Nico T. Mutters

Human dose response relation for airborne exposure to Coxiella burnetii

BackgroundThe recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population.MethodsA human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework.ResultsThe dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55).ConclusionsTo our knowledge this is the first human dose–response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population.

Control of the Spread of Vancomycin-Resistant Enterococci in Hospitals: Epidemiology and Clinical Relevance

BACKGROUND The spread of vancomycin-resistant enterococci (VRE), particularly E. faecium, in hospitals leads to many cases of colonization, but only sporadic infections. Detailed and valid risk assessment is needed so that patients at risk can be protected from VRE infection. The principal aims of risk assessment must include not only lowering VRE-associated morbidity and mortality in patients at risk, but also refraining from unnecessary anti-infective measures among those who are not at risk. METHODS We selectively searched the PubMed database for pertinent articles on the epidemiology and clinical relevance of VRE in order to derive a uniform and practical hygiene strategy from the available scientific evidence. RESULTS Only low-level evidence is available for the interventions studied to date, and most of the recommendations that have been issued can be characterized as expert opinion. As a rule, VRE are not highly pathogenic; they tend to have high rates of colonization, but low rates of infection. The risk factors for colonization with VRE include (among others) the administration of antibiotics and immunosuppressants, prior hospitalization, diarrhea, intubation, and other invasive treatments. The areas of highest risk are hematology/oncology wards, liver transplantation wards, dialysis units, and neonatology wards. CONCLUSION The chain of infection can be broken by improved and consistently applied standard hygienic measures (hand and surface disinfection). Some patients are nonetheless at elevated risk of VRE infection. In specific clinical situations, the optimal protection of these patients against VRE infection demands the obligatory enforcement of stricter hygienic measures (contact isolation).

Bed occupancy rates and hospital-acquired infections--should beds be kept empty?

There is growing evidence that bed occupancy (BO) rates, overcrowding and understaffing influence the spread of hospital-acquired infections (HAIs). In this article, a systematic review of the literature is presented, summarizing the evidence on the adverse effects of high BO rates and overcrowding in hospitals on the incidence of HAIs. A Pubmed database search identified 179 references, of which 44 were considered to be potentially relevant for full-text review. The majority (62.9%) focused on methicillin-resistant Staphylococcus aureus-associated infection or colonization. Only 12 studies were found that provided a statistical analysis of the impact of BO on HAI rates. The median BO rate of the analysed studies was 81.2%. The majority of studies (75%) indicated that BO rates and understaffing directly influence the incidence of HAIs. Only three studies showed no significant association between BO rates and the incidence of HAIs. Interestingly, only one of the included studies detected a seasonal trend in the BO rate. The present review shows an association between BO rates and the spread of HAIs in various settings. Because the evidence on this topic is limited, we conclude that further research is needed in order to analyse the rationale of a threshold BO rate, because keeping beds empty is comparatively costly.

Controversies in guidelines for the control of multidrug-resistant Gram-negative bacteria in EU countries

The various guidelines that are available for multidrug-resistant Gram-negative bacteria are useful, and contain broad areas of agreement. However, there are also important areas of controversy between the guidelines in terms of the details of applying contact precautions, single-room isolation and active surveillance cultures, differences in the approach to environmental cleaning and disinfection, and whether or not to perform staff and patient cohorting, healthcare worker screening or patient decolonization. The evidence-base is extremely limited and further research is urgently required to inform an evidence-based approach to multidrug-resistant Gram-negative bacteria prevention and control.

STROBE-AMS: recommendations to optimise reporting of epidemiological studies on antimicrobial resistance and informing improvement in antimicrobial stewardship

Objectives To explore the accuracy of application of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool in epidemiological studies focused on the evaluation of the role of antibiotics in selecting resistance, and to derive and test an extension of STROBE to improve the suitability of the tool in evaluating the quality of reporting in these area. Methods A three-step study was performed. First, a systematic review of the literature analysing the association between antimicrobial exposure and acquisition of methicillin-resistant Staphylococcus aureus and/or multidrug-resistant Acinetobacter baumannii was performed. Second, articles were reviewed according to the STROBE checklist for epidemiological studies. Third, a set of potential new items focused on antimicrobial-resistance quality indicators was derived through an expert two-round RAND-modified Delphi procedure and tested on the articles selected through the literature review. Results The literature search identified 78 studies. Overall, the quality of reporting appeared to be poor in most areas. Five STROBE items, comprising statistical analysis and study objectives, were satisfactory in <25% of the studies. Informative abstract, reporting of bias, control of confounding, generalisability and description of study size were missing in more than half the articles. A set of 21 new items was developed and tested. The new items focused particularly on the study setting, antimicrobial usage indicators, and patients epidemiological and clinical characteristics. The performance of the new items in included studies was very low (<25%). Conclusions Our paper reveals that reporting in epidemiological papers analysing the association between antimicrobial usage and development of resistance is poor. The implementation of the newly developed STROBE for antimicrobial stewardship (AMS) tool should enhance appropriate study design and reporting, and therefore contribute to the improvement of evidence to be used for AMS programme development and assessment.

Low risk of apparent transmission of vancomycin-resistant Enterococci from bacteraemic patients to hospitalized contacts

BACKGROUND Vancomycin-resistant enterococci (VRE) are primarily opportunistic pathogens with incalculable clinical significance. In addition, the effectiveness of isolation in VRE is often not easily assessed. The goals of this study were to estimate the transmissibility of VRE of patients with VRE bacteraemia to other hospitalized patients and to document reliable epidemiologic data on all VRE cases in a large health care center. METHODS A prospective survey on in-patients colonized and/or systemically infected with VRE was conducted at a 2,000-bed tertiary care university hospital in Germany. All roommates of VRE bacteraemia patients were analyzed. Pulsed-field gel electrophoresis was performed to assess clonal relatedness. RESULTS 16,507 Screening tests were performed on 9,258 patients, of which 560 tested positive for VRE (6.1%). Nineteen patients also suffered from VRE bacteraemia, an incidence of 3.4%. This cohort was multimorbid and had high rates of exposure to external risk factors (eg, previous hospital stay prior to admission, 78.9%). The transmission rate to contacts was low (3.5%). Contact time of negative contacts was significantly lower than that of VRE-positive contacts (19.3 hours vs 72.0 hours, respectively, P < .006). CONCLUSION VRE bacteraemia was found exclusively in multimorbid patients, transmission occurred seldom, and average contact time of positive contacts was very high. The risk of transmission of VRE from bacteraemic patients to hospitalized contacts is low.

Contact precautions for preventing nosocomial transmission of extended-spectrum β lactamase-producing Escherichia coli: a point/counterpoint review

Contact precautions have been recommended for hospitalized patients colonized or infected with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC). Despite such recommendations, a steady, worldwide increase of ESBL-EC has been reported. We discuss arguments in favor of and against contact precautions for ESBL-EC carriers. Healthcare settings with high ESBL-EC colonization pressure, extended hospital stay, and close contact between patients may serve as amplification platforms, further accelerating transmission. However, the evidence base for justifying the implementation of contact precautions for all ESBL-EC carriers remains weak. Until more high-level evidence is available, we support the attitude that hospitals and countries should carefully evaluate their decision on whether to implement contact precautions for ESBL-EC carriers. It is likely that a majority of patients and wards do not need to rely on contact precautions for preventing nosocomial ESBL-EC transmission in nonepidemic settings, without harming patient safety, providing sufficient compliance with standard precautions and ongoing surveillance.

Costs and possible benefits of a two-tier infection control management strategy consisting of active screening for multidrug-resistant organisms and tailored control measures.

BACKGROUND Multidrug-resistant organisms (MDROs) are an economic burden, and infection control (IC) measures are cost- and labour-intensive. A two-tier IC management strategy was developed, including active screening, in order to achieve effective use of limited resources. Briefly, high-risk patients were differentiated from other patients, distinguished according to type of MDRO, and IC measures were implemented accordingly. AIM To evaluate costs and benefits of this IC management strategy. METHODS The study period comprised 2.5 years. All high-risk patients underwent microbiological screening. Gram-negative bacteria (GNB) were classified as multidrug-resistant (MDR) and extensively drug-resistant (XDR). Expenses consisted of costs for staff, materials, laboratory, increased workload and occupational costs. FINDINGS In total, 39,551 patients were screened, accounting for 24.5% of all admissions. Of all screened patients, 7.8% (N=3,104) were MDRO positive; these patients were mainly colonized with vancomycin-resistant enterococci (37.3%), followed by meticillin-resistant Staphylococcus aureus (30.3%) and MDR-GNB (28.3%). The median length of stay (LOS) for all patients was 10 days (interquartile range 3-20); LOS was twice as long in colonized patients (P<0.001). Screening costs totalled 255,093.82€, IC measures cost 97,701.36€, and opportunity costs were 599,225.52€. The savings of this IC management strategy totalled 500,941.84€. Possible transmissions by undetected carriers would have caused additional costs of 613,648.90-4,974,939.26€ (i.e. approximately 600,000-5 million €). CONCLUSION Although the costs of a two-tier IC management strategy including active microbiological screening are not trivial, these data indicate that the approach is cost-effective when prevented transmissions are included in the cost estimate.

Education in infection control: A need for European certification

Healthcare-associated infections are common adverse events in acute-care medicine, causing significant morbidity and mortality. There has been a significant increase in the commitment to infection prevention and control (IPC) among European countries in recent years. However, there is still heterogeneity in training opportunities and IPC qualifications. The European Union promotes the harmonization of IPC strategies among member states. The European Centre for Disease Prevention and Control (ECDC)-commissioned Training in Infection Control in Europe project sets the stage for harmonization of IPC activities in Europe by issuing a list of core competencies for IPC professionals. European certification of IPC training and professionals would be the next logical step, which must be achieved by close collaboration between different stakeholders in Europe such as the ECDC, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Union of Medical Specialities, and the national IPC societies. Therefore, the ESCMID has launched the new European Committee on Infection Control to take the lead in the implementation of a European (board) certificate for IPC professionals.

Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

The National Reference Centre for Staphylococci and Enterococci in Germany has received an increasing number of clinical linezolid-resistant E. faecium isolates in recent years. Five isolates harbored a cfr(B) variant gene locus the product of which is capable of conferring linezolid resistance. The cfr(B)-like methyltransferase gene was also detected in Clostridium difficile. Antimicrobial susceptibility was determined for cfr(B)-positive and linezolid-resistant E. faecium isolates and two isogenic C. difficile strains. All strains were subjected to whole genome sequencing and analyzed with respect to mutations in the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B) variant locus. To evaluate methyltransferase function, the cfr(B) variant of Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp. Ribosomal target site mutations were detected in E. faecium strains but absent in clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218 which was present in C. difficile Ox3196, truncated in some E. faecium and absent in C. difficile Ox3206. The latter finding explains the lack of linezolid and chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first time a direct correlation of elevated linezolid MICs in C. difficile upon cfr acquisition. Tn6218 insertion sites revealed novel target loci for integration, both within the bacterial chromosome and as an integral part of plasmids. Importantly, the very first plasmid-association of a cfr(B) variant was observed. Although we failed to measure cfr(B)-mediated resistance in transformed laboratory strains the occurrence of the multidrug resistance gene cfr on putatively highly mobile and/or extrachromosomal DNA in clinical isolates is worrisome with respect to dissemination of antibiotic resistances.