Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

IMPORTANCE: The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

[COVID-19 deaths among residents of inpatient nursing homes in Munich-causes and places of death]. / COVID-19-Sterbefälle bei Bewohnern vollstationärer Pflegeeinrichtungen in München ­ Todesursachen und Sterbeorte.

INTRODUCTION: The new infectious disease COVID-19 first appeared in China in December 2019. So far, a systematic evaluation of death certificates of COVID-19-associated deaths of residents in inpatient nursing homes has not been presented. METHODS: Death certificates of all deaths in Munich in the death period from 1 March to 31 July 2020 were analyzed. Inclusion criteria were the presence of "Corona, COVID-19, SARS-CoV-2" on the death certificates. Standardized, anonymized data entry was performed. The collected data were analyzed descriptively. RESULTS: During the study period, a total of 5840 persons died, 281 (4.8%) of whom died of confirmed COVID-19 disease. Of those, 72 deaths involved residents of Munich nursing facilities. The most frequent causes of death were respiratory insufficiency (54 cases) and multiple organ failure (9 cases). On the death certificates, an average of two preexisting diseases had been reported; the average age at death was 88 years. All deaths of nursing home residents occurred in association with nosocomial COVID-19 outbreaks, which affected one-third of the facilities. The vast majority of these homes did not have a COVID-19 hygiene plan in place at the time. DISCUSSION: One quarter of all COVID-19 deaths in Munich occurred in the context of nosocomial outbreaks in elderly, chronically ill residents of nursing facilities. Evidence of inadequate risk assessment and inadequate hygiene management emerged. In the opinion of the authors, the appropriate structures for adequate hygiene management must be created and a hygiene regulation must be issued in which the tasks and responsibilities of the facility operators are defined.

[COVID-19- and influenza-associated deaths in Munich as of March 2020-a standardized analysis of death certificates]. / COVID-19- und influenzaassoziierte Sterbefälle in München ab März 2020 ­ eine standardisierte Auswertung von Todesbescheinigungen.

INTRODUCTION: In light of the current COVID-19 pandemic, the idea arose to conduct a study to comparatively evaluate deaths from two respiratory transmissible infectious diseases (pandemic COVID-19 and seasonal influenza) by means of death certificates received by the health department. METHODS: Death certificates of all deaths in Munich in the death period from 1 March-31 December 2020 were analyzed. The predefined inclusion criteria were the indication of "Corona, COVID-19, SARS-CoV­2, Influenza (A/B)" on the death certificates. Standardized data entry was performed. The collected data were analyzed descriptively in aggregated form. RESULTS: A total of 12,441 persons died during the study period, 1029 (8.3%) from confirmed COVID-19 and 22 (0.1%) from influenza. The two collectives matched well in the parameters studied. The mean age at death was approximately 80 years and the most common site of death was in hospital. Infectious disease was the cause of death in more than 90% of cases. The most common causes of death were acute respiratory distress syndrome/respiratory failure and multiorgan failure. An average of two previous illnesses were reported, most commonly diseases of the circulatory system and nervous system. There was no influenza death in the second pandemic wave. DISCUSSION: In this study, COVID-19- and influenza-associated deaths were compared for the first time. The deaths of both collectives matched well in the parameters studied, but still require verification in a larger study given the small numbers of influenza cases. An English full-text version of this article is available at SpringerLink as Supplementary Information.

[Forensic postmortem examination service: challenges and opportunities]. / Forensischer Leichenschaudienst: Herausforderungen und Chancen.

The external examination of a corpse is regulated by federal law and presents physicians and police with a series of challenges. Mostly GPs, but practically every licensed physician, are obliged to complete death certificates, resulting in a very large number of potential physicians, which at the same time means only a small number of cases for each individual. Consequently, this sensitive topic often lacks the experience needed.As already shown in several studies, only very limited possibilities for the correct determination of the cause of death are generally present at the inquest. The legal provisions also represent a certain basic problem, from which further pitfalls can arise.In Munich, the medical association, in cooperation with the Institute of Legal Medicine, organizes a 24­h service with at least one physician on standby, which ensures quality assurance and/or enhancement of this postmortem service through continuous education and further training as well as monthly meetings. The principles and considerations concerning the practicability of such a system will be discussed in this paper.

[Death certificates-an underestimated source of information for statistics, judicature, public health, and science]. / Todesbescheinigungen ­ eine unterschätzte Informationsquelle für Statistik, Rechtspflege, öffentliche Gesundheit und Wissenschaft.

The thorough external examination of a corpse and the correct completion of the death certificate are medical duties with far-reaching consequences. Data obtained from the death certificates are the basis for mortality statistics and for scientific research. They can be helpful in uncovering criminal offences or for the surveillance of medical facilities. For many years the deficiencies of external post-mortem examinations and death certificates have been discussed in professional journals.The important task of analysing all death certificates is performed by the local health authorities. This is the only opportunity for quality control and, if necessary, the doctors who issued the death certificate must be asked for corrections. This also improves the quality of the mortality statistics and contributes to the administration of justice.Additionally, important information for routine duties of the public health authorities can be obtained from the death certificates concerning the monitoring of narcotics, the supervision of medical facilities and the adherence to notification requirements for infectious diseases. Furthermore, death certificates contain relevant data for selected medical research projects.The high information content of death certificates is widely unknown and should be used by the health authorities comprehensively and systematically. Enough qualified staff needs to be allocated to further secure the important task of quality control of death certificates.

[Surveillance of Supervised Flat-Sharing Communities Requiring Intensive Home Care: Results and Conclusions]. / Schwerpunktüberprüfung ambulanter Wohngemeinschaften der außerklinischen Intensivpflege im Stadtgebiet München ­ Ergebnisse und Rückschlüsse.

BACKGROUND: Patients with intensive care and long-term mechanical ventilation needs are increasingly cared for in supervised flat-sharing communities. The municipal public health and environment department of Munich audited nursing services between April 2015 and August 2016. METHODS: The structural analysis of the nursing services was conducted using standardised checklists, and statistical analysis was performed. In agreement with the residents and providers of the nursing service, flats were inspected. RESULTS: 20 of the 43 supervised flat-sharing communities in Munich were designed for intensive care patients. Nine nursing services took care of them. Monitoring of organizational structures and hygiene management were found to be positive. There was room for improvement in practical implementation of hygiene standards. Requirements for personal qualifications and for emergencies such as electrical power outages have to be regulated. CONCLUSION: It was shown that regular consulting, instructions and auditing by the municipal public health and environment department have a positive effect on hygiene and emergency management. National and binding agreements still need to be worked out.

Air quality in the operating room: Surgical site infections, HVAC systems and discipline - position paper of the German Society of Hospital Hygiene (DGKH).

In recent years, there has been an ongoing discussion about the value of laminar airflow (LAF=low turbulence displacement ventilation) in the operating room for prevention of surgical site infections (SSI). Some publications, e.g., from the WHO, issued the demand to no longer build LAF ceilings in operating rooms. The present statement deals critically with this position and justifies the use of LAF ceilings in different ways: Many of the papers cited by the WHO and others for the case against LAF do not provide reliable data.The remaining studies which might be used for answering the question give quite different results, also in favor of LAF.The size of the LAF ceiling in many studies is not given or mostly too small in comparison to actual technical requirements.LAF in different countries can mean quite different techniques (e.g., the US in comparison to Germany) so that the results of studies that do not take this into account may not be comparable.LAF has positive effects in terms of reducing particulate and bacterial load, associated with increased airflow in the surgical working area. A reduction of carcinogenic substances in the air may also be assumed, which would increase workers' safety. Thus, this paper recommends building LAF ceilings in the future as well, depending on the operations intended. Further, this paper gives an overview of possible reasons for surgical site infections and highlights the importance of discipline in the operating theatre.

[Clostridium difficile-associated deaths from 2013-2016 in Munich and Nuremberg : Reporting behavior and patient characteristics]. / Clostridium-difficile-assoziierte Todesfälle 2013­2016 in München und Nürnberg : Meldeverhalten und Patientencharakteristika.

BACKGROUND: A number of risk factors for C. difficile infection (CDI) are described in the literature, in particular an antibiotic therapy 4-6 weeks before disease, an age of >65 years, immunosuppression and living in a long-term care facility. Increasing incidence rates have been reported for Germany. CDI is the fourth most common nosocomial infection with 6.4%. AIM: Due to the amendment of the Infection Protection Act of 01.05.2016, the proportion of all deaths that are C. difficile-associated deaths should be investigated to determine the extent to which the obligation to report is fulfilled in the case of a severe CDI. The epidemiological situation in Munich and Nuremberg should also be investigated and the characteristics of the deceased should be analyzed. MATERIAL AND METHODS: A review of all death certificates for the period from 1 January 2013 to 30 June 2016 was carried out according to defined inclusion criteria for clostridia infection. All data were anonymized, standardized and statistically evaluated. RESULTS: Almost every hundredth death is associated with C. difficile. Medical and outbreak reports are very poor and do not reflect the real situation. The age of the deceased and increased factors for the acquisition of a CDI correspond to the literature. The collected data from both cities show a good congruence. CONCLUSION: For the first time, data from the health authorities can be submitted on the proportion of all deaths that are C. difficile-associated deaths, reporting behavior and patient characteristics in cases of severe CDI. This is a serious disease, especially for older people with regard to the existence of risk factors, and its frequency and effects are significantly underestimated.

[Antibiotic consumption surveillance - state of implementation in Munich hospitals : Latest survey by the Munich public health department on the implementation of § 23 Infection protection act]. / Antibiotika-Verbrauchs-Surveillance und Antibiotic Stewardship ­ Stand der Umsetzung in Münchner Kliniken : Aktuelle Abfrage des Gesundheitsamtes München zur Umsetzung des § 23 des Infektionsschutzgesetzes (IfSG).

BACKGROUND: On 4 August 2011 a modification of the infection protection act became law, meaning that antibiotic consumption surveillance and evaluation of data on the local resistance situation became obligatory for hospitals. Four years after the modification of the infection protection act became law, the Munich public health department aimed to evaluate the state of implementation of antibiotic consumption surveillance in Munich hospitals and to ascertain which antibiotic stewardship (ABS) structures have already been established. METHODS: A questionnaire was sent to Munich hospitals about their antibiotic management structural data and state of implementation of legal requirements. RESULTS: Only 32 % of the hospitals have qualified ABS-experts available. In 76 % of the hospitals persons responsible for antibiotic consumption surveillance are appointed, while in 12 % persons responsible for antibiotic consumption surveillance are at least partly released from their normal work for this activity. Twenty-one hospitals (21 %) conduct antibiotic consumption surveillance taking into account all antiinfective agents mentioned in the Robert Koch-Institute (RKI) guidelines. Of these, 19 (76 %) did this on basis of World Health Organizations ATC/DDD-system (anatomical therapeutic chemical [ATC] classification system which uses defined daily doses [DDD]). The data on antibiotic consumption is evaluated in 72 % of the hospitals, 68 % take account of the local resistance situation. In 96 %, in-house lists of antiinfectives are available; in 80 %, in-house guidelines for antibiotic treatment are available. Fourty-four percent of the hospitals take part in a national surveillance. CONCLUSIONS: For the first time data were collected on implementation of antibiotic consumption surveillance in hospitals, which has been required by law since 2011. An incomplete implementation of legal requirements was demonstrated. It was found that structural and personnel prerequisites are often missing, that release from normal work for this additional duty is rarely granted and that the evaluation of data is often either missing or does not correspond to the legal requirements by omitting to take account of the local resistance situation. The hygienic control of hospitals by the public health service was extended by an additional subject. To carry out this very specialized task in a competent way, an ABS-qualification for public health staff is essential from the perspective of the authors.

[Multidrug-resistant organisms and C. difficile in Munich acute-care clinics: Results from a point prevalence study of clinical routine data]. / Multiresistente Erreger (MRE) und C. difficile in Münchner Akutkliniken : Ergebnisse einer Punktprävalenzuntersuchung aus klinischen Routinedaten.

To combat multidrug resistant organisms (MRDOs), networks have been established all over Germany. Here we show here how those networks can survey the prevalence of MRDOs and C. difficile (CD), as well as structure data (e.g. staffing with hygiene control personnel), with reasonable efforts. We conducted a questionnaire-based point prevalence survey in May 2012. The prevalence (colonisation or infection) of inpatient cases with methicillin-resistant S. aureus (MRSA), vancomycin resistant S. aureus (VRSA), vancomycin resistant E. faecalis/E. faecium (VR-E. faecalis/VR-E. faecium), extended-spectrum-beta-lactamase-producing E. coli (ESBL-EC) and K. pneumoniae (ESBL-KP), multiresistant Acinetobacter spp. (MAB), multiresistant Pseudomonas spp. (MRP), carbapenemase-producing Enterobacteriaceae (CRE) as well as infections with Clostridium difficile (CD) were assessed. Out of 45 hospitals asked to participate, 89% sent back forms. Forms were filled out mostly by infection control personnel. In total 7154 patients were included. The most frequently reported MDROs were MRSA (prevalence: 1.37% of all included patients), ESBL-EC (1.12%), ESBL-KP (0.43%) and VRE (0.38%). VRSA and CRE were not reported. The prevalence of MRP (0.13%) and MAB (0.03%), was very low. The most frequently reported pathogen was CD (1.66%). Point prevalence surveys are a feasible way to gain regional data on the epidemiology of MDROs and to raise local awareness. Staffing with infection control personnel remains an issue, given the prevalence of nosocomial pathogens.

One-day point prevalence of emerging bacterial pathogens in a nationwide sample of 62 German hospitals in 2012 and comparison with the results of the one-day point prevalence of 2010.

BACKGROUND: Antibiotic resistance of bacterial pathogens is an emerging problem worldwide. To combat multidrug resistant organisms (MRDOs) networks of care providers have been established in all states in Germany. The HICARE-network, a project to combat MRDOs, founded by the Federal Ministry of Education and Research, has published data from 2010 of a voluntary, German-wide, multicenter point-prevalence survey in 2011 conducted in collaboration with the German Society of Hospital Hygiene. The aim of the present survey was the re-evaluation of the situation in 2012. METHOD: The survey was conducted as a voluntary, anonymous, point-prevalence in May 2012 using routine data of microbiological diagnostics of the hospitals. As in the former survey of 2010 it was differentiated between primary, secondary and tertiary care hospitals and only data from intensive care units, surgical and medical wards were collected. Based on the survey form used in 2010, an updated version was used including more pathogens and corrected issues observed in the former survey. Methicillin-resistant Staphylococcus aureus (MRSA) (total as well as separated in hospital-acquired (HA), community-acquired (CA) and lifestock-associated (LA) MRSA), vancomycin resistant Staphylococcus aureus (VRSA/GRSA), vancomycin resistant Enterococcus faecalis resp. Enterococcus faecium (VR-E. faecalis resp. VR-E. faecium), extended-spectrum-beta-lactamase-building (ESBL) E. coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), multiresistant Acinetobacter spp. (MAB), multiresistant Pseudomonas spp. (MRP), carbapenemase-producing Enterobacteriaceae (CRE) as well as Clostridium difficile (CD) infections and severe infections requiring ICU-treatment were included in the survey along with additional data on screening strategy, the equipment with infection control staff and possible confounders. RESULTS: Out of 1,550 hospitals asked to participate, 62 returned data (4%). Data from 56 hospitals including primary (26), secondary (20) and tertiary (10) care hospitals were analyzable (3.6%). The most frequently reported organisms were MRSA 1.53% [CI95: 1.32-1.75], followed by CDAD 1.30% [CI95: 1.11-1.50], ESBL-EC 0.97% [CI95: 0.80-1.14], and ESBL-KP 0.27% [CI95: 0.18-0.36], regardless of the level of care. Prevalence of MRDOs depended on the level of care and on the type of ward, as expected. Overall prevalence was highest on intensive care wards, and prevalences were remarkably high on medical wards compared to surgical wards. All tertiary care providers employed their own infection control nurse, while only ~70% of the secondary and primary care hospitals did. Surprisingly, in two of the ten participating tertiary care providers neither an internal nor an external infection control doctor was available. DISCUSSION: With more than 13,000 patients in 56 hospitals distributed all over Germany, the survey included more than three times as many patients as the first survey and therefore not only adds valuable information about the epidemiology of emerging nosocomial pathogens, but also helps to raise awareness of the problem of antibacterial resistance in Germany. The prevalences reported seem to be comparable to the results of the former survey and of other surveys published. Some hospitals reported to have no infection control personnel available at all. This statement is in line with another survey published in this issue.

Quantitative analysis of an anti-viral immune escape compound ML-7 in feline plasma using ultra performance liquid chromatography/electrospray ionization mass spectrometry.

An analytical method for the quantitative measurement of ML-7, a product with possible anti-immune escape activity for feline infectious peritonitis virus (FIPV), in feline plasma was developed and validated. The sample preparation consists of a solid-phase extraction step on an MCX cartridge. ML-7 and ML-9, used as the internal standard for the analysis, were separated on an ACQUITY UPLC™ BEH C(18) reversed-phase column (1.7 µm, 50 mm × 2.1 mm I.D.), using isocratic elution with acetonitrile and 0.1% formic acid in water as the mobile phase. Both compounds were subsequently quantified in MRM mode on a Micromass(®) Quattro Premier™ XE triple quadrupole mass spectrometer. The use of a Thermo Scientific(®) Exactive™ orbitrap mass spectrometer made it possible to confirm the proposed fragmentation pattern of both ML-7 and ML-9. A validation study according to EC requirements was carried out, in which the method showed good performance. Linear behaviour was observed in the 1-2500 ng ml(-1) range, which is relevant for real sample analysis. Accuracy and precision were within the criteria requested by the EC requirements throughout this concentration range. Extraction recovery of ML-7 was 72%. Matrix effect for ML-7 was not higher than 8%. The method was successfully used for the monitoring of ML-7 in feline plasma after intravenous, subcutaneous or oral administration of an ML-7 formulation, for the determination of pharmacokinetic parameters, with a limit of quantification of 1 ng ml(-1) and a limit of detection of 0.4 ng ml(-1). The proposed method also shows good characteristics for the analysis of ML-7 in plasma of other animal species and human plasma.

In vitro assessment of the feline cell-mediated immune response against feline panleukopeniavirus, calicivirus and felid herpesvirus 1 using 5-bromo-2'-deoxyuridine labeling.

In this study an in vitro assay was optimized to detect feline proliferating lymphocytes as an assessment for the cell-mediated immune response. For this purpose, 5-bromo-2'-deoxyuridine (BrdU) labeling was chosen because of its sensitivity and the possibility of further characterization of proliferating cells. The assay was optimized by selecting the best batch and concentration of fetal bovine serum, ß-mercaptoethanol concentration, cell density, BrdU incubation time and antigen presenting cell type. Cats were vaccinated with the attenuated Nobivac vaccine Tricat and the peripheral blood lymphocyte proliferation responses were quantified upon in vitro restimulation with inactivated and infectious feline panleukopenia virus (FPV), feline calicivirus (FCV) and felid herpesvirus 1 (FeHV-1). Proliferation signals were detected with inactivated FeHV-1 in the CD8(+) but not in the CD8(-) T lymphocyte population, with inactivated FCV and FPV in both CD8(-) and CD8(+) T lymphocyte populations. Restimulation with infectious FCV caused significant proliferation in the CD8(-) T lymphocyte population only while infectious FPV and FeHV-1 seemed to suppress lymphocyte proliferation in both T cell populations. Additional IFN-γ quantification in the culture supernatant revealed a large correlation between the proliferation signals and IFN-γ production, indicating that BrdU labeling is a very reliable technique to assess and characterize feline lymphoproliferative responses to viral antigens in vitro.