Epidemiology and outcomes of vancomycin-resistant enterococcus infections: a systematic review and meta-analysis.

Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however, remains fragmented. We aimed to summarize recent studies on VRE epidemiology and outcomes in hospitals, long-term-care facilities (LTCFs) and nursing homes worldwide based on current epidemiological reports. We searched MEDLINE/PubMed, the Cochrane Library, and Web of Science for observational studies, which reported on VRE faecium and faecalis infections in in-patients published between January 2014 and December 2020. Outcomes were incidence, infection rate, mortality, length of stay (LOS), and healthcare costs. We conducted a meta-analysis on mortality (PROSPERO registration number: CRD42020146389). Of 681 identified publications, 57 studies were included in the analysis. Overall quality of evidence was moderate to low. VRE incidence was rarely and heterogeneously reported. VRE infection rate differed highly (1-55%). The meta-analysis showed a higher mortality for VRE faecium bloodstream infections (BSIs) compared with VSE faecium BSIs (risk ratio, RR 1.46; 95% confidence interval (CI) 1.17-1.82). No difference was observed when comparing VRE faecium vs VRE faecalis BSI (RR 1.00, 95% CI 0.52-1.93). LOS was higher in BSIs caused by E. faecium vs E. faecalis. Only three studies reported healthcare costs. In contrast to previous findings, our meta-analysis of included studies indicates that vancomycin resistance independent of VRE species may be associated with a higher mortality. We identified a lack of standardization in reporting outcomes, information regarding healthcare costs, and state-of-the-art microbiological species identification methodology, which may inform the set-up and reporting of future studies.

Secular trends of bloodstream infections during neutropenia in 15 181 haematopoietic stem cell transplants: 13-year results from a European multicentre surveillance study (ONKO-KISS).

OBJECTIVES: Antibacterial resistance is emerging in patients undergoing haematopoietic stem cell transplantation (HSCT), and most data on the epidemiology of bloodstream infections (BSI)-causing pathogens come from retrospective single-centre studies. This study sought to investigate trends in the epidemiology of BSI in HSCT patients from a prospective multicentre cohort. METHODS: We investigated changes in the incidence of causative organisms of BSI during neutropenia among adult HSCT patients for 2002-2014. The data were collected from a prospective cohort for infection surveillance in 20 haematologic cancer centres in Germany, Austria and Switzerland (ONKO-KISS). RESULTS: A total of 2388 of 15 181 HSCT patients with neutropenia (1471 allogeneic (61.6%) and 917 autologous (38.4%) HSCT) developed BSI (incidence 15.8% per year). The incidence of Gram-negative BSI increased over time both in patients after allogeneic HSCT (allo-HSCT) and autologous HSCT (auto-HSCT). BSI caused by Escherichia coli in allo-HSCT patients increased from 1.1% in 2002 to 3.8% in 2014 (3/279 vs. 31/810 patients, p <0.001), and the incidence of BSI caused by enterococci increased from 1.8% to 3.3% (5 vs. 27 patients, p <0.001). In contrast, the incidence of BSI due to coagulase-negative staphylococci decreased in allo-HSCT patients from 8.2% to 5.1%, (23 vs. 40 patients, p <0.001) and in auto-HSCT patients from 7.7% to 2.0% (13/167 vs. 30/540 patients; p = 0.028 for period 2002-2011). No significant trends were observed for the incidence of BSI due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or extended-spectrum ß-lactamase-producing Enterobacteriaceae. The BSI case fatality remained unchanged over the study period (total of 477 fatalities, 3.1%). CONCLUSIONS: The incidence of Gram-negative BSI significantly increased over time in this vulnerable patient population, providing evidence for reevaluating empiric therapy for neutropenic fever in HSCT patients.

Provision and consumption of alcohol-based hand rubs in European hospitals.

Hand hygiene is considered to be the most effective way of preventing microbial transmission and healthcare-associated infections. The use of alcohol-based hand rubs (AHRs) is the reference standard for effective hand hygiene. AHR consumption is a valuable surrogate parameter for hand hygiene performance, and it can be easily tracked in the healthcare setting. AHR availability at the point of care ensures access to optimal agents, and makes hand hygiene easier by overcoming barriers such as lack of AHRs or inconvenient dispenser locations. Data on AHR consumption and availability at the point of care in European hospitals were obtained as part of the Prevention of Hospital Infections by Intervention and Training (PROHIBIT) study, a framework 7 project funded by the European Commission. Data on AHR consumption were provided by 232 hospitals, and showed median usage of 21 mL (interquartile range (IQR) 9-37 mL) per patient-day (PD) at the hospital level, 66 mL/PD (IQR 33-103 mL/PD) at the intensive-care unit (ICU) level, and 13 mL/PD (IQR 6-25 mL/PD) at the non-ICU level. Consumption varied by country and hospital type. Most ICUs (86%) had AHRs available at 76-100% of points of care, but only approximately two-thirds (65%) of non-ICUs did. The availability of wall-mounted and bed-mounted AHR dispensers was significantly associated with AHR consumption in both ICUs and non-ICUs. The data show that further improvement in hand hygiene behaviour is needed in Europe. To what extent factors at the national, hospital and ward levels influence AHR consumption must be explored further.

Epidemiology of healthcare associated infections in Germany: Nearly 20 years of surveillance.

OBJECTIVE: To describe the epidemiology of healthcare-associated infections (HAI) in hospitals participating in the German national nosocomial infections surveillance system (KISS). METHOD: The epidemiology of HAI was described for the surveillance components for intensive care units (ITS-KISS), non-ICUs (STATIONS-KISS), very low birth weight infants (NEO-KISS) and surgical site infections (OP-KISS) in the period from 2006 to 2013. In addition, risk factor analyses were performed for the most important infections of ICU-KISS, NEO-KISS and OP-KISS. RESULTS: Data from a total of 3,454,778 ICU patients from 913 ICUs, 618,816 non-ICU patients from 142 non-ICU wards, 53,676 VLBW from 241 neonatal intensive care units (NICU) and 1,005,064 surgical patients from operative departments from 550 hospitals were used for analysis. Compared with baseline data, a significant reduction of primary bloodstream infections (PBSI) and lower respiratory tract infections (LRTI) was observed in ICUs with the maximum effect in year 5 (or longer participation) (incidence rate ratio 0.60 (CI95 0.50-0.72) and 0.61 (CI95 0.52-0.71) respectively). A significant reduction of PBSI and LRTI was also observed in NEO-KISS when comparing the baseline situation with the 5th year of participation (hazard ratio 0.70 (CI95 0.64-0.76) and 0.43 (CI95 0.35-0.52)). The effect was smaller in operative departments after the introduction of OP-KISS (OR 0.80; CI95 0.64-1.02 in year 5 or later for all procedure types combined). Due to the large database, it has not only been possible to confirm well-known risk factors for HAI, but also to identify some new interesting risk factors like seasonal and volume effects. CONCLUSIONS: Participating in a national surveillance system and using surveillance data for internal quality management leads to substantial reduction of HAI. In addition, a surveillance system can identify otherwise not recognized risk factors which should - if possible - be considered for infection control management and for risk adjustment in the benchmarking process.

National European guidelines for the prevention of Clostridium difficile infection: a systematic qualitative review.

BACKGROUND: Clostridium difficile is the most frequent infectious cause of nosocomial diarrhoea and a major topic in infection prevention. AIM: To overview current national European guidelines for C. difficile infection (CDI) prevention and review the recommendations in respect of their evidence base and conformity to each other and the European Centre for Disease Control and Prevention (ECDC) guidance. METHODS: In 34 European countries, the ECDC healthcare-associated infection (HCAI) surveillance National Contact Points and other HCAI experts (NCPs) were invited to complete an online questionnaire and to supply their guidelines. Guidelines not available in English, French or German were translated into English. For the qualitative analysis, a matrix with key measures based on the 2008 ECDC guidance was established. The review process was conducted independently by two reviewers. RESULTS: All 34 NCPs responded to the questionnaire and supplied 15 guidelines in total. Six of 34 (18%) countries reported having used the ECDC guidance as a basis for the development or revision of their national guideline. There was wide variation in the scope and detailing. Only six of the documents and the ECDC guidance supplied a rating for the strength of recommendations. The rating systems varied in how the categories were defined. Furthermore, the stated strength for similar measures varied across different guidelines. CONCLUSION: The ECDC guidance has not yet had a strong influence on the development or revision of national CDI prevention guidelines. One possible explanation for the variations is the necessity to adapt recommendations to national conditions. The use of internationally recognized instruments for the development of guidelines could help to improve their quality. Recommendations about monitoring or auditing the implementation would make them more useful.

Public reporting of healthcare-associated infection data in Europe. What are the views of infection prevention opinion leaders?

BACKGROUND: There is increasing interest in public reporting of healthcare-associated infection (HAI) data in Europe, mostly for patient safety reasons. But it is uncertain whether patients and other stakeholders benefit from them. AIM: To obtain the views of European infection control opinion leaders and provide information about public reporting of HAI in Europe. METHODS: European Centre for Disease Prevention and Control HAI surveillance National Contact Points and other opinion leaders in infection control from 34 European countries were invited to complete questionnaires about HAI reporting in their countries and to provide their personal views about public reporting. The issue was discussed during two discussion rounds in 2010 and 2012. FINDINGS: Response rates were 100% and 93.9% for the two surveys. Current practices on publishing HAI data vary widely across Europe. Many experts support the idea of publishing HAI data. All representatives from the seven countries with established public reporting were in favour of such practice. After the first discussion round, 12 experts changed their opinion. Finally, the majority of the experts acknowledged the positive influence on hospitals by increasing competition on the basis of quality, but they are hesitant about publishing infection rates as these can be misinterpreted by patients and need standardization and validation. CONCLUSION: Opinion leaders in infection control in Europe acknowledged the positive influence of public reporting on hospital performance and resulting efforts to reduce infections. They were in favour of reporting of individual hospital data if (i) process indicators rather than outcome data are reported, and (ii) delivery of surveillance is monitored by external audits.

Initially fewer bloodstream infections for allogeneic vs. autologous stem-cell transplants in neutropenic patients.

Chemotherapy and/or radiotherapy used as conditioning regimens before autologous or allogeneic haematopoietic cell transplantations (HCTs) cause neutropenia, which is the main reason for bloodstream infections. Autologous HCTs are considered to be superior to allogeneic HCTs in terms of infection outcome. A previous analysis suggested that patients with allogeneic HCTs are exposed to a reduced infection hazard and that an unfavourable infection outcome of allogeneic HCTs may be mediated through prolonged neutropenia. Therefore, we investigated whether allogeneic HCTs initially lead to fewer infections. We evaluated data from a prospective non-randomized multi-centre cohort study, with a total of 1616 patients. Of these, 703 patients received autologous and 913 patients received allogeneic HCTs from January 2000 to June 2004. The retrospective analysis used simultaneous confidence bands for the cumulative infection probability in the presence of competing risks. Patients with allogeneic HCTs experienced fewer infections during the early phase of neutropenia. As patients with autologous HCTs are not necessarily subject to antibiotic prophylaxis, a future study should investigate this policy. A limitation of the analysis is that it did not find the effect of crossing cumulative infection probabilities to be significant.

[Healthcare-associated infection rates: measuring and comparing. Experiences from the German National Nosocomial Infection Surveillance System (KISS) and from other surveillance systems]. / Nosokomiale Infektionsraten: Messen und Vergleichen. Erfahrungen mit dem Krankenhaus-Infektions-Surveillance-System (KISS) und anderen Surveillance-Systemen.

Surveillance of nosocomial infections is meanwhile a cornerstone of infection prevention activities in hospitals. The objective of this article is to compare healthcare-associated infection rates in intensive care patients, neonatal intensive care patients and operated patients (ICU-KISS, OP-KISS, NEO-KISS) of the German nosocomial infection surveillance system (KISS) with the corresponding data of the US American National Healthcare Safety Network (NHSN) and the European Centre for Disease Prevention and Control (ECDC). In general, the methodological differences among the three surveillance systems are minor but there are some exceptions. Therefore, differences between countries have to be interpreted very carefully as they may be due to differences in diagnostics, patient mix, types of interventions, length of stay, selection of participating hospitals, post-discharge surveillance activities and interpretation of case definitions. Organizational aspects, such as mandatory participation with public disclosure on infection rates may also have an impact.

[Infection control in the operating room: preventive measures and isolation precautions in cases of multidrug resistant pathogens]. / Infektionskontrolle im OP: Präventions- und Isolierungsmaßnahmen bei multiresistenten Erregern.

BACKGROUND: Providing surgical treatment for patients colonised or infected with multidrug resistant organisms (MDROs) is daily routine in German hospitals. However, there is uncertainty about the application of adequate infection control measures in the OR. One of the reasons is that specific guidelines are not available. MATERIAL AND METHODS: We evaluated current practice in surgical departments of selected German university medical centres using a questionnaire. In addition, centres were asked to provide in-house standard operating procedures (SOP), if available. RESULTS: Nineteen questionnaires from 19 departments within 4 centres and 5 in-house SOPs were ana-lysed. The results showed a broad spectrum of applied infection control measures. Wide variations existed both within centres and within departments of the same centre regardless of existing in-house standards. CONCLUSIONS: Guidelines addressing perioperative infection control measures for patients harbouring MDROs should be developed with a focus on practicability to reduce both transmission of MDROs and unreasonable measures. Implementation of existing SOPs can be a target for optimisation.

Correlations between bed occupancy rates and Clostridium difficile infections: a time-series analysis.

A time-series analysis was performed to identify the impact of bed occupancy rates and length of hospital stay on the incidence of Clostridium difficile infections (CDI). Between January 2003 and July 2008, a mean incidence of 0·5 CDI cases/1000 patient days was recorded. Application of a multivariate model (R2=0·50) showed that bed occupancy rates on general wards (P<0·01) and length of stay in intensive care units (ICUs) (P<0·01) influenced the incidence of CDI. Overcrowding on general wards and long periods in ICUs were identified as being positively associated with the incidence of CDI.

Infection control--a European research perspective for the next decade.

A symposium was held in June 2009 near Freiburg in Germany. Twenty-nine attendees from several European countries participated, most of whom are actively involved in research and hospital infection prevention and control. The following topics were presented and discussed: isolation and screening for control of multidrug-resistant organisms; impact of the environment on healthcare-associated infection (HAI); new technologies to control infection--state of evidence; surveillance of HAI; methodological challenges and research priorities for infection control and control of HAI: learning from each other in a united Europe. This Leader summarises the main issues for debate and the number of consensus points agreed amongst delegates.

Epidemiology meets econometrics: using time-series analysis to observe the impact of bed occupancy rates on the spread of multidrug-resistant bacteria.

Two multivariate time-series analyses were carried out to identify the impact of bed occupancy rates, turnover intervals and the average length of hospital stay on the spread of multidrug-resistant bacteria in a teaching hospital. Epidemiological data on the incidences of meticillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing bacteria were collected. Time-series of bed occupancy rates, turnover intervals and the average length of stay were tested for inclusion in the models as independent variables. Incidence was defined as nosocomial cases per 1000 patient-days. This included all patients infected or colonised with MRSA/ESBL more than 48h after admission. Between January 2003 and July 2008, a mean incidence of 0.15 nosocomial MRSA cases was identified. ESBL was not included in the surveillance until January 2005. Between January 2005 and July 2008 the mean incidence of nosocomial ESBL was also 0.15 cases per 1000 patient-days. The two multivariate models demonstrate a temporal relationship between bed occupancy rates in general wards and the incidence of nosocomial MRSA and ESBL. Similarly, the temporal relationship between the monthly average length of stay in intensive care units (ICUs) and the incidence of nosocomial MRSA and ESBL was demonstrated. Overcrowding in general wards and long periods of ICU stay were identified as factors influencing the spread of multidrug-resistant bacteria in hospital settings.

[Effectiveness and risks of isolation precautions in patients with MRSA and other multidrug-resistant bacteria]. / Patienten mit multiresistenten Erregern: Wirksamkeit und Risiko von Isolierungsmassnahmen bei "MRSA & Co."

The transmission of multidrug-resistant organisms (MRSA, VRE and ESBL producing bacteria) occurs predominantly if health-care workers are not compliant with hand hygiene procedures. The impact of single-room isolation in transmission prevention is often overestimated. As long as hand disinfection is not performed before and after patient contact and gloves are not removed, a single room will not prevent transmission by -itself. Understaffing is additionally worsening the situation. There is no consistent evidence sup-port-ing strict single-room isolation even though data show supportive tendencies. Social isolation is one of the risks that should be considered as well as the economic impact of using shared rooms as a single room. Up-to-date, evidence-based standard operating procedures and individual infection control recommendations should take these considerations into account. In general, contact precautions including isolation in a single room are performed in MRSA and VRE-positive patients. If a single room cannot be provided in a given case (a common problem in intensive care units), contact precautions can be performed in a shared room as an alternative. The problem of establishing an optimal compliance with standard precautions (especially hand hygiene) throughout all professional groups should be addressed. Additional precautions, including single-room isolation, should be implemented critically if indicated.

[Epidemiology of and preventive measures for multiresistant pathogens]. / Epidemiologie von und Präventionsmassnahmen bei multiresistenten Erregern.

Multidrug-resistant organisms (MROs) are increasing all over the world. The most important MROs are methicillin-resistant S. aureus, followed by vancomycin-resistant enterococci and extended-spectrum beta-lactamase (ESBL)-producing bacteria. The latter are not yet of much importance in ophthalmology. MROs can cause serious infections and must be considered in empiric therapy of nosocomial infections. To prevent further spread, standard and contact precautions have to be followed, and antibiotic stewardship needs to be introduced.

Extended-spectrum beta-lactamase-producing Enterobacter cloacae in mobile dialysis units in the medical and surgical departments of a university hospital: a case-control study.

The objective of this case-control study was to investigate the source of contamination and risk factors for colonisation and infection during an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Enterobacter cloacae in the University Medical Center Freiburg. A risk factor analysis was performed on 23 patients with ESBL-producing E. cloacae in the medical and surgical departments by comparing them with 46 non-colonised controls, who were matched for ward and length of hospital stay. For these, a risk factor analysis was conducted. Suspected sources for transmission of ESBL were examined and staff received training in infection control measures. The higher risk in colonised patients was attributed to dialysis with mobile units [odds ratio (OR): 4.00; 95% confidence interval (CI): 1.05-15.234; P=0.04]. Dialysis units were examined, but no contamination was found. Improvement in dialysis procedures, additional staff training and renewed training in standard precautions led to a substantial fall in case numbers. Risk factor analysis showed that colonised patients carried more invasive devices than controls (central venous catheter: OR: 2.50; 95% CI: 0.74-8.45; P=0.14; Foley catheter: 5.08; 0.61-42.23; P=0.13) and were given a greater number of different antibiotics (penicillins: 2.52; 0.71-8.89; P=0.15; fluoroquinolones: 2.37; 0.77-7.28; P=0.13). The differences in mobile dialysis frequency and antibiotic use between cases and controls were relevant, although the latter was not statistically significant. It was possible to contain the high frequency of ESBL colonisation or infection by reinforcing infection control measures and training the staff involved.

[Transmission of multidrug-resistant bacteria in ambulatory settings]. / Ubertragung von Problemkeimen im ambulanten Bereich.

Multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) und extended-spectrum beta-lactamase (ESBL-) producing bacteria are an ever-expanding challenge regarding infection control and prevention strategies also in ambulatory healthcare settings. The most important transmission mode for MDROs is direct or indirect contact involving the hands of healthcare workers. Strict adherence to standard precautions (and especially adherence to alcoholic handrub use) is essential in prevention of cross-transmission. Additional measures contribute to the control of MDROs: These include flagging of patients' records, establishing standards of care for patients with MDROs, continuing education of staff, disclosure of information to other involved healthcare providers and guideline-based antibiotic treatment and prophylaxis. Optimised cooperation of ambulatory healthcare providers and hospitals regarding management and control of MDROs (networking) is a promising future option.

Skin disinfection with octenidine dihydrochloride for central venous catheter site care: a double-blind, randomized, controlled trial.

To compare the efficacy of two commercially available, alcohol-based antiseptic solutions for preparation and care of central venous catheter (CVC) insertion sites, with and without octenidine dihydrochloride, a double-blind, randomized, controlled trial was undertaken in the haematology units and in one surgical unit of two university hospitals. Adult patients with a non-tunnelled CVC were randomly assigned to two different skin disinfection regimens at the insertion site: 0.1% octenidine with 30% 1-propanol and 45% 2-propanol, and as control 74% ethanol with 10% 2-propanol. Endpoints were (i) skin colonization at the insertion site; (ii) positive culture from the catheter tip (> or = 15 CFU); and (iii) occurrence of CVC-associated bloodstream infection (defined according to criteria set by the CDC). Four hundred patients with inserted CVC were enrolled from May 2002 through April 2005. Both groups were similar in respect of patient characteristics and co-morbidities. Skin colonization at the CVC insertion site during the first 10 days was significantly reduced by octenidine treatment (relative difference octenidine vs. control: 0.21; 95%CI: 0.11-0.39, p <0.0001). Positive culture of the catheter tip was significantly less frequent in the octenidine group (7.9%) than in the control group (17.8%): OR = 0.39 (95%CI: 0.20-0.80, p 0.009). Patients treated with octenidine had a non-significant reduction in catheter-associated bloodstream infections (4.1% vs. 8.3%; OR = 0.44; 95%CI: 0.18-1.08, p 0.081). Side effects were similar in both groups. This randomized controlled trial supports the results of two observational studies demonstrating octenidine in alcoholic solution to be a better option than alcohol alone for the prevention of CVC-associated infections.

[Nosocomial infections: MRSA und CDAD as a challenge]. / Nosokomiale Infektionen : Herausforderung MRSA und CDAD.

Inadequate antibiotic prescribing and poor adherence to infection control guidelines are the main reasons for the development and spread of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (CD), the most important cause of antibiotic-associated diarrhoea (AD) and colitis. Both CDAD and MRSA infection are associated with significant morbidity, excess mortality and substantial consumption of resources. Increases in the incidence of both infections have been observed in Germany and represent a challenge to clinicians, infection control practitioners, quality management teams und hospital administration. Prudent use of antibiotics, in particular critical prescribing of fluoroquinolones and cephalosporins, is an important component in programmes aiming at an effective prevention of MRSA and CDAD. Other similarly important components are minimization of pathogen transmission between patients and healthcare personnel by isolation and contact precautions, early detection of MRSA carriers and MRSA decolonization treatment. It must be ascertained that patients nursed in isolation rooms receive medical care of similar high quality as all other patients. Over the last years, there has been no major breakthrough in therapy and outcomes in both CDAD and MRSA infection. Close collaboration between hospitals, nursing homes and primary care institutions will be critical for better control of MRSA and CDAD.