Epidemiologie von Kolonisationen und Infektionen mit multiresistenten enteralen Erregern und Präventionsstrategien im Krankenhaus

Multiresistente enterale Erreger sind in deutschen Intensivstationen weit verbreitet. Surveillance-Systeme wie die stationsbezogene Erregersurveillance im KISS erfassen die in der klinischen Routine entdeckten Fälle in standarsierter Form, können Aufschluss über das den jeweiligen Einrichtungen bekannte Vorkommen multiresistenter Erreger geben und ermöglichen Vergleiche. Allerdings muss angesichts der unter Studienbedingungen sehr viel höheren Prävalenz davon ausgegangen werden, dass den Einrichtungen nicht alle asymptomatischen Kolonisationen mit multiresistenten enteralen Erreger bekannt sind. Zu den möglichen Gründen gehören im Vergleich weniger umfangreiche Screeningprotokolle, aber auch Limitationen bei den verfügbaren Screeningmethoden. Die Kontaktisolierung als vertikale, gezielte Präventionsstrategie hat sich nicht als vorteilhaft erwiesen, um die Verbreitung multiresistenter Gramnegativer Enterobakterien im Krankenhaus zu reduzieren. Neben den Limitationen bei der Identifikation der Träger und dem zeitlichen Verzug zwischen Screeningentnahme und Befundmitteilung an das klinische Behandlungsteam liegt das auch daran, die Verbreitung nicht nur exogen durch Transmissionen zwischen Patientinnen, sondern auch durch endogene Selektionsmechanismen erfolgt. Wir fanden erste Hinweise, dass als selektionierende Substanzen für multiresistente Enterobacterales nicht nur Antibiotika oder Protonenpumpeninhibitoren in Frage kommen, sondern auch andere klinisch häufig genutzte Substanzen wie Glukokortikoide, Opioide oder β2-Rezeptor-Agonisten. Allerdings sind auch Transmissionen zwischen Krankenhauspatienten nicht immer eindeutig nachzuweisen und damit Präventivmaßnahmen prinzipiell zugänglich. Mit der Ganzgenomanalyse ist in den letzten Jahren eine neue Methode in die klinische Routinediagnostik aufgenommen worden, die es ermöglicht, die molekulare Epidemiologie der Erreger in nie dagewesener Tiefe zu untersuchen. Die Zunahme einer bestimmten Stammlinie von VREfm, mittels cgMLST als ST117 CT71 identifiziert, war epidemiologisch über räumliche, organisatorische und zeitliche Zusammenhänge aus klinischer Sicht nicht nachvollziehbar. Neue Analysemethoden unter Einbezug des bei dieser Spezies besonders relevanten akzessorischen Genoms konnten kürzer zurückliegende Transmissionsereignisse im Krankenhaus besser abbilden und sind damit für Ausbruchsuntersuchungen besser geeignet. Zunehmende Berichte über plasmidgetragene Ausbrüche legen nahe, dass auch bei gramnegativen Erregern das akzessorische Genom bei Transmissionsanalysen im Krankenhaus mitbetrachtet werden sollte. Angesichts der Limitationen hinsichtlich der Detektion und derzeit mangelnder spezifischer Präventionskonzepte sollte die Prävention weniger problematischer endemischer Erreger wie z.B. der 3MRGN Enterobacterales im Krankenhaus vor allem auf horizontale Maßnahmen fokussieren und diese optimieren. Gleichzeitig sollten Selektionsmechanismen und Transmissionshäufigkeiten für die jeweiligen Spezies, Resistenzphänotypen und mobilen genetischen Elemente sowie begünstigende Faktoren auf Erreger- und Wirtsseite untersucht werden, damit spezifische Maßnahmen für Hochrisiko-Klone und besondere vulnerable Personengruppen entwickelt werden können

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients

Purpose: Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. Methods: We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charite Universitatsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. Results: Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112-8.697) and SAPS (OR 1.063, CI95 1.028-1.098) to be independent risk factors for CAPA. Conclusion: In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA

Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken in Deutschland – Update

Vancomycin-resistente Enterokokken (VRE) gehören zu den in Deutschland gemäß § 23 Abs. 4 IfSG zu erfassenden Erregern und werden in vielen deutschen Kliniken häufig beobachtet. Der Nachweis von VRE ist in den zurückliegenden Jahren auf einem stabil hohen Niveau in Deutschland und bewegt sich leicht oberhalb des EU-Durchschnitts. Die Krankheitslast durch invasive VRE-Infektionen ist hingegen nachweislich ansteigend. Das Nationale Referenzzentrum für Staphylokokken und Enterokokken beobachtet diese Entwicklungen und berichtet über die Situation von VRE und Enterokokken mit besonderen Antibiotikaresistenzen im Zeitraum 2021/2022. Darüber hinaus wird auf allgemeine VRE-Resistenzsta¬tistiken nationaler Erhebungssysteme und -studien hingewiesen.Peer Reviewe

Infection control strategies for multidrug-resistant Gram-negative bacteria and antibiotic stewardship in German ICUs

Einleitung Multiresistente Gram-negative Erreger (MRGN) haben sich in den letzten Jahren dramatisch verbreitet, darunter insbesondere Bakterien, die eine Betalaktamase mit erweitertem Spektrum (ESBL) bilden. Bisher war wenig über die in Krankenhäusern eingesetzten Präventionsmaßnahmen bei Patienten mit ESBL und über weitere Maßnahmen im Kampf gegen die Verbreitung multiresistenter Erreger bekannt, z.B. das Management der Antibiotikaverordnung im Sinne von Antibiotic Stewardship (ABS). Ziel dieser Arbeit war eine Bestandsaufnahme der Empfehlungen deutscher Intensivstationen (ITS) zum Umgang mit ESBL-Bildnern. Außerdem wurde festgestellt, inwieweit ABS-Strategien zur Verbesserung des Antibiotikamanagements zur Anwendung kommen. In einem zweiten Teil wurde untersucht, ob die bestehenden Maßnahmen und Empfehlungen den Neuerwerb von ESBL-Bildnern auf den Stationen beeinflussten. Methodik Die ITS wurden befragt, ob schriftliche Richtlinien zum Umgang mit ESBL-Bildnern vorlagen und ob ABS-Strategien zur Sicherstellung einer rationalen Antibiotikatherapie eingesetzt wurden. Zur Umfrage eingeladen wurden ITS, die das Krankenhausinfektions-Surveillance (KISS)-System zur Überwachung nosokomialer Infektionen nutzten. Um die Effektivität der einzelnen Präventionsmaßnahmen abzuschätzen wurden die Empfehlungen mit der Erregerstatistik aus KISS assoziiert. Ergebnisse Der Rücklauf der Fragebögen lag erwartungsgemäß bei 61% (355 von 579 angeschriebenen ITS). Fast alle ITS (N=331, 93%) gaben an, schriftliche Empfehlungen für den Umgang mit ESBL- Bildnern zu haben. Einzelzimmerpflege für ESBL-Patienten verlangten 18% der ITS (n=60), und 24% (79) forderten ein generelles Screening auf ESBL bei Aufnahme. Viele ITS hatten bereits ABS-Strategien implementiert, die Teilnahme an Surveillance-Systemen für Antibiotikaverbrauch und bakterielle Resistenzen (<25%) sowie die Beschäftigung von Infektiologen für die Verordnung antimikrobieller Substanzen (14%) waren aber noch selten. Relevante Auswirkungen einzelner Präventionsmaßnahmen, insbesondere von Screening- oder Isolierungsmaßnahmen, konnten in dieser Arbeit nicht festgestellt werden. Unabhängige Risikofaktoren für neu auf der ITS festgestellte ESBL waren ein hoher Kolonisationsdruck [Incidence rate ratio (IRR) 2,74, p<0,001], die Größe des Krankenhauses von mehr als 600 Betten (IRR 1,55, p<0,05) sowie die regionale Verteilung im Osten und Westen Deutschlands im Vergleich zum Norden, Süden und Südwesten (alle p<0,01). Krankenhäuser mit eingegliedertem Mikrobiologischen Labor nahmen doppelt so häufig an Surveillance-Systemen für Antibiotika-Verbrauch (34%) und Resistenzentwicklung (32%) teil, wie Krankenhäuser mit externen Laboren (15 und 14%, p<0,001). Schlussfolgerung Im Jahr 2011 gaben viele ITS Empfehlungen für den Umgang mit ESBL-Bildnern an, die den 2012 veröffentlichten KRINKO-Empfehlungen1 entsprachen oder sogar darüber hinausgingen. Erste Ansätze zur ABS sind bereits auf vielen Stationen verbreitet. Allerdings besteht gerade bei wirksamen Methoden wie der Teilnahme an Surveillance-Systemen zum Antibiotikaverbrauch und zur Resistenzentwicklung sowie der Beschäftigung von Experten für ABS noch erhebliches Verbesserungspotential. Zukünftigen Untersuchungen zur Wirksamkeit und zur Anwendung einzelner Präventions- und ABS-Maßnahmen können diese Ergebnisse als Bezugsgröße dienen.Introduction Multidrug-resistant organisms have spread dramatically over the past years, and particularly Extended spectrum beta-lactamase (ESBL) -producing Gram-negative bacteria have become a major concern worldwide. Little information is available on infection control policies for ESBL- carriers and antibiotic prescription management in German hospitals. The objective of this cross-sectional study was to determine the prevalence and components of infection control policies for ESBL-carriers and antibiotic stewardship measures in German intensive care units (ICUs). In addition, we analyzed the impact of infection control and antibiotic stewardship measures on ESBL-acquisition rates. Methods A questionnaire survey was sent to all ICUs participating in the German nosocomial infection surveillance system (KISS, n = 579) in October 2011. Data on infection control policies and antibiotic management structures were collected and analyzed by structural hospital and ICU factors. Results The questionnaire was completed by 355 German ICUs (response rate 61%). Most ICUs reported to have written infection control policies for ESBL-carriers (93%). Single rooms for ESBL-carriers were required by 18% of the ICUs, and 24% had a surveillance screening policy on admission. Only a small proportion of ICUs participated in surveillance systems for antibiotic consumption and bacterial resistance (<25%) and the employment of physicians specialized in the prescription of antimicrobial medication was still rare (14 %). In this project, we could not detect an influence of ESBL- policies such as contact isolation or screening procedures on ESBL-acquisition rates. Factors affecting ESBL-acquisition in the multivariate analysis were a high ESBL-admission prevalence [incidence rate ratio [IRR] 2.74, p<0,001), a large hospital size of more than 600 beds (IRR 1.55, p<0.05) and the geographic location in the east and west of the country compared with the other regions (all p<0.01). Of note, Hospitals with their own microbiological laboratory report participation in surveillance networks for antimicrobial use (34 %) and bacterial resistance (32 %) twice as often as hospitals with external laboratories (15 and 14 %, respectively, p<0.001). Conclusions Most infection control policies for ESBL-carriers in 2011 already covered or went beyond the guidelines published in 2012. Accordingly, many ICUs reported to have some antibiotic stewardship policies established. However, strategies widely considered effective, such as the systematic cross-institutional surveillance of antimicrobial use and bacterial resistance in a standardized manner or the employment of infectious disease specialists, are still scarce. This study provides a benchmark for future infection control and antibiotic stewardship programs

Clinical evaluation of a web-based personalized recommendation system with electronic health record interface to optimize healthcare resources during SARS-CoV-2 surges

Abstract During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called “CovApp”. The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp’s recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings

Local prevalence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae intestinal carriers at admission and co-expression of ESBL and OXA-48 carbapenemase in Klebsiella pneumoniae : A prevalence survey in a Spanish University Hospital

Objective To assess the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) faecal carriers at admission in a University Hospital in Spain. Design Prevalence survey. Setting Pneumology, gastroenterology, urology and neurosurgery units at a university tertiary hospital in Madrid (Spain). Participants A total of 10 643 patients aged 18 and older admitted from March 2014 to April 2016 with a rectal swab taken at admission or as soon as possible within the first 48 hours. Primary and secondary outcome measures Prevalence of ESBL-E faecal carriers and prevalence of ESBL-E infections at admission. Results The prevalance of ESBL-E carriers at admission was 7.69% (CI 95% 7.18 to 8.19). Most of the isolates were Escherichia coli (77.51%), followed by Klebsiella pneumoniae (20.71%). Eighty-eight (10.41%) of ESBL-E were simultaneous ESBL and carbapenemase (CP) producers, 1.83% in the case of E. coli and 42.86% among K. pneumoniae isolates. Of the ESBL typed, 52.15% belonged to the cefotaximases (CTX-M-15) type and 91.38% of the CP were oxacillinase (OXA-48) type. Only 0.43% patients presented an active infection by ESBL-E at admission. Conclusions The prevalence found in our study is very similar to that found in literature. However, we found a high percentage of simultaneous ESBL and CP producers, particularly in K. pneumoniae. Despite the high prevalence of colonised patients, the ESBL-infection rate at admission was very low

Quantification of time delay between screening and subsequent initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales : A post hoc subgroup analysis of the R-GNOSIS WP5 Trial

Abstract Objectives: The aim of this study was to quantify the time delay between screening and initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales (ESBL-E). Methods: This study was a secondary analysis of contact isolation periods in a cluster-randomized controlled trial that compared 2 strategies to control ESBL-E (trial no. ISRCTN57648070). Patients admitted to 20 non-ICU wards in Germany, the Netherlands, Spain, and Switzerland were screened for ESBL-E carriage on admission, weekly thereafter, and on discharge. Data collection included the day of sampling, the day the wards were notified of the result, and subsequent ESBL-E isolation days. Results: Between January 2014 and August 2016, 19,122 patients, with a length of stay ≥2 days were included. At least 1 culture was collected for 16,091 patients (84%), with a median duration between the admission day and the day of first sample collection of 2 days (interquartile range [IQR], 1–3). Moreover, 854 (41%) of all 2,078 ESBL-E carriers remained without isolation during their hospital stay. In total, 6,040 ESBL-E days (32% of all ESBL-E days) accrued for patients who were not isolated. Of 2,078 ESBL-E-carriers, 1,478 ESBL-E carriers (71%) had no previous history of ESBL-E carriage. Also, 697 (34%) were placed in contact isolation with a delay of 4 days (IQR, 2–5), accounting for 2,723 nonisolation days (15% of ESBL-E days). Conclusions: Even with extensive surveillance screening, almost one-third of all ESBL-E days were nonisolation days. Limitations in routine culture-based ESBL-E detection impeded timely and exhaustive implementation of targeted contact isolation.</p

Emergence of ESBL-producing Escherichia coli ST131-C1-M27 clade colonizing patients in Europe

Background: The ST131 Escherichia coli clone is associated with the global dissemination of ESBLs. It has been hypothesized that ST131 could take advantage of better colonizing abilities. However, the data on colonization prevalence of ESBL-ST131 in European hospitals are scarce. Objectives: To assess the prevalence of the ST131 clone and its microbiological characteristics among colonizing ESBL-producing E. coli (ESBL-Ec) from hospitalized patients in four European hospitals (Berlin, Geneva, Madrid and Utrecht) during the R-GNOSIS study. Methods: ESBL-Ec isolates (n = 688) were obtained from rectal swabs of hospitalized patients from March 2014 to February 2015 using selective media. The ST131 clone and its subclones were sought using PCR and positive isolates were further studied. blaESBL genes were characterized (PCR and sequencing), antibiotic susceptibility testing was performed, clonal relationships were studied by PFGE and fimH allele and O type (PCR) were assessed. Results: ST131 prevalence was 20.5% (141/688); C1/H30R1 isolates were significantly more prevalent in Geneva (49%) and C2/H30Rx in Madrid (67%). C1/H30R1 isolates showed less resistance to amikacin than C2/H30Rx (4% versus 35%) and all were susceptible to penicillin/inhibitor combinations. CTX-M-15 was the most common enzyme (49%) followed by CTX-M-27 (27%). C1/H30R1 isolates were significantly associated with CTX-M-27 (72%) and all of these isolates belonged to the C1-M27 clade. Moreover, C2/H30Rx isolates and CTX-M-15 were also significantly related (88%). Conclusions: The predominance of C2/H30Rx-CTX-M-15 in Madrid and C1/H30R1-CTX-M-27 in Geneva demonstrates a changing epidemiology of ESBLs in Europe caused by ST131 subclones; in particular, the emergence of the C1-M27 clade in Europe

Epidemiology of Clostridioides difficile Infections in Germany, 2010–2019: A Review from Four Public Databases

Abstract Introduction Clostridioides difficile infection (CDI) is a recognized global threat especially for vulnerable populations. It is of particular concern to healthcare providers as it is found in both hospital and community settings, with severe courses, frequent recurrence, high mortality and substantial financial impact on the healthcare system. The CDI burden in Germany has been described and compared by analysing data from four different public databases. Methods Data on hospital burden of CDI have been extracted, compared, and discussed from four public databases for the years 2010–2019. Hospital days due to CDI were compared to established vaccine preventable diseases, such as influenza and herpes zoster, and also to CDI hospitalisations in the United States (US). Results All four databases reported comparable incidences and trends. Beginning in 2010, population-based hospitalised CDI incidence increased to a peak of > 137/100,000 in 2013. Then, incidence declined to 81/100,000 in 2019. Hospitalised patients with CDI were predominantly > 50 years of age. The population-based incidence of severe CDI was between 1.4 and 8.4/100,000 per year. Recurrence rates were between 5.9 to 6.5%. More than 1,000 CDI deaths occurred each year, with a peak of 2,666 deaths in 2015. Cumulative CDI patient days (PD) were between 204,596 and 355,466 each year, which exceeded cumulated PD for influenza and herpes zoster in most years, though year-to-year differences were observed. Finally, hospitalized CDI incidence was higher in Germany than in the US, where the disease is well recognized as a public health threat. Conclusions All four public sources documented a decline in CDI cases since 2013, but the disease burden remains substantial and warrants continued attention as a severe public health challenge