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Biomedical subjects

M J Bonten

Publications and source records attributed to M J Bonten.

At least 19 recordsLinked to original sources
PubMed2005

Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumonia.

The Dutch Working Party on Antibiotic Policy (SWAB) develops evidence-based guidelines, aimed at optimalisation of antibiotic use and limitation of the spread of antimicrobial resistance. A revision of the SWAB guideline for the treatment of community-acquired pneumonia (CAP), published in 1998, was considered necessary because of changes in resistance patterns and new insights into the epidemiology, diagnostics and treatment of CAP. In contrast to the former version, this guideline is transmural and has been drawn up according to the recommendations for evidence-based guideline development by a multidisciplinary committee consisting of experts from all relevant professional societies. The 'severity of disease' exhibited by the patient with pneumonia on admission is considered important for the choice of the optimum empirical treatment strategy. Severely ill patients are treated empirically with a drug directed against multiple potential pathogens, including Legionella spp. Classification according to 'severity of disease' can be accomplished with a validated scoring system (Pneumonia Severity Index or CURB-65 score) or pragmatically, based on the site of treatment: an outpatient setting, a clinical ward or an intensive care unit. The Legionella urine antigen test plays an important role in decisions on the choice of initial antibiotic treatment.

Anti-Bacterial Agents↗
PubMed2004

[Vancomycin resistant enterococci in the Netherlands].

Enterococci (Enterococcus faecalis and Enterococcus faecium) are relatively avirulent enteric bacteria that usually only cause infections in immunocompromised patients. Antimicrobial treatment, however, is hampered as enterococci are intrinsically resistant to many antibiotics. For years, vancomycin was considered the last available antibiotic. Plasmid-mediated resistance against vancomycin among enterococci was first described in the nineteen-eighties and since then incidences of infection caused by vancomycin-resistant enterococci (VRE) have increased dramatically, especially in the United States. In 2000, three outbreaks of VRE occurred in hospitals in the Netherlands and a set of infection-control measures was proposed to limit further transmission. These measures were based on the simultaneous isolation of VRE from multiple patients. All three outbreaks were controlled by these measures and no new outbreaks in Dutch hospitals have been reported since then. Epidemiological studies have shown that hospital outbreaks on three continents were caused by a subpopulation of E. faecium, which is characterized by the presence of a potential virulence gene (variant esp) and resistance to amoxicillin. This 'hospital strain' of E. faecium has probably been prevalent within hospital settings for some time, but only became clinically relevant when it had acquired vancomycin-resistance. Current advice is to implement the set of infection control measures formulated in 2000, only in those patients colonized by amoxicillin-resistant VRE. The potential dangers of VRE were recently underlined by the proven transmission of the vancomycin-resistance gene from VRE to methicillin-resistant Staphylococcus aureus (MRSA) in two patients in the United States. It is in the interest of the patients that prevalence of VRE and MRSA in Dutch hospitals should be kept as low as possible.

Disease Outbreaks↗
PubMed2001

Understanding the spread of antibiotic resistant pathogens in hospitals: mathematical models as tools for control.

As microorganisms become more resistant to antimicrobial agents, effective infection control measures will become increasingly important. However, despite multiple studies on infection prevention, few data exist on the quantitative effects of the individual aspects of infection control strategies. The combination of epidemiologic surveillance, molecular genotyping, observational studies on compliance, and mathematical modeling may improve our ability to determine the quantitative effects of individual infection control measures. This may help to design more effective infection control programs. In this study, we review several of the models that have been published and speculate on the usefulness of mathematical modeling for improving the prevention of infection.

Anti-Bacterial Agents↗
PubMed2001

Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.

UNLABELLED: Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. KEYWORDS: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects

Administration, Topical↗
PubMed2001

Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients.

CONTEXT: Although meta-analyses of randomized trials have shown that selective digestive decontamination (SDD) prevents nosocomial pneumonia in critically ill patients, the influence of trial quality on the effectiveness of SDD has not been rigorously evaluated. OBJECTIVE: To assess the methodological quality of individual studies of SDD and its relation to the reported effects on pneumonia and mortality. DESIGN: Thirty-two studies were identified in a MEDLINE and reference list search and their methodological quality was assessed using a scoring system (range, 0-13 points) based on allocation and concealment, patient selection, patient characteristics, blinding of the intervention, and the definition of pneumonia. MAIN OUTCOME MEASURE: Methodological quality of the primary trials and its effect on the relative risk reductions (RRRs) of SDD on pneumonia and mortality. RESULTS: The mean (SD) methodological quality score was 7.8 (2.9) (range, 1-11). The RRRs ranged from -0.1 to 1.0 for pneumonia and from -0.1 to 0.6 for mortality. The methodological quality score was associated with the RRR for pneumonia so that for each quality-point added, the RRR decreased by 5.8% (95% confidence interval, 2.4%-9.3%). No association between trial quality and the impact of SDD was found on mortality. Of the individual trial quality characteristics, patient selection, allocation of intervention, and blinding most strongly influenced the treatment effect. CONCLUSIONS: The inverse relationship between methodological quality score and the benefit of SDD on the incidence of pneumonia may have resulted in overly optimistic estimates of SDD in prior meta-analyses. This emphasizes the importance of rigorous trial design in evaluating preventive interventions in the intensive care unit.

Antibiotic Prophylaxis↗
PubMed2001

Variant esp gene as a marker of a distinct genetic lineage of vancomycin-resistant Enterococcus faecium spreading in hospitals.

In the USA, vancomycin-resistant Enterococcus faecium (VREF) is endemic in hospitals, despite lack of carriage among healthy individuals. In Europe, however, hospital outbreaks are rare, but VREF carriage among healthy individuals and livestock is common. We used amplified fragment-length polymorphism analysis to genotype 120 VREF isolates associated with hospital outbreaks and 45 non-epidemic isolates from the USA, Europe, and Australia. We also looked for the esp virulence gene in these isolates and in 98 VREF from animals. A specific E. faecium subpopulation genetically distinct from non-epidemic VREF isolates was found to be the cause of the hospital epidemics in all three continents. This subpopulation contained a variant of the esp gene that was absent in all non-epidemic and animal isolates. Identification of the variant esp gene will be important in guiding infection-control strategies, and the Esp protein could be a new target for antibacterial therapy.

Bacterial Proteins↗
PubMed2001

[Optimizing antibiotics policy in the Netherlands. VI. SWAB advice: no selective decontamination of intensive care patients on mechanical ventilation].

The Working Party on Antibiotic Policy (Dutch acronym is SWAB) has issued a guideline in which the pro and cons of the routine use of selective decontamination (SD) in patients in intensive care (IC) on mechanical ventilation are compared in order to decide whether SD is indicated. The effectiveness of SD in IC patients was evaluated in 28 prospective, randomized studies. In most studies a significant reduction in the incidence of pneumonia was demonstrated. The incidence of pneumonia in the control groups varied from 5 to 85%. The reduction in the incidence of pneumonia seems to have no effect on duration of mechanical ventilation and IC unit stay or the use of antibiotics. No effect on IC mortality was demonstrated. However, only major reductions could have been demonstrated with the size of the studies carried out so far. A significant reduction of about 20% was suggested in two meta-analyses. The validity of these meta-analyses is questionable. Based on the data available, it is not possible to reach the conclusion that SD will be cost-effective. The size of the studies is too small and the study duration too short to prove that the use of SD, if applied on a large scale, might not eventually lead to development of resistance. Selection of micro-organisms that are already intrinsically resistant or had already acquired resistance to one of the agents used, has been demonstrated. In the absence of clearly demonstrated advantages (decrease in mortality, reduction in the use of antibiotics, cost-effectiveness), the routine use of SD in IC patients on mechanical ventilation is not recommended.

Antibiotic Prophylaxis↗
PubMed2001

The development of ventilator-associated pneumonia does not change aspects of mechanical ventilation.

OBJECTIVE: To evaluate whether the development of ventilator-associated pneumonia (VAP) is associated with changes in ventilation parameters. DESIGN: Matched case-control study. SETTING: Mixed intensive care unit of a university hospital. PATIENTS: From a large database we selected 33 patients with VAP, diagnosed with quantitative cultures of bronchoscopically obtained specimens. In addition, 33 other mechanically ventilated patients who did not develop VAP were selected (controls). Patients with VAP and controls were matched on seven variables representing severity of illness: duration of ventilation until matching, diagnosis on admission, renal function, liver function, preceding infection, preceding surgery and immunosuppressive therapy. Each patient with VAP was matched to a single control. Variables regarding type and mode of ventilation and interpretation of chest radiographs were not included in the matching procedure. MEASUREMENTS AND RESULTS: Characteristics of mechanical ventilation (mode of ventilation, tidal volume, expired minute ventilation, peak airway pressures, mean airway pressures, level of positive end-expiratory pressure, arterial oxygen tension(PaO2)/fractional inspired oxygen (FIO2) ratio), were compared on the day of diagnosis of VAP (or matching for controls) and 2 and 4 days before. Although there was a significant difference in PaO2/FIO2 ratios between cases and controls on the day of diagnosis of VAP, the change in PaO2/FIO2 ratios during the days of study were not statistically different between patients developing VAP and controls. No significant differences were found for any of the other variables of ventilation at any of the three time points studied, nor were there significant differences in changes of these parameters within individual patients. CONCLUSIONS: Characteristics and parameters of mechanical ventilation are not influenced by the development of VAP. It is, therefore, unlikely that these variables are useful in the diagnostic work-up of VAP.

Case-Control Studies↗
PubMed2001

Vancomycin-resistant enterococci: why are they here, and where do they come from?

Vancomcyin-resistant enterococci (VRE) have emerged as nosocomial pathogens in the past 10 years, causing epidemiological controversy. In the USA, colonisation with VRE is endemic in many hospitals and increasingly causes infection, but colonisation is absent in healthy people. In Europe, outbreaks still happen sporadically, usually with few serious infections, but colonisation seems to be endemic in healthy people and farm animals. Vancomycin use has been much higher in the USA, where emergence of ampicillin-resistant enterococci preceded emergence of VRE, making them very susceptible to the selective effects of antibiotics. In Europe, avoparcin, a vancomycin-like glycopeptide, has been widely used in the agricultural industry, explaining the community reservoir in European animals. Avoparcin has not been used in the USA, which is consistent with the absence of colonisation in healthy people. From the European animal reservoir, VRE and resistance genes have spread to healthy human beings and hospitalised patients. However, certain genogroups of enterococci in both continents seem to be more capable of causing hospital outbreaks, perhaps because of the presence of a specific virulence factor, the variant esp gene. By contrast with the evidence of a direct link between European animal and human reservoirs, the origin of American resistance genes remains to be established. Considering the spread of antibiotic-resistant bacteria and resistance genes, the emergence of VRE has emphasised the non-existence of boundaries between hospitals, between people and animals, between countries, and probably between continents.

Animal Husbandry↗
PubMed2001

Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.

Although recommended durations of antimicrobial therapy for ventilator-associated pneumonia (VAP) range from 7 to 21 d, these are not based on prospective studies and little is known about the resolution of symptoms after start of antibiotics. Resolution of these symptoms was investigated in 27 patients. VAP was diagnosed on clinical, radiographic, and microbiological criteria, including quantitative cultures of bronchoalveolar lavage. All patients received appropriate antibiotic therapy. Highest temperatures, leukocyte counts, Pa(O(2))/FI(O(2)) ratios, and semiquantitative cultures of endotracheal aspirates were recorded from start of therapy until Day 14. Resolution was defined as the first day that these parameters fulfilled the following definition: temperature < or = 38 degrees C, leukocytes < or = 10 x 10(9)/L, Pa(O(2))/FI(O(2)) ratio > or = 25 kPa, and no or +1 of bacterial growth of etiologic pathogens in cultures of endotracheal aspirate. VAP was caused by Enterobacteriaceae (n = 14), P. aeruginosa (n = 7), S. aureus (n = 6), H. influenzae (n = 3), and S. pneumoniae (n = 1). H. influenzae and S. pneumoniae were eradicated from tracheal aspirates, whereas Enterobacteriaceae, S. aureus, and P. aeruginosa persisted, despite in vitro susceptibility to antibiotics administered. Significant improvements were observed for all clinical parameters, most apparently within the first 6 d after start of antibiotics. Newly acquired colonization, especially with P. aeruginosa and Enterobacteriaceae, occurred in the second week of therapy. Six patients developed a recurrent episode of VAP, four of them with P. aeruginosa. Clinical responses to therapy for VAP occur within the first 6 d of therapy, endotracheal colonization with Gram-negative bacteria persists despite susceptibility to therapy, and acquired colonization usually occurs in the second week of therapy and frequently precedes a recurrent episode.

Adult↗
PubMed2000

[What is to be done with vancomycin-resistant enterococcal infections?].

Recently, three epidemics in Dutch hospitals were caused by vancomycin-resistant enterococci (VRE). Although the number of infections was small, spread of colonization was extensive and many infection control measures were necessary to prevent further spread. VRE are relatively avirulent bacteria. However, few, if any, antibiotics are available for treatment of infections caused by VRE and the genetic code for resistance may be transferable to other, more virulent, bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Although colonization and infection with MRSA have become endemic in many surrounding countries, such a situation has been prevented in the Netherlands by employing an aggressive 'search and destroy' policy. Although many questions regarding the optimal approach of VRE remain unanswered, a similar policy as employed for MRSA will not be possible. In contrast to MRSA, colonization with VRE occurs in the open population, no populations with increased risk for colonization appear to be definable and colonization cannot be eradicated. Based on common sense, a differentiated approach seems indicated in which extensive infection control measures should only be implemented when spread of a single genotype has been demonstrated. A reference laboratory should be created for uniform genotyping.

Anti-Bacterial Agents↗
PubMed2000

[Vancomycin-resistant Enterococcus faecium outbreak in a nephrology ward].

In April 2000, an outbreak of vancomycin-resistant Enterococcus faecium (VRE) was discovered in an internal medicine/nephrology and dialysis ward of the Eemland Hospital, Amersfoort, the Netherlands. Although enterococci are considered relatively non-virulent, VRE are resistant to almost all commercially available antibiotics. Surveillance cultures were obtained from all patients at the ward, all patients visiting the dialysis ward and the environment of patients. VRE were determined and clustering of strains was analysed using molecular genotyping. In all, 12 patients were colonized with the outbreak strain. Transmission of VRE usually occurs via the hands of health care workers. The ward was closed for new admissions, patients were divided in cohorts of colonized and non-colonized patients, and rooms were disinfected after patient discharge. Infection control measures (such as handwashing and use of gloves and gowns) were enforced and prescriptions of vancomycin and cephalosporins were reduced. With these measures the outbreak could be controlled. Epidemiological analysis demonstrated that earlier admission and previous use of ciprofloxacin, amoxicillin and amoxicillin-clavulanic acid were risk factors for colonization. A nearby hospital was a possible source of this outbreak.

Aged↗
PubMed2000

[Epidemiologic increase of various genotypes of vancomycin-resistant Enterococcus faecium in a university hospital].

After a report of a possible relationship between an outbreak of vancomycin-resistant enterococci (VRE) in a nearby hospital and earlier admission of two of the patients with this VRE in the University Medical Centre of Utrecht (UMCU), the Netherlands, an extensive search for VRE carriers was started in the UMCU. In the study period of two months, VRE carriership was diagnosed in 51 patients in nine of the 11 wards investigated. Twenty-six patients in eight wards were colonized with the same VRE genotype as in the nearby hospital; spread was demonstrated in three wards. In addition, six patients of one ward were colonized with a second genotype and seven other patients with a third genotype, while 12 patients were carriers of a unique genotype. Most carriers were found in the internal medicine/nephrology and dialysis ward. Far-reaching measures (such as cohort nursing, admission stops, use of gowns and gloves, disinfection and restriction of use of vancomycin) taken in the four wards where spread was demonstrated, appeared effective but in three wards, spread was again demonstrated later. Frequent readmissions and transfers of patients appear to play an important part in this matter. None of the 51 colonized patients developed a serious VRE infection.

Carrier State↗
PubMed2000

Infection control in intensive care units and prevention of ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is considered the most frequent infection in the intensive care unit (ICU), although incidence rates depend on the diagnostic methods. Because VAP has been associated with increased mortality and greater costs for medical care, prevention remains an important goal for intensive care medicine. Selective digestive decontamination (SDD), the most frequently studied method of infection prevention, is still controversial despite more than 30 prospective randomized trials and 6 metaanalyses. SDD reduces the incidence of VAP diagnoses, but beneficial effects on duration of ventilation or ICU stay, antibiotic use, and patient survival have not been shown unequivocally. Although recent metaanalyses suggest a 20% to 40% decrease in ICU mortality for SDD used with systemic prophylaxis, this benefit should be confirmed in a large, prospective, randomized study, preferably with a cost-benefit analysis. Selection of pathogens resistant to the antibiotics used in SDD remains the most important drawback of SDD, rendering SDD contraindicated in wards with endemic resistant problems. Other methods of infection prevention that do not create a selective growth advantage for resistant microorganisms may be more useful. Among these are the use of endotracheal tubes with the possibility of continuous aspiration of subglottic secretions, oropharyngeal decontamination with antiseptics, or the semirecumbent treatment position of patients. Although these methods were successful in single studies, more data are needed. Notwithstanding the potential benefits of these interventions, such classic infection control measures as handwashing remain the cornerstone of infection prevention.

Antibiotic Prophylaxis↗
PubMed2000

Selective digestive decontamination in patients in intensive care. The Dutch Working Group on Antibiotic Policy.

Selective digestive decontamination (SDD) is the most extensively studied method for the prevention of infection in patients in intensive care units (ICUs). Despite 27 prospective randomized studies and six meta-analyses, routine use of SDD is still controversial. In this review, we summarize the available scientific information on effectiveness of SDD in ICU patients. The effects of SDD have been studied in different combinations of the concept, using different antibiotics. Comparison of the individual studies, therefore, is difficult. In most studies, SDD resulted in significant reductions in the number of diagnoses of ventilator-associated pneumonia. However, incidences of ventilator-associated pneumonia in control groups ranged from 5% to 85%. Moreover, these reductions in incidences of ventilator-associated pneumonia in individual studies were not associated with improved patient survival, reductions of duration of ventilation or ICU stay, or reductions in antibiotic use. The numbers of patients studied are too small to determine effects on patient survival. Although two meta-analyses suggested a 20% mortality reduction when using the full concept of SDD (topical and systemic prophylaxis) these results should be interpreted with caution. Formal cost-benefit analyses of SDD have not been performed. SDD is associated with the selection of microorganisms that are intrinsically resistant to the antibiotics used. However, the studies are too small and too short to investigate whether SDD will lead to development of antibiotic resistance. As long as the benefits of SDD (better patient survival, reduction in antibiotic use or improved cost-effectiveness) have not been firmly established, the routine use of SDD for mechanically ventilated patients is not advised.

Antibiotic Prophylaxis↗
PubMed1999

Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs.

Vancomycin-resistant enterococci (VRE) recently have emerged as a nosocomial pathogen especially in intensive-care units (ICUs) worldwide. Transmission via the hands of health-care workers is an important determinant of spread and persistence in a VRE-endemic ICU. We describe the transmission of nosocomial pathogens by using a micro-epidemiological framework based on the transmission dynamics of vector-borne diseases. By using the concept of a basic reproductive number, R0, defined as the average number of secondary cases generated by one primary case, we show quantitatively how infection control measures such as hand washing, cohorting, and antibiotic restriction affect nosocomial cross-transmission. By using detailed molecular epidemiological surveillance and compliance monitoring, we found that the estimated basic reproductive number for VRE during a study at the Cook County Hospital, Chicago, was approximately 3-4 without infection control and 0.7 when infection control measures were included. The impact of infection control was to reduce the prevalence from a predicted 79% to an observed 36%. Hand washing and staff cohorting are the most powerful control measures although their efficacy depends on the magnitude of R0. Under the circumstances tested, endemicity of VRE was stabilized despite infection control measures, by the constant introduction of colonized patients. Multiple stochastic simulations of the model revealed excellent agreement with observed pattern. In conjunction with detailed microbiological surveillance, a mathematical framework provides a precise template to describe the colonization dynamics of VRE in ICUs and impact of infection control measures. Our analyses suggest that compliance for hand washing significantly in excess of reported levels, or the cohorting of nursing staff, are needed to prevent nosocomial transmission of VRE in endemic settings.

Anti-Bacterial Agents↗