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Biomedical subjects

Marc J M Bonten

Publications and source records attributed to Marc J M Bonten.

At least 19 recordsLinked to original sources
PubMed2006

Growth condition-dependent Esp expression by Enterococcus faecium affects initial adherence and biofilm formation.

A genetic subpopulation of Enterococcus faecium, called clonal complex 17 (CC-17), is strongly associated with hospital outbreaks and invasive infections. Most CC-17 strains contain a putative pathogenicity island encoding the E. faecium variant of enterococcal surface protein (Esp). Western blotting, flow cytometric analyses, and electron microscopy showed that Esp is expressed and exposed on the surface of E. faecium, though Esp expression and surface exposure are highly varied among different strains. Furthermore, Esp expression depends on growth conditions like temperature and anaerobioses. When grown at 37 degrees C, five of six esp-positive E. faecium strains showed significantly increased levels of surface-exposed Esp compared to bacteria grown at 21 degrees C, which was confirmed at the transcriptional level by real-time PCR. In addition, a significant increase in surface-exposed Esp was found in half of these strains when grown at 37 degrees C under anaerobic conditions compared to the level in bacteria grown under aerobic conditions. Finally, amounts of surface-exposed Esp correlated with initial adherence to polystyrene (R(2) = 0.7146) and biofilm formation (R(2) = 0.7535). Polystyrene adherence was competitively inhibited by soluble recombinant N-terminal Esp. This study demonstrates that Esp expression on the surface of E. faecium (i) varies consistently between strains, (ii) is growth condition dependent, and (iii) is quantitatively correlated with initial adherence and biofilm formation. These data indicate that E. faecium senses and responds to changing environmental conditions, which might play a role in the early stages of infection when bacteria transit from oxygen-rich conditions at room temperature to anaerobic conditions at body temperature. In addition, variation of surface exposure may explain the contrasting findings reported on the role of Esp in biofilm formation.

Adaptation, Physiological↗
PubMed2006

Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial.

OBJECTIVES: To compare the effectiveness of an early switch to oral antibiotics with the standard 7 day course of intravenous antibiotics in severe community acquired pneumonia. DESIGN: Multicentre randomised controlled trial. SETTING: Five teaching hospitals and 2 university medical centres in the Netherlands. PARTICIPANTS: 302 patients in non-intensive care wards with severe community acquired pneumonia. 265 patients fulfilled the study requirements. INTERVENTION: Three days of treatment with intravenous antibiotics followed, when clinically stable, by oral antibiotics or by 7 days of intravenous antibiotics. MAIN OUTCOME MEASURES: Clinical cure and length of hospital stay. RESULTS: 302 patients were randomised (mean age 69.5 (standard deviation 14.0), mean pneumonia severity score 112.7 (26.0)). 37 patients were excluded from analysis because of early dropout before day 3, leaving 265 patients for intention to treat analysis. Mortality at day 28 was 4% in the intervention group and 6% in the control group (mean difference 2%, 95% confidence interval -3% to 8%). Clinical cure was 83% in the intervention group and 85% in the control group (2%, -7% to 10%). Duration of intravenous treatment and length of hospital stay were reduced in the intervention group, with mean differences of 3.4 days (3.6 (1.5) v 7.0 (2.0) days; 2.8 to 3.9) and 1.9 days (9.6 (5.0) v 11.5 (4.9) days; 0.6 to 3.2), respectively. CONCLUSIONS: Early switch from intravenous to oral antibiotics in patients with severe community acquired pneumonia is safe and decreases length of hospital stay by 2 days. TRIAL REGISTRATION: Clinical Trials NCT00273676 [ClinicalTrials.gov].

Administration, Oral↗
PubMed2006

Selective digestive tract decontamination--will it prevent infection with multidrug-resistant gram-negative pathogens but still be applicable in institutions where methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are endemic?

The purposes of selective decontamination of the digestive tract are to treat infections that may be incubating at the time a patient is admitted to an intensive care unit (ICU), by intravenous administration of antibiotics during the first days of a stay in the ICU, and to prevent ICU-acquired infections, by topical application of antibiotics in the oropharynx and the gastrointestinal tract. Despite multiple trials in which a considerable reduction in the incidence of ventilator-associated pneumonia was demonstrated, major objections against the routine use of selective decontamination of the digestive tract have included a lack of demonstrated reductions in mortality rates and in length of stay (in individual trials), a lack of cost-efficacy data, and the threat of selection of multidrug-resistant bacteria. Recently, 2 controlled, randomized studies reported significant reductions in mortality rates among patients in ICUs who underwent selective decontamination of the digestive tract in combination with reduced selection of antibiotic-resistant pathogens. However, those studies were performed in settings where levels of antibiotic resistance are low, and some methodological issues remain unresolved. If these beneficial results are confirmed, the question of how to balance these benefits against the expected enhanced selection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and, possibly, multidrug-resistant gram-negative bacteria will emerge.

Anti-Bacterial Agents↗
PubMed2006

Identification of high-risk enterococcal clonal complexes: global dispersion and antibiotic resistance.

Vancomycin-resistant Enterococcus faecium spread dramatically in hospital settings in the USA in the 1990s and reached endemicity at the turn of the century. Similarly, rising prevalence rates are currently observed in several European countries, with prevalence rates of greater than 10% reported in seven of these. On the basis of multilocus sequence typing (MLST), the population structure of E. faecium was elucidated and the existence of a distinct high-risk enterococcal clonal complex, designated clonal complex-17 (CC17), which is associated with the majority of hospital outbreaks and clinical infections in five continents, was revealed. This complex is correlated with ampicillin and quinolone resistance and with the presence of a putative pathogenicity island. Preliminary MLST data suggest that similar hospital-adapted complexes might also exist in E. faecalis.

Ampicillin Resistance↗
PubMed2006

Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study.

OBJECTIVE: To compare the effectiveness of discontinuing treatment with amoxicillin after three days or eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment. DESIGN: Randomised, double blind, placebo controlled non-inferiority trial. SETTING: Nine secondary and tertiary care hospitals in the Netherlands. PARTICIPANTS: Adults with mild to moderate-severe community acquired pneumonia (pneumonia severity index score < or = 110). INTERVENTIONS: Patients who had substantially improved after three days' treatment with intravenous amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days. MAIN OUTCOME MEASURES: The primary outcome measure was the clinical success rate at day 10. Secondary outcome measures were the clinical success rate at day 28, symptom resolution, radiological success rates at days 10 and 28, and adverse events. RESULTS: Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three day treatment group. In the three day and eight day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval--9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%,--9% to 15%). Both groups had similar resolution of symptoms. Radiological success rates were 86% compared with 83% at day 10 (difference 3%,--10% to 16%) and 86% compared with 79% at day 28 (difference 6%,--7% to 20%). Six patients (11%) in the placebo group and 13 patients (21%) in the active treatment group reported adverse events (P = 0.1). CONCLUSIONS: Discontinuing amoxicillin treatment after three days is not inferior to discontinuing it after eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment.

Administration, Oral↗
PubMed2006

Reduction in acquisition of vancomycin-resistant enterococcus after enforcement of routine environmental cleaning measures.

BACKGROUND: The role of environmental contamination in nosocomial cross-transmission of antibiotic-resistant bacteria has been unresolved. Using vancomycin-resistant enterococci (VRE) as a marker organism, we investigated the effects of improved environmental cleaning with and without promotion of hand hygiene adherence on the spread of VRE in a medical intensive care unit. METHODS: The study comprised a baseline period (period 1), a period of educational intervention to improve environmental cleaning (period 2), a "washout" period without any specific intervention (period 3), and a period of multimodal hand hygiene intervention (period 4). We performed cultures for VRE of rectal swab samples obtained from patients at admission to the intensive care unit and daily thereafter, and we performed cultures of environmental samples and samples from the hands of health care workers twice weekly. We measured patient clinical and demographic variables and monitored intervention adherence frequently. RESULTS: Our study included 748 admissions to the intensive care unit over a 9-month period. VRE acquisition rates were 33.47 cases per 1000 patient-days at risk for period 1 and 16.84, 12.09, and 10.40 cases per 1000 patient-days at risk for periods 2, 3, and 4, respectively. The mean (+/-SD) weekly rate of environmental sites cleaned increased from 0.48+/-0.08 at baseline to 0.87+/-0.08 in period 2; similarly high cleaning rates persisted in periods 3 and 4. Mean (+/-SD) weekly hand hygiene adherence rate was 0.40+/-0.01 at baseline and increased to 0.57+/-0.11 in period 2, without a specific intervention to improve adherence, but decreased to 0.29+/-0.26 in period 3 and 0.43+/-0.1 in period 4. Mean proportions of positive results of cultures of environmental and hand samples decreased in period 2 and remained low thereafter. In a Cox proportional hazards model, the hazard ratio for acquiring VRE during periods 2-4 was 0.36 (95% confidence interval, 0.19-0.68); the only determinant explaining the difference in VRE acquisition was admission to the intensive care unit during period 1. CONCLUSIONS: Decreasing environmental contamination may help to control the spread of some antibiotic-resistant bacteria in hospitals.

Anti-Bacterial Agents↗
PubMed2006

Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.

RATIONALE: Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality. Although oral decontamination with antibiotics reduces incidences of VAP, it is not recommended because of potential selection of antibiotic-resistant pathogens. We hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and oral and endotracheal colonization. OBJECTIVES: To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP. METHODS: Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a randomized, double-blind, placebo-controlled trial with three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every 6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms. Endotracheal colonization was monitored twice weekly. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics were comparable. The daily risk of VAP was reduced in both treatment groups compared with PLAC: 65% (hazard ratio [HR]=0.352; 95% confidence interval [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 significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms, whereas CHX mostly affected gram-positive microorganisms. Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients. No differences in duration of mechanical ventilation, intensive care unit stay, or intensive care unit survival could be demonstrated. CONCLUSIONS: Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP.

Administration, Topical↗
PubMed2006

Selective decontamination of the digestive tract: cumulating evidence, at last?

Selective decontamination of the digestive tract (SDD), an infection-control strategy designed to prevent nosocomial pneumonia in mechanically ventilated patients, has been implemented in numerous studies for more than 2 decades, but its role remains controversial. Sentinel studies in the 1960s and 1970s identified a link between colonization of the upper respiratory tract and subsequent increased risk of developing nosocomial pneumonia in critically ill patients. Studies in the 1980s found that prophylaxis with topical and systemic antibiotics to decontamination of the upper respiratory tract and gastrointestinal tract (particularly depleting gram-negative aerobic bacteria) was associated with lower rates of infections. However, impact on survival was not substantiated. However, several recent studies (including randomized trials and meta-analyses) suggest that SDD may improve survival in selected cohorts of critically ill patients in intensive care units (ICUs). Because liberal use of SDD (or any antimicrobial prophylactic strategy) may lead to escalating antimicrobial resistance, the risk of resistance varies according to local pathogens and resistance patterns. This review describes the development of the SDD concept, discusses recently published trials, and develops points for discussion and research. Additional studies are required to further define appropriate indications and limitations of this preventative strategy.

Anti-Bacterial Agents↗
PubMed2006

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 degrees , or standard care (i.e., supine position) with a backrest elevation of 10 degrees . 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 degrees . 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 degrees and 16.1 degrees at day 1 and day 7, respectively, for the supine group and 28.1 degrees and 22.6 degrees at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45 degrees 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 degrees for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28 degrees vs. 10 degrees ) did not prevent the development of VAP.

APACHE↗
PubMed2006

Multilocus sequence typing scheme for Enterococcus faecalis reveals hospital-adapted genetic complexes in a background of high rates of recombination.

A multilocus sequence typing (MLST) scheme based on seven housekeeping genes was used to investigate the epidemiology and population structure of Enterococcus faecalis. MLST of 110 isolates from different sources and geographic locations revealed 55 different sequence types that grouped into four major clonal complexes (CC2, CC9, CC10, and CC21) by use of eBURST. Two of these clonal complexes, CC2 and CC9, are particularly fit in the hospital environment, as CC2 includes the previously described BVE clonal complex identified by an alternative MLST scheme and CC9 includes exclusively isolates from hospitalized patients. Identical alleles were found in genetically diverse isolates with no linkage disequilibrium, while the different MLST loci gave incongruent phylogenetic trees. This demonstrates that recombination is an important mechanism driving genetic variation in E. faecalis and suggests an epidemic population structure for E. faecalis. Our novel MLST scheme provides an excellent tool for investigating local and short-term epidemiology as well as global epidemiology, population structure, and genetic evolution of E. faecalis.

Alleles↗
PubMed2006

Extensive hospital-wide spread of a multidrug-resistant enterobacter cloacae clone, with late detection due to a variable antibiogram and frequent patient transfer.

A hospital-wide increase in the number of patients with aminoglycoside-resistant Enterobacter cloacae (AREC) isolated from clinical cultures was detected in December 2002 using a classical surveillance system (CSS). CSS refers to a strategy based on the recognition of an increased incidence of a species with a particular antibiogram at certain wards in a limited period. Since clonal spread was suspected, hospital records were reviewed for E. cloacae culture-positive patients. Based upon genotyping of 139 clinical E. cloacae isolates from 80 patients, it was concluded that 53 patients had had clinical cultures with a single AREC clone since April 2001. Determinants for unnoticed spread were investigated retrospectively, as was the possibility that a computer-assisted surveillance method would have detected this outbreak at an earlier stage. Determinants associated with late detection of clonal spread were the following: (i) the absence of a hospital-wide increase in incidence of E. cloacae cases for 1.5 years, (ii) the long time interval between cases, (iii) the hospital-wide occurrence of new cases, due to a high number of patient transfers between wards, (iv) the large variety of clinical sites, and (v) the high variability of antibiograms (n = 33). Retrospective application of a recently described computer-assisted surveillance method as well as an "in-house"-developed algorithm resulted in earlier detection of the outbreak of 6 and 12 months, respectively. These findings suggest that computerized tools for surveillance may recognize resistance trends that are too complex to be detected by manual review and indicate the need for prospective evaluation of such algorithms.

Algorithms↗
PubMed2006

High-level ciprofloxacin resistance from point mutations in gyrA and parC confined to global hospital-adapted clonal lineage CC17 of Enterococcus faecium.

To substantiate a common genetic background of ciprofloxacin-resistant Enterococcus faecium, 32 ciprofloxacin-resistant (Cip(r)) and 31 ciprofloxacin-susceptible (Cip(s)) isolates from outbreaks, clinical infections, surveillances, and animals from 10 different countries were genotyped by multilocus sequence typing. Additionally, susceptibilities to ampicillin and vancomycin and the presence of esp were determined and the quinolone resistance-determining regions of parC, gyrA, parB, and gyrE were sequenced. High-level Cip(r) (MIC > or = 64 microg/ml) due to point mutations in the quinolone resistance-determining region was unique to a distinct hospital-adapted genetic complex in E. faecium, previously designated CC17. Low-level Cip(r) (MIC = 4 microg/ml) in non-CC17 strains is not attributable to point mutations in any subunit of the topoisomerase genes, and the mechanism of resistance remains unclear. Acquisition of mutations in parC and gyrA, leading to high-level Cip(r), is, in addition to ampicillin resistance and the presence of a putative pathogenicity island, another cumulative step in hospital adaptation of CC17.

Base Sequence↗
PubMed2005

Can we predict septic shock in patients with hospital-acquired pneumonia?

Hospital-acquired pneumonia is a serious and potentially life-threatening complication, with reported pneumonia-attributable mortality rates as high as 50%. Rapid diagnosis and immediate institution of adequate empirical antimicrobial treatment are of paramount importance in patient management. Nevertheless, some patients deteriorate and develop respiratory insufficiency, septic shock and a multiorgan dysfunction syndrome. Early recognition of these patients might help in reducing morbidity and mortality. Elevated systemic levels of proinflammatory cytokines (IL-1beta, IL-6, IL-8 and IL-10) at the time of diagnosis of hospital-acquired pneumonia appear to be indicative of subsequent progression to septic shock. Should this now become a part of patient management?

Biomarkers↗
PubMed2005

Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection.

BACKGROUND: Rapid diagnostic tests with a high sensitivity for lower respiratory tract infection (LRTI) could lead to improved patient care and reduce unnecessary antibiotic use and associated costs. Diagnostic yields, feasibility, and costs of real-time polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swab specimens in the routine diagnostic work-up for LRTI were determined. METHODS: In a randomized controlled trial, nasopharyngeal and oropharyngeal swab specimens from patients admitted for antibiotic treatment of LRTI were evaluated by means of real-time PCR for respiratory viruses and atypical pathogens, as well as by conventional diagnostic procedures. Real-time PCR results for patients in the intervention group were reported to the treating physician; results for patients in the control group were not made available. RESULTS: A total of 107 patients (mean age [+/- standard deviation], 63.6+/-16.3 years) were included, of whom 55 were allocated to the intervention group. The pathogens detected most frequently were influenza virus (14 patients), Streptococcus pneumoniae (8), coronavirus (6), Staphylococcus aureus (5), and rhinoviruses (5). Real-time PCR increased the diagnostic yield from 23 cases (21% of patients) to 47 cases (43% of patients), compared with conventional diagnostic tests. The detection of viral pathogens by PCR was associated with the winter season, less infiltrates on chest radiographs, lower C-reactive protein levels, and shorter duration of symptoms. Use of real-time PCR results resulted in partial or total cessation of antibiotic treatment for 6 patients (11%; 95% confidence interval, 2-19), but overall antibiotic use was comparable in the intervention group and the control group (median duration of treatment, 10.0 vs. 9.0 days; P=not significant). Use of real-time PCR increased treatment and diagnostic costs with 318.17 per patient. CONCLUSIONS: Implementation of real-time PCR for the etiological diagnosis of LRTI increased the diagnostic yield considerably, but it did not reduce antibiotic use or costs.

Adult↗
PubMed2005

Control of vancomycin-resistant enterococci: one size fits all?

Infection caused by vancomycin-resistant enterococci (VRE) is associated with high morbidity and mortality rates; it poses a serious threat, in particular, to immunosuppressed patients. It generates high costs and challenges infection-control programs. Here, we look at the insights that mathematical models offer into the epidemiology of VRE colonization and infection, the potential benefits of various infection-control interventions, and the possibility of designing a tailored approach to controlling VRE. Models show that epidemics of VRE infection in diverse institutions may differ in the relative contributions of cross-transmission and the influx of new cases, as well as in the various mechanisms of local transmission. They also highlight the phenomenon of decreasing returns associated with many interventions and, hence, the need to identify the most important routes of transmission, to break the weakest links in the chain of transmission, and to contain the influx of cases of VRE infection. These observations also provide insights into the management of infection with other antibiotic-resistant nosocomial pathogens.

Anti-Bacterial Agents↗