Selective decontamination of the digestive tract: the mechanism of action is control of gut overgrowth

Silvestri, Luciano; Cal, Miguel A. de la; Saene, H. K. F. van

doi:10.1007/s00134-012-2690-1

Cited by 92 publications

(64 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the first (which was also the first positive) randomised controlled trial in 1987, 95 SDD has been tested in more than 65 randomised controlled trials studying more than 15000 patients. 96 The findings are unambiguous: patients who receive SDD are less likely to develop multiorgan failure 91 or die 96 than patients who do not (figure 2). Nevertheless, clinical use of SDD remains uncommon, especially in North America, due to perceived risk of antimicrobial resistance, although this concern is not supported by large clinical trials and meta-analyses.…”

Section: Gut-derived Sepsis: the Inarguable And The Unknownmentioning

confidence: 99%

“…106 SDD is the most thoroughly studied intervention in critical care research, and has unambiguous benefits in the prevention of infections, multiorgan failure, and death. 91,96 Early intensive-care studies of probiotics suggest that they decrease the risk of pneumonia and shorten the length of stay in the intensive-care unit for ventilated patients 150 and decrease systemic infections in high-risk postoperative patients. 151 Improved survival has been reported in a mouse model of sepsis.…”

Section: Important Clinical Lessons and Areas For Further Studymentioning

confidence: 99%

See 1 more Smart Citation

The microbiome and critical illness

Dickson

2016

The Lancet Respiratory Medicine

356

344

View full text Add to dashboard Cite

The central role of the microbiome in critical illness is supported by a half century of experimental and clinical study. The physiological effects of critical illness and the clinical interventions of intensive care substantially alter the microbiome. In turn, the microbiome predicts patients’ susceptibility to disease, and manipulation of the microbiome has prevented or modulated critical illness in animal models and clinical trials. This Review surveys the microbial ecology of critically ill patients, presents the facts and unanswered questions surrounding gut-derived sepsis, and explores the radically altered ecosystem of the injured alveolus. The revolution in culture-independent microbiology has provided the tools needed to target the microbiome rationally for the prevention and treatment of critical illness, holding great promise to improve the acute and chronic outcomes of the critically ill.

show abstract

Section: Gut-derived Sepsis: the Inarguable And The Unknownmentioning

confidence: 99%

Section: Important Clinical Lessons and Areas For Further Studymentioning

confidence: 99%

The microbiome and critical illness

Dickson

2016

The Lancet Respiratory Medicine

356

344

View full text Add to dashboard Cite

show abstract

“…In fact, it is a great paradox that the sheer volume of studies on this practice might be greater (and more supportive) than in almost any aspect of critical care, yet this has not translated to a change in clinical practice. Specifically, there have been over 60 randomized controlled trials and over 10 meta-analyses on SDD in over 15,000 patients, demonstrating a reduction of lower airway infection of 72% and bloodstream infection by 37% (54;55). …”

Section: Targeting the Microbiomementioning

confidence: 99%

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness

Klingensmith

Coopersmith

2016

Critical Care Clinics

310

200

View full text Add to dashboard Cite

Synopsis All elements of the gut – the epithelium, the immune system, and the microbiome – are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU.

show abstract

“…Remarkably, the original SDD protocol uses 100 mg colistin sulfate four times a day (2). One milligram of colistin sulfate is equivalent to about 0.670 mg of pure colistin base (Fagron; colistin sulfate certificate of analysis, 2011), which has been assigned a potency of 30,000 IU per mg (3).…”

mentioning

confidence: 99%

“…For successful decontamination, AGNB should ideally be sensitive to both decontaminating agents (2).…”

mentioning

confidence: 99%

Inappropriate Dose of Enteral Antimicrobials Promotes Resistance

et al. 2013

View full text Add to dashboard Cite

d W e read with interest the South African study based on a collection of separate case reports (1). The authors hypothesized that selective digestive decontamination (SDD) using enteral colistin (i.e., polymyxin E) and tobramycin probably contributed to the selection and carriage of a colistin-resistant OXA-181-producing Klebsiella pneumoniae strain. We argue that the use of an inappropriate protocol of enteral decontamination is more likely responsible for both the failure to eliminate intestinal carriage of K. pneumoniae and the selection of colistin-resistant K. pneumoniae.Interestingly, the authors used their own decontaminating regimen that included a 2% colistin-tobramycin paste applied three times a day into the oropharynx, combined with a solution of 1 million IU colistin and 80 mg tobramycin administered three times a day into the gut via a nasogastric tube. Three main points should be addressed on this decontaminating protocol.First, the dosage of the oropharyngeal paste is not specified. Generally, half a gram of 2% polymyxin E-tobramycin paste or gel four times a day has been shown to clear aerobic Gram-negative bacilli (AGNB) from the oropharynx (2).Second, and most importantly, the enteral dose of 1 million IU colistin three times a day might be too low to achieve successful decontamination, i.e., eradication of the OXA-181-producing K. pneumoniae from the gut. Remarkably, the original SDD protocol uses 100 mg colistin sulfate four times a day (2). One milligram of colistin sulfate is equivalent to about 0.670 mg of pure colistin base (Fagron; colistin sulfate certificate of analysis, 2011), which has been assigned a potency of 30,000 IU per mg (3). Therefore, the original SDD protocol consists of about 2 million IU colistin four times a day. This daily dose is approximately three times higher than that used by the South African researchers. Early studies on SDD have shown that high doses of enteral colistin are required to suppress AGNB because colistin is moderately inactivated by fecal and food compounds (4, 5).Third, although the investigators do not report it explicitly, the OXA-181-producing K. pneumoniae strain was almost certainly resistant to tobramycin, the second component of SDD. For successful decontamination, AGNB should ideally be sensitive to both decontaminating agents (2).The failure to decontaminate the gut from AGNB may cause gut overgrowth, which is the ideal condition for the de novo development of new clones following increased spontaneous mutation, resulting in polyclonality (6). The low colistin levels in the gut will kill sensitive clones but allow mutating ones to become resistant to colistin.Interestingly, in a recent large Dutch study of about 6,000 patients using the original protocol of SDD (7), the acquisition rates of colistin-resistant AGNB in the respiratory tract were low and comparable during SDD and standard care (8).We believe that this study provides a basis for the conclusion that colistin resistance may be caused by the administration of an inappropriately...

show abstract

Selective decontamination of the digestive tract: the mechanism of action is control of gut overgrowth

Cited by 92 publications

References 134 publications

The microbiome and critical illness

The microbiome and critical illness

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness

Inappropriate Dose of Enteral Antimicrobials Promotes Resistance

Contact Info

Product

Resources

About