Systemic tobramycin concentrations during selective decontamination of the digestive tract in intensive care unit patients on continuous venovenous hemofiltration

OBJECTIVE: To study whether selective decontamination of the digestive tract (SDD) results in detectable serum tobramycin concentrations in intensive care unit (ICU) patients with acute renal failure treated with continuous venovenous hemofiltration (CVVH). DESIGN AND SETTING: Prospective, observational, single-center study in a mixed medical-surgical ICU. PATIENTS: Adult ICU patients receiving SDD for at least 3 days and being treated with CVVH because of acute renal failure. MEASUREMENTS AND RESULTS: Tobramycin serum concentrations were measured at the 3rd day after start of CVVH and every 3 days thereafter. Detectable serum concentrations of tobramycin were found in 12 (63%) of 19 patients and in 15 (58%) of the 26 samples. With a toxic tobramycin concentration defined as more than 2.0 mg/l, we found one patient with a toxic concentration of 3.0 mg/l. In three other patients tobramycin concentrations of >or=1.0 mg/l were found. CONCLUSIONS: In patients with acute renal failure treated with CVVH, administration of SDD with tobramycin can lead to detectable and potentially toxic serum tobramycin concentration

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

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

The role of admission surveillance cultures in patients requiring prolonged mechanical ventilation in the intensive care unit

We undertook a prospective observational cohort study in intensive care unit (ICU) patients requiring mechanical ventilation for four days or more to evaluate normal and abnormal bacterial carriage on admission detected by surveillance cultures of throat and rectum. We assessed the importance of surveillance and diagnostic cultures for the early detection of resistance to third generation cephalosporins employed as the parenteral component of the selective decontamination of the digestive tract. Finally, we sought the risk factors of abnormal carriage on admission to the ICU. During the 58-month study 621 patients were included: 186 patients (30%) carried abnormal flora including methicillin-resistant Staphylococcus aureus (MRSA) and aerobic Gram negative bacilli (AGNB) on admission to the ICU Both MRSA and AGNB carriers were more commonly present in the hospital group of patients than in patients referred from the community (P < 0.001), although overgrowth was equally present both in community and in hospital patients. The incidence of infections during ICU stay was higher in abnormal (n=120, 64.5%) than in normal carriers (n=185, 42.5%) (P < 0.0001), with an odds ratio of 2.46 (95% confidence interval 1.72 to 3.51). Third generation cephalosporins covered ICU admission flora in 482 (78%) of the studied population. AGNB resistant to cephalosporins and MRSA were detected in surveillance cultures of 139 patients (22%), while the same resistant micro-organisms were identified only in 49 diagnostic samples (7.9%). Parenteral cephalosporins were modified in patients with abnormal flora (P < 0.0001). One hundred and ninety-six patients received antibiotics before admission to the ICU and 42% carried AGNB resistant to cephalosporins. Previous antibiotic use was the only risk factor for abnormal carriage in the multivariate analysis (OR 3.5; 95% confidence interval 2.1 to 5.8). The knowledge of carriage on admission using surveillance cultures may help intensivists to identify patients with abnormal carriage on admission and resistant bacterial strains at an early stage even when diagnostic samples are negative. Third generation cephalosporins covered admission flora in about 80% of the enrolled population and were modified in patients with abnormal flora who received antibiotic therapy before ICU admission. Our finding of overgrowth present on admission may justify the immediate administration of enteral antimicrobials

Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial.

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin-resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6-h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit-acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus