Impact of digestive and oropharyngeal decontamination on the intestinal microbiota in ICU patients

Selective digestive microbial decontamination (SDD) is hypothesized to benefit patients in intensive care (ICU) by suppressing Gram-negative potential pathogens from the colon without affecting the anaerobic intestinal microbiota. The purpose of this study was to provide more insight to the effects of digestive tract and oropharyngeal decontamination on the intestinal microbiota by means of a prospective clinical trial in which faecal samples were collected from ICU patients for intestinal microbiota analysis. The faecal samples were collected from ICU patients enrolled in a multicentre trial to study the outcome of SDD and selective oral decontamination (SOD) in comparison with standard care (SC). Fluorescent in situ hybridization (FISH) was used to analyze the faecal microbiota. The numbers of bacteria from different bacterial groups were compared between the three regimens. The total counts of bacteria per gram faeces did not differ between regimens. The F. prausnitzii group of bacteria, representing an important group among intestinal microbiota, was significantly reduced in the SDD regimen compared to the SC and SOD. The Enterobacteriaceae were significantly suppressed during SDD compared to both SOD and SC; enterococci increased in SDD compared to both other regimens. The composition of the intestinal microbiota is importantly affected by SDD. The F. prausnitzii group was significantly suppressed during SDD. This group of microbiota is a predominant producer of butyrate, the main energy source for colonocytes. Reduction of this microbiota is an important trade-off while reducing gram-negative bacteria by SDD

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med 29

Abstract Objective: The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). Philosophy: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. Interventions to prevent ICU infection: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring 'early'; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop 'late'; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. Endpoints: (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. Results: Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of Intensive Care Med (2003) 29:677-690 DOI 10.1007/s00134-003-1722-2 R E V I

Quinolones and colonization resistance in human volunteers

The suppression of alimentary canal flora by the three quinolones nalidixic acid, ciprofloxacin and pefloxacin was investigated in fifteen volunteers. They received the three quinolone compounds in tablet form both uncoated and colon-coated. Escherichia coli suppression was poor under nalidixic acid, but complete under ciprofloxacin and pefloxacin for both administration forms. The indigenous anaerobic flora contributing to the control of aerobic Streptococcus faecalis and Candida albicans in the intestines ('colonization resistance') was not affected by nalidixic acid and pefloxacin, and only slightly by ciprofloxacin. Out of the three quinolone compounds, only colon-coated pefloxacin was associated with a considerable absorption rate at colonic level. Using these criteria of successful Escherichia coli clearing from the intestinal canal--left the indigenous flora more or less intact (in a 'selective' way)--and a good absorption rate, pefloxacin is found to be superior to ciprofloxacin and nalidixic acid. These results suggest that a colon-coated tablet with a low dose of pefloxacin is a promising administration form in the therapy of recurrent urinary tract infections and diarrhoeal diseases and in the prevention of gut colonization in immunocompromised host

Antibiotic Policies in the Intensive Care Unit Why Does an Intensivist Need an Antibiotic Policy?

Every intensive care unit (ICU) should have well-structured guidelines on the use of antimicrobial agents to guarantee that patients requiring intensive care receive appropriate antimicrobials for a relevant period to prevent and treat infections. These guidelines should meet the therapeutic needs of the consultants and allow the intensivist, clinical microbiologist, and pharmacist to monitor efficacy, toxicity, including allergy and diarrhea, and side-effects, such as the emergence of resistant strains and subsequent outbreaks of superinfections. Calculation of infection rates is only feasible following the implementation of an antibiotic policy. Apart from audit and research, antimicrobial guidelines aid educational programs and enable the clinical pharmacist to control drug expenditure

Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: A systematic review of randomised controlled trials

Meta-analyses of randomised controlled trials of selective digestive decontamination have clinical outcome measures, mainly pneumonia and mortality. This meta-analysis has a microbiological endpoint and explores the impact of selective digestive decontamination on Gram-negative and Gram-positive carriage and severe infections. We searched electronic databases, Cochrane Register of Controlled Trials, previous meta-analyses and conference proceedings with no language restrictions. We included randomised controlled trials which compared the selective digestive decontamination protocol with no treatment or placebo. Three reviewers independently applied selection criteria, performed the quality assessment and extracted the data. The outcome measures were carriage and severe infection due to Gram-negative and Gram-positive bacteria. Odds ratios were pooled with the random effect model. Fifty-four randomised controlled trials comprising 9473 patients were included; 4672 patients received selective digestive decontamination and 4801 were controls. Selective digestive decontamination significantly reduced oropharyngeal carriage (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.07 to 0.23), rectal carriage (OR 0.15, 95% CI 0.07 to 0.31), overall infection (OR 0.17, 95% CI 0.10 to 0.28), lower respiratory tract infection (OR 0.11, 95% CI 0.06 to 0.20) and bloodstream infection (OR 0.35, 95% CI 0.21 to 0.67) due to Gram-negative bacteria. Reduction in Gram-positive carriage was not significant. Gram-positive lower airway infections were significantly reduced (OR 0.52, 95% CI 0.34 to 0.78). Gram-positive bloodstream infections were not significantly increased (OR 1.03, 95% CI 0.75 to 1.41). The association of parenteral and enteral antimicrobials was superior to enteral antimicrobials in reducing carriage and severe infections due to Gram-negative bacteria. This meta-analysis confirms that selective digestive decontamination mainly targets Gram-negative bacteria; it does not show a significant increase in Gram-positive infection