SEATTLE—As multiresistant microorganisms become increasingly common, critical care physicians are arriving at the conclusion that less may be more when it comes to antimicrobial therapy for nosocomial pneumonia in the ICU. In a session at the annual meeting of the American Thoracic Society,[1] leaders in the management of ventilator-associated pneumonia (VAP) explored ways to limit overall antibiotic use while improving individual outcomes. Strategies included prompt initiation of treatment, “de-escalation” and tailoring of therapy to culture findings, and halting antibiotic administration as soon as patients improve.

“Antibiotic resistance is an issue that’s driving much of the thinking about management of nosocomial pneumonia,” remarked Michael S. Niederman, MD, Professor of Medicine at Stony Brook University and Chairman of Medicine at Winthrop-University Hospital in Mineola, New York. He reviewed data gathered by the National Nosocomial Infection Surveillance System from 112 medical ICUs in the 1990s: “Half of all Staphylococcus aureus was methicillin-resistant. If we look at Pseudomonas aeruginosa, 20% were generally resistant to imipenem, to quinolones, and to third-generation cephalosporins.” More than 35% of the Enterobacteriaceae were found to be resistant to third-generation cephalosporins, he added.

This burgeoning of antimicrobial resistance parallels massive growth in antibiotic use in the United States. Furthermore, within individual institutions, use of an antimicrobial agent correlates directly with the likelihood of emergence of resistance to that agent. Thus, meeting ICU patients’ immediate needs for treatment while preserving the efficacy of available antimicrobial agents presents a major challenge.

ADEQUATE INITIAL THERAPY CRUCIAL

Traditional antibiotic therapy for VAP typically starts by administering a relatively narrow-spectrum antibiotic and then modifying or expanding treatment to cover microbiologically identified organisms, observed Marin H. Kollef, MD, Associate Professor of Medicine at Washington University in St. Louis. “The problem with that,” he remarked, “is that it results in inadequate therapy.” Rather, broad-spectrum treatment should begin before microbiological results become available. Dr. Kollef and colleagues found that a delay of one day or more in receiving appropriate treatment increased a VAP patient’s risk for death in the hospital almost eightfold.[2] Thus, he emphasized, “giving antibiotic therapy up front appears to be an important determinant of outcome and may, in fact, be the most important determinant of outcome that we as clinicians have any control over.”

DE-ESCALATING ANTIBIOTIC USE

In patients with VAP, “prior antimicrobial therapy is the most important factor leading to the acquisition of resistance,” stressed Carlos M. Luna, MD, an Associate Professor of Internal Medicine at the University of Buenos Aires. He observed, “By the time of diagnosis of VAP, the bacteria responsible for new infections may be resistant to the antibiotics that have been given … as previous antibiotic therapy.” The likelihood of this finding underscores the need to consider a patient’s medication history before prescribing antimicrobials.

A strategy termed “de-escalation” serves to balance the need for prompt initiation of appropriate therapy in each patient with the aim of limiting development of microbial multiresistance. The approach, said Dr. Kollef, involves “assessing the risk for resistant pathogens in our patients, selecting a broad regimen initially to cover those likely pathogens, and then narrowing it aggressively.” He added, “When we talk about narrowing the regimen, we’re talking not only about narrowing its spectrum but also about the duration of therapy as well.”

SHORT COURSE OFTEN ENOUGH

Although the optimal duration of antimicrobial treatment for VAP has yet to be determined, “most patients in the ICU are, in fact, treated with a long-duration [course] of antibiotics,” noted Jean E. Chastre, MD, a Professor of Medicine at Hôpital Pitié-Salpêtrière of the University of Paris. “Shortening the duration of treatment of patients with nosocomial pneumonia may have some advantages,” he suggested.

Given the correlation between antibiotic use and development of resistance within an ICU, routinely prescribing shorter antibiotic courses could minimize the emergence of multidrug resistance. But might abbreviating antibiotic use also increase the risk for recurrence? To answer this question, Dr. Chastre and colleagues conducted a study to rank the risk factors for recurrence of pulmonary infection in VAP patients.[3] Because infection recurrence was found to be associated most strongly with variables at baseline, he concluded, “the rate of recurrence of the pulmonary infection is essentially linked to the severity of the pulmonary disease, and probably not so much to the duration of antimicrobial treatment.”

Dr. Chastre also summarized the results of another study that examined resolution of signs of infection, such as bacterial burden, leukocyte count, fever, and PaO2:FIO2 ratio.[4] He pointed out, “After only six days of antimicrobial treatment, in most patients these parameters returned to normal values,” a finding that suggests that short courses of antibiotics can yield good outcomes. He also described a three-step comprehensive VAP treatment protocol that reduces the duration of antibiotic administration.[5] Initial broad-spectrum antimicrobial treatment combined imipenem, a quinolone, and vancomycin according to the specific resistance profile for a particular ICU. Within 48 hours, therapy was then “streamlined” according to each patient’s microbiological data. Total duration of antibiotic use was also significantly shortened, from a mean of 14.8 days to a mean of 8.6 days. When the new protocol was used, noted Dr. Chastre, “no excess mortality was observed, and the percentage of patients with a secondary … lung infection decreased from nearly 25% to less than 10%.” The percentage of recurrent infections with multiresistant organisms also decreased slightly.

Dr. Chastre and colleagues likewise examined the effect of shortening the antibiotic courses for 402 VAP patients in 51 French ICUs. Patients were randomized to receive either an eight-day or a 15-day course of antibiotics. Again, neither mortality at day 60 nor pulmonary infection recurrence rates differed significantly between the two groups. Therefore, by routinely using short courses, Dr. Chastre concluded, “it’s possible to decrease the total amount of antibiotics used in the ICU.” Among patients with recurrent pulmonary infection, the percentage of microorganisms found to be multiresistant was slightly lower in the short-course group. Thus, he reasoned, “using such a strategy may have the same clinical efficacy, but with a major advantage, because it’s possible to decrease the total amount of antibiotics in the ICU, and therefore, it’s probably possible to decrease the emergence of multiresistant microorganisms.”

—Mimi Zucker, PhD

References
1. Kollef MH, Torres A, chairs. Pneumonia in the ICU: a fresh look. Presented at: annual meeting of the American Thoracic Society; Tuesday, May 20, 2003; Seattle, Wash.
2. Iregui M, Ward S, Sherman G, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122:262-268.
3. Combes A, Figliolini C, Trouillet JL, et al. Factors predicting ventilator-associated pneumonia recurrence. Crit Care Med. 2003;31:1102-1107.
4. Dennesen PJ, van der Ven AJ, Kessels AG, et al. Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. Am J Respir Crit Care Med. 2001;163:1371-1375.
5. Ibrahim EH, Ward S, Sherman G, et al. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med. 2001;29:1109-1115.

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