Ventilator-Associated Pneumonia

Figure 1

Ventilator-associated pneumonia (VAP), which is usually defined as an infection occurring more than 48 hours after hospital admission in a patient requiring mechanical ventilation, is an entity that should be viewed as a subcategory of health care-associated pneumonia (HCAP). HCAP includes any patient who was hospitalized in an acute care hospital for 2 or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic. VAP is the most frequent intensive care unit (ICU)-acquired infection among patients receiving mechanical ventilation. In contrast to infections of other frequently involved organs (e.g., urinary tract and skin), for which mortality is low, the mortality rate for VAP ranges from 20 to 50% and can reach 70% in some specific settings or when lung infection is caused by high-risk pathogens or when initial antibiotic therapy is inappropriate. This issue of Seminars in Respiratory and Critical Care Medicine includes contributions from world-renowned experts in the field of VAP who have provided state-of-the-art information on important aspects of the clinical management of this dreadful disease.

In the first article, Isakow and Kollef describe an evidence-based approach of modifiable risk factors for preventing VAP. They reviewed all the literature concerning modifiable risk factors and respiratory care for the prevention of VAP and presented a very detailed and comprehensive discussion of each potential prophylactic measure. Some very simple, safe, inexpensive, and logical measures, including avoiding nasal insertion of endotracheal and gastric tubes; keeping patients in the semirecumbent position, especially in the case of enteral nutrition; and removal of tubing condensate may have a tremendous impact on the frequency of VAP in mechanically ventilated patients. However, because respiratory tract colonization of ICU patients is generally very complex, corresponding to a mix of self-colonization and cross-transmission, only a multifaceted and multidisciplinary program can be effective.

In the second article, Bonten and Krueger describe the rationale of selective decontamination of the digestive tract (SDD) as an infection control strategy designed to prevent VAP. After more than 20 years, SDD is still a controversial issue in intensive care medicine. Nevertheless, the debate is now enriched with results from large clinical trials in well-defined patient populations. The extremely beneficial outcomes of some of these recent studies should be confirmed, preferably in multicenter trials, because liberal use of SDD (or any antimicrobial prophylactic strategy) may lead to escalating antimicrobial resistance.

Because antibiotic resistance has become a worldwide concern, the debate as to whether infections caused by resistant bacteria are associated with higher mortality has been ongoing. As rightly underscored by Combes and colleagues, resistant strains do not appear to be more virulent than those susceptible to the usual antibiotics. Thus differences in outcome may principally relate to patient characteristics before or at the time of infection onset, and to high rates of inappropriate empirical antimicrobial treatment prescribed for antibiotic-resistant infections.

Two articles in this issue provide up-to-date information regarding how to improve the diagnosis of bacterial infection in mechanically ventilated patients. In the first one, Dr. Gibot discusses why the measurement of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 in bronchoalveolar lavage fluid may be useful as a diagnostic tool. Of course, like every biomarker, sTREM-1 will never substitute for a broad microbiological examination, and its interpretation must be correlated with a careful clinical evaluation. Nevertheless, in the difficult context of sepsis, sTREM-1 may accelerate and improve the diagnostic process, especially in patients having received prior antibiotics before evaluation. In the second one, Dr. Fagon reviews the potential advantages of a diagnostic strategy based on fiberoptic bronchoscopy and quantitative cultures in ventilated patients with signs suggestive of pneumonia. Although the true impact of this decision tree on patient outcome remains controversial, being able to withhold antimicrobial treatment from some patients without infection may constitute a distinct advantage in the long term by minimizing the emergence of resistant microorganisms in the ICU and redirecting the search for another (the true) infection site.

Five articles, by Drs. Niederman, Kiem and Schentag, Eggimann and Revelly, Goldstein and colleagues, and Lam and Wunderink, are devoted to the treatment of the disease. In the first one, Dr. Niederman underscores that antimicrobial therapy of patients with VAP should follow a two-stage process. The first stage involves administering broad-spectrum antibiotics to avoid inappropriate treatment in patients with true bacterial pneumonia. The second stage focuses on achieving this objective without overusing and abusing antibiotics, combining several different steps, such as stopping therapy in patients with a low probability of the disease, streamlining treatment once the etiologic agent is known, and shortening duration of therapy to 7 or 8 days, as dictated by the patient's clinical response to therapy and information about the bacteriology of the infection.

Antibiotic therapy is generally considered to be appropriate or concordant when in vitro susceptibilities of the administered antibiotics cover the isolated pathogens. However, we need to go a step further and improve the way we give antibiotics to patients with VAP, as reviewed by Drs. Kiem and Schentag. Scrupulous attention must be given to optimal doses, routes of administration, and pharmacodynamic characteristics of each agent used to treat this infection.

The commonly cited reason to use combination therapy is to achieve synergy in the therapy of Pseudomonas aeruginosa or other difficult to treat gram-negative bacilli. However, synergy has only been clearly documented to be valuable in vitro and in patients with neutropenia or bacteremic infection, which is uncommon in VAP. Based on a comprehensive and detailed review of all data, Drs. Eggimann and Revelly suggest that therapy could be switched to monotherapy in most patients after 3 or 5 days, provided that initial therapy was appropriate, the clinical course appears favorable, and the microbiological data do not point to a very difficult to treat microorganism.

In the following article, Goldstein and colleagues make a strong case for shortening the duration of antimicrobial therapy to 7 or 8 days in most patients with VAP who receive appropriate antimicrobial therapy and have a good clinical response within the first days of treatment. Prolonged therapy simply leads to colonization with antibiotic-resistant bacteria, which may precede a recurrent episode of VAP. These authors also provide detailed information on the new therapeutic possibilities offered by aerosolized antibiotics in mechanically patients. Aerosol can markedly increase tissue penetration of antibiotics in foci of pneumonia as compared with intravenous administration.

In the next article, Drs. Lam and Wunderink discuss how to prevent and treat VAP caused by methicillin-resistant Staphylococcus aureus. These fascinating bacteria have evolved many mechanisms of virulence and resistance to conventional antibiotics, and thus pose a significant and somewhat unique challenge to critical care physicians.

Treatment failure can be anticipated in ~30 to 40% of patients developing VAP, and this situation is associated with adverse outcomes and mortality. In the final article of this issue, Dr. Domínguez and colleagues review the epidemiology of this complication. As emphasized by these authors, the lack of response to empirical antibiotic treatment should be recognized early in the course of VAP, and a clear strategy for clarifying the causes of failure should be implemented. Resolution of VAP depends not only on the accuracy of microbial diagnosis but also on comorbidities, the response of the host to the infection, concomitant infections, or the correct clinical diagnosis.

This issue of Seminars should be a valuable resource for clinicians providing care for patients with VAP. We believe the information presented here will be instructive and of practical value to our readers.