieve adequate therapy for severe infection? *

George H. Karam; Michael S. Niederman

    loading  Checking for direct PDF access through Ovid

Excerpt

The current literature is replete with studies documenting that the outcome of patients with severe infections, such as ventilator-associated pneumonia and sepsis, is improved if empirical antibiotic therapy is provided promptly and with “adequate” therapy (1–4). Although the definitions of adequate therapy generally require that patients receive an antimicrobial regimen that is active against the recovered pathogens (1, 2), discussions of the topic vary with regard to the role for combination therapy (if necessary), the need for using the right antibiotic dose and dosing interval to optimize efficacy, and the need to use an agent that penetrates to the site of infection. Recently Kollef et al. (1) distinguished between two different reasons for inadequate therapy when they applied the term initially delayed appropriate antibiotic treatment: 1) a delay in writing the antibiotic orders (which was the basis for initially delayed appropriate antibiotic treatment in 76% of patients studied with ventilator-associated pneumonia) and 2) the presence of a bacterial species resistant to the initially prescribed antibiotic regimen (3). Not surprisingly, hospital mortality was 69.7% in the 33 ventilator-associated pneumonia patients in this study who were classified as having initially delayed appropriate antibiotic treatment as compared with 28.4% in the 74 ventilator-associated pneumonia patients who did not have initially delayed appropriate antibiotic treatment (3).
Ideally, adequate therapy should be achieved frequently and should be based on the physicians’ knowledge of pharmacology, local patterns of antibiotic resistance, and expected clinical outcomes. Given the complexities of these issues, there are practical limitations to achieving this goal, yet to increase the likelihood of providing adequate therapy to critically ill patients, each hospital may need to design its own protocol for antibiotic usage. In one study, when a protocol of broad-spectrum antibiotics (imipenem plus ciprofloxacin plus vancomycin) was used instead of therapy based on the best judgment of the clinician, appropriate usage increased from 48% to 94% and was often accompanied by a shorter duration of therapy and a more frequent simplification of the initial empirical therapy regimen once culture data became available (5). This latter practice has been termed de-escalation and implies the importance of focusing on a narrow-spectrum regimen, whenever possible, after starting with a broad-spectrum regimen aimed at ensuring initially adequate empirical therapy (6).
In the current issue of Critical Care Medicine, Dr. Leone and colleagues (7) applied such an approach of using a protocol of broad-spectrum initial empirical therapy, coupled with a commitment to de-escalation, in 107 patients with septic shock. A source of infection was defined in 91 patients, and 78 had an associated positive culture, with pleuropulmonary and intraabdominal sources predominating (60% of all infections). The infections were a mix of Gram-positive (39%), Gram-negative (53%), and other organisms (8%), with 12% being polymicrobial. Most importantly, a total of 89% of all patients received adequate empirical therapy, and they had a 59% mortality at 30 days, compared with a 78% mortality for those receiving inadequate therapy. Despite commonly using adequate therapy, mortality was high, probably as a reflection of the severe illness present in these patients. How was it possible to achieve such a high rate of adequate therapy? It was likely directly related to the finding that very few patients were infected with resistant Gram-positive or Gram-negative organisms. This finding made it possible to de-escalate therapy in 52 of the 81 patients who were alive after 48 hrs to either a monotherapy or narrow-spectrum antimicrobial regimen.
    loading  Loading Related Articles