ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers.

SCOPE: The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. METHODS: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. RECOMMENDATIONS: The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis.

OBJECTIVES: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. METHODS: In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. RESULTS: Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. CONCLUSIONS: In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD.

Burden of highly resistant microorganisms in a Dutch intensive care unit.

BACKGROUND: The occurrence of highly resistant microorganisms (HRMOs) is a major threat to critical care patients, leading to worse outcomes, need for isolation measures, and demand for second-line or rescue antibiotics. The aim of this study was to quantify the burden of HRMOs in an intensive care unit (ICU) for adult patients in a university hospital in the Netherlands. We evaluated local distribution of different HRMO categories and proportion of ICU-imported versus ICU- acquired HRMOs. Outcome of HRMO-positive patients versuscontrols was compared. METHODS: In this prospective single-centre study, culture results of all ICU patients during a four-month period were recorded, as well as APACHE scores, ICU mortality and length of stay (LOS) in the ICU. RESULTS: 58 of 962 (6.0%) patients were HRMO positive during ICU stay. The majority (60%) of those patients were HRMO positive on ICU admission. HRMO-positive patients had significantly higher APACHE scores, longer LOS and higher mortality compared with controls. CONCLUSIONS: Our study suggests that a large part of antibiotic resistance in the ICU is imported. This underscores the importance of a robust surveillance and infection control program throughout the hospital, and implies that better recognition of those at risk for HRMO carriage before ICU admission may be worthwhile. Only a small minority of patients with HRMO at admission did not have any known risk factors for HRMO.

Use of selective digestive tract decontamination in European intensive cares: the ifs and whys.

BACKGROUND: Several studies have shown that the use of selective digestive tract decontamination (SDD) reduces mortality. However, fear for increasing multidrug resistance might prevent wide acceptance. A survey was performed among the units registered in the European Registry for Intensive Care (ERIC), in order to investigate the number of ICUs using SDD and the factors that prevented the use of SDD. METHODS: One invitation to the electronic survey was sent to each ERIC unit. The survey focused on department characteristics (intensive care type, local resistance levels), local treatment modalities (antibiotic stewardship) and doctors' opinions (collaborative issues concerning SDD). All ICU's in countries participating in the European Centre for Disease Prevention and Control resistance surveillance program were analysed. RESULTS: Seventeen percent of the ICUs registered in the ERIC database used SDD prophylaxis. Most of these ICUs were located in the Netherlands or Germany. ICUs using SDD were four times more likely to use antibiotic stewardship. Also larger ICUs were more likely to use SDD. On the contrary, resistance to antibiotics was not related to the use of SDD. Also the doctor's opinion that SDD is proven in cluster-randomized trials was not a determinant for not using SDD. CONCLUSION: SDD is used in a minority of the European ICUs registered in the ERIC database. Larger ICUs and ICUs with a prudent antibiotic policy were more likely to use SDD. Neither antibiotic resistance nor the cluster randomized study design were determinants of the non-use of SDD.

Selective decontamination of the oral and digestive tract in surgical versus non-surgical patients in intensive care in a cluster-randomized trial.

BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated. METHODS: This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes. RESULTS: The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86 (95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6 per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to treat of 18. CONCLUSION: Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations.

Decontamination of the digestive tract and oropharynx in ICU patients.

BACKGROUND: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance. RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.)

[Less ventilator-associated pneumonia after oral decontamination with chlorhexidine; a randomised trial]. / Minder beademingspneumonieën door orale decontaminatie met chloorhexidine; gerandomiseerde trial.

OBJECTIVE: To determine the effect of oral decontamination with either chlorhexidine (CHX, 2%) or the combination chlorhexidine-colistin (CHX-COL, 2%-2%) on the frequency and the time to onset of ventilator-associated pneumonia in Intensive Care patients. DESIGN: Double blind, placebo-controlled, multicentre, randomised trial. METHODS: Consecutive ICU patients needing at least 48 h of mechanical ventilation were enrolled in a randomized trial with 3 arms: CHX, CHX-COL, and placebo (PLAC). The trial medication was administered in the oral cavity every 6 h. Oropharyngeal swabs were obtained daily and analysed quantitatively for Gram-positive and Gram-negative microorganisms. Endotracheal colonisation was monitored twice weekly. Ventilator-associated pneumonia was diagnosed on the basis of a combination of clinical, radiological and microbiological criteria. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX-COL. Baseline characteristics in the three groups were comparable. The daily risk of ventilator-associated pneumonia was reduced in both treatment groups compared to PLAC: 65% (HR= 0.352; 95% CI: 0.160-0.791; p = 0.012) for CHX and 55% (HR= 0.454; 95%/ CI: 0.224-0.925; p = 0.030) for CHX-COL. CHX-COL provided a significant reduction in oropharyngeal colonisation with both Gram-negative and Gram-positive microorganisms, whereas CHX significantly affected only colonisation with Gram-positive microorganisms. There were no differences in the duration of mechanical ventilation, ICU-stay or ICU-survival. CONCLUSION: Oral decontamination of the oropharyngeal cavity with chlorhexidine or the combination chlorhexidine-colistin reduced the incidence and the time to onset ofventilator-associated pneumonia.

[Mechanical ventilation in acute respiratory distress syndrome (ARDS): lung protecting strategies for improved alveolar recruitment]. / Mechanische beademing bij 'acute respiratory distress'-syndroom (ARDS): longbeschermende strategieën voor betere alveolaire rekrutering.

For patients with acute respiratory distress syndrome (ARDS) the most important objective of mechanical ventilation is opening and keeping open the alveoli to achieve adequate oxygenation, without further damaging the lungs or negatively affecting the circulation. Alveolar recruitment is achieved by making use of positive end-expiratory pressure (PEEP). The best PEEP level is that with which the largest improvement in oxygen transport and lung compliance is achieved, without a decrease in the stroke volume of the left ventricle. In addition to the usual volume-controlled ventilation with PEEP, pressure-limited ventilation is also possible. In this a preselected pressure is never exceeded, whereas a maximum inspiratory airflow at the start of inspiration provides more opportunity for gaseous exchange. The oxygenation can possibly be further improved by increasing the inspiration-expiration ratio. As a result of the reduced expiratory period the alveoli which tend to collapse at the end of a normal expiration are kept open. Mechanical ventilation with a lower tidal volume decreases mortality. Ventilation in a prone position increases the end-expiratory lung volume and reduces the intrapulmonary shunt and the regional differences in the degree of ventilation. These factors possibly contribute to preventing ventilation-induced lung damage. Administration of natural surfactant during the ventilation of patients with ARDS seems to be a highly promising strategy; the clinical effectiveness still needs to be demonstrated.

Outbreak of a susceptible strain of Acinetobacter species 13 (sensu Tjernberg and Ursing) in an adult neurosurgical intensive care unit.

Between December 1999 and June 2000, an outbreak caused by Acinetobacter emerged on the neurosurgical intensive care unit of our hospital. It was shown using automated ribotyping using Eco RI and pulsed-field gel electrophoresis that the outbreak was caused by spread of a single strain, which was identified by ribotyping and amplified ribosomal DNA restriction analysis as Acinetobacter DNA group 13TU (sensu Tjernberg and Ursing). The outbreak strain, which showed no antibiotic resistance, was identified in 23 patients, five of whom developed an infection. The organism was also isolated from various environmental sites. Cross-transmission among patients continued despite contact isolation of colonized patients and reinforcement of basic disinfection procedures. Eventually, after implementation of additional stringent measures such as cohorting of positive patients and daily disinfection of the floor, the outbreak was brought under control. This study demonstrates that apart from Acinetobacter baumanii, Acinetobacter 13TU strains, even when they are fully susceptible, may cause outbreaks that are difficult to control. Correct identification to the species level of Acinetobacter by genotypic methods is necessary to get insight in the importance of the different Acinetobacter genomic species in hospital epidemiology.

Long-term propofol infusion and cardiac failure in adult head-injured patients.

Five adult patients with head injuries inexplicably had fatal cardiac arrests In our neurosurgical intensive-care unit after the introduction of a sedation formulation containing an increased concentration of propofol. To examine the possible relation further, we did a retrospective cohort analysis of head-injured adults admitted to our unit between 1996 and 1999 who were sedated and mechanically ventilated. 67 patients met the inclusion criteria, of whom seven were judged to have died from propofol-infusion syndrome. The odds ratio for the occurrence of the syndrome was 1.93 (95% CI 1.12-3.32, p=0.018) for every mg/kg per h increase in mean propofol dose above 5 mg/kg per h. We suggest that propofol infusion at rates higher than 5 mg/kg per h should be discouraged for long-term sedation in the intensive-care unit.

Evaluation of the physical structure of fodder beets, potatoes, pressed beet pulp, brewers grains, and corn cob silage.

The physical structure of fodder beets, raw potatoes, ensiled pressed sugar beet pulp, ensiled brewers grains, and corn cob silage was evaluated in diets containing concentrates and either corn silage or grass silage as the roughage source. In one series of experiments, the chewing activity of eight cows was measured over 4 d. The beet pulp and fodder beets were added to the two roughage sources at two ratios [20:80 and 35:65, dry matter (DM) basis]. Potatoes, brewers grains, and corn cob silage were fed in a fixed amount (5 to 6 kg of DM) with corn silage. The chewing indexes (eating and ruminating time per kilogram of DM ingested) for fodder beets and beet pulp averaged 34.3 and 32.3 min/kg of DM, respectively, and were hardly affected by the nature of the roughage or by the inclusion ratio. The chewing indexes for potatoes, brewers grains, and corn cob silage were 23.7, 56.6, and 41.6 min/kg of DM, respectively. In another series of experiments using 8 to 11 cows, the ratio of roughage to concentrates was lowered weekly by 5 percentage units, and the critical rough-age portion of the diet was determined (i.e., the amount just before a lack of physical structure was observed). The roughage source was either fed alone or supplemented with about 4 kg of DM of the experimental feed. The critical roughage portion of the diet decreased when the experimental feeds were added; the decrease was greatest with ensiled pressed beet pulp and was lowest with corn cob silage.

Does hypercarbia develop faster during laparoscopic herniorrhaphy than during laparoscopic cholecystectomy? Assessment with continuous blood gas monitoring.

The use of CO2 to create and maintain a pneumoperitoneum during laparoscopic surgery may lead to hypercarbia and acidosis. CO2 is also insufflated into the preperitoneal space to create and maintain a pneumopreperitoneum for laparoscopic herniorrhaphy. This study examined the influence of CO2 pneumopreperitoneum on the development of hypercarbia and acidosis assessed with continuous intraarterial blood gas monitoring. Changes in blood gas values were measured with both continuous intraarterial and intermittent blood gas monitoring. Over a 4-mo period, blood gas values of 14 patients undergoing laparoscopic herniorrhaphy (pneumopreperitoneum) were compared with those of 13 patients undergoing laparoscopic cholecystectomy (pneumoperitoneum) in a tertiary referral center. Additionally, heart rate and blood pressure were measured during stable ventilation at constant insufflation pressure. Pneumopreperitoneum resulted in a significantly faster development of hypercarbia (P = 0.023) and acidosis (P = 0.027) than pneumoperitoneum. These results were not explained when corrected for changes in hemodynamic and ventilatory variables using analysis of covariance. We conclude that the more rapid development of hypercarbia and acidosis during pneumopreperitoneum can be explained by increased CO2 absorption through an increasing gas exchange area during the procedure and through a larger wound bed.

[Treatment of an infrarenal aortic aneurysm using a transfemorally-placed endoprosthesis: initial results in 9 patients in The Netherlands]. / Behandeling van een infrarenaal aorta-aneurysma door middel van een transfemoraal ingebrachte endoprothese: eerste ervaringen bij 9 patiënten in Nederland.

OBJECTIVE: To describe the first experiences with transfemoral aortic endoprostheses for treatment of aortic aneurysms in the Netherlands. SETTING: University Hospital Utrecht, The Netherlands. METHOD: Patient selection was based on information presented on CT and angiography films. Only patients with an asymptomatic aneurysm and non-dilated aortic segments both distal from the renal arteries and proximal to the aortic bifurcation were selected. Of 71 patients screened only nine candidates were selected. RESULTS: The placement of the endoprosthesis was initially successful in all patients. The duration of the operation varied from 60 to 160 min. An intimal lesion of the common femoral artery occurred in one patient. In three cases leakage of contrast material outside the prosthesis but inside the aneurysm was seen on the postoperative CT angiogram. In one patient the endoprosthesis had to be replaced by a conventional aortic tube graft on the second postoperative day. After the procedure the patients stayed in hospital for another 3 to 20 days (median: 5). CONCLUSION: Endovascular treatment of infrarenal abdominal aneurysm is a promising technique. The main advantages to the patient are that laparotomy is not necessary and that the hospital stay is reduced.