Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection?

Abstract

Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used concurrent controls, 14 studies used historic controls. To test this assumption, three observations from the two types of studies were compared. (i) The differences between observed and expected event rates for each study were used to perform a meta-analysis. This revealed that the summary odds ratios for bacteremia and respiratory infection were marked by significant heterogeneity (P > 0.95) and inconsistencies between those derived from studies with concurrent versus studies with historic controls. (ii) Where the data were available, the rates of acquisition of colonization in control groups were higher in studies with concurrent controls than in studies with historic controls. (iii) At least four studies with concurrent controls have shown a pattern of pathogenic isolates consistent with cross-infection between groups. These results are contrary to the initial assumption and suggest the possibility that SDD represents a major cross-infection hazard.Colonization and infection with gram-negative bacteria occur commonly in patients requiring prolonged intubation in intensive care units (ICUs) (12,20,62). Moreover, pneumonia is the most common fatal nosocomial infection, with mortality rates of 20 to 50% (12). In most instances, colonization of the gastrointestinal and respiratory tracts with pathogenic gramnegative bacteria precedes the development of infection in these patients. As an approach to prevent this progression from colonization through infection, the use of topical nonabsorbable antibiotics to selectively decontaminate the digestive tract (SDD) has been evaluated in 14 studies with historic controls (7,18,21,23,31,33,36,37,50,(52)(53)(54)63) and 26 studies with concurrent controls (1, 3, 4, 7, 9, 10, 15, 19, 22, 25, 27, 29, 32, 38, 42, 44-46, 49, 54-56, 58, 63, 65).A meta-analysis based on 22 randomized studies (4,142 patients) reported convincing evidence of a favorable effect of SDD on the incidence of respiratory infection (RI) with a reduction of approximately 63% (51). There may also be a difference in mortality as great as 20%, but this was shown to be statistically significant only when three studies (25,46,54) which had failed specific inclusion criteria for this meta-analysis were subsequently included. A criticism of this meta-analysis is that it failed to address the striking variability in RI rates in the control groups. In general, these rates were high (Ͼ40%) in studies in which a beneficial effect had been shown in contrast to studies that had not shown a beneficial effect (5).The interpretation of these studies is controversial (30,34,57,59,61). Issues of patient mix, study size, and design have been considered. In these studies, observer blinding is inherently difficult ...

Genotypes of Klebsiella oxytoca Isolates from Patients with Nosocomial Pneumonia Are Distinct from Those of Isolates from Patients with Antibiotic-Associated Hemorrhagic Colitis

“…The gastropulmonary or rectopulmonary hypothesis (32) currently proposes that nosocomial pneumonia, especially ventilator-associated pneumonia (VAP), is caused by Gram-negative bacteria originating from the GI tract (33,34). In contrast, our findings provide evidence that the colonization of the two main K. oxytoca habitats (lower GI tract and respiratory tract) requires distinct genetic backgrounds.…”

The Perfidious Effect of Topical Placebo: Calibration of Staphylococcus aureus Ventilator-Associated Pneumonia Incidence within Selective Digestive Decontamination Studies versus the Broader Evidence Base

“…Selective digestive decontamination (SDD), an extensively studied method for VAP prevention (9,10), achieves decreased colonization with aerobic Gram-negative bacilli at the oropharynx (11) through the use of topical antibiotic paste. However, SDD may increase colonization with Gram-positive bacteria (12,13), including staphylococci (14,15).…”

Selective decontamination of the digestive tract in critically ill patients treated in intensive care units: a mixed-methods feasibility study (the SuDDICU study)

“…4 Since the Cochrane review, additional primary research has been published, which also showed a mortality benefit (OR 0.63; 95% CI 0.46 to 0.87). 5,6 However, a degree of controversy exists, with Hurley et al 7 challenging that, across these studies, the incidence of ventilator-associated pneumonia (VAP) at baseline was significantly lower in the ventilated control groups than in the SDD groups, which could falsely give the impression of benefit. 8 Nonetheless, if the documented mortality benefit could be realised in UK practice, then it could prevent as many as 2000-3000 avoidable deaths per annum.…”