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The aims of this work were the systematic and evidence-based generation and answering of frequently asked questions (FAQ) regarding contact with multi-drug resistant pathogens (MDR) including aspects of veterinary and human medicine for the public health service (PHS) and the general population.In order to determine the information needs of the population, guideline-based expert interviews with veterinarians and physicians were conducted in five surveys. In addition, information about the project was published in two journals and the participants were asked to submit open questions from their daily routine with respect to MDR. The results of the interviews and project calls were divided into categories, and frequently mentioned topics were prepared as FAQ. For answering the FAQ, a systematic literature search in the databases Pubmed and Wiley Online Library was conducted. A panel of experts subsequently evaluated the FAQ drafts, and a consensus was reached in case of conflicting results. Thereafter, the FAQs were evaluated by physicians and veterinarians of the PHS.Nine FAQs were generated in total. In addition to a survey of the current state of research, recommendations were made for private dealing with non-medical contact with MDR at the interface of human and veterinary medicine. The recommendations depended on the respective setting and the type of animal contact. Different recommendations were given for the handling of MDR in pets, farm animals, animals in communal facilities and animals used for animal-assisted therapies. The most important measure against the spread of MDR between humans and animals proved to be regular and careful handwashing.Mixed methods were used to ensure the quality of the FAQ. Limitations were found in the literature search. Not all submitted questions could be answered with the available literature. In the future, the FAQ should be continuously updated and extended.ZIEL: Ziel der Arbeit ist die systematische und evidenzbasierte Generierung und Beantwortung von Frequently asked questions (FAQs) zum Umgang mit multiresistenten Erregern (MRE) an der Schnittstelle von Veterinär-und Humanmedizin für den öffentlichen Gesundheitsdienst (ÖGD) sowie für die Allgemeinbevölkerung.Zur Ermittlung des Informationsbedürfnisses der Bevölkerung wurden zu fünf Erhebungszeitpunkten leitfadengestützte Experteninterviews mit Veterinär-und Humanmedizinern durchgeführt. Zusätzlich wurden in zwei Fachzeitschriften über das Projekt informiert sowie Mediziner dazu aufgerufen offene Fragen aus dem Arbeitsalltag zum Umgang mit Tieren hinsichtlich MRE, einzureichen. Die. Ergebnisse der Interviews und Projektaufrufe wurden in Kategorien gegliedert und häufig genannte Themen wurden als FAQs aufbereitet. Die Beantwortung der FAQs erfolgte mit einer systematischen Literaturrecherche in den Datenbanken Pubmed und Wiley Online Library. Innerhalb eines Expertengremiums wurden die FAQ-Entwürfe anschließend diskutiert und bei widersprüchlichem Forschungsstand ein Konsens erarbeitet. Im Anschluss wurden die FAQs von Humanmedizinern des ÖGD evaluiert.Insgesamt wurden neun FAQs generiert. Neben dem Stand der Forschung, wurden Empfehlungen für den privaten, nicht-medizinischen Umgang mit MRE an der Schnittstelle von Human-und Veterinärmedizin ausgesprochen. Die Empfehlungen sind abhängig von den Eigenschaften des jeweiligen Settings, bei dem Menschen und Tiere aufeinandertreffen sowie der Art des Tierkontakts. So wurden unterschiedliche Empfehlungen für den Umgang mit MRE bei Heimtieren, bei Nutztieren, bei Tieren in Gemeinschaftseinrichtungen, sowie bei Therapietieren ausgesprochen. Als wichtigste Maßnahme gegen eine Verbreitung von MRE zwischen Menschen und Tieren hat sich das regelmäßige und sorgfältige Händewaschen erwiesen.Um die Qualität der FAQs gewährleisten zu können, wurden diese multimodal generiert und beantwortet. Einschränkungen in der Qualität zeigten sich bei der Literaturrecherche. Nicht alle eingereichten Themenbereiche konnten mit der zur Verfügung stehenden Literatur bearbeitet werden. In der Zukunft sollten die FAQs kontinuierlich aktualisiert und erweitert werden.

The prevalence of antimicrobial-resistant bacteria and methicillin-sensitiveThe objective of this study was to evaluate the prevalence of MSSA, MRSA, and ESBL among healthy newborns. Additionally, mother-to-newborn transmission rates were investigated as well as antibiotic susceptibility of MSSA, MRSA, and ESBL isolates.Swabs of 658 newborns and their mothers were collected to investigate the presence of MSSA, MRSA, and ESBL. Swabs were taken from the nose and umbilicus immediately after birth. Additional swabs were taken from the nose, perianal area, and umbilicus 3 days after birth. Samples were screened and further characterized using culture and molecular methods.Prevalence of MSSA, MRSA, and ESBL colonization was 10.9, 0.5, and 2.6%, respectively. There was no association between the colonization status of the newborn and infections at any time point. Mother-to-newborn transmission rates (confirmed by PFGE) were 53.6% for MSSA/MRSA and 100% for ESBL. Maternal carriage of MSSA, MRSA, or ESBL was a risk factor for colonization of the newborn. Some isolates were resistant to the antibiotics recommended for therapy, including clindamycin and daptomycin for MSSA/MRSA isolates and ertapenem, fosfomycin, and tigecyclin for ESBL isolates.No association between infections and the newborns' colonization status could be detected. Maternal colonization played an important role in newborn colonization, but not every case of colonization could be explained by mother-to-newborn transmission. General screening of pregnant women and healthy newborns in the absence of other risk factors is not necessary. To prevent the possibility of transmission in the healthcare setting, professionals, pregnant women, parents, hospital visitors, and obstetricians should receive regular training on appropriate hygiene measures. With regard to the emergence of resistance to recommended antibiotics, an antibiogram should be conducted before treating MSSA/MRSA/ESBL infections to ensure the efficacy of the antibiotics.

Summary Background In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. Methods A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. Findings Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3–4·3) and the median serial interval was 4·0 days (3·0–5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0–99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2–32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6–8·9; 11 of 217) among non-household, high-risk contacts. Interpretation Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. Funding All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Background Diphtheria is mainly caused by diphtheria-toxin-producing strains of Corynebacterium diphtheriae and Corynebacterium ulcerans. The recommended first-line antibiotic is penicillin or erythromycin, but reliable susceptibility data are scarce. Objectives To define WT MIC distributions of 12 antimicrobial agents and provide data for the determination of tentative epidemiological cut-off values (TECOFFs) for potentially toxigenic corynebacteria and to evaluate the potential usefulness of a gradient test (Etest) for susceptibility testing of penicillin, erythromycin and clindamycin. Methods For the 421 human or veterinary isolates from the period 2011–17, MICs of 12 antimicrobial agents were determined. Etest performance was evaluated for penicillin, erythromycin and clindamycin. Results MIC distributions were characterized and TECOFFs could be set for 11 out of 24 antibiotic/species combinations. The current EUCAST clinical breakpoints, predominantly determined for Corynebacterium species other than C. diphtheriae and C. ulcerans, divide the WT MIC distributions of penicillin and clindamycin, thereby making reproducible susceptibility testing of C. diphtheriae and C. ulcerans difficult. For erythromycin, 4% of C. diphtheriae and 2% of C. ulcerans had MICs higher than those for WT isolates. Phenotypically detectable resistance to other antibiotics was rare. Etest underestimated MICs of penicillin and lower concentrations needed to be included for erythromycin, while for clindamycin the Etest was not a good surrogate method. Conclusions MIC distributions based on reference broth microdilution for potentially toxigenic Corynebacterium spp. were developed. For five and six agents, TECOFFs were suggested for C. diphtheriae and C. ulcerans, respectively, but for Corynebacterium pseudotuberculosis the number of isolates was too low.

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child’s sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae. Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.

The impact of colonization with antimicrobial-resistant bacteria (AMRB) and methicillin-sensitive Staphylococcus aureus (MSSA) of healthy pregnant women is not described in detail in Germany. In this study, we screened for MSSA and AMRB, especially for methicillin-resistant S. aureus (MRSA) as well as extended-spectrum beta-lactamase (ESBL)-producing E. coli. Potential risk factors for colonization with AMRB/MSSA and the potential effects of colonization with these on the obstetric population were investigated. From October 2013 until December 2015 pregnant women were screened before birth for colonization with AMRB/MSSA from the mammillae, nose, perianal and vaginal area. Before birth, the expectant mother was administered a standardized interview questionnaire by a trained interviewer. Data from the hospital admission records were also included. Samples from 651 pregnant women were analyzed. Colonization with MSSA was detected in 14.3% (n = 93), AMRB in 3.5% [(n = 23); MRSA: n = 3/ESBL: n = 20]. Significantly more colonization of AMRB/MSSA could be detected in women who had previously given birth compared to women who were nulliparous (p

Background and aim As a consequence of socioeconomic and political crises in many parts of the world, many European Union/European Economic Area (EU/EEA) countries have faced an increasing number of migrants. In the German federal state of Bavaria, a mandatory health screening approach is implemented, where individuals applying for asylum have to undergo a medical examination that includes serological testing for HIV and hepatitis B, screening for tuberculosis, and until September 2015, stool examination for Salmonella spp. and Shigella spp.. Methods: Data from mandatory screening of all first-time asylum seekers in Bavaria in 2015 was extracted from the mandatory notification and laboratory information system and evaluated. Results: The HIV positivity and hepatitis B surface antigen (HBsAg) positivity rate of tested samples from asylum seekers were 0.3% and 3.3%, respectively, while detection rate of active tuberculosis was between 0.22% and 0.38%. The rates for HIV, hepatitis B, and tuberculosis among asylum seekers were similar to the corresponding prevalence rates in most of their respective countries of birth. Only 47 Salmonella spp. (0.1%) were isolated from stool samples: 45 enteric and two typhoid serovars. Beyond mandatory screening, louse-borne relapsing fever was found in 40 individuals. Conclusions: These results show that mandatory screening during 2015 in Bavaria yielded overall low positivity rates for all tested infectious diseases in asylum seekers. A focus of mandatory screening on specific diseases in asylum seekers originating from countries with higher prevalence of those diseases could facilitate early diagnosis and provision of treatment to affected individuals while saving resources.

Resistance to β-lactam antibiotics, including third-generation cephalosporins, is of major concern for animal and human health. In this study, extended-spectrum β-lactamase (ESBL) / plasmid-mediated AmpC (pAmpC) β-lactamase -producing Escherichia coli isolates from German livestock farms were characterised and associations of these isolate characteristics with farm-related factors were investigated across different types of livestock. A total of 469 isolates originating from 150 farms (34 broiler farms, 38 fattening pig farms, 43 dairy cattle farms, 35 beef cattle farms) was included in the analyses. ESBL-gene family, phylogroup and phenotypic antimicrobial susceptibility for several antimicrobial agents were determined. This data was used to define different profiles characterising the isolates. Multivariate analyses using a distance-based non-parametric approach were performed to investigate associations between the profiles of the isolates and farm-related factors (e.g. management, husbandry, and environment of the farms). Co-occurrence of ESBL-gene families were not found in any of the isolates analysed. Sixty-eight percent of the isolates carried blaCTX-M variant genes. The frequency of phylogroups was as follows: A (55%), B1 (35%), D (17%) and B2 (3%). The most frequent phenotypic non-wildtype profile was non-wildtype status of solely cefepime (27%). Profiles of isolates from broilers differed substantially from those of other isolates. Associations between farm-related factors and characteristics profiles differed, depending on the isolate characteristics included in the analyses. Some factors describing the farm environment, like waterfowl in the surrounding of the farm, were associated with all tested profiles. The epidemiological method applied defines distances between isolates on basis of isolate characteristics data and is capable of analysing associations between isolate characteristics and epidemiological factors. As additional data, such as plasmid characteristics, gene type, or sequence information could be included in future studies, the method is suitable to identify points of action to reduce the occurrence of antimicrobial resistant bacteria.

A European multi-country outbreak of Salmonella Enteritidis phage type (PT) 14b occurred from March to November 2014 associated with the consumption of eggs. The outbreak involved more than 400 human cases from France, Luxembourg, Austria and the United Kingdom. In 2016–2017, it has been re-evaluated combining recent epidemiological results with latest molecular data. The outbreak was traced back to one large Bavarian egg producer with four distinct premises, three located in Bavaria, one in the Czech Republic. The outbreak isolates of S. Enteritidis PT 14b were grouped into three closely related clades by whole genome sequencing. Two of these clades could be referred to two Bavarian premises of the egg producer on the basis of epidemiological and molecular data, while epidemiological data presumably linked the third clade to another premises of the egg producer. Interestingly and in contrast to the situation in other European countries where several outbreaks were documented, all notified 91 laboratory-confirmed cases of S. Enteritidis PT 14b from Bavaria were sporadic, singular cases not belonging to any epidemiological outbreaks. In conclusion, as demonstrated here, the resolution of food-related outbreaks with such a high discriminatory power is rare in outbreak investigation.

Objective Antimicrobial resistant bacteria (AMR) are of public health and economic relevance. However, there is a lack of data regarding AMR colonization in pregnant women and in newborns. Furthermore, there are few studies analyzing hospital’s net income (revenues and costs). Study design The cross-sectional study took place in two Bavarian clinics. Available data regarding women and newborns were collected using a standardized questionnaire, personal IDs and medical records in addition to AMR/MSSA screening. Economic data consisted of estimated hospitalization costs, calculated using a billing system called G-DRG (German-Diagnosis Related Groups) as well as real hospitalization costs (e.g. staff, medical and non-medical infrastructure costs). Results Data from 635 pregnant women and 566 newborns were included. While AMR colonization has shown no significant association with clinical complications, or net hospital income; primipara status and medical condition during pregnancy did. AMR colonization did not have a significant influence on the health status of pregnant women or of the newborns. Net hospital income for pregnant women was mostly negative in 2014. In 2014 and 2015 the majority of the cases had a net income between ±€ 1000. Newborns with clinical complications differed significantly in Apgar score at 1 min, weight, body length and AMR colonization of the pregnant woman and/or the newborn (p Conclusion Results indicate that colonization does not lead to increased costs during hospitalization considering real hospitalization costs as well as G-DRG estimated costs. Both DRG groups had similar MSSA and AMR prevalence and health status. In future studies, a Centralized Cost Accounting as billing method and an improved possibility of AMR coding in G-DRG catalog would be desirable.

Up to now, little has been known about the prevalence and clinical relevance of colonisation of asymptomatic pregnant women with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) or extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. In this two-centre cross-sectional study, we evaluated the performance and importance of screening at different times and different locations for colonisation in pregnant women and newborns. Between October 2013 and December 2015, four samples were collected from pregnant women, two from newborns at birth and three from 3-day-old newborns. Samples were screened on culturing media and were confirmed with molecular methods. MSSA was used as a surrogate for MRSA, as the two share most microbiologic characteristics and colonisation patterns. Of 763 pregnant women, 14.5% (111) were colonised with MSSA, 0.4% (3) with MRSA and 2.6% (20) with ESBL-producing E. coli. Of 658 newborns, 0.9% (10) were colonised with MSSA at birth and 13.1% (70) at 3 days old, 0.5% (3) were colonised with MRSA and 2.6% (17) with ESBL-producing E. coli. Nasal sampling identified 91.0% of MSSA-colonised pregnant women and 60.0% of newborns. In newborns, nasal and umbilical sampling at 3 days after birth discovered 84.0% of colonised cases. For ESBL-producing E. coli, the perianal region was positive in all colonised pregnant women and in 88.2% of colonised newborns. Combining nasal and perianal swabs is optimal when screening for antibiotic-resistant bacteria in pregnant women. Nasal, perianal and umbilical sample collection from 3-day-old newborns significantly increased the sensitivity compared to screening immediately after birth.

Ampicillin and vancomycin are important antibiotics for the therapy of Enterococcus faecalis infections. The ampicillin resistance gene pbp5 is intrinsic in Enterococcus faecium. The vanC1 gene confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Both genes are chromosomally located. Resistance to ampicillin and vancomycin was determined in 484 E. faecalis of human and porcine origin by microdilution. Since E. faecalis are highly skilled to acquire resistance genes, all strains were investigated for the presence of pbp5 (and, in positive strains, for the penicillin-binding protein synthesis repressor gene psr) and vanC1 (and, in positive strains, for vanXYc and vanT) by using polymerase chain reaction (PCR). One porcine and one human isolate were phenotypically resistant to ampicillin; no strain was vancomycin resistant. Four E. faecalis (3/1 of porcine/human origin) carried pbp5 (MIC=1 mg/L), and four porcine strains were vanC1 positive (minimum inhibitory concentration [MIC]=1 mg/L). Real-time reverse transcriptase (RT)-PCR revealed that the genes were not expressed. The psr gene was absent in the four pbp5-positive strains; the vanXYc gene was absent in the four vanC1-positive strains. However, vanT of the vanC gene cluster was detected in two vanC1-positive strains. To our knowledge, this is the first report on the presence of pbp5, identical with the "E. faecium pbp5 gene," and of vanC1/vanT in E. faecalis. Even if resistance is not expressed in these strains, this study shows that E. faecalis have a strong ability to acquire resistance genes-and potentially to spread them to other bacteria. Therefore, close monitoring of this species should be continued.

Leptospirosis is a zoonotic disease with global distribution, caused by spirochaetes of the genus Leptospira. Transmission of Leptospira interrogans serovar Icterohaemorrhagiae, the causative agent of Weil's disease, to humans usually results from exposure to the urine of infected, but mostly asymptomatic, rodents, either by direct contact or indirectly through contaminated soil or water. Although regarded as a re-emerging infectious disease, human leptospirosis is probably underdiagnosed due to its often unspecific clinical appearance and difficulties in culturing leptospires. Therefore, more rapid and specific diagnostic procedures are needed. Here we describe a novel real-time quantitative PCR system developed for the accurate and fast diagnosis of pathogenic Leptospira spp. Its usefulness in the management of a patient with rat bite-associated multiorgan failure is demonstrated.

Severe necrotizing fasciitis was diagnosed in a 53-year-old man in Germany in 2012. Toxigenic Corynebacterium ulcerans was grown from a wound swab sample. One of the patient´s 2 dogs was found to harbor a toxigenic C. ulcerans strain. Results of next generation sequencing of both isolates supported recent zoonotic transmission of this bacterial pathogen.

The seawater bacterium Vibrio alginolyticus was detected in 5 of 20 water samples from seawater aquaria (from 3 of 5 units) and also from the surface of diseased stony corals. A total of 45 isolates were differentiated biochemically, of which 13 isolates (29%) proved to be V. alginolyticus. All those strains produced the virulence factors caseinase and lipase, 11 strains amylase and gelatinase. 7 strains showed lecithinase activity and 2 strains produced hemolysins. All examined strains showed a marked toxicity to vero cells proven by the MTT-bioassay, but no toxicity to plant cells with the saline alga Asteromonas gracilis as model. The isolates were mostly resistant to beta-lactam antibiotics, macrolides and lincomycin. However, they proved to be susceptible to aminoglycoside- and polypeptide-antibiotics as well as to tetracyclines, chloramphenicol, florfenicol, enrofloxacin and sulfamethoxazol-trimethoprim. The possible participation of this bacterium in the bleaching and dying of stony corals is mentioned as well as its role as human pathogen.

Summary In 2010, two independent cases of cutaneous diphtheria caused by toxigenic C. ulcerans were identified in Germany. Both patients had intense occupational contact with pigs. Diagnostic work-up comprising biochemical differentiation, rpoB sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis, real-time tox PCR and Elek test as well as public health measures including an intensified source tracing involving 83 asymptomatic pigs of an associated pig farm are presented.

The rapid identification of the potentially toxigenic Corynebacterium species, C. diphtheriae, C. ulcerans and C. pseudotuberculosis is essential for diagnosis and treatment of diphtheria and diphtheria-like diseases. We used matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in comparison with classical microbiological and molecular methods on 116 Corynebacterium strains. All 90 potentially toxigenic Corynebacterium strains collected by the German National Consiliary Laboratory on Diphtheria in a period of more than ten years were correctly identified by MALDI-TOF MS. We propose an algorithm for fast and reliable diagnosis of diphtheria incorporating MALDI-TOF MS, real-time tox PCR and Elek testing.