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Biomedical subjects

M J M Bonten

Publications and source records attributed to M J M Bonten.

17 recordsLinked to original sources

[Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs].

A 63-year-old woman with a kidney transplant was admitted with endocarditis caused by meticillin-resistant Staphylococcus aureus (MRSA). Once her antibiotic therapy had been adjusted to the sensitivity-pattern of the bacterial strain she recovered, without the need for surgical intervention. The isolated S. aureus was typed by multi-locus sequence typing as sequence type 398, a MRSA-strain that has recently been isolated from a high percentage of Dutch pigs. This is the first report of a life-threatening infection with this pig MRSA. This strain is genetically different from the globally dispersed nosocomial MRSA-strains, and also from the strains that have been epidemic for several years in the USA as the causative agent ofcommunity-acquired skin infections. The Dutch Working Group on Infection Prevention (WIP) has recently adjusted its guidelines to halt further spread of this strain, and advises that the population at risk (pig breeders, slaughterhouse personnel and veterinarians) be held in isolation when hospitalised until MRSA colonisation has been excluded. The patient described here, however, did not belong to this population at risk.

Animals↗

[Colistin as last resort in 2 patients with pulmonary infection with multiresistant nosocomial bacteria].

A 57-year-old man requiring ventilation after gastric-tube reconstruction (due to oesophageal carcinoma) and a 16-year-old boy with thoracic trauma developed pneumonia caused by Pseudomonas aeruginosa and other pathogens. Their infections persisted during treatment with antibiotics. The antibiotic colistin was added and the clinical condition improved in both patients after 3-4 weeks. Eventually, they both were transferred to a rehabilitation clinic. The use of colistin was abandoned in the 1970s due to alleged nephro- and neurotoxicity. In recent observational studies, the drug appeared to cause fewer toxic side-effects than previously thought. Colistin is only registered for inhaled use for lung infections and for resistant pulmonary infections in patients with cystic fibrosis, but it may also be effective in the treatment of other patients with multidrug-resistant, Gram-negative bacteria.

Adolescent↗

Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects of interventions and rapid diagnostic testing.

Control of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) has been unsuccessful in most countries. Yet, some countries have maintained low endemic levels by implementing nationwide MRSA-specific infection control measures, such as "search & destroy" (S&D). These strategies, however, are not based on well designed studies, and their use in countries with high levels of endemicity is controversial. We present a stochastic three-hospital model and an analytical one-hospital model to quantify the effectiveness of different infection control measures and to predict the effects of rapid diagnostic testing (RDT) on isolation needs. Isolation of MRSA carriers identified by clinical cultures is insufficient to control MRSA. However, combined with proactive search (of high-risk patients on admission and/or contacts of index patients), it will maintain prevalence levels <1%. Concerted implementation of S&D in countries with high nosocomial endemicity reduces nosocomial prevalence to <1% within 6 years. Stepwise implementation of control measures can reduce isolation capacities needed. RDT can reduce isolation needs by >90% in low-endemic settings and by 20% in high-endemic settings. Surveillance of colonization and improved hand hygiene can markedly increase control efficacy. These findings strongly suggest that: (i) causality exists between S&D and low MRSA prevalence; (ii) isolating MRSA carriers identified by clinical cultures as a single measure is insufficient for control; (iii) a combined approach of isolation and screening confers efficacy; and (iv) MRSA-prevalence levels can be reduced to <1% in high-endemic settings by S&D or a stepwise approach to interventions. RDT can markedly enhance feasibility.

Carrier State↗

Genotyping and preemptive isolation to control an outbreak of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Control of vancomycin-resistant Enterococcus faecium (VRE) in European hospitals is hampered because of widespread asymptomatic carriage of VRE by healthy Europeans. In 2000, our hospital (The University Medical Center Utrecht, Utrecht, The Netherlands) was confronted with a large outbreak of VRE. INTERVENTION: On the basis of genotyping (by pulsed-field gel electrophoresis), epidemic and nonepidemic VRE strains were distinguished, and infection-control measures were exclusively targeted toward epidemic VRE. The outbreak was retrospectively divided into 3 periods of different infection-control measures. Compliance with use of alcohol-based hand rubs was enforced during all periods. Period I involved active surveillance, isolation of carriers, and cohorting (duration, 4 months); preemptive isolation of high-risk patients for VRE colonization was added in period II (7 months); and cohorting and preemptive isolation were abandoned in period III (18 months). METHODS: When the outbreak was identified, 27 patients in 6 wards were colonized; 93% were colonized with an epidemic VRE strain. Detection rates of nonepidemic VRE were 3.5%, 3.0%, and 2.9% among 683, 810, and 977 screened patients in periods I, II, and III, respectively, comparable to a prevalence of 2% (95% confidence interval [CI], 1%-3.5%) among 600 nonhospitalized persons. The relative risks of detecting epidemic VRE in periods II and III, compared with period I, were 0.67 (95% CI, 0.41-1.10) for period II and 0.02 (95% CI, 0.002-0.6) for period III. Infection-control measures were withheld for patients colonized with nonepidemic VRE (76 [54%] of 140 patients with a test result positive for VRE). Use of alcohol-based hand rubs increased by 31%-275% in outbreak wards. CONCLUSION: Genotyping-targeted infection control, isolation of VRE carriers, enhancement of hand-hygiene compliance, and preemptive isolation successfully controlled nosocomial spread of epidemic VRE infection.

Disease Outbreaks↗

Prognostic factors for early clinical failure in patients with severe community-acquired pneumonia.

For patients with community-acquired pneumonia (CAP), clinical response during the first days of treatment is predictive of clinical outcome. As risk assessments can improve the efficiency of pneumonia management, a prospective cohort study to assess clinical, biochemical and microbiological predictors of early clinical failure was conducted in patients with severe CAP (pneumonia severity index score of >90 or according to the American Thoracic Society definition). Failure was assessed at day 3 and was defined as death, a need for mechanical ventilation, respiratory rate >25/min, PaO2 <55 mm Hg, oxygen saturation <90%, haemodynamic instability, temperature >38 degrees C or confusion. Of 260 patients, 80 (31%) had early clinical failure, associated mainly with a respiratory rate >25/minute (n = 34), oxygen saturation <90% (n = 28) and confusion (n = 20). In multivariate logistic regression analysis, failure was associated independently with altered mental state (OR 3.19, 95% CI 1.75-5.80), arterial PaH <7.35 mm Hg (OR 4.29, 95% CI 1.53-12.05) and PaO2 <60 mm Hg (OR 1.75, 95% CI 0.97-3.15). A history of heart failure was associated inversely with clinical failure (OR 0.30, 95% CI 0.10-0.96). Patients who failed to respond had a higher 28-day mortality rate and a longer hospital stay. It was concluded that routine clinical and biochemical information can be used to predict early clinical failure in patients with severe CAP.

Academic Medical Centers↗

Are active microbiological surveillance and subsequent isolation needed to prevent the spread of methicillin-resistant Staphylococcus aureus?

BACKGROUND: Infection-control strategies usually combine several interventions. The relative value of individual interventions, however, is rarely determined. We assessed the effect of daily microbiological surveillance alone (e.g., without report of culture results or isolating colonized patients) as an infection-control measure on the spread of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a medical intensive care unit (MICU). METHODS: Colonization of patients with MSSA and MRSA was assessed by cultures of nasal swabs obtained daily and, if a patient was intubated, by cultures of additional endotracheal aspirates. Pulsed-field gel electrophoresis was used to determine relatedness between MSSA or MRSA isolates in surveillance cultures (i.e., cultures of nasal swab specimens obtained daily) and those in clinical cultures (i.e., any other culture performed for clinical purposes). Adherence to infection-control measures by health care workers (HCWs) was determined by observations of HCW-patient interaction. RESULTS: During a 10-week period, surveillance cultures were performed for 158 patients. Fifty-five patients (34.8%) were colonized with MSSA, and 9 (5.7%) were colonized with MRSA. Sixty-two patients were colonized before admission to the hospital (53 had MSSA, and 9 had MRSA). Two patients appeared to have acquired MSSA in the MICU, but, on the basis of genotyping analysis, we determined that this was not the result of cross-acquisition. CONCLUSION: Surveillance cultures and genotyping of MRSA and MSSA isolates demonstrated the absence of cross-transmission among patients in the MICU, despite ongoing introduction of these pathogens. Reporting culture results and isolating colonized patients, as suggested by some guidelines, would have falsely suggested the success of such infection-control policies.

Anti-Bacterial Agents↗

Computer-assisted decision support for the diagnosis and treatment of infectious diseases in intensive care units.

Diagnosing nosocomial infections in critically ill patients admitted to intensive care units (ICUs) is a challenge because signs and symptoms are usually non-specific for a particular infection. In addition, the choice of treatment, or the decision not to treat, can be difficult. Models and computer-based decision-support systems have been developed to assist ICU physicians in the management of infectious diseases. We discuss the historical development, possibilities, and limitations of various computer-based decision-support models for infectious diseases, with special emphasis on Bayesian approaches. Although Bayesian decision-support systems are potentially useful for medical decision making in infectious disease management, clinical experience with them is limited and prospective evaluation is needed to determine whether their use can improve the quality of patient care.

Bayes Theorem↗

Vancomycin-resistant enterococci: consequences for therapy and infection control.

Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens, initially in the USA, but now also in Europe, where hospital outbreaks are being reported with increasing frequency, although the incidence of VRE infections remains extremely low in most European countries. The recently demonstrated in-human transmission of vancomycin resistance from VRE to methicillin-resistant Staphylococcus aureus (MRSA) in two American patients underscores the potential danger of a coexisting reservoir of both pathogens. As MRSA is already endemic in many European hospital settings, prevention of endemicity with VRE seems relevant, but should be balanced against the costs associated with the implementation of effective strategies. The presence of a large community reservoir of VRE in Europe could hamper the feasibility of infection control strategies. Although the prevalence of colonisation amongst healthy subjects has apparently decreased after the ban on avoparcin use in the agricultural industry, a large proportion of admitted patients are still potential sources of VRE transmission. With no risk profile available to identify these carriers, effective screening, followed by barrier precautions for carriers, seems to be impossible. Recent studies, however, have suggested that hospital outbreaks are almost exclusively caused by specific genogroups of VRE that can be characterised phenotypically and genotypically (e.g., co-resistance to ampicillin and the presence of the variant esp gene). Based on our own experience, we propose that VRE infection control programmes should be restricted to patients colonised with these VRE strains. If such a strain is cultured from a clinical sample, surveillance amongst contact patients is recommended and barrier precautions should be implemented in the case of documented spread.

Anti-Bacterial Agents↗

Predicted effects on antibiotic use following the introduction of British or North American guidelines for community-acquired pneumonia in The Netherlands.

This study evaluated the possible changes in antibiotic use that might follow the implementation of British or North American guidelines for the treatment of community-acquired pneumonia (CAP) in The Netherlands. Patients admitted for mild, moderate and severe CAP were evaluated prospectively. Volume of antibiotic use, based upon guidelines of the British Thoracic Society (BTS), the Infectious Diseases Society of America (IDSA) or the American Thoracic Society (ATS), was estimated and compared to current practice. For 248 patients, current antibiotic use was 3087 defined daily doses. Antibiotic use would increase by 38% if based on ATS guidelines, by 23% if based on IDSA guidelines, and by 21% if based on BTS guidelines. The most significant increase in antibiotic use would occur for cases of moderate CAP, with incremental antibiotic costs of 1 750 000-3 500 000 Euros in The Netherlands.

Adult↗

[The increase in pneumonia-related morbidity and mortality among adults in the Netherlands and possible explanations for it].

As seen in several national registration systems, the morbidity and mortality due to pneumonia-related disease has increased in the Netherlands in the past 10 years. It is unlikely that the observed increase in mortality due to pneumonia is purely the result of the registration system used or misclassification. An increase in the elderly population is the most likely, albeit only partial, explanation. An increase in underlying diseases such as chronic obstructive pulmonary disease and diabetes mellitus is also a possible explanation. Increased antibiotic resistance, inadequate treatment or a shift in the spectrum of micro-organisms causing pneumonia are less likely explanations. Reducing the morbidity and mortality due to pneumonia demands an integrated approach aimed at elderly patients or patients with co-existing disease and executed by specialists in the fields of geriatrics, internal medicine, pulmonary disease and infectious diseases.

Aged↗

Do cultures contribute to optimisation of antibiotic therapy in the intensive care unit?

Obtaining diagnostic microbiological cultures before initiating empirical antimicrobial therapy is part of the diagnostic work-up of intensive care patients with a clinical suspicion of infection. However, it is unknown to what extent these cultures provide a microbiological cause of infection and to what extent antimicrobial therapy is influenced. During a 6-month period, all episodes of suspected clinical infection were analysed and categorised as non-microbiologically proven infection (non-MPI) or MPI. Effects of culture results on antibiotic therapy were analysed for episodes of respiratory tract infection. Invasive diagnostic techniques were not routinely used for diagnosis of respiratory tract infections. Among 212 patients admitted, 147 episodes of clinical suspicion of infection were recorded (104 for respiratory tract infection) and 1147 microbiological cultures were obtained (0.64 culture per patient day). Antibiotics were administered on 1111 (62%) of 1803 patients days. Of the respiratory tract infections, 571 cultures resulted in 49 (47%) MPI. Cover with empirical antibiotics was inappropriate in 7 of 104 cases (8%) of respiratory infections. In 12 cases (11.5%) empirical therapy could have been changed based on culture results. Negative cultures were never followed by cessation of therapy, but the duration of treatment was significantly shorter for non-MPI. Forty-seven percent of respiratory tract infections were microbiologically confirmed and, based on culture results, empirical antimicrobial therapy could have been influenced in 11.5% of cases of respiratory tract infections. These findings provide aspects to evaluate and improve the diagnostic work-up of infections in the ICU.

Anti-Bacterial Agents↗

Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates.

In vitro susceptibility to 15 beta-lactam antibiotics was evaluated using Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program. Piperacillin/tazobactam was the most active penicillin against Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%, 87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was most effective against Escherichia coli, Proteus mirabilis and Enterobacter cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6% of isolates susceptible). Carbapenems had excellent activity (> or =99.5% of all isolates). ESBL-production was confirmed with the ESBL-Etest and disk diffusion test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6% of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.

Aztreonam↗

How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review.

BACKGROUND: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone. METHODS: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP. RESULTS: Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies. CONCLUSIONS: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.

Anti-Bacterial Agents↗

[Community acquired pneumonia; no reason to revise current Dutch antibiotic guidelines].

Community-acquired pneumonia is an important cause of hospital admission and mortality in the adult population. The recommended antibiotic for pneumonia caused by Streptococcus pneumoniae is a beta-lactam antibiotic and, for so-called atypical pathogens, a macrolide. In the US and elsewhere, the current recommendation is to start with a beta-lactam antibiotic and a macrolide or with one of the new quinolones. The available literature consists largely of retrospective studies. Because of possible selection bias in these analyses and inconsistencies in reported outcomes, it is not possible to draw any well-founded conclusions from these studies. Reasons for a possible additional benefit of adding a macrolide to the therapy could include: a higher prevalence of undiagnosed atypical pathogens, the anti-inflammatory effects of macrolides, and resistance of the main pathogens against beta-lactam antibiotics. None of these appear to play a significant role. There is no need to revise Dutch guidelines.

4-Quinolones↗

Algorithm to determine cost savings of targeting antimicrobial therapy based on results of rapid diagnostic testing.

A rapid diagnosis of pneumococcal pneumonia may allow the earlier use of narrow-spectrum antimicrobial therapy. It is unknown, however, whether rapid diagnostic testing of patients hospitalized with community-acquired pneumonia (CAP) admitted to hospital lowers costs. Therefore, an algorithm to calculate the costs associated with the diagnosis and treatment of CAP was formulated. Subsequently, the algorithm was applied to clinical data for 122 consecutively admitted patients with CAP whose sputum samples were Gram stained and whose urine was tested for Streptococcus pneumoniae antigen. The costs of initial antimicrobial therapy, personnel, and materials were measured. Compared to the most expensive empirical regimen, rapid diagnostic testing would result in cost savings per patient (PP) of 3.51 Euros for Gram staining and 8.11 Euros for urinary pneumococcal antigen testing (1 Euro is equal to 1.13 US dollars, from 2000 to 2002). Compared to the cheapest regimen, Gram staining would increase the cost by 2.25 Euros PP, and urinary antigen testing would increase the cost by 24.26 Euros PP. In our setting, the use of rapid diagnostic testing would not lower costs. Cost savings depend, however, on the differences in the prices of the different antibiotics chosen and the proportion of evaluable and positive samples.

Adult↗

Acquisition and duration of vancomycin-resistant enterococcal carriage in relation to strain type.

In May 2000, the first outbreak of vancomycin-resistant Enterococcus faecium (VREF) was detected in the University Medical Center Utrecht in the nephrology ward. The question arose why some VREF strains spread among hospitalized patients, whereas other strains do not. Thirty patients who were found to be colonized with VREF between May and November 2000 were included in the study. Molecular typing confirmed that 19 of them carried an identical epidemic strain which harbored the esp gene while 11 were colonized by nonepidemic strains that were all esp negative. Acquisition of the outbreak strain was significantly associated with diabetes mellitus, renal transplantation, and extensive use of antibiotics, especially cephalosporins, in the 2-month period before the first isolation of VREF. To establish the duration of colonization, prospective surveillance of VREF carriage for a 6-month period starting from the first isolation of VREF was realized for 20 patients. After 6 months, VREF was still recovered from 60% of carriers of the outbreak strain versus 20% of carriers of nonepidemic strains (P < 0.01). However, antibiotic use during the follow-up period was significantly higher by carriers of the outbreak strain than by carriers of nonepidemic strains. The fact that the outbreak strain was recovered for a longer period of time than nonepidemic strains may facilitate dissemination of the strain. The results support a careful restrictive antibiotic policy for wards at risk for spread of VREF and implementation of isolation precautions for patients who are colonized with esp-positive outbreak strains.

Adolescent↗

Detection of enterococcal surface protein gene (esp) and amplified fragment length polymorphism typing of glycopeptide-resistant Enterococcus faecium during its emergence in a Greek intensive care unit.

The emergence of glycopeptide-resistant Enterococcus faecium (GREF) in a Greek intensive care unit was studied by amplified fragment length polymorphism analysis and esp gene detection. Three GREF clones harboring the esp gene were recovered from 17 out of 21 patients, indicating the dissemination of genetically homogenous and virulent strains of GREF.

Adolescent↗