Low Proportion of Linezolid and Daptomycin Resistance Among Bloodborne Vancomycin-Resistant Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus Infections in Europe

Vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant health burden. We investigated linezolid and daptomycin resistance among VREF and MRSA in the EU/EEA between 2014 and 2018. Descriptive statistics and multivariable logistic regression were used to analyze 6,949 VREF and 35,131 MRSA blood isolates from patients with bloodstream infection. The population-weighted mean proportion of linezolid resistance in VREF and MRSA between 2014 and 2018 was 1.6% (95% CI 1.33–2.03%) and 0.28% (95% CI 0.32–0.38%), respectively. Daptomycin resistance in MRSA isolates was similarly low [1.1% (95% CI 0.75–1.6%)]. On the European level, there was no temporal change of daptomycin and linezolid resistance in MRSA and VREF. Multivariable regression analyses showed that there was a higher likelihood of linezolid and daptomycin resistance in MRSA (aOR: 2.74, p < 0.001; aOR: 2.25, p < 0.001) and linezolid in VREF (aOR: 1.99, p < 0.001) compared to their sensitive isolates. The low proportion of linezolid and daptomycin resistance in VREF and MRSA suggests that these last-resort antibiotics remain effective and will continue to play an important role in the clinical management of these infections in Europe. However, regional and national efforts to contain antimicrobial resistance should continue to monitor the trend through strengthened surveillance that includes genomic surveillance for early warning and action.Peer Reviewe

The epidemiology of carbapenem resistance in Acinetobacter baumannii complex in Germany (2014–2018): an analysis of data from the national Antimicrobial Resistance Surveillance system

Background Carbapenem-resistant Acinetobacter baumannii complex (CRABC) has globally emerged as a serious public health challenge. This study aimed to describe epidemiological trends and risk factors of carbapenem resistance in A. baumannii complex isolates in Germany between 2014 and 2018. Methods We analysed 43,948 clinical A. baumannii complex isolates using 2014 to 2018 data from the German Antimicrobial Resistance Surveillance system. We applied descriptive statistics and uni- and multivariable regression analyses to investigate carbapenem resistance in A. baumannii complex isolates. Results The proportion of carbapenem resistance in clinical A. baumannii complex isolates declined from 7.6% (95% confidence interval [95% CI] 4.4–12.7%) in 2014 to 3.5% (95% CI 2.5–4.7%) in 2018 (adjusted OR [aOR] 0.85 [95% CI 0.79–0.93, p ≤ 0.001]). Higher mean CRABC proportions for 2014 to 2018 were observed in secondary care hospitals (4.9% [95% CI 3.2–7.5%], aOR 3.6 [95% CI 2.4–5.3, p ≤ 0.001]) and tertiary care hospitals (5.9% [95% CI 3.0–11.2%], aOR 5.4 [95% CI 2.9–10.0, p ≤ 0.001) compared to outpatient clinics (1.3% [95% CI 1.1–1.6%]). CRABC proportions in hospitals varied between German regions and ranged between 2.4% (95% CI 1.6–3.5%) in the Southeast and 8.8% (95% CI 4.2–17.3%) in the Northwest. Lower CRABC proportions were observed in younger patients (< 1 year: 0.6% [95% CI 0.2–1.3%]; 1–19 years: 1.3% [95% CI 0.7–2.5%]) than adults (20–39 years: 7.7% [95% CI 4.4–13.0%]; 40–59 years: 6.2% [4.2–8.9%]; 60–79 years: 5.8% [95% CI 4.0–8.3%]). In the 20–39 year old patient age group, CRABC proportions were significantly higher for men than for women (14.6% [95% CI 8.6–23.6%] vs. 2.5% [95% CI 1.3–4.5%]). A. baumannii complex isolates from lower respiratory infections were more likely to be carbapenem-resistant than isolates from upper respiratory infections (11.4% [95% CI 7.9–16.2%] vs. 4.0% [95% CI 2.7–6.0%]; adjusted OR: 1.5 [95% CI 1.2–1.9, p ≤ 0.001]). Conclusions In contrast to many other regions worldwide, carbapenem resistance proportions among clinical A. baumannii complex isolates are relatively low in Germany and have declined in the last few years. Ongoing efforts in antibiotic stewardship and infection prevention and control are needed to prevent the spread of carbapenem-resistant A. baumannii complex in Germany.Peer Reviewe

Bugs That Can Resist Antibiotics but Not Men: Gender-Specific Differences in Notified Infections and Colonisations in Germany, 2010–2019

Data from surveillance networks show that men have a higher incidence rate of infections with anti-microbial-resistant (AMR) pathogens than women. We systematically analysed data of infections and colonisations with AMR pathogens under mandatory surveillance in Germany to quantify gender-specific differences. We calculated incidence-rates (IR) per 100,000 person–years for invasive infections with Methicillin-resistant Staphylococcus aureus (MRSA), and for infections or colonisations with carbapenem-non-susceptible Acinetobacter spp. (CRA), and Enterobacterales (CRE), using the entire German population as a denominator. We limited the study periods to years with complete notification data (MRSA: 2010–2019, CRA/CRE: 2017–2019). We used Poisson regression to adjust for gender, age group, federal state, and year of notification. In the study periods, IR for all notifications were 4.2 for MRSA, 0.90 for CRA, and 4.8 for CRE per 100,000 person-–years. The adjusted IR ratio for infections of men compared to women was 2.3 (95% confidence interval [CI]: 2.2–2.3) for MRSA, 2.2 (95%CI: 1.9–2.7) for CRA, and 1.7 (95%CI: 1.6–1.8) for CRE. Men in Germany show about double the risk for infection with AMR pathogens than women. This was also true for colonisations, where data were available. Screening procedures and associated hygiene measures may profit from a gender-stratified approach.Peer Reviewe

Antimicrobial Resistance and the Spectrum of Pathogens in Dental and Oral-Maxillofacial Infections in Hospitals and Dental Practices in Germany

Data on microbiological profiles in odontogenic infections are scarce. This study aimed to analyze the spectrum of pathogens and antimicrobial resistance in clinical isolates from dental and oral-maxillofacial clinical settings in Germany. We analyzed 20,645 clinical isolates (dental practices: n = 5,733; hospitals: n = 14,912) from patients with odontogenic infections using data (2012–2019) from the German Antimicrobial-Resistance-Surveillance (ARS) system. A total of 224 different species from 73 genera were found in clinical isolates from dental practices, and 329 different species from 97 genera were identified in isolates from hospital patients. In both hospitals and dental practices Streptococcus spp. (33 and 36%, respectively) and Staphylococcus spp. (21 and 12%, respectively) were the most frequently isolated microorganisms. In Streptococcus spp. isolates from hospitals, penicillin and aminopenicillin resistance proportions were 8.0% (95%CI 4.7–14.9%) and 6.9% (95%CI 4.7–9.9%), respectively. Substantially lower resistance proportions of penicillin and aminopenicillin were observed in dental practices [2.6% (95%CI 1.4–4.7%) and 2.1% (95%CI 1.1–4.0%), respectively]. Among Staphylococcus aureus isolates from hospital patients methicillin resistance proportions were 12.0% (95%CI 9.7–14.8%), which was higher than in isolates from dental practices (5.8% (95%CI 4.1–8.1%)]. High clindamycin and macrolide resistance proportions (>17%) were observed in Streptococcus spp. and Staphylococcus aureus isolates. In Klebsiella spp. isolates carbapenem resistance proportions were <1%. In sum, substantial antibiotic resistance was observed in isolates from odontogenic infections, which calls for strengthened efforts in antibiotic stewardship and infection prevention and control measures in both hospitals and dental practices.Peer Reviewe

SARS-CoV-2 outbreaks in hospitals and long-term care facilities in Germany: a national observational study

Background: Outbreaks of coronavirus disease (COVID-19) in hospitals and long-term care facilities (LTCFs) pose serious public health threats. We analysed how frequency and size of SARS-CoV-2 outbreaks in hospitals and LTCFs have altered since the beginning of the pandemic, in particular since the start of the vaccination campaign. Methods: We used mandatory notification data on SARS-CoV-2 cases in Germany and stratified by outbreak cases in hospitals and LTCFs. German vaccination coverage data were analysed. We studied the association of the occurrence of SARS-CoV-2 outbreaks and outbreak cases with SARS-CoV-2 cases in Germany throughout the four pandemic waves. We built also counterfactual scenarios with the first pandemic wave as the baseline. Findings: By 21 September 2021, there were 4,147,387 SARS-CoV-2 notified cases since March 2020. About 20% of these cases were reported as being related to an outbreak, with 1% of the cases in hospitals and 4% in LTCFs. The median number of outbreak cases in the different phases was smaller (≤5) in hospitals than in LTCFs (>10). In the first and second pandemic waves, we observed strong associations in both facility types between SARS-CoV-2 outbreak cases and total number of notified SARS-CoV-2 cases. However, during the third pandemic wave we observed a decline in outbreak cases in both facility types and only a weak association between outbreak cases and all cases. Interpretation: The vaccination campaign and non-pharmaceutical interventions have been able to protect vulnerable risk groups in hospitals and LTCFs. Funding: No specific fundingPeer Reviewe

Erfassung der SARS-CoV-2-Testzahlen in Deutschland (Stand 26.8.2020)

Das Robert Koch-Institut erfasst wöchentlich die Anzahl der in Deutschland durchgeführten SARS-CoV-2-Tests, sowie einige Begleitinformationen. Hierfür werden deutschlandweit Daten von Universitätskliniken, Forschungseinrichtungen sowie klinischen und in der ambulanten Versorgung tätigen Laboren zusammengeführt. Der Artikel im Epidemiologischen Bulletin 35/2020 geht u. a. auf die Sensitivität und Spezifität der diagnostischen Tests und die Rolle falsch-positiver Testergebnisse für die Bewertung der Lage in Deutschland sowie auf die Testkapazitäten ei

Erratum zu: Erfassung der Labortestungen auf SARS-CoV-2 in Deutschland

Peer Reviewe

Resampling-based tuning of ordered model selection

In dieser Arbeit wird die Smallest-Accepted Methode als neue Lepski-Typ Methode für Modellwahl im geordneten Fall eingeführt. In einem ersten Schritt wird die Methode vorgestellt und im Fall von Schätzproblemen mit bekannter Fehlervarianz untersucht. Die Hauptkomponenten der Methode sind ein Akzeptanzkriterium, basierend auf Modellvergleichen für die eine Familie von kritischen Werten mit einem Monte-Carlo-Ansatz kalibriert wird, und die Wahl des kleinsten (in Komplexität) akzeptierten Modells. Die Methode kann auf ein breites Spektrum von Schätzproblemen angewandt werden, wie zum Beispiel Funktionsschätzung, Schätzung eines linearen Funktionals oder Schätzung in inversen Problemen. Es werden allgemeine Orakelungleichungen für die Methode im Fall von probabilistischem Verlust und einer polynomialen Verlustfunktion gezeigt und Anwendungen der Methode in spezifischen Schätzproblemen werden untersucht. In einem zweiten Schritt wird die Methode erweitert auf den Fall einer unbekannten, möglicherweise heteroskedastischen Fehlerstruktur. Die Monte-Carlo-Kalibrierung wird durch eine Bootstrap-basierte Kalibrierung ersetzt. Eine neue Familie kritischer Werte wird eingeführt, die von den (zufälligen) Beobachtungen abhängt. In Folge werden die theoretischen Eigenschaften dieser Bootstrap-basierten Smallest-Accepted Methode untersucht. Es wird gezeigt, dass unter typischen Annahmen unter normalverteilten Fehlern für ein zugrundeliegendes Signal mit Hölder-Stetigkeits-Index s > 1/4 und log(n) (p^2/n) klein, wobei n hier die Anzahl der Beobachtungen und p die maximale Modelldimension bezeichnet, die Anwendung der Bootstrap-Kalibrierung anstelle der Monte-Carlo-Kalibrierung theoretisch gerechtfertigt ist.In this thesis, the Smallest-Accepted method is presented as a new Lepski-type method for ordered model selection. In a first step, the method is introduced and studied in the case of estimation problems with known noise variance. The main building blocks of the method are a comparison-based acceptance criterion relying on Monte-Carlo calibration of a set of critical values and the choice of the model as the smallest (in complexity) accepted model. The method can be used on a broad range of estimation problems like function estimation, estimation of linear functionals and inverse problems. General oracle results are presented for the method in the case of probabilistic loss and for a polynomial loss function. Applications of the method to specific estimation problems are studied. In a next step, the method is extended to the case of an unknown possibly heteroscedastic noise structure. The Monte-Carlo calibration step is now replaced by a bootstrap-based calibration. A new set of critical values is introduced, which depends on the (random) observations. Theoretical properties of this bootstrap-based Smallest-Accepted method are then studied. It is shown for normal errors under typical assumptions, that the replacement of the Monte-Carlo step by bootstrapping in the Smallest-Accepted method is valid, if the underlying signal is Hölder-continuous with index s > 1/4 and log(n) (p^2/n) is small for a sample size n and a maximal model dimension p

The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS)

Background Due to limited therapeutic options, vancomycin-resistant Enterococcus faecium (VREF) is of great clinical significance. Recently, rising proportions of vancomycin resistance in enterococcal infections have been reported worldwide. This study aims to describe current epidemiological trends of VREF in German hospitals and to identify factors that are associated with an increased likelihood of vancomycin resistance in clinical E. faecium isolates. Methods 2012 to 2017 data from routine vancomycin susceptibility testing of 35,906 clinical E. faecium isolates from 148 hospitals were analysed using data from the German Antimicrobial Resistance Surveillance System. Descriptive statistical analyses and uni- and multivariable regression analyses were performed to investigate the impact of variables, such as year of sampling, age and region, on vancomycin resistance in clinical E. faecium isolates. Results From 2014 onwards the proportions of clinical E. faecium isolates exhibiting resistance to vancomycin increased from 11.2% (95% confidence interval [CI] 9.4–13.3%) to 26.1% (95% CI 23.1–29.4%) in 2017. The rise of VREF proportions is primarily observed in the southern regions of Germany, whereas northern regions do not show a major increase. In the Southwest and Southeast, VREF proportions increased from 10.8% (95% CI 6.9–16.5%) and 3.8% (95% CI 3.0–11.5%) in 2014 to 36.7% (95% CI 32.9–40.8%) and 36.8% (95% CI 29.2–44.7%) in 2017, respectively. VREF proportions were considerably higher in isolates from patients aged 40–59 years compared to younger patients. Further regression analyses show that in relation to secondary care hospitals, E. faecium samples collected in specialist care hospitals and prevention and rehabilitation care centres are more likely to be vancomycin-resistant (odds ratios: 2.4 [95% CI 1.2–4.6] and 2.4 [95% CI 1.9–3.0], respectively). No differences in VREF proportions were found between female and male patients as well as between different clinical specimens. Conclusion The proportion of VREF is increasing in German hospitals, particularly in southern regions in Germany. Increased efforts in infection control and antibiotic stewardship activities accounting for local resistance patterns are necessary to combat the spread of VREF in Germany.Peer Reviewe