Frank H. van Tiel

Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study.

Context:Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy of this intervention in a larger patient population, however, are unknown. Objective:Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP. Design:In a prospective multicentered trial, critically ill patients undergoing mechanical ventilation were randomly assigned to the semirecumbent position, with a target backrest elevation of 45°, or standard care (i.e., supine position) with a backrest elevation of 10°. Main Outcome Measures:Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device. A deviation of position was defined as a change of the randomized position >5°. Diagnosis of VAP was made by quantitative cultures of samples obtained by bronchoscopic techniques. Results:One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group. Baseline characteristics were comparable for both groups. Average elevations were 9.8° and 16.1° at day 1 and day 7, respectively, for the supine group and 28.1° and 22.6° at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45° was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients. VAP was diagnosed in eight patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group (NS), after a mean of 6 (range, 3–9) and 7 (range, 3–12) days, respectively. There were no differences in numbers of patients undergoing enteral feeding, receiving stress ulcer prophylaxis, or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups. Conclusions:The targeted backrest elevation of 45° for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28° vs. 10°) did not prevent the development of VAP.

Clinical implications of azole resistance in Aspergillus fumigatus, The Netherlands, 2007-2009.

The prevalence and spread of azole resistance in clinical Aspergillus fumigatus isolates in the Netherlands are currently unknown. Therefore, we performed a prospective nationwide multicenter surveillance study to determine the effects of resistance on patient management strategies and public health. From June 2007 through January 2009, all clinical Aspergillus spp. isolates were screened for itraconazole resistance. In total, 2,062 isolates from 1,385 patients were screened; the prevalence of itraconazole resistance in A. fumigatus in our patient cohort was 5.3% (range 0.8%-9.5%). Patients with a hematologic or oncologic disease were more likely to harbor an azole-resistant isolate than were other patient groups (p<0.05). Most patients (64.0%) from whom a resistant isolate was identified were azole naive, and the case-fatality rate of patients with azole-resistant invasive aspergillosis was 88.0%. Our study found that multiazole resistance in A. fumigatus is widespread in the Netherlands and is associated with a high death rate for patients with invasive aspergillosis.

Aspergillosis due to Voriconazole Highly Resistant Aspergillus fumigatus and Recovery of Genetically Related Resistant Isolates From Domiciles

BACKGROUND Azole resistance is an emerging problem in Aspergillus fumigatus and complicates the management of patients with Aspergillus-related diseases. Selection of azole resistance may occur through exposure to azole fungicides in the environment. In the Netherlands a surveillance network was used to investigate the epidemiology of resistance selection in A. fumigatus. METHODS Clinical A. fumigatus isolates were screened for azole resistance in 8 university hospitals using azole agar dilution plates. Patient information was collected using an online questionnaire and azole-resistant A. fumigatus isolates were analyzed using gene sequencing, susceptibility testing, and genotyping. Air sampling was performed to investigate the presence of resistant isolates in hospitals and domiciles. RESULTS Between December 2009 and January 2011, 1315 A. fumigatus isolates from 921 patients were screened. A new cyp51A-mediated resistance mechanism (TR46/Y121F/T289A) was observed in 21 azole-resistant isolates from 15 patients in 6 hospitals. TR46/Y121F/T289A isolates were highly resistant to voriconazole (minimum inhibitory concentration ≥16 mg/L). Eight patients presented with invasive aspergillosis due to TR46/Y121F/T289A, and treatment failed in all 5 patients receiving primary therapy with voriconazole. TR46/Y121F/T289A Aspergillus fumigatus was recovered from 6 of 10 sampled environmental sites. CONCLUSIONS We describe the emergence and geographical migration of a voriconazole highly resistant A. fumigatus that was associated with voriconazole treatment failure in patients with invasive aspergillosis. Recovery of TR46/Y121F/T289A from the environment suggests an environmental route of resistance selection. Exposure of A. fumigatus to azole fungicides may facilitate the emergence of new resistance mechanisms over time, thereby compromising the use of azoles in the management of Aspergillus-related diseases.

Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial

IMPORTANCE Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION trialregister.nlIdentifier: NTR1780.

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units

ObjectiveAlthough the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DesignBased on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. Data SourcePublished data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were

Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness of a national guideline

351 per patient (

Molecular Characterization of Staphylococcus aureus Bloodstream Isolates Collected in a Dutch University Hospital between 1999 and 2006

32 per patient per day). All other costs were derived from the hospital administrative database for all individual patients. Results of Base-Case AnalysisPrevention of VAP led to mean total costs of

Cross-border dissemination of methicillin-resistant Staphylococcus aureus, Euregio Meuse-Rhin region

16,119 and

Problems in diagnosing nosocomial pneumonia in mechanically ventilated patients: a review.

18,268 for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. Results of Sensitivity AnalysisPrevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than

Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of treatment failure

2,500, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. ConclusionsThis study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.