Modelling interventions and contact networks to reduce the spread of carbapenem-resistant organisms between individuals in the ICU.

BACKGROUND: Contact precautions are widely used to prevent the transmission of carbapenem-resistant organisms (CROs) in hospital wards. However, evidence for their effectiveness in natural hospital environments is limited. OBJECTIVE: To determine which contact precautions, healthcare worker (HCW)-patient interactions, and patient and ward characteristics are associated with greater risk of CRO infection or colonization. DESIGN, SETTING AND PARTICIPANTS: CRO clinical and surveillance cultures from two high-acuity wards were assessed through probabilistic modelling to characterize a susceptible patient's risk of CRO infection or colonization during a ward stay. User- and time-stamped electronic health records were used to build HCW-mediated contact networks between patients. Probabilistic models were adjusted for patient (e.g. antibiotic administration) and ward (e.g. hand hygiene compliance, environmental cleaning) characteristics. The effects of risk factors were assessed by adjusted odds ratio (aOR) and 95% Bayesian credible intervals (CrI). EXPOSURES: The degree of interaction with CRO-positive patients, stratified by whether CRO-positive patients were on contact precautions. MAIN OUTCOMES AND MEASURES: The prevalence of CROs and number of new carriers (i.e. incident CRO aquisition). RESULTS: Among 2193 ward visits, 126 (5.8%) patients became colonized or infected with CROs. Susceptible patients had 4.8 daily interactions with CRO-positive individuals on contact precautions (vs 1.9 interactions with those not on contact precautions). The use of contact precautions for CRO-positive patients was associated with a reduced rate (7.4 vs 93.5 per 1000 patient-days at risk) and odds (aOR 0.03, 95% CrI 0.01-0.17) of CRO acquisition among susceptible patients, resulting in an estimated absolute risk reduction of 9.0% (95% CrI 7.6-9.2%). Also, carbapenem administration to susceptible patients was associated with increased odds of CRO acquisition (aOR 2.38, 95% CrI 1.70-3.29). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, the use of contact precautions for patients colonized or infected with CROs was associated with lower risk of CRO acquisition among susceptible patients, even after adjusting for antibiotic exposure. Further studies that include organism genotyping are needed to confirm these findings.

Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

Advising parents of asthmatic children on passive smoking: randomised controlled trial.

OBJECTIVE: To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke. DESIGN: Randomised controlled trial. SETTING: Tayside and Fife, Scotland. PARTICIPANTS: 501 families with an asthmatic child aged 2-12 years living with a parent who smoked. INTERVENTION: Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child's health. MAIN OUTCOME MEASURES: Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention. RESULTS: At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (-0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking. CONCLUSIONS: A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child's health is being affected by parental smoking, the parent's smoking needs to be addressed as a separate issue from the child's health.

What determines levels of passive smoking in children with asthma?

BACKGROUND: Children with parents who smoke are often exposed to high levels of environmental tobacco smoke, and children with asthma are particularly susceptible to the detrimental effects of passive smoking. Data were collected from parents who smoke and from their asthmatic children. The families are currently taking part in a randomised controlled trial to test an intervention designed to reduce passive smoking in children with asthma. This paper reports on the baseline data. Questionnaire data and cotinine levels were compared in an attempt to assess exposure and to identify factors which influence exposure of the children. The aim of the study was to identify the scope for a reduction in passive smoking by these children. METHODS: A sample of 501 families with an asthmatic child aged 2-12 years was obtained. Factors influencing passive smoking were assessed by interviewing parents. Cotinine levels were measured from saliva samples using gas liquid chromatography with nitrogen phosphorous detection. RESULTS: Cotinine levels in children were strongly associated with the age of the child, the number of parents who smoked, contact with other smokers, the frequency of smoking in the same room as the child, and crowding within the home. Parental cotinine levels, the amount smoked in the home, and whether the home had a garden also exerted an independent effect on cotinine levels in the children. CONCLUSIONS: Many children are exposed to high levels of environmental tobacco smoke and their cotinine levels are heavily dependent upon proximity to the parent who smokes. Parents who smoke have a unique opportunity to benefit their child's health by modifying their smoking habits within the home.

Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.

We have cloned, sequenced, and expressed cDNAs encoding wild type human glutaryl-CoA dehydrogenase subunit, and have expressed a mutant enzyme found in a patient with glutaric acidemia type I. The mutant protein is expressed at the same level as the wild type in Escherichia coli, but has less than 1% of the activity of wild-type dehydrogenase. We also present evidence that the glutaryl-CoA dehydrogenase transcript is alternatively spliced in human fibroblasts and liver; the alternatively spliced mRNA, when expressed in E.coli, encodes a stable but inactive protein. Purified expressed human glutaryl-CoA dehydrogenase has kinetic constants similar to those of the previously purified porcine dehydrogenase. The primary translation product from in vitro transcribed glutaryl-CoA dehydrogenase mRNA is translocated into mitochondria and processed in the same manner as most other nuclear-encoded mitochondrial proteins. Human glutaryl-CoA dehydrogenase shows 53% sequence similarity to porcine medium chain acyl-CoA dehydrogenase, and these similarities were utilized to predict structure-function relationships in glutaryl-CoA dehydrogenase.