Impact of selective decontamination of the digestive tract on fungal carriage and infection: systematic review of randomized controlled trials

Objective To determine the impact of the antifungal component of selective decontamination of the digestive tract on fungal carriage, infection and fungaemia.Design Meta-analysis of randomized controlled trials of selective decontamination of the digestive tractStudy selection Data sources included Medline, Embase, Cochrane Register of Controlled Trials, previous meta-analyses, personal communications and conference proceedings, without restriction of language or publication status. All randomized trials were selected that compared oropharyngeal and/or intestinal administration of antifungals amphotericin B or nystatin, as part of selective decontamination protocol, with no treatment in the controls. There were 42 randomized controlled trials with a total of 6,075 critically ill patients.Methods Three reviewers independently applied selection criteria, performed quality assessment and extracted the data. The main outcome measures were patients with fungal carriage, patients with fungal infections and patients with fungaemia. Odds ratios were pooled with the random effect model.Measurements and results Enteral antifungals significantly reduced fungal carriage (odds ratio 0.32, 95% confidence interval 0.19–0.53) and overall fungal infections (0.30, 0.17–0.53). Fungaemia was not significantly reduced in the treatment group (0.89, 0.16–4.95).Conclusions Antifungals, as part of selective decontamination of the digestive tract, reduce fungal carriage and infection but not fungaemia in critically ill patients and may justify the inclusion of an antifungal component in the decontamination protocol.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

Intestinal decontamination in a polyvalent ICU

A double blind, placebo-controlled trial was performed to test the efficacy of prevention of nosocomial infections by selective digestive decontamination. Placebo or tobramycin (80 mg) and colistin (100 mg) was given four times daily via the gastric tube. Amphotericin B (500 mg/6h) was administered to all patients. As our ICU is divided into two separate subunits, intestinal decontamination or placebo was administered alternatively to patients of the two subunits during two 3-month periods, separated by a 2-month period without prevention. The decontamination (n=97) and placebo groups (n=84) were similar with respect to age, sex, severity score and diagnostic categories on admission. Intestinal decontamination alone failed to significantly reduce the number of infected patients (26% vs 34.5%,P=0.20), but was effective on ICU-acquired infections (0.33 vs 0.60,p=0.02) especially gram-negative infection rates (0.17 vs 043,p=0.01). The onset of the first ICU-acquired infection was delayed (9 vs 13 days,p<0.001) and incidence of pneumonia (2 vs 13 cases,p<0.01) including bacterial pneumonia (0 vs 8 cases,p<0.01) was significantly decreased. However, mean ICU stay and mortality were not significatly modified by intestinal decontamination.     

Selective decontamination of the digestive tract improves survival in patients receiving differential lung ventilation

In a review of the literature on differential lung ventilation (DLV) the average mortality was found to be 47%. The major cause of death (66%) was infection. The effect of a novel infection prevention regimen on the colonisation and infection rate of the respiratory tract and on outcome was studied in polytrauma patients. Nineteen patients who presented with asymmetric pulmonary contusion were treated with DLV (103±72 h) and conventional mechanical ventilation (CMV) (16±10 days). They were treated with selective decontamination of the digestive tract with topical non-absorbable antibiotics in combination with systemic antibiotic prophylaxis starting immediately after admission. In one patient colonisation of the respiratory tract was found with Staphylococcus aureus. This disappeared after continued systemic antibiotic prophylaxis. Colonisation with hospital-acquired Gram-negative bacteria or yeasts was not observed. No patient developed pneumonia throughout the period on conventional mechanical ventilation or on DLV. One patient died from cerebral injury. It is concluded that prolonged endobronchial intubation for DLV can be used without increased risk for pneumonia with this antibiotic regimen and that the very low mortality in this study may be attributed to the prevention of infectious complications.     

Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract

Objective: To evaluate the effect of a method of Selective Decontamination of the Digestive Tract (SDD) on colonization, nosocomial infection (NI), bacterial resistance, mortality and economic costs.Design: Randomized, double blind, placebo controlled study.Setting: Polyvalent intensive care unit (ICU) of a tertiary care hospital with 27 beds.Patients: 101 patients with >3 days of mechanical ventilation and >5 days of stay, without infection at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG).Interventions: The TG was given Cefotaxime i.v. (6 g/day) for the first four days and an association of Polymyxin E, Tobramycin and Amphothericin B at the oropharyngeal and gastrointestinal level throughout the whole stay.Results: In the TG, colonization by gram-negative agents at oropharyngeal, tracheal and gastrointestinal level fell significantly. There was a significant drop in the overall, respiratory and urinary NI (26% vs 63%,p<0.001; 15% vs 46%,p<0.001; 9% vs 31%,p<0.01). The overall mortality and NI related mortality was less in the TG (21% vs 44%,p<0.05; 2% vs 20%,p<0.01). The economic costs, mechanical ventilation time and length of stay were similar. The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG (38% vs 15% and 38% vs 9%,p<0.001).Conclusions: colonization by gram-negative bacilli, NI and the mortality related to it can be modified by SDD. Continuous bacteriological surveillance is necessary.     

Clinical use of selective decontamination: The concept

Infections can be classified according to: (1) the type of offending microorganism (virus, bacteria, fungi, parasites), (2) according to the clearance by the defence system (T cell dependent/independent) and (3) in case bacteria are the causative agents in Gram-positive and Gram-negative infections. The latter classification in Gram-positive and Gram-negative infections has appeared to have a practical consequence. Gram-negative bacteria, often involved in major infections and yeasts, appear to play practically no role in the intestinal ecological system. Consequently, it is nowadays increasingly attempted to eliminate Gram-negative bacteria and yeasts selectively from the digestive tract with antimicrobial agents. Selective suppression of Gram-positive bacteria may severely affect the ecosystem of the digestive tract. This selective suppression of Gram-negatives must be continued as long as patients are immunocompromised (locally or systemically) and is called selective decontamination of the digestive tract.     

选择性肠道去污对非感染性创伤患者合并血清降钙素原升高的治疗作用

目的探讨选择性肠道去污治疗对非感染性创伤合并血清降钙素原升高患者的影响。 方法将80例伴有血清降钙素原升高的非感染性创伤患者分为实验组和对照组,每组40例。其中实验组患者给予选择性肠道去污治疗,对照组给予生理盐水对照处理。连续监测所有患者血清降钙素原及内毒素水平的变化。并于治疗14 d后观察有无急性肾损伤发生。 结果实验组患者血清降钙素原治疗后第7、9、11、13天分别为（1.29 ± 0.26）、（0.89 ± 0.15）、（0.56 ± 0.16）、（0.50 ± 0.18）μg/L,内毒素水平分别为（82 ± 12）、（53 ± 8）、（47 ± 8）、（34 ± 6）EU/L,对照组患者治疗后第7、9、11、13天分别血清降钙素原为（3.90 ± 0.64）、（3.52 ± 0.45）、（3.98 ± 0.78）、（3.56 ± 0.08）μg/L,内毒素水平分别为（101 ± 18）、（113 ± 17）、（108 ± 13）、（96 ± 16）EU/L,实验组患者血清降钙素原（t=23.906、35.279、27.236、36.406,P均< 0.05）及内毒素均明显低于对照组患者（t=5.705、20.407、24.989、22.901,P均< 0.05）。同时,对照组发生急性肾损伤风险高于实验组（27/40 vs. 15/40,χ²=7.218,P<0.05）。 结论非感染性创伤合并降钙素原升高的患者为肠源性感染,选择性肠道去污治疗可明显降低血清降钙素原及内毒素水平,从而减小后续治疗中发生急性肾损伤的风险。     

Selective decontamination in intensive care practice: A review of clinical experience

Acquired infection is a common problem in intensive care and in a general ICU the infection rate can exceed 80% in patients ventilated beyond 5 days. SDD, adapted from regimes used in neutropenic patients, was first introduced to the ICU situation in Groningen. This article reviews 10 published trials of SDD in ICU. The trial designs vary but all show a significant reduction in both colonisation rates and acquired infection rates. Infection rates were reduced from 10%–78% to 3%–10% in the SDD treated groups. Of the 10 trials 2 showed an overall reduction in mortality 2 showed a reduction in infection-related mortality and 1 showed a reduction in mortality amongst trauma patients. Although further evaluation of trials is required SDD now appears to be of proven efficacy in certain groups of high risk patients within ICU.     

Prevention of pneumonia by selective decontamination of the digestive tract (SDD)

Prevention of respiratory tract infections is only possible when the pathogenesis is known. Three types of infection can be distinguished: primary endogenous infections, caused by pathogens carried in the throat at the commencement of mechanical ventilation, generally develop early and can only be prevented by intravenous antibiotics. Secondary endogeneous infections, caused by hospital-acquired pathogens, generally develop later and can be prevented by selective decontamination of the digestive tract (SDD). The GI-tract is decontaminated by oral nonabsorbable antibiotics and for oropharyngeal decontamination a sticky antibiotic ointment is used. To date 16 controlled SDD trials in intensive care have been fully published. In all except one study, the pneumonia rate decreased significantly from 40%–50% in controls to about 10% in SDD-treated patients. All studies showed a consistent reduction of ventilator days, ICU-stay and an improved outcome in SDD-treated patients. However, in only few studies did these differences reach statistical significance. Seclection of resistant strains has not been observed during prolonged use of SDD. Sucralfate reduces the pneumonia rate compared to H₂-blockers or antacids by not interfering with the gastric barrier. However, gastric colonization is reduced rather than eliminated and sucralfate has almost no effect on oropharyngeal or tracheal colonization. Whether sucralfate is significantly better than a placebo remains to be established. SDD is superior to sucralfate in preventing both colonization and infection.     

Effects of selective decontamination on gram-negative colonisation, infections and development of bacterial resistance in esophageal resection

Patients undergoing an esophageal resection because of carcinoma are at risk of developing postoperative respiratory tract infections. These patients were studied with respect to preceding colonisation with gram-negative bacilli and the effect of selective decontamination (SD) in decreasing this phenomenon, thereby reducing gram-negative infections. We randomised prospectively 114 patients into a test group receiving SD-medication (n=56) and a control group receiving conventional prophylaxis. Postoperatively, all patients were admitted to the intensive care unit and mechanically ventilated. The preoperative administration of SD-medication resulted in adequate decontamination within 3–4 days in most patients, and SD could prevent gram-negative colonisation and infections effectively. Discontinuation of SD showed gram-negative (re-)colonisation, and resulted in 12 infections in 4 patients having late complications. This indicates that prolonged use in these patients might be beneficial. This new antibiotic prophylaxis proved effective, without causing an increase in bacterial resistance.     

The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients

122 multiple trauma patients staying in the ICU for 5 or more days and needing mechanical ventilation were investigated to determine the effect of selective decontamination of the digestive tract on prevention of infection. The (retrospectively studied) control group of 59 patients received no antibiotic prophylaxis. The infection rate during ICU-stay was 81%. Most infections were caused by potentially pathogenic microorganisms (PPM) from the oral cavity or the intestines (i.e. endogenous infections). The oropharynx and the intestines were rapidly colonised with ICU-associated gram-negative bacilli. After 2 weeks more than 80% of patients were found colonised. This secondary colonisation of the digestive tract is a very important stage in the pathogenesis of infections. Sixty-three patients were selectively decontaminated with nonabsorbable antibiotics, administered through the gastric tube even if peristalsis was absent. Emphasis was laid on the selective decontamination of the oral cavity, using topical application of an antibiotic paste. With this technique the oral cavity was free of PPM within 3 days in most patients. No secondary colonisation was found. Rectal colonisation decreased significantly after 5 days. Secondary colonisation occurred in 9 patients with PPM sensitive to the antibiotics used. The prophylactic regimen included systemic cefotaxim, directed against early endogenous infection. The suppression and after some time the absence of the endogenous source of PPM resulted in a significant reduction of colonisation and infection. The total infection rate decreased to 16%.     

Selective decontamination of the digestive tract and oropharynx: new findings for an old approach still under discussion

Evaluation of: De Smet ANGA, Kluytmans JAJW, Cooper BS et al. Decontamination of the digestive tract and oropharynx in ICU patients. N. Engl. J. Med. 360(1), 20–31 (2009).

One of the most severe complications that can develop during treatment at an intensive-care unit is nosocomial infections, especially ventilator-associated pneumonia. The fact that these infections are mainly caused by contamination of pathogens from the digestive and oropharyngeal tracts prompted the idea of selectively decontaminating these two organ systems. Although many reports have been published about reducing the prevalence of ventilator-associated pneumonia and, most importantly, mortality by selective decontamination of the digestive and oropharyngeal tract, there are still many open questions. Furthermore, prophylactic decontamination of these two organ systems is not recommended in international guidelines. This article discusses a recently published study involving more than 5000 patients and illuminates the results in the context of other recent findings concerning this topic.     

Survival benefit of the full selective digestive decontamination regimen

Purpose

We assessed the impact of the full protocol of selective decontamination of the digestive tract (SDD) using parenteral and enteral antimicrobials on mortality.

Materials and Methods

A systematic review was performed searching MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and conferences proceedings. We included all randomized controlled trials (RCTs) comparing the full protocol of SDD, including oropharyngeal and intestinal administration of antibiotics combined with the parenteral component, with no treatment or placebo. The primary end points were overall mortality, mortality attributable to infection, early, and late mortality.

Results

Twenty-one RCTs on 4902 patients were included. Overall mortality was significantly reduced (odds ratio [OR], 0.71; 95% confidence interval [CI]; 0.61-0.82; P < .001). There was a nonsignificant reduction in infection-related mortality (6 RCTs; OR, 0.40; 95% CI, 0.10-1.59; P = .19) and early mortality (4 RCTs; OR, 0.64; 95% CI, 0.34-1.19; P = 0.16), and a significant reduction in late mortality (5 RCTs; OR, 0.56; 95% CI, 0.40-0.77; P < .001). The subgroup analysis showed a significant mortality reduction in successfully decontaminated patients (OR, 0.58; 95% CI, 0.45-0.77; P < .001), and when parenteral and enteral antimicrobials were administered to every patient receiving treatment in the intensive care unit (OR, 0.59; 95% CI, 0.42-0.82; P < .001).

Conclusions

The findings strongly indicated that the full protocol of SDD reduces mortality in critically ill patients, in particular when successful decontamination is obtained. Eighteen patients should be treated with SDD to prevent one death.     

Short-term impact of the European Consensus Conference on the use of selective decontamination of the digestive tract with antibiotics in ICU patients

Because it remained controversial, the use of selective digestive decontamination (SDD) in patients in the intensive care unit (ICU) was chosen as the topic of the first European Consensus Conference in Intensive Care Medicine (ECCICM) in December, 1991. The Consensus Bureau decided to assess the impact of this conference 2 years afterwards. For this purpose, a questionnaire was sent to the members of the European Society of Intensive Care Medicine, the Societé de Réanimation de Langue Française and the Societé Française d'Anesthesie et Réanimation before the conference. The recommendations following the conference discouraged the systematic use of SDD in ventilated patients and urged the monitoring of bacterial resistance and adapting antibiotics to epidemiology of the units. Two years after the conference, the same questionnaire was sent to those physicians who had responded to the first one. Eighteen percent used SDD for all ventilated patients and 17% remain users after 2 years. Among the occasional (32%) or continual (17%) users of SDD, the regimens used were mostly intravenous cefotaxime (60% of systemic antibiotics) and a topical combination of polymixin E, tobramycin, and amphotericin B (62% of overall topical combinations). The antibiotics used were unchanged after 2 years in almost all cases.In conclusion, the short-term impact of the Consensus Conference on SDD in ICU patients has been poor. This may be related to the continuing insufficiency of strong, definite data regarding the impact of this technique upon mortality and the theoretical risk of resistance to antibiotics, thus allowing physicians to stick to their policies until there is new evidence.Drs. A. Artigas, D. Bihari, A. Durocher, M. Hemmer, m. Langer, F. Nicolas, P. de Rohan Chabot, H.P. Schuster and A. Tenaillon are the members of the Bureau of the European Consensus Conferences in Intensive Care Medicine (ECCIM) and Dr. J. Carlet is the secretary of ECCIM     

Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis

In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of >6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p(0.001); trachea 19 vs 11 (p(0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p(0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients but in the present study the host setting appeared to be the major determinant of outcome.     

Clinical components and associated behavioural aspects of a complex healthcare intervention: Multi-methods study of selective decontamination of the digestive tract in critical care

BackgroundThis study sought to identify and describe the clinical and behavioural components (e.g. the what, how, when, where and by whom) of ‘selective decontamination of the digestive tract’ (SDD) as routinely implemented in the care of critically ill patients.MethodsMulti-methods study, consisting of semi-structured observations of SDD delivery, interviews with clinicians and documentary analysis, conducted in two ICUs in the UK that routinely deliver SDD. Data were analysed within-site to describe clinical and behavioural SDD components and synthesised across-sites to describe SDD in context.ResultsSDD delivery involved multiple behaviours extending beyond administration of its clinical components. Not all behaviours were specified in relevant clinical documentation. Overall, SDD implementation and delivery included: adoption (i.e. whether to implement SDD), operationalisation (i.e. implementing SDD into practice), provision (i.e. delivery of SDD) and surveillance (i.e. monitoring the ecological effects). Implementation involved organisational, team and individual-level behaviours. Delivery was perceived as easy by individual staff, but displayed features of complexity (including multiple interrelated behaviours, staff and contexts).ConclusionsThis study is the first to formally outline the full spectrum of clinical and behavioural aspects of SDD. It identified points in the delivery process where complex behaviours occur and outlined how SDD can be interpreted and applied variably in practice. This comprehensive specification allows greater understanding of how this intervention could be implemented in units not currently using it, or replicated in research studies. It also identified strategies required to adopt SDD and to standardise its implementation.     

Uncertain relevance of gastric colonization in the seriously ill

We have studied the temporal relationship for the same micro-organisms between gastric colonization and both nasopharyngeal colonization and major clinical infections in 100 consecutive, long-stay, intensive care patients. 67% of patients developed positive gastric cultures, mainly with aerobic Gram-negative bacilli andC. albicans; 33% developed positive nasopharyngeal cultures with similar organisms, but in only 8% was the same organism previously cultured from the stomach; 48% of patients developed infections, mainly respiratory, but commonly with different organisms. The presence of a positive gastric culture was not associated with gastric pH, bleeding, severity of illness, or mortality. The results fail to confirm that an ascending migration of organisms from the stomach is frequent or that there is a relationship between gastric colonization and clinical infections. Firm therapeutic recommendation in these areas may be premature.Supported by the Victor Hurley Medical Research Foundation, Royal Melbourne Hospital, Australia     

选择性消化道去污染预防肠源性感染的研究

[目的 ]探讨选择性消化道去污染 (SDD)对体外循环风湿性心脏病瓣膜置换术病人肠源性感染的影响。 [方法 ]选择风湿性心脏病瓣膜置换术体外循环病人 2 8例 ,随机分为对照组和SDD组 ,对照组行常规术前肠道准备 ,即饮食准备和清洁灌肠 ;SDD组在常规准备的基础上进行选择性消化道去污染干预。检测两组病人肠道菌群、内毒素水平的变化。 [结果 ]体外循环后病人体内内毒素水平显著增高 (P <0 .0 1) ;选择性消化道去污染能减少肠道革兰氏阴性菌群数量和降低体内内毒素水平 (P <0 .0 5 )。 [结论 ]选择性消化道去污染是去除肠道潜在致病菌、预防肠源性内毒素血症的有效肠道准备方法。     

Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance

Objective To assess the distribution of bacterial species and antimicrobial resistance in an ICU during long-term use of selective digestive decontamination (SDD) in the context of national reference data.Design and setting Five-year prospective observational study in a 24-bed interdisciplinary surgical ICU of a university hospital (study ICU) participating in the project “Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units” (SARI; reference ICUs).Patients Resistance data were obtained from all patients; patients intubated for at least 2 days received SDD (colistin, tobramycin, amphotericin B).Interventions and measurements SDD was performed in 1,913 of 7,270 patients. Antimicrobial resistance was examined in 4,597 (study ICU) and 46,346 (reference ICUs) isolates.Results Methicillin-resistant Staphylococcus aureus (MRSA) remained stable (2.76 and 2.58 isolates/1000 patient days) in the study ICU; this was below the German average (4.26 isolates/1000 patient days). Aminoglycoside- and betalactam-resistant Gram-negative rods did not increase during SDD use. Aminoglycoside resistance of Pseudomonas aeruginosa was 50% below the mean value of SARI (0.24 vs. 0.52 isolates/1,000 patient days). The relative frequency of enterococci and coagulase-negative staphylococci (CNS) was higher than in the SARI ICUs (23.2% vs. 17.3%, and 25.0% vs. 20.6%, respectively).Conclusion Routine 5-year-use of SDD was not associated with increased antimicrobial resistance in our ICU with low baseline resistance rates. Vigorous surveillance and control measures to search and destroy MRSA were considered a mandatory component of the SDD program. The relative increase in enterococci and CNS is of concern requiring further investigation.