Impact of Oral Chlorhexidine on Bloodstream Infection in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Oropharyngeal overgrowth of microorganisms in the critically ill is a risk factor for lower respiratory tract infection and subsequent invasion of the bloodstream. Oral chlorhexidine has been used to prevent pneumonia, but its effect on bloodstream infection never has been assessed in meta-analyses. The authors explored the effect of oral chlorhexidine on the incidence of bloodstream infection, the causative microorganism, and on all-cause mortality in critically ill patients. DESIGN: Systematic review and meta-analysis of published studies. SETTING: Intensive care unit. PARTICIPANTS: The study comprised critically ill patients receiving oral chlorhexidine (test group) and placebo or standard oral care (control group). INTERVENTIONS: PubMed and the Cochrane Register of Controlled Trials were searched. Odds ratios (ORs) were pooled using the random-effects model. MEASUREMENTS AND MAIN RESULTS: Five studies including 1,655 patients (832 chlorhexidine and 823 control patients) were identified. The majority of information was from studies at low or unclear risk bias; 1 study was at high risk of bias. Bloodstream infection and mortality were not reduced significantly by chlorhexidine (OR 0.74; 95% confidence interval [CI] 0.37-1.50 and OR 0.69; 95% CI 0.31-1.53, respectively). In the subgroup of surgical, mainly cardiac, patients, chlorhexidine reduced bloodstream infection (OR 0.47; 95% CI 0.22-0.97). Chlorhexidine did not affect any microorganism significantly. CONCLUSION: In critically ill patients, oropharyngeal chlorhexidine did not reduce bloodstream infection and mortality significantly and did not affect any microorganism involved. The presence of a high risk of bias in 1 study and unclear risk of bias in others may have affected the robustness of these findings.

Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials.

OBJECTIVE: We examined the impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and meetings proceedings. STUDY SELECTION: We included all randomized trials comparing both oropharyngeal and intestinal administration of antibiotics in selective decontamination of the digestive tract with or without a parenteral component, with placebo or standard therapy used in the controls. DATA EXTRACTION: Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary end point was the number of patients with multiple organ dysfunction syndrome developing during intensive care unit stay. Secondary end points were overall mortality and multiple organ dysfunction syndrome-related mortality. Odds ratios were pooled with the random effect model. DATA SYNTHESIS: We identified seven randomized trials including 1270 patients. Multiple organ dysfunction syndrome was found in 132 of 637 patients (20.7%) in the selective decontamination of the digestive tract group and in 219 of 633 patients (34.6%) in the control group (odds ratio, 0.50; 95% confidence interval, 0.34-0.74; p < .001). Overall mortality for selective decontamination of the digestive tract vs. control patients was 119 of 637 (18.7%) and 145 of 633 (22.9%), respectively, demonstrating a nonsignificant reduction in the odds of death (odds ratio, 0.82; 95% confidence interval, 0.51-1.32; p = .41). In five studies including 472 patients, multiple organ dysfunction syndrome-related mortality was demonstrated in 31 of 239 (13%) patients in selective decontamination of the digestive tract group and 37 of 233 (15.9%) in the controls (odds ratio, 0.84; 95% confidence interval, 0.48-1.41; p = .54). CONCLUSIONS: Selective decontamination of the digestive tract reduces the number of patients with multiple organ dysfunction syndrome. Mortality was not significantly reduced, probably because of the small sample size.

Antibiotic-resistant bacteria and infection in children with cerebral palsy requiring mechanical ventilation.

INTRODUCTION: Severe and chronic illness can alter the bacterial flora carried in the oropharynx and gut. There are little data on the bacterial flora of children with chronic neurologic impairment. OBJECTIVES: To assess carriage of abnormal bacterial flora, antibiotic-resistant bacteria, infection, and mortality in children with cerebral palsy (CP) admitted for pediatric intensive care. DESIGN: Prospective observational single center cohort study. SETTING: Twenty-bed regional pediatric intensive care unit (PICU) in a university-affiliated tertiary referral children's hospital. PATIENTS: All children with an established diagnosis of CP admitted to PICU and ventilated for four or more days during a 6-yr period. MEASUREMENTS: Surveillance samples of throat and rectum were taken at admission to PICU and twice a week thereafter. Diagnostic samples were obtained on clinical indication. MAIN RESULTS: Fifty-three children with a total of 77 admissions were included. Most (90%) of the children with CP had moderate to severe functional limitations. Eighty-nine percent of the children with CP (47/53) carried abnormal bacterial flora/potential pathogens, most frequently Pseudomonas and Klebsiella species. Forty-seven percent (22/47) had antibiotic-resistant bacteria. Thirty-five children (66%) developed 86 infections during their PICU admission. Lower airways and blood were the two most commonly infected sites-Pseudomonas aeruginosa and coagulase-negative Staphylococci, the predominant infecting microorganisms. Sixty-five percent (56/86) of infections were primary endogenous infections, 21% (18/86) exogenous, and 9% (8/86) secondary endogenous. Carriage of abnormal bacterial flora, antibiotic-resistant bacteria, and infection rate was significantly higher than that of children of comparative age without CP ventilated for four or more days on PICU. Nine (17%) of the children with CP died in PICU and 4 of the deaths were infection related. CONCLUSIONS: In children with moderate to severe chronic neurologic impairment admitted to PICU, there is a high rate of carriage of abnormal bacteria/potential pathogens, antibiotic-resistant bacteria, and infection.

Selective Digestive Decontamination Attenuates Organ Dysfunction in Critically Ill Burn Patients.

OBJECTIVE: To evaluate whether selective decontamination of the digestive tract (SDD) attenuates organ dysfunction in critically ill burn patients. BACKGROUND: The effect of SDD on the development and progression of organ dysfunction, as an important determinant of mortality in burned patients, is still unknown. We asked whether organ dysfunction is mitigated by treatment with SDD. METHODS: Patients with burns >20% of total body surface or suspected inhalation injury from a randomized placebo-controlled trial were analyzed to determine the relationship between treatment received (placebo or SDD) and the severity of organ dysfunction as measured by the area under the curve of the Sequential Organ Failure Assessment (SOFA) score (and its individual components) from day 1 to day 7 of admission. RESULTS: One hundred seven patients (53 in the SDD group and 54 in the placebo group) were included. Survival was significantly higher in SDD-treated patients (48 of 53, 90.6%) than in placebo-treated patients (39 of 54, 72.2%, P = 0.013). Total (P < 0.01) and respiratory (P < 0.01), cardiovascular (P = 0.04) and hematological (not reaching statistical significance, P = 0.07) organ dysfunction was associated with mortality after adjusting for predicted mortality. In multivariate logistic regression, SDD treatment was independently associated with total (P < 0.01), respiratory (P = 0.02), and hematological (P < 0.01) dysfunction over the first week postinjury. CONCLUSIONS: The beneficial effect of SDD on mortality in critically ill burned patients is accompanied by a reduction in the degree of organ dysfunction. SDD seems to be a valuable therapeutic strategy to prevent organ dysfunction and, more specifically, respiratory and hematological dysfunction in severely ill burn patients.

Enteral vancomycin to control methicillin-resistant Staphylococcus aureus outbreak in mechanically ventilated patients.

BACKGROUND: Screening for and treating gut carriage of methicillin-resistant Staphylococcus aureus (MRSA) may control transmission and subsequent endemicity of MRSA. OBJECTIVE: Enteral vancomycin was evaluated as a measure to control an outbreak of MRSA infection in the intensive care unit (ICU). METHODS: During the 8-month study of sequential design, 176 patients were admitted, 65 (37%) of whom required a minimum of 3 days of ventilation. Forty-four patients were studied in the first 5 months, during which traditional measures were reinforced (control group). During the following 3 months, 13 of 21 patients developed MRSA carriage and received 2 g/day of enteral vancomycin, with high standards of hygiene maintained (treatment group). RESULTS: Thirty-three MRSA infections occurred in 22 patients (50%) in the control group, whereas 2 patients (9.5%) had 2 MRSA infections in the treatment group (P <.05 for carriage, infection rates, and episodes). Of the 33 MRSA infections in the control group, 27 were due to MRSA acquired in the ICU, whereas the 2 infections in the treatment group were primary endogenous (ie, caused by MRSA present in the patient's admission flora). The probability of developing an MRSA infection was reduced in patients receiving enteral vancomycin compared with patients in the control group (odds ratio, 0.37; 95% CI, 0.24-0.58). Enteral vancomycin significantly reduced the level of MRSA carriage; the mean carriage index was 1.01 in the control group versus 0.58 in the test group (P <.05). Neither vancomycin-resistant enterococci nor vancomycin-intermediate Staphylococcus aureus were isolated from either surveillance or diagnostic samples. CONCLUSIONS: The eradication of MRSA gut carriage by enteral vancomycin in a small subset of ICU patients was effective in the control of an MRSA outbreak.

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

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 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. CONCLUSIONS: The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.

Selective digestive tract decontamination in critically ill patients.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) has been proposed to prevent endogenous and exogenous infections and to reduce mortality in critically ill patients. Although the efficacy of SDD has been confirmed by randomized controlled trials (RCTs) and systematic reviews, SDD has been the subject of intense controversy, based mainly on an insufficient evidence of efficacy and on concerns about resistance. AREAS COVERED: This article reviews the philosophy, the current evidence on the efficacy of SDD and the issue of emergence of resistance. All SDD RCTs were searched using Embase and Medline, with no restriction of language, gender or age. Personal archives were also explored, including abstracts from major scientific meetings; references in papers and published meta-analyses on SDD were crosschecked. Up-to-date evidence of the impact of SDD on carriage, infections and mortality is presented, and the efficacy of SDD in selected patient groups was investigated, along with the problem of the emergence of resistance. EXPERT OPINION: SDD significantly reduces the number of infections of the lower respiratory tract and bloodstream, multiple organ failure and mortality. It also controls resistance, particularly when the full protocol of parenteral and enteral antimicrobials is used.