Prevention of Ventilator-associated Pneumonia by Oral Decontamination
Just Another SDD Study?

Didier Pittet, M.S., Philippe Eggimann, M.D., and Bina Rubinovitch, M.D.

Infection Control Program and Medical Intensive Care Unit, Department of Internal Medicine, University of Geneva Hospitals, Geneva, Switzerland

	ARTICLE

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Ventilator-associated pneumonia (VAP) is a leading morbid outcome among critically ill patients with a reported incidence of 1.5 to 3% per day of mechanical ventilation. Although not universally documented, it has been associated with 20 to 30% increased risk of mortality and likely prolongs the length of ICU stay (1). Considerable efforts have been invested to develop and evaluate methods for reducing the incidence of VAP (2).

Upper digestive tract colonization by potentially pathogenic microorganisms of either endogenous or exogenous origin assumes a major role in the pathogenesis of subsequent VAP. The concept of selective decontamination of the digestive tract (SDD) is to prevent infection by modulating the carriage of these microorganisms from the oropharynx, stomach, and gut, but the relative role of each of these colonization sites has not yet been determined. Traditionally, SDD consists of nonabsorbable antibiotics applied topically to the oropharynx and/or through a nasogastric tube. In most instances, treatment with parenteral antibiotics is added in the first days after ICU admission to prevent early infections.

Ever since the observation by Stoutenbeeck and colleagues (3) in 1984 of an important reduction in the incidence of VAP in a nonrandomized comparison with a historical control group, dozens of randomized controlled trials have followed. Unfortunately, lack of standard protocols, trials in heterogeneous populations, or with insufficient numbers of patients made it difficult to derive meaningful conclusions from individual studies. During the nineties, several meta-analyses confirmed a significant reduction in infection, but the estimated impact on mortality was less evident and generated considerable controversy on the cost-effectiveness of therapy (4, 5). Recently, D'Amico and colleagues (6) conducted a refined meta-analysis in which 33 trials combining 5,727 patients were included. The effect of prophylaxis was evaluated for two distinct SDD categories: a regimen combining topical and parenteral antibiotics, or topical antibiotics only. A strong protective effect was observed for the combined regimen, both regarding the incidence of VAP and overall mortality. A clear though less extreme protection was found for topical antibiotics only, but without any impact on mortality.

The protective effect of SDD is primarily attributed to the parenteral component, which partially explains why its routine use has never become a standard of care in ICU patients (7, 8). SDD has become unpopular mainly because of concerns regarding short- and long-term emergence of antibiotic resistance, increasing costs, and enhanced mortality when inappropriate empirical antibiotic treatment of VAP is used (7, 9). These topics remain unresolved by currently available data and expert opinions reflect the same reservations (www.cdc.gov/ epo/mmwr/preview/http://mmwrhtml/00045365.htm) (8).

In this issue of the Journal (pp. 382-388), Bergmans and colleagues (10) report a study designed to address a focused hypothesis regarding the role of SDD in preventing VAP, i.e., that colonization of the oropharynx only, and not of the stomach or gut, is responsible for subsequent infection. Consistent with their hypothesis, topical application of antibiotic paste (gentamicin, colistin, vancomycin) to the oral cavity of mechanically ventilated patients modulated oropharyngeal carriage of potentially pathogenic microorganisms, did not interfere with gastrointestinal colonization, and significantly reduced the incidence of late-onset VAP.

Does this work bring new insights into the controversial issue of SDD?

First, in contrast to previous SDD studies, the demonstration of a reduction in the orotracheal colonization without impact on the endogenic flora of the stomach and gut is significant. This provides a fresh look at the pathogenesis of VAP and the rigorous methodology of the study clearly points to the pivotal role of oropharyngeal colonization in the development of subsequent VAP.

Second, the study suggests that SDD may reduce the use of antibiotics with potential impact on additional costs, increased risk of adverse events and, most importantly, increased risk of emergence of antibiotic resistancea priority target of healthcare management (11). Unfortunately, these investigators measured overall antibiotic use without specification, and the impact on the reduction of utilization, directly derived from prevention of VAP, could not be demonstrated.

Third, considering the major importance of intestinal flora in the development and spread of resistance to antibiotics, VAP prevention by modulating oropharyngeal colonization and preserving the endogenous gut flora or minimizing the overgrowth of resistant organisms, may impose as a primary measure in the future. However, this can be achieved only in conditions where the use of parenteral antibiotics is strictly controlled and limited.

The uniqueness of the setting in which this study was conducted limits its generalizability: the impact of SDD took place in an apparently highly efficient infection-control program where the epidemiology of microbial and antimicrobial influences markedly differs from many other European or US hospitals (9, 12). For instance, Bergmans and colleagues (10) did not detect any Acinetobacter or Stenotrophomonas spp. among pathogens causing VAP over 2 yr. In addition, 90% of their gram-negative bacteria were susceptible to gentamicin, and methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) have been rarely isolated in these hospitals for many years. In contrast, in a study reported from France in 1998 (12), MRSA accounted for 61% of pathogens causing VAP, A. baumanii for 9%, S. maltophilia for 2.4%, and 45% of gram-negative bacteria were resistant to gentamicin. Finally, the use of topical vancomycin is worrisome considering its potential for VRE selection, a major concern for many hospitals worldwide and most healthcare settings in the US.

In conclusion, more studies in varied settings are required before the suggested preventive strategy could be widely recommended. Careful surveillance for resistance acquisition is strictly mandatory in any case. Nevertheless, this study is not "just another SDD study" and it contributes significantly to our knowledge about the pathogenesis and potential for prevention of VAP by modulating oropharyngeal colonization.

	Footnotes

	References

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