Decontamination of the Digestive Tract and Oropharynx in ICU Patients
de Smet AM, Kluytmans JA, Cooper BS, et al
N Engl J Med. 2009;360:20-31
Critically ill patients often require prolonged hospital care, which may be complicated by nosocomial infections. Some data have suggested that nosocomial respiratory infections may be reduced with the use of prophylactic antibiotic regimens, such as selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). The study authors sought to determine whether SDD or SOD would improve clinical outcomes in intensive care unit (ICU) patients, and thus evaluated these 2 regimens in 13 ICUs in The Netherlands. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of only oropharyngeal application of these antibiotics. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible for inclusion; each ICU was randomized to 1 of 3 regimens (SDD, SOD, or standard care) over 6 months. The primary endpoint of the study was 28-day mortality. Five thousand nine hundred thirty-nine patients were enrolled (N = 1990 for standard care, N = 1904 for SOD, and N = 2045 for SDD), and crude mortality at 28 days was not different between the groups (27.5%, 26.6%, and 26.9%, respectively). In a regression model adjusting for age, sex, severity of illness (Acute Physiology and Chronic Health Evaluation [APACHE] II score), intubation status, and medical specialty, the odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard care group, were 0.86 (95% confidence interval [CI] = 0.74-0.99) and 0.83 (95% CI = 0.72-0.97), respectively. On the basis of the adjusted analyses, the study authors concluded that mortality was reduced by approximately 3.5% with SDD and by 2.9% with SOD.
Viewpoint
This study suggested that in severely ill ICU patients with an overall mortality of nearly 30%, decontamination strategies may improve survival. Unfortunately, several limitations of the study preclude direct application of these results to patient care. First, the effect on mortality was only evident after complex statistical modeling to adjust for factors that may also have contributed to differences in survival. Second, there was no clear reduction in nosocomial infections as expected, which raises the question of how survival may have been improved if not through prevention of infectious complications. (Crude incidences of bacteremia were reduced for Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae, but respiratory infections were not prevented as expected). Third, although surveillance was undertaken to assess changes in resistance or the emergence of resistant pathogens, the time period for this assessment was short and likely insufficient to exclude these occurrences, particularly for nosocomial infections, such as Clostridium difficile colitis. In addition, unlike most ICUs in North America, no methicillin-resistant S aureus (MRSA) infections were identified in any group, and SDD has been associated with increased prevalence of MRSA infections. Finally, there was no discrete clinical benefit that may explain the improvement in survival because there were no differences in the duration of mechanical ventilation, ICU, or hospital length of stay. Although provocative, the data from this study do not demonstrate a clear clinical benefit of either SDD or SOD, nor does it help us to understand the mechanisms by which improvements may accrue.
Abstract