Digestive decontamination in burn patients: A systematic review of randomized clinical trials and observational studies.

OBJECTIVE: The objective of this systematic review is to assess the effect of selective digestive decontamination (SDD) or non-absorbable enteral antibiotics (EA) on mortality, the incidence of infection and its adverse effects in burn patients. MATERIAL AND METHODS: Systematic review of randomized clinical trials (RCT) or observational studies enrolling burn patients, and comparing SDD or EA prophylaxis with placebo or no treatment. The search includes Pubmed/Medline, EMBASE, WOS, Cochrane Library (1970-2015). Bibliographic references were also reviewed, as well as communications presented at conferences (2012-2015), without language restrictions. Two reviewers inspected each reference identified by the search independently; the risk of bias was assessed with the Cochrane Collaboration method for RCT and the Newcastle Ottawa Scale for observational studies. RESULTS: Five RCT and 5 observational studies were identified enrolling a total of 1680 patients. The overall methodological quality of the studies was poor. The pooled effect of RCT using EA was OR: 0.62 (95% CI: 0.20-1.94). The only RCT using SDD reported OR 0.20 (95% CI: 0.09-0.81). The incidence of Enterobacteriaceae bloodstream was lower in cases treated with SDD or EA. The incidence of pneumonia was only reduced in the studies using SDD. None of the studies reported an increase in antibiotic resistance but in one RCT SDD was associated to an increase in methicillin-resistant Staphylococcus aureus infections, that was controlled with enteral vancomycin. CONCLUSIONS: SDD and EA have shown a beneficial effect in burn patients. Both practices are safe. Higher quality RCTs should be conducted to properly assess the efficacy and safety of SDD in this population.

Is selective digestive decontamination useful in controlling aerobic gram-negative bacilli producing extended spectrum beta-lactamases?

AIMS: To identify outbreak episodes of either carriage or infection due to extended spectrum beta-lactamases producing aerobic Gram-negative bacilli (AGNB-ESBL); to establish whether AGNB-ESBL, sensitive to tobramycin, become resistant over time; and to evaluate the impact of selective decontamination of the digestive tract (SDD) on abnormal carriage of AGNB-ESBL. DESIGN AND SETTING: All children admitted to the pediatric intensive care unit (PICU) over a 12-month period had biweekly surveillance cultures of throat and rectum and diagnostic cultures when clinically indicated. All AGNB were tested for ESBL, and the positive isolates were sent for molecular typing. The PICU uses SDD (parenteral cefotaxime and enteral polymyxin E/tobramycin) to control abnormal carriage. Patients who had at least one AGNB-ESBL were included in the study. RESULTS: During the study period, 1,101 children were admitted to the PICU. There were 39 patients (3.5%) with a total of 236 cultures positive for AGNB-ESBL. Twenty-eight patients (2.5%) were carriers, and 11 (1%) had proven infections. Organisms isolated from the first culture were 14 patients with Klebsiella pneumoniae, 8 with Enterobacter cloacae, 7 with Citrobacter freundii, 5 with Klebsiella oxytoca, and 5 with Escherichia coli. In the first sample, 59% of isolates showed tobramycin resistance. Molecular typing confirmed that there were five different strains of K. pneumoniae and that similar strains were not isolated in the same period. CONCLUSIONS: SDD is an effective measure to control AGNB-ESBL and to avoid outbreak episodes of either carriage or infection. When tobramycin resistance is found, replacing it with another aminoglycoside based on antibiogram may be more effective in achieving AGNB clearance.

Gut overgrowth of vancomycin-resistant enterococci (VRE) results in linezolid-resistant mutation in a child with severe congenital neutropenia: a case report.

A child with severe congenital neutropenia was monitored with microbiologic surveillance cultures for 3 years. He had recurrent bacterial infections and carriage of vancomycin-resistant enterococci. Resistance to linezolid emerged in the colonizing vancomycin-resistant enterococci after each course of this antibiotic when enterococci were present in overgrowth in the gut before treatment. The child was successfully treated for his congenital neutropenia by unrelated donor stem cell transplantation.

High mortality of invasive pneumococcal disease compared with meningococcal disease in critically ill children.

OBJECTIVE: To ascertain outcome, patterns of disease, incidence of concurrent infection, superinfection and penicillin resistance in children requiring intensive care for Streptococcus pneumoniae infection and compare it to a similar disease pattern, namely Neisseria meningitidis b infection. DESIGN AND SETTING: Prospective cohort study in a regional paediatric intensive care unit (PICU). PATIENTS AND PARTICIPANTS: Children with invasive pneumococcal and meningococcal disease requiring intensive care. MEASUREMENTS AND RESULTS: The study included 22 children with invasive pneumococcal disease (IPD), median age 14 months (interquartile range 3-52), median Paediatric Index of Mortality (PIM) 0.051 (0.028-0.066), median length of PICU stay 8.5 days (4-13). Four patients died, three (13.5%) attributable to IPD. Incidence of concurrent infection 27%. There were no superinfections. All S. pneumoniae were sensitive to cefotaxime; one isolate (3.7%) was resistant to penicillin. There were 186 children with meningococcal disease (MD), with a higher PIM (median 0.068, 0.033-0.108), older age (29 months, 10.7-77.9) and shorter length of PICU stay (median 3 days, 2-6). Eight (4.3%) children died from MD. Incidence of concurrent and superinfection was 18% and 6%, respectively in children with MD. All N. meningitidis cases were sensitive to cefotaxime and penicillin. The standardized mortality ratio was considerably higher with IPD (2.0) than with MD (0.52). CONCLUSIONS: In invasive pneumococcal disease preventative measures including early recognition, immediate antibiotic therapy and vaccination need to be taken in the community, similar to the control of meningococcal disease. Invasive pneumococcal disease should command the same respect as meningococcal disease.

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 tract. STUDY 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.

Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.

BACKGROUND AND AIMS: Endotoxin, derived from intestinal aerobic Gram-negative bacilli (AGNB), could be an important monocyte activator in chronic heart failure (CHF). The effect of selective decontamination of the digestive tract (SDD) on intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation (FMD) was studied in patients with severe CHF. METHODS AND RESULTS: Ten patients with CHF (NYHA class III-IV) were enrolled in a non-placebo controlled pilot trial involving the administration of SDD (polymyxin B, tobramycin) for 8 weeks. One patient was later excluded due to cardiac transplantation. Before treatment, after 4 and 8 weeks therapy, and 6 weeks post-treatment, monocyte CD14 expression, intracellular monocyte production of interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumour necrosis factor (TNF)-alpha with and without lipopolysaccharide (LPS) stimulation were measured. Concentrations of endotoxin and cytokines (IL-1beta, IL-6, TNF-alpha) were also determined. AGNB in faeces, intestinal endotoxin and FMD were assessed at baseline, after 4 weeks of treatment and 6 weeks post-treatment. SDD eradicated intestinal AGNB (P<0.00001) and decreased faecal endotoxin concentrations (P<0.00001). There was a significant decline in monocyte CD14 expression (P=0.03) and in IL-1beta (P=0.0001), IL-6 (P=0.02) and TNF-alpha (P=0.0002) production after 4 and 8 weeks of treatment in the basal state and for IL-1beta (P=0.008) and IL-6 (P=0.005) after LPS stimulation. FMD significantly improved at 4 weeks and returned to baseline after treatment discontinuation (P=0.002). Circulating concentrations of endotoxin and cytokines remained unchanged. CONCLUSION: Reduction of the intestinal endotoxin pool led to a decrease in monocyte CD14 expression and intracellular cytokine production in patients with severe CHF. The improvement of peripheral endothelial function could be a marker of the anti-inflammatory effect of SDD.

Infections in patients requiring ventilation in intensive care: application of a new classification.

OBJECTIVE: To classify infections according to the carrier state determined by surveillance cultures of throat and rectum, rather than by the traditional criterion of the time of onset after admission. METHODS: An observational cohort study of 3 months' duration was performed in a mixed medical---surgical intensive care unit (ICU) in a district general hospital of a subset of patients requiring mechanical ventilation for 3 days. Surveillance cultures from throat and rectum were obtained on admission to the ICU and then twice weekly to distinguish carriage of potentially pathogenic microorganisms (PPM) brought in by the patient from microorganisms acquired during the ICU stay. RESULTS: Out of the total population of 104 patients, 21 patients were enrolled over 3 months. Eight patients (38%) developed 12 infections, half of which were of primary endogenous pathogenesis and caused by Haemophilus influenzae, Candida albicans and Pseudomonas aeruginosa carried by the patients on admission. The remaining six were of secondary endogenous pathogenesis and caused by Acinetobacter baumannii and Pseudomonas aeruginosa acquired in the unit. CONCLUSIONS: Traditional classifications of hospital infection are challenged. If the traditional 48-h cut-off point was used, then 9 of 12 cases (75%) of infection would have been classified as nosocomial, whereas using the method based on the carrier state, 50% of all infections were caused by microorganisms carried by the patient on admission to the ICU. Moreover, we believe that the distinction between primary endogenous, secondary endogenous and exogenous is valid because these three types of infection each require different control methods.