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Purpose Epidemic keratoconjunctivitis (EKC) is one of the most severe ocular viral infections. The aim of this interruptive time series study was to quantitatively evaluate the effectiveness of a hygienic EKC outbreak management concept developed in our ophthalmological department. Methods All patients with suspected EKC in the period from August to November 2018 were included in the study. Data were retrospectively collected from the patient’s medical documents and records. The disease was diagnosed clinically and confirmed by virus detection through polymerase chain reaction (PCR) from conjunctival swabs. With the beginning of the epidemic, an outbreak management plan was implemented to reduce the nosocomial spread. Results The outbreak lasted 77 days (20th August 2018 to 4th November 2018) and affected a total of 120 patients. This corresponds to a mean of 1.5 patients per outbreak day. The median age was 58 [1–92] years. Of all patients, 61 (50.8%) were female. Conjunctival swabs were collected in 100/120 (83.3%) cases, the adenovirus being detected in all positive smears (63/63, 100%). The implementation of our outbreak management plan reduced significantly the number of EKC cases per outbreak day and resulted in a reduction of the basic reproduction number by a factor of 2.2. Conclusion The detection of EKC together with the immediate implementation of hygienic outbreak measures can significantly reduce the spread of infection. The implementation of a strict outbreak management concept can significantly reduce the number of EKC cases, thus avoiding possible complications and therefore unnecessary health-related costs.

Background. In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. Conclusion. Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS.

In diesem Beitrag werden einige Besonderheiten der Infektionspravention bei intensivmedizinisch behandelten Fruh und Neugeborenen dargestellt. Erganzend finden sich Hinweise zum krankenhaushygienischen Management der SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Pandemie und zur Antibiotic Stewardship in der neonatologischen Intensivmedizin.

Three German patients developed nosocomial pneumonia after cardiac surgery and had Burkholderia cepacia complex detected in respiratory specimens. Two patients died of septic multi-organ failure. Whole-genome sequencing detected genetically identical B. cepacia complex strains in patient samples, from a batch of octenidine mouthwash solution, which had been used for nursing care, as well as in samples obtained from the manufacturer during production. Contamination of medical products during manufacturing may lead to international outbreaks.

BACKGROUND Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2–specific immunity correlate with disease severity. METHODS In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general. CONCLUSION Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung., COVID-19 patients with severe disease have higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals.

Due to the worldwide COVID-19 outbreak it is mandatory for health care workers to develop containment strategies. Recently published data showed, that cancer patients might have a higher risk for severe course of the disease. We therefore developed a strategy of screening and containment for SARS-CoV-2 for hospitalized cancer patients. Our approach includes a temporary isolation in a so-called floating zone and testing strategy for screening of asymptomatic individuals by pooling of samples before RT-PCR amplification. Patients as far as health care professionals got tested twice a week. Nurses and physicians entered the floating zone with full body protection. Within 8 weeks we tested 418 individuals (professionals and patients) in total. Only 2 patients had COVID-19 without documented further transmission of SARS-CoV-2. We therefore think that our strategy might be a useful approach to protect inpatients with cancer at high risk for SARS-CoV-2 infection during this ongoing pandemic.

ObjectivesTo evaluate the restart of the German Bundesliga (football (soccer)) during the COVID-19 pandemic from a medical perspective.MethodsParticipants were male professional football players from the two highest German leagues and the officials working closely with them. Our report covers nine match days spread over 9 weeks (May to July 2020). Daily symptom monitoring, PCR testing for SARS-CoV-2 RNA twice weekly, and antibody tests (on two occasions—early during the phase in May 2020 and in the week of the last match) were conducted. Target variables were: (1) onset of typical COVID-19 symptoms, (2) positive PCR results, and (3) IgG seroconversion against SARS-CoV-2. All detected seroconversions were controlled by neutralisation tests.FindingsSuspicious symptoms were reported for one player; an immediate additional PCR test as well as all subsequent diagnostic and antibody tests proved negative for coronavirus. Of 1702 regularly tested individuals (1079 players, 623 officials members), 8 players and 4 officials tested positive during one of the first rounds of PCR testing prior to the onset of team training, 2 players during the third round. No further positive results occurred during the remainder of the season. 694 players and 291 officials provided two serum samples for antibody testing. Nine players converted from negative/borderline to positive (without symptoms); two players who initially tested positive tested negative at the end of the season. 22 players remained seropositive throughout the season. None of the seroconversions was confirmed in the neutralisation test.ConclusionProfessional football training and matches can be carried out safely during the COVID-19 pandemic. This requires strict hygiene measures including regular PCR testing.

Background Non-pharmaceutical measures to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be carefully tuned as they can impose a heavy social and economic burden. To quantify and possibly tune the efficacy of these anti-SARS-CoV-2 measures, we have devised indicators based on the abundant historic and current prevalence data from other respiratory viruses. Methods We obtained incidence data of 17 respiratory viruses from hospitalized patients and outpatients collected by 37 clinics and laboratories between 2010-2020 in Germany. With a probabilistic model for Bayes inference we quantified prevalence changes of the different viruses between months in the pre-pandemic period 2010-2019 and the corresponding months in 2020, the year of the pandemic with noninvasive measures of various degrees of stringency. Results We discovered remarkable reductions δ in rhinovirus (RV) prevalence by about 25% (95% highest density interval (HDI) [−0.35,−0.15]) in the months after the measures against SARS-CoV-2 were introduced in Germany. In the months after the measures began to ease, RV prevalence increased to low pre-pandemic levels, e.g. in August 2020 δ=−0.14 (95% HDI [−0.28,0.12]). Conclusions RV prevalence is negatively correlated with the stringency of anti-SARS-CoV-2 measures with only a short time delay. This result suggests that RV prevalence could possibly be an indicator for the efficiency for these measures. As RV is ubiquitous at higher prevalence than SARS-CoV-2 or other emerging respiratory viruses, it could reflect the efficacy of noninvasive measures better than such emerging viruses themselves with their unevenly spreading clusters.

Head-to-head analyses of immunogenicity and reactogenicity between the authorized homologous vaccine-regimens and heterologous combinations thereof are currently limited. Using a convenience cohort of 331 healthy individuals, we show that humoral and cellular immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n=66) or mRNA-1273 (n=101) is equivalent or superior to homologous mRNA-regimens (n=43 BNT162b2, n=59 mRNA-1273), and more pronounced than after homologous ChAdOx1-nCoV-19 vaccination (n=62). Levels of spike-specific CD8 T cells were highest in both heterologous regimens, and significantly higher than all three homologous combinations. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 were higher than respective combinations with BNT162b2. Polyfunctional T-cell levels were highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens were well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming and mRNA-1273-boosting. In conclusion, immunogenicity after heterologous vector/mRNA-boosting and homologous mRNA-regimens is superior to homologous vector-regimens with notable differences between mRNA vaccines.

Objectives Surgical masks are usually contaminated during dental treatment. So far it has not been investigated whether a surgical mask itself can be a source of microbial transmission. The aim of this study was therefore to investigate the microbiological contamination of surgical masks during dental treatment and the transfer of microorganisms from the mask to the hands. Materials and methods Five dental treatment modalities were studied: carious cavity preparation (P-caries, n = 10), tooth substance preparation (P-tooth, n = 10), trepanation and root canal treatment (P-endo, n = 10), supragingival ultrasonic application (US-supra, n = 10), and subgingival periodontal ultrasonic instrumentation (US-sub, n = 10). Bacterial contamination of mask and gloves worn during treatment was tested by imprinting on agar plates. Additionally, before masks were tested, their outer surface was touched with a new sterile glove. This glove was also imprinted on agar. Bacteria were identified by MALDI TOF mass spectrometry. Colony-forming units (CFU) were scored: score 0: 0 CFU, score 1: 2 CFU, score 2: > 102 CFU, score 3: dense microbial growth. Results All masks and all gloves used during treatment displayed bacterial contamination (sample scores 0/1/2/3: masks 0/46/3/1 and gloves 0/31/10/9). After touching the masks with new sterile gloves, microorganisms were recovered with the following contamination scores: P-caries: 4/6/0/0, P-tooth: 2/8/0/0: P-endo: 7/3/0/0, US-supra: 0/9/1/0, US-sub: 2/8/0/0. No statistically significant differences were detected between the treatment modalities. Streptococci spp. and Staphylococci spp. representing the oral and cutaneous flora dominated. Conclusions Surgical masks are contaminated after aerosol-producing dental treatment procedures. Used masks have a potential to be a source of bacterial contamination of the hands. Clinical relevance Dental staff should avoid touching the outer surface of masks with their hands to prevent transmission of pathogens. It is recommendable to change the mask after each treated patient followed by hand disinfection.

Background Microbial contamination of dental professionals’ facial protective equipment and skin from aerosols and droplets generated during dental treatment has not been studied in all aspects so far. Our aim was therefore to investigate and compare treatment-related bacterial contamination of the forehead skin and surgical mask of dental practitioners. Methods We analyzed samples from 67 consecutive aerosol-producing conservative-preventive dental treatments. Sterile nylon swabs were used to collect samples from the forehead skin before and after performing treatment. Contact samples were obtained from the used surgical face masks. Samples were cultivated on agar under aerobic and anaerobic conditions. Bacteria were classified by MALDI-TOF mass spectrometry. The frequency of detection of obligate and facultative oral bacteria, as well as an increase in bacterial abundance, were examined (bacterial scoring: 0: no growth on agar; 1: 2 colonies; 2: >102 colonies; 3: dense bacterial growth). Results Bacteria were detected in 95% of the skin swabs and 76% of mask samples. Median bacterial scores were 2 for the forehead skin samples before and after treatment, and 1 for samples obtained from masks. Obligate and facultative oral bacteria were more frequent (6% and 30%) in samples from forehead skin after treatment. Samples taken from the forehead skin after treatment showed increased scores for these bacteria (28%). Five percent of samples were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Obligate anaerobes were present in 3% of samples. Conclusions Although exposed during treatment, the forehead skin was significantly less contaminated with obligate oral bacteria than expected based on the surgical face mask findings. Forehead skin samples showed an increase in bacteria in the after treatment, which can be attributed to aerosol-producing procedures. We hypothesize that the forehead’s physiological skin flora may offer some protection against contamination with other microorganisms.

Introduction The coronavirus lockdown in 2020 resulted in a worldwide suspension of professional sports. The first major professional football league to restart after the lockdown was the German Bundesliga. This study investigates whether the injury incidence increased after the restart of the season with only 9 days of regular preparation time and without any friendly matches in comparison to three control periods. Materials and methods In a prospective cohort study, injury analysis (at least 1 day of absence from official football matches or training sessions) of the German Bundesliga registry was standardised according to Hägglund et al. (Br J Sports Med 39:340–346, 2005) and Fuller et al. (Clin J Sports Med 16:97–106, 2006) for data collection and to previous publications for the validated use of media sources for injury registration. The study period after the lockdown in May and June of the 2019–2020 season was compared to three control periods: the period directly before the lockdown, the beginning of the 2019–2020 season and the 2018–2019 season final. Results The nine match days after the restart of the 2019–2020 season showed an overall injury incidence of 4.9 per 1000 h football. This rate was significantly lower than that of the previous season final (9 last match days, overall injury incidence: 6.9 per 1000 h football; p p > 0.05) or the winter break (8 match days; incidence: 5.6/1000 h, p > 0.05). Conclusion The period after the unexpected break in the 2019–2020 season due to the coronavirus lockdown and the rapid return to competition showed no increase in the injury rate compared to the pre-lockdown period and a lower injury rate than in the previous season final. The unintentional mid-season rest with its potential for physical recovery and individual fitness training seems to have had a positive effect on injury occurrence.

Background Bacterial contamination of dental professionals’ facial skin and protective equipment from treatment-related aerosols and droplets are poorly studied. Methods This prospective study analyzed samples from 67 consecutive aerosol-producing dental treatments. Sterile nylon swabs served to collect samples from dental professionals’ foreheads before and after exposure. Contact samples were obtained from used surgical masks. Samples were incubated on agar under aerobic and anaerobic conditions. Bacteria were classified by MALDI-TOF mass spectrometry. We determined the frequencies of obligate and facultative oral bacteria and scored bacterial growth (0: none; 1: < 100 colonies; 2: >100 colonies; 3: dense). Results Bacteria were detected in 95% of skin-swab and 76% of mask samples. Median bacterial scores were 2 for forehead samples before and after treatment, and 1 for masks. Obligate and facultative oral bacteria were more frequent (6% and 30%) in samples from exposed forehead skin, which also showed increased bacterial scores (28%). 5% of samples contained methicillin-sensitive Staphylococcus aureus; 3% contained obligate anaerobes. Conclusion Exposed forehead skin was significantly less contaminated with obligate oral bacteria than expected based on surgical mask findings. Exposed forehead skin showed increased contamination attributable to aerosol-producing procedures. The forehead’s physiological skin microbiota may offer some protection against bacterial contamination.

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles., In healthy adults, booster vaccination with an mRNA vaccine, irrespective of the vaccine used for the first dose, was well tolerated and elicited higher levels of spike-specific antibodies and spike-specific T cells than booster vaccination with ChAdOx1 nCov-19.

Objectives Elite professional football players and staff are a unique group that might give insight into the epidemiology of SARS-CoV-2 infections in Germany and thus can serve as a model for a geographical distribution and an estimation of undetected infections. Methods In this prospective cohort study seroprevalence was determined twice in May and June 2020 in players and staff from German Bundesliga. As screening assays a commercial ELISA (Euroimmun) and a CLIA (Roche) was used and an in-house neutralisation assay (NT) as gold standard. Participants were tested twice weekly using PCR from nasopharyngeal and/or oropharyngeal swabs. Results Seroprevalence (NT used as confirmation) in 2,164 samples from 1,184 players and staff was rather similar in May (23/1157 (1.99%)) and in June (21/1007 (2.09%)). All participants were PCR negative during the study period. Significant regional differences in seroprevalence were not observed. When comparing seroprevalence with the cumulative incidence of infections derived from the German notification system (subgroup matching to cohort; men, age: 20-69), IgG was found 8-10 times more frequently, pointing to a high rate of undetected infections. ELISA and CLIA correlated only moderately (Kappa 0.52). Conclusions Seroprevalence with high quality diagnostic in Germany seemed to be around 2%. The number of undetected infections seems to be 8-10 times higher than notification data. Quality of antibody assays is rather variable, thus results should ideally be confirmed at least by a second assay to prove IgG positivity., Graphical abstract Image 1

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.

Clostridioides difficile is the leading cause of antibiotic-associated nosocomial diarrhea, but extra-intestinal manifestations are rare. We describe the first documented case of bacteraemia with pacemaker pocket and lead infection with the toxigenic C. difficile ribotype 014 with a lack of abdominal symptoms. The patient underwent pacemaker extraction and treatment with intravenous and oral vancomycin. Genotyping and molecular subtyping revealed clonality between pacemaker and intestinal isolates. This case illustrates the risk of intravascular device infections due to C. difficile. Even asymptomatic C. difficile colonization might pose a risk for prosthetic material infection., Graphical Abstract Graphical Abstract

Background In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19 accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially, as the majority of these pathogens are specifically treatable. Case Presentation We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms after completing a half-marathon one week before admission. As infection with SARS-CoV2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. Conclusion Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance of adhering to established treatment guidelines, scrutinizing treatment modalities and not forgetting other potential causes of severe pneumonia or ARDS.

Since 2012, a colonization screening (CoS) for multidrug-resistant Gram-negative bacteria (MRGN) in very low birth weight infants (VLWBI) was implemented in order to provide a basis for an effective empiric therapy of subsequent nosocomial infections (NI). According to antibiotic stewardship, carbapenems should be reserved for NI caused by MRGN or severe NI. We examined whether the CoS increased the first-line use of carbapenems. In this retrospective cohort analysis, we enrolled all VLBWI before (2009–2011) and after (2012–2014) the introduction of CoS (2012) at a tertiary university neonatal intensive care and neonatal intermediate care unit (NIMC) in Germany. Rectal swabs were used to detect MRGN colonization (on admission and weekly until discharge from the NIMC). The use of carbapenems was measured by days of therapy (DoT). To exclude the replacement of carbapenems by other antibiotics, antibiotic therapy for late-onset sepsis (LOS) was assessed by DoT and length of therapy (LoT). In 55/201 (27.4%) VLBWI, CoS detected MRGN colonization. Compared to the cohort prior to the introduction of CoS (n = 191), a significant decrease in LoT (p < 0.001) and total DoT (p < 0.001) was seen (n = 201). This was due to a significant decrease in LoT (p < 0.001) and total DoT (p < 0.001) in the birth weight category of 1,000–1,499 g. In these infants, DoT for carbapenems (p = 0.009) was significantly lower, possibly caused by a significant decline of LOS (25 episodes vs. 39 episodes, p = 0.025). Conversely, no significant differences in LoT and total DoT were seen in infants with a birth weight

Observational Study Background: There are inconsistent data on the risk factors for Clostridium difficile infection (CDI) in the literature. Aims: To use two C. difficile infection (CDI) case-control study groups to compare risk factors in hospitalized patients with diarrhea across different countries. Methods: A multi-center group of CDI cases/controls were identified by standardized testing from seven countries from the prior EUropean, multi-center, prospective bi-annual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhea (EUCLID). A second group of CDI cases/controls was identified from a single center in Germany [parallel study site (PSS)]. Data were extracted from the medical notes to assess CDI risk factors. Univariate analyses and multivariate logistic regression models were used to identify and compare risk factors between the two groups. Results: There were 253 and 158 cases and 921 and 584 controls in the PSS and EUCLID groups, respectively. Significant variables from univariate analyses in both groups were age ≥65, number of antibiotics (OR 1.2 for each additional antibiotic) and prior hospital admission (all p < 0.001). Congestive heart failure, diabetes, admission from assisted living or Emergency Department, proton pump inhibitors, and chronic renal disease were significant in PSS (all p < 0.05) but not EUCLID. Dementia and admitted with other bacterial diseases were significant in EUCLID (p < 0.05) but not PSS. Following multivariate analyses, age ≥ 65, number of antibiotics and prior hospital admission were consistently identified as CDI risk factors in each individual group and combined datasets. Conclusion: Our results show that the same CDI risk factors were identified across datasets. These were age ≥ 65 years, antibiotic use and prior hospital admission. Importantly, the odds of developing CDI increases with each extra antibiotic prescribed. The present study was supported by a research grant from Pfizer Inc. The original EUCLID study was initiated and wholly supported financially by Astellas Pharmaceuticals Europe info:eu-repo/semantics/publishedVersion

Franziska C Trudzinski,1 Frederik Seiler,1 Heinrike Wilkens,1 Carlos Metz,1 Annegret Kamp,1 Robert Bals,1 Barbara Gärtner,2 Philipp M Lepper,1 Sören L Becker2–4 1Department of Internal Medicine V – Pneumology, Allergology and Critical Care Medicine, ECLS Center Saar, University Medical Center Saarland and Saarland University, 2Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany; 3Swiss Tropical and Public Health Institute, 4University of Basel, Basel, Switzerland Background: Endoscopic lung volume reduction (eLVR) is a therapeutic option for selected patients with COPD and severe emphysema. Infectious exacerbations are serious events in these vulnerable patients; hence, prophylactic antibiotics are often prescribed postinterventionally. However, data on the microbiological airway colonization at the time of eLVR are scarce, and there are no evidence-based recommendations regarding a rational antibiotic regimen.Objective: The aim of this study was to perform a clinical and microbiological analysis of COPD patients with advanced emphysema undergoing eLVR with endobronchial valves at a single German University hospital, 2012–2017.Patients and methods: Bronchial aspirates were obtained prior to eLVR and sent for microbiological analysis. Antimicrobial susceptibility testing of bacterial isolates was performed, and pathogen colonization was retrospectively compared with clinical parameters.Results: At least one potential pathogen was found in 47% (30/64) of patients. Overall, Gram-negative bacteria constituted the most frequently detected pathogens. The single most prevalent species were Haemophilus influenzae (9%), Streptococcus pneumoniae (6%), and Staphylococcus aureus (6%). No multidrug resistance was observed, and Pseudomonas aeruginosa occurred in&nbsp

OBJECTIVES Influenza vaccination was used to assess whether induction of immunity or side effects are influenced by the timing of the last training session before vaccination. METHODS Forty-five healthy athletes (36 male, 23 ± 8 yr, ≥5 training sessions per week, predominantly national competition level) were vaccinated with the tetravalent influenza vaccine; blood samples were collected immediately before and 1, 2, and 26 wk after vaccination. Athletes were randomly assigned to vaccination within 2 h after the last training session versus after 24-26 h. Influenza-specific T cells were quantified after stimulation with the vaccine based on intracellular cytokine staining. Antibodies (IgA, IgG, IgM) were quantified by enzyme-linked immunosorbent assay and neutralization assay. Participants documented resulting side effects and training restrictions using a standardized diary. RESULTS Both groups showed an increase in influenza-reactive CD4 T-cell levels, which peaked 1 wk after vaccination (fold changes to baseline; median (interquartile range), 3.7 (3.0-5.4; P < 0.001) in the 2-h group; 4.6 (2.8-7.4; P < 0.001) in the 26-h group) with no difference between groups (P = 0.52). Influenza-specific antibodies showed a significant increase after vaccination in both groups (at least 1.4-fold, each P < 0.001, no group differences; P = 0.24-0.97 for different antibody types). Only antibodies toward the Brisbane strain showed a trend toward significant differences in neutralization titers between groups (4-fold (2-17.8) in the 2-h group, 16-fold (4-32.9) in the 26-h group; P = 0.06), whereas other specificities did not differ (P = 0.16-0.72). No intergroup differences were found for side effects; no athlete reported a loss of training time due to the vaccination or its side effects. CONCLUSION Infection prophylaxis in elite athletes by influenza vaccination seems to be effective and safe. Timing of vaccination after prior training does not seem to require specific constraints.

Safety and efficacy of vaccinations during pregnancy have been a matter of debate. In the aftermath of the 2009 H1N1 influenza pandemic, a growing body of research has emerged, which points toward the importance of adhering to influenza vaccination recommendations for pregnant women. The same applies for vaccination against pertussis. Some vaccines (e.g., live attenuated) are still contraindicated during pregnancy. However, data indicate that these vaccines do not result in fetal impairment when administered accidentally during pregnancy. In the following, we provide a review on vaccination-related safety and efficacy aspects in pregnant women, shedding some light on potential barriers that stymie vaccination uptake among pregnant women and introducing strategies to overcome these barriers.

Clostridium (Clostridioides) difficile is a major cause of nosocomial diarrhoea. A first inter-laboratory ring trial was performed in four European countries to evaluate the genotyping and antibiotic susceptibility testing (AST) accuracy. Six C. difficile isolates representing the epidemiologic important ribotypes (RT), RT001, RT002, RT010, RT014, RT027, and RT078 were blinded and send to 21 participating laboratories. Participants tested the samples with their genotyping and AST methods in use for concordance with reference. A total of 21 genotyping- and 14 antimicrobial susceptibility data sets were obtained. Ribotyping (11 participants) correctly identified most RTs (median 91% concordance rate) except for RT002, which was misidentified in 4/11 reports. However, this isolate was correctly asserted to RT002 after an update of a publicly available ribotyping database. Multilocus sequence typing, surface layer sequence typing, DNA microarray based genotyping, and whole genome sequencing, which were used by 1–3 participants, identified all six isolates correctly. AST was done by epsilometry by the participants and compared to agar dilution data determined by the coordinating reference centre. Susceptibilities against metronidazole, moxifloxacin, and vancomycin were correctly identified in 235 of 237 cases and in accordance to agar dilution as the gold standard. Genotyping of the C. difficile test strains revealed a remarkable high concordance on the level of ribotypes with a wide variety of methods. Epsilometry appears to be a reliable method for AST of C. difficile isolates in routine clinical microbiology laboratories.

Compliance of elite athletes with vaccination recommendations is low mainly based on concerns about side-effects and perceived poor vaccine efficacy due to continued physical training. We therefore employed seasonal influenza vaccination to investigate the effect of regular physical training on vaccine-induced cellular and humoral immunity in elite athletes and controls. Lymphocyte subpopulations and vaccine-specific T-cells were quantified and functionally characterized from 45 athletes and 25 controls before, and 1, 2 and 26 weeks after vaccination. Moreover, influenza-specific antibodies and their neutralizing function were quantified. Both groups showed a significant increase in vaccine-reactive CD4 T-cell levels which peaked one week after vaccination (p 0.0001). The increase was significantly more pronounced in athletes (4.1-fold) compared to controls (2.3-fold; p = 0.0007). The cytokine profile changed from multifunctional T-cells co-producing IFNγ, IL-2 and TNFα to cells with restricted cytokine expression. This change in functionality was associated with a significant increase in CTLA-4 expression (p 0.0001), which again was more pronounced in athletes. Likewise, the increase in neutralizing antibodies was stronger in athletes (p = 0.004 for H1N1; p = 0.032 for H3N2). In conclusion, both groups mounted a strong vaccine-specific cellular and humoral immunity after standard vaccination. The more pronounced increase in specific T-cells and neutralizing antibodies indicates that high frequency and intensity of training enhance vaccine-responses in elite athletes.

This survey evaluates whether the Cystic Fibrosis (CF)-specific infection prevention and control (IPC) recommendations released by the Commission for Hospital Hygiene and Infection Prevention (KRINKO) in 2012 have been implemented in specialized German CF facilities. Of 35 participating centers (response rate 32.7%), 37% care for more than 100 patients and 44% treat mainly adults. Clinics for adult CF patients report a shortage of qualified personnel for intensified environmental cleaning. Some hospitals struggle to provide single patient rooms with an adjacent sanitary area to segregate CF patients strictly. Most centers offer at least one decolonization cycle (including systemic and inhalative antibiotics) to patients colonized with MRSA. In CF centers in Germany, the KRINKO IPC recommendations are considered helpful by the attending physicians and thoroughly implemented. There is room for improvement concerning strict segregation of inpatients with CF in single patient rooms, in particular in large CF centers mainly caring for adults.

Dermatosurgery occupies an exceptional position among all surgical disciplines. Above all, this includes the fact that, with very few exceptions, the vast majority of surgical interventions can be performed under local or regional anesthesia, usually in smaller procedure rooms that are spatially separated from larger operating suites. Thus, peri- and postinterventional patient monitoring is the responsibility of the dermatosurgeon and his team. Though inherently smaller, this team still has to observe numerous perioperative requirements that - in larger surgical specialties - would be attended to by a host of various specialists working in concert. Said requirements include hygienic aspects, knowledge concerning pre- and intraoperative patient monitoring, managing surgical site infections, adequate postsurgical pain management, as well as detailed pharmacological knowledge with respect to common local anesthetics and the toxic and allergic reactions associated therewith. Not only does this require interdisciplinary collaboration and shared responsibility for the patient. It also necessitates the development and implementation of quality-oriented and evidence-based guidelines that, in the dermatosurgical setting, usually extend far beyond the scope of the specialty per se. The objective of the present CME article is the condensed presentation of interdisciplinary aspects relating to the most important perioperative issues.

The objective of this study was to assess the impact of microbiological test reports that provide specific written recommendations on the appropriate management of Staphylococcus aureus bacteremia (SAB). We performed a retrospective analysis of laboratory and clinical data of all SAB patients treated at one German University hospital, 2012–2015. Among 467 included patients, methicillin-resistant S. aureus (MRSA) accounted for 15.2% of all SAB cases. All-cause in-hospital mortality was 25.2%, and was significantly elevated in individuals aged >55 years, in MRSA bacteremia and if the source of infection remained unidentified. Focus identification was achieved in 71.1%, with the most prevalent foci being catheter-associated bloodstream infection (23.1%), soft tissue infection (15.4%), osteomyelitis (5.1%) and endocarditis (4.9%). Standardized written recommendations on microbiological test reports led to a significant increase of transesophageal echocardiography, additional imaging studies for focus identification and more frequent follow-up blood cultures, but no significant effect on mortality was observed.

Reported rates of C. difficile infection (CDI) have increased in many settings; however, these can be affected by factors including testing density (test-density) and diagnostic methods. We aimed to describe the impact of multiple factors on CDI rates. Hospitals (n = 182) across five countries (France, Germany, Italy, Spain, and UK) provided data on; size and type of institution, CDI testing methodology, number of tests/month and patient-bed-days (pbds)/month over one year. Incidence rates were compared between countries, different sized institutions, types of institutions and testing method. After univariate analyses, the highest CDI rates were observed in Italy (average 11.8/10,000pbds/hospital/month), acute/primary hospitals (12.3/10,000pbds/hospital/month), small hospitals (16.7/10,000pbds/hospital/month), and hospitals using methods that do not detect toxin (NO-TOXIN) (e.g. GDH/NAAT or standalone NAAT) (10.7/10,000pbds/hospital/month). After adjusting for test-density, highest incidence rates were still in Italy, acute/primary hospitals and those using NO-TOXIN. The relative rate in long-term healthcare facilities (LTHCFs) increased, but size of institution no longer influenced the CDI rate. Test-density appears to have the largest effect on reported CDI rates. NO-TOXIN testing still influences CDI rates, even after adjusting for test-density, which is consistent with tests that ‘overcall’ true CDI. Low test-density can mask the true burden of CDI, e.g. in LTHCFs, highlighting the importance of good quality surveillance.

Objective Infections with Borrelia burgdorferi can cause Lyme disease with multiorganic involvement such as (myo)carditis or joint manifestations. Musculoskeletal complaints possibly mimicking some of these symptoms are common among elite athletes. This study aimed to determine seroprevalence and incidence of B. burgdorferi antibodies in professional football players. Design Prospective observational study. Setting Healthy professional football players. Participants Five hundred thirty-five men in the first and second German league. Interventions Two screening assays were used to examine immunoglobulin M (IgM) and immunoglobulin G (IgG) against B. burgdorferi: an enzyme immunoassay (EIA) and a chemiluminescence assay (CLIA). In case of a positive or equivocal result, an immunoblot including in vivo antigens was performed. Main outcome measures Course of IgM and IgG against B. burgdorferi in overall 1529 blood samples. Results A total of 96.4% of all results were concordant between EIA and CLIA. Considering only samples with identical results in both assays, prevalence was 1.6%. A positive IgM was detected in 2.3%. No player showed any symptoms of Lyme disease. A seroconversion to IgG was not found. Three players developed a positive IgM corresponding to an incidence of 1032/100 000 person-years. Depending on the assay, 49% to 75% of positive or equivocal screening results could not be confirmed by immunoblot. Conclusions Seroprevalence and incidence of B. burgdorferi among healthy male professional football players are low. Therefore, infections with B. burgdorferi have to be regarded a rare differential diagnosis in professional football in Central Europe. The low confirmation rate of positive screening assays points to an unspecific immune activation.

OBJECTIVE As reconstitution of virus-specific T-cells is critical to control cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we characterized the dynamics in CMV-specific T-cell reconstitution after SCT. METHODS Cytomegalovirus-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I-specific pentamers using flow cytometry. RESULTS Cytomegalovirus-specific CD4 T-cells reconstituted after a median of 2.3 (IQR, 2.0-3.0) weeks following autografting, and 4.0 (IQR, 3.0-5.6) weeks after allografting, with CMV-specific T-cells originating from donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8 T-cells did not differ (P = .58). Factors delaying the time to initial reconstitution of CMV-specific CD4 T-cells included a negative recipient serostatus (P = .016) and CMV-viremia (P = .026). Percentages of CMV-specific CD4 T-cells significantly increased over time and reached a plateau after 90 days (P = .043). Relative CMV-specific CD4 T-cell levels remained higher in long-term transplant recipients compared with those in controls (P

Flavonifractor plautii (formerly Eubacterium plautii) is an anaerobic gram positive rod shaped bacterium belonging to the family of Clostridiales, and a common member of the human gut microbiome. However, it is very rarely isolated from clinical human specimens, so data about its clinical significance are scarce. Here we report of a bloodstream infection due to F. plautii following gangrenous cholecystitis in a 69 year old man. After cholecystectomy and empirical antimicrobial treatment with ceftriaxone and metronidazole the patient recovered.F. plautii was the only bacterium detected in blood culture, suggesting that it might have been causative for cholecystitis. Antimicrobial resistance testing identified decreased susceptibilities against linezolid and penicillin indicating that a targeted therapy might be necessary. F. plautii can be considered a potential pathogen for cholecystitis. Keywords: Sepsis, Anaerobe, Gall bladder, Antibiotic resistance, Susceptibility

International audience; The spread of infectious diseases and vaccination history are common subjects of epidemiological and immunological research studies. Multiplexed serological assays are useful tools for assessing both current and previous infections as well as vaccination efficacy. We developed a serological multi-pathogen assay for hepatitis A, B and C virus, cytomegalovirus (CMV), Toxoplasma gondii, and Helicobacter pylori using a bead-based multiplex assay format. The multi-pathogen assay consisting of 15 antigens was utilized for the analysis of the serological response in elderly individuals of an influenza vaccination study (n = 34). The technical assay validation revealed a mean intra-assay precision of coefficient of variation (CV) = 3.2 ± 1.5% and a mean inter-assay precision of CV = 8.2 ± 5.3% across all 15 antigens and all tested samples, indicating a robust test system. Furthermore, the assay shows high sensitivities (ranging between 94% and 100%) and specificities (ranging between 93% and 100%) for the different pathogens. The highest seroprevalence rates in our cohort were observed for hepatitis A virus (HAV; 73.5%), followed by CMV (70.6%), T. gondii (67.6%) and H. pylori (32.4%). Seroprevalences for hepatitis B virus (HBV, 8.8%) and hepatitis C virus (HCV, 0%) were low. The seroprevalences observed in our study were similar to those from other population-based studies in Germany. In summary, we conclude that our multiplex serological assay represents a suitable tool for epidemiological studies.

Introduction: Endoscopic lung volume reduction (eLVR) is a therapeutic option for selected patients with severe emphysema. Exacerbations are serious adverse events in these frail patients. However, the microbial airway colonisation is widely unknown. We performed a microbiological analysis of bronchial aspirate specimens (BRAS) from patients undergoing eLVR. Methods: Retrospective analysis of COPD GOLD III and IV patients with advanced emphysema undergoing eLVR at Saarland University Medical 03/2012- 02/2016. According to an institutional protocol, patients received an oral antibiotic therapy with Sultamicillin and steroids for five days after eLVR. Results: Of 96 analysed patients, 51 individuals (53.1%) were male. All patients showed severe airflow limitation and hyperinflation. Lung functional testing showed an average FEV1 of 0.72±0.31L, 27.0±10.2%pred; RV 5.7±1.3L, 265.2± 66.1%pred; TLC 7.9±1.9L, 137.4±20%pred; and RV/TLC 72.7±7.8. Microbiological test results were available for 57 patients (60.6%). At least one organism was detected in 27 specimens (47.4%), mainly of bacterial origin (n=20; 35.1%). Fungi were detected in 7 samples (12.3%), whereas no mycobacteria were found. The most prevalent bacteria were Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus. Gram-negative Enterobacteriaceae were also found, but these were not multi-drug resistant. Pseudomonas aeruginosa occurred in Conclusion: The analysed samples did not yield high rates of multi-drug resistant gram-negative bacteria. Our results do not support empirical peri-interventional antibiotic treatment with anti-pseudomonal agents.

Zusammenfassung Nutzen und Risiken von Impfungen unterscheiden sich bei Leistungssportlern und der Allgemeinbevolkerung, deswegen muss fur Sportler eine separate Nutzen-Risiko-Bewertung durchgefuhrt werden, die in spezielle Impfempfehlungen mundet. Generell empfohlen sind Impfungen gegen Tetanus, Diphtherie, Pertussis, Influenza, Hepatitis A (HAV), Hepatitis B (HBV), FSME, Masern, Mumps und Varizella. Unter besonderen Bedingungen konnen Impfungen gegen Gelbfieber, Japan-B-Enzephalitis, Poliomyelitis, Typhus, Meningokokken, Pneumokokken und Haemophilus influenzae Typ b (Hib) wichtig sein. Es gibt zahlreiche Moglichkeiten Nebenwirkungen von Impfungen zu reduzieren, z.B. durch den besten Impfzeitpunkt, die Auswahl des Impfstoffes und die Impftechnik.

Objective.To establish the source and contamination routes resulting in positive clinical and surveillance microbiological cultures with carbapenem-resistant, GIM-1 metallo-β-lactamase–positiveAcinetobacter pitiiandAcinetobacter radioresistensfrom 21 patients in 8 departmentsDesign.Retrospective, descriptive study.Setting.A 1,300-bed tertiary care academic medical facility consisting of 90 buildings linked by a pneumatic transport system (PTS).Methods.Microbiological workup of the cluster strains included matrix-assisted laser desorption/ionization time-of-flight species identification, phenotypic carbapenemase tests, polymerase chain reaction–based genotyping of carbapenemase, and pulsed-field gel electrophoresis. Outbreak management procedures were employed according to institutional regulations.Results.The rarity of GIM-1Acinetobacterspecies in the hospital and region, the lack of epidemiological links between patients, and the fact that in some patients the apparent colonization was clearly nonnosocomial prompted the suspicion of a pseudo-outbreak. Numerous environmental cultures were positive for GIM-1-positiveAcinetobacter(including archived sample requisition forms, PTS capsules, cultures from line-diverter and dispenser stations, and sterilized transport capsules following PTS delivery). Moreover, it was observed that condensation fluid from subterranean PTS tubing resulted in water entry in PTS capsules, possibly conferring specimen contamination. After extensive system disinfection, environmental surveys of the PTS were negative, and no further positive patient specimens were encountered.Conclusions.This is the first report of a PTS-associated pseudo-outbreak. The large number of falsely positive patient-related specimens in conjunction with the potential hazard of airborne and contact spread of multidrug-resistant microorganisms (in this case, GIM-1 carbapenem-resistantAcinetobacterspecies) underscores the need for implementation of infection control–based monitoring and operating procedures in a hospital PTS.

Expression of the inhibitory receptor programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific CD4 T cells defines a phenotype associated with CMV viremia in transplant recipients. Moreover, CD28(-) CD27(-) double negativity is known as a typical phenotype of CMV-specific CD4 T cells. Therefore, the co-expression of inhibitory receptors on CD28(-) CD27(-) CD4 T cells was assessed as a rapid, stimulation-independent parameter for monitoring CMV complications after transplantation. Ninety-three controls, 67 hemodialysis patients and 81 renal transplant recipients were recruited in a cross-sectional and longitudinal manner. CMV-specific CD4 T cell levels quantified after stimulation were compared to levels of CD28(-) CD27(-) CD4 T cells. PD-1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression on CD28(-) CD27(-) CD4 T cells were related to viremia. A percentage of ≥0.44% CD28(-) CD27(-) CD4 T cells defined CMV seropositivity (93.3% sensitivity, 97.1% specificity), and their frequencies correlated strongly with CMV-specific CD4 T cell levels after stimulation (r = 0.73, p < 0.0001). Highest PD-1 expression levels on CD28(-) CD27(-) CD4 T cells were observed in patients with primary CMV viremia and reactivation (p < 0.0001), whereas CTLA-4 expression was only elevated during primary CMV viremia (p < 0.05). Longitudinal analysis showed a significant increase in PD-1 expression in relation to viremia (p < 0.001), whereas changes in nonviremic patients were nonsignificant. In conclusion, increased PD-1 expression on CD28(-) CD27(-) CD4 T cells correlates with CMV viremia in transplant recipients and may serve as a specific, stimulation-independent parameter to guide duration of antiviral therapy.

Background Here we describe a cluster of hospital-acquired Clostridium difficile infections (CDI) among 26 patients with osteoarticular infections. The aim of the study was to define the source of C. difficile and to evaluate the impact of general infection control measures and antibiotic stewardship on the incidence of CDI. Methods Epidemiological analysis included typing of C. difficile strains and analysis of possible patient to patient transmission. Infection control measures comprised strict isolation of CDI patients, additional hand washings, and intensified environmental cleaning with sporicidal disinfection. In addition an antibiotic stewardship program was implemented in order to prevent the use of CDI high risk antimicrobials such as fluoroquinolones, clindamycin, and cephalosporins. Results The majority of CDI (n = 15) were caused by C. difficile ribotype 027 (RT027). Most RT027 isolates (n = 9) showed high minimal inhibitory concentrations (MIC) for levofloxacin, clindamycin, and remarkably to rifampicin, which were all used for the treatment of osteoarticular infections. Epidemiological analysis, however, revealed no closer genetic relationship among the majority of RT027 isolates. The incidence of CDI was reduced only when a significant reduction in the use of fluoroquinolones (p = 0.006), third generation cephalosporins (p = 0.015), and clindamycin (p = 0.001) was achieved after implementation of an intensified antibiotic stewardship program which included a systematic review of all antibiotic prescriptions. Conclusion The successful reduction of the CDI incidence demonstrates the importance of antibiotic stewardship programs focused on patients treated for osteoarticular infections.

Mycobacterium chimaera, a non-tuberculous mycobacterium, was recently identified as causative agent of deep-seated infections in patients who had previously undergone open-chest cardiac surgery. Outbreak investigations suggested an aerosol-borne pathogen transmission originating from water contained in heater-cooler units (HCUs) used during cardiac surgery. Similar thermoregulatory devices are used for extracorporeal membrane oxygenation (ECMO) and M. chimaera might also be detectable in ECMO treatment settings. We performed a prospective microbiological study investigating the occurrence of M. chimaera in water from ECMO systems and in environmental samples, and a retrospective clinical review of possible ECMO-related mycobacterial infections among patients in a pneumological intensive care unit. We detected M. chimaera in 9 of 18 water samples from 10 different thermoregulatory ECMO devices; no mycobacteria were found in the nine room air samples and other environmental samples. Among 118 ECMO patients, 76 had bronchial specimens analysed for mycobacteria and M. chimaera was found in three individuals without signs of mycobacterial infection at the time of sampling. We conclude that M. chimaera can be detected in water samples from ECMO-associated thermoregulatory devices and might potentially pose patients at risk of infection. Further research is warranted to elucidate the clinical significance of M. chimaera in ECMO treatment settings.

Die Dermatochirurgie nimmt hinsichtlich vieler Punkte eine Sonderstellung unter den operativen Fachern ein. Hierzu gehort in erster Linie die Tatsache, dass bis auf wenige Ausnahmen fast alle Eingriffe traditionell in Lokal- bzw. Regionalanasthesie und oft auch in raumlich-infrastruktureller Trennung von den grosen Zentral-Operationssalen stattfinden konnen. Die peri- und postoperative Uberwachung obliegt dabei dem dermatochirurgischen Operationsteam. Das sui generis kleinere OP-Team hat somit eine ganze Reihe perioperativer Notwendigkeiten zu beachten, um die sich in den "grosen" chirurgischen Fachern eine Vielzahl verschiedener beteiligter Fachgruppen gemeinsam kummern. Hierzu gehoren neben Hygieneaspekten, Kenntnissen in der Uberwachung der Patienten sowie dem Aspekt der surgical site infections auch Fragen zur postoperativen Schmerztherapie sowie detailliertes pharmakologisches Wissen uber die zur Anwendung kommenden Lokalanasthetika und das Handling der damit assoziierten toxischen und allergischen Reaktionen. Eine interdisziplinare Zusammenarbeit und Verantwortung fur den Patienten ist notwendig und erfordert die Erarbeitung und Umsetzung qualitatsorientierter und evidenzbasierter Handlungsanweisungen, die im dermatochirurgischen OP-Setting meist weit uber das eigentliche Fach hinausgehen. Ziel dieses Weiterbildungsartikels soll die komprimierte Darstellung der genannten fachubergreifenden Standpunkte bezuglich der wichtigsten perioperativen Aspekte sein.

Background Plasmablastic posttransplant lymphoma is a rare subtype of monomorphic B-cell posttransplant lymphoproliferative disorder (PTLD). There is little published clinical data to guide treatment. Methods The German prospective PTLD registry D2006-2012 records baseline features, treatment, and outcome of rare PTLD subtypes in adults after solid organ transplantation. Treatment is at the discretion of the local physician. Clinical data on the patients in the registry is collected before, during, and at least 4 weeks, 6 months, 12 and 24 months after treatment. Results Eight cases of plasmablastic posttransplant lymphoma were reported to the registry until 2011. The majority occurred as late PTLD in male heart transplant recipients. Extranodal manifestations were common in stage I and in stage IV disease. Histological Epstein-Barr virus (EBV) association was confirmed in five of eight cases. MYC/IGH rearrangement was present in two of six patients examined. Although five of eight patients died from early disease progression, we observed that long-term survival can be achieved in localized (2/3) and in disseminated disease (1/5) by immunosuppression reduction (IR) followed by immediate systemic chemotherapy. However, all patients with cytogenetic aberrations and patients with non-EBV-associated PTLD were refractory to IR and to chemotherapy. Chemotherapy parallel to IR was associated with a high rate of infectious complications. Conclusions In this series, IR and local therapy were not sufficient to treat plasmablastic posttransplant lymphoma even in localized disease whereas IR and systemic chemotherapy (CHOP-21) could achieve lasting complete remissions. Cytogenetic aberrations and lack of EBV association were linked with poor outcome.

Post-transplantation lymphoproliferative disorder (PTLD) with plasmacellular differentiation has been reported as a rare subtype of monomorphic B-cell post-transplant lympho-proliferation with histological and immunophenotypical features of plasmacytoma in the non-transplant population. Here we present clinical, laboratory and histopathological features, treatment and outcome of 8 patients from the German prospective PTLD registry. Clinically, extranodal manifestations were common while osteolytic lesions were rare and none of the patients had bone marrow involvement. Immunohistochemistry showed light chain restriction and expression of CD138 without CD20 expression in all samples. An association with Epstein-Barr virus was found in 3 out of 8 cases. We suggest that the Ann Arbor classification is most useful for this disease entity and report a generally good response to treatment including reduction of immuno-suppression, surgery and irradiation in localized disease and systemic chemotherapy analogous to plasmacell myeloma in advanced disease.

Summary IL-6 and IL-10 have previously been implicated in the pathogenesis of post-transplant lymphoproliferative disorders (PTLD) and, like peripheral lymphocyte populations, are markers of immune status that are amenable to study in vivo. Thus, we analyzed cytokine plasma levels as well as lymphocyte subsets in a longitudinal analysis of 38 adult transplant recipients undergoing treatment for PTLD. Pretherapeutically, we found significantly elevated IL-6 (13.8 pg/ml) and IL-10 plasma levels (54.7 pg/ml) – in the case of IL-10, even higher in treatment nonresponders than in responders (116 vs. 14 pg/ml). Over time, however, IL-10 levels did not correlate with the course of disease, whereas those of IL-6 did, falling in responders and rising in nonresponders. These findings were independent of histological EBV-status, treatment type, and total peripheral T-cell counts, which were significantly reduced in patients with PTLD. Our observations support the idea that although IL-10 is important for creating a permissive environment for post-transplant lymphoma development, IL-6 is associated with PTLD proliferation. The analysis of lymphocyte subsets further identified HLA-DR+ CD8+ lymphocyte numbers as significantly different in non-PTLD controls (33%), treatment responders (44%) and nonresponders (70%). Although the specificity of these cells is unclear, their increase might correlate with the impaired tumor-specific cytotoxic-T-lymphocyte (CTL)-response in PTLD.

A survey-based, cost–benefit analysis was performed comparing blood screening strategies with vaccination strategies for the reduction of transfusion transmission of HBV. 231 whole blood donors and 126 apheresis donors were eligible and completed a questionnaire detailing their donation habits. The cost–benefit analysis included current mandatory HBV testing (HbsAg + anti-Hbc, A1), A1 with additional nucleic acid testing (NAT) for minipool (A2) or individual donation testing (A3), as well as HBV vaccination strategies using time-dependant (B1) or titre dependent booster vaccination solely (B2), or B2 in addition to current mandatory testing procedures (B3). Different cost models were applied using a 5% rate of discount. Absolute costs for current mandatory testing procedures (A1) over 20 years in Germany were €1009 million. Additional NAT would lead to incremental costs of 43% (A2) or 339% (A3), respectively. Vaccination strategies B1 and B2 showed cost-reductions relative to A1 of 30% and 14%, respectively. The number of remaining HBV infections could be reduced from 360 (for A1) to 13, using vaccination, compared with 144 or 105 remaining infections for A2 or A3, respectively. Absolute cost per prevented infection is similar (€2.0 million) for A2 and B3. HBV vaccination offers the near-elimination of transfusion infections while representing a potential cost-reduction.

1. Epstein–Barr virus (EBV)-associated diseases and therapeutic approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 2. Technical aspects of EBV viral load measurement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 3. Interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 3.1. What is being measured. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 3.2. EBV viral load in IM in immunocompetent patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 3.3. EBV viral load in tumours of immunocompetent individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 3.3.1. EBV viral load in nasopharyngeal carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 3.3.2. EBV viral load in other tumours of immunocompetent individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 3.4. EBV viral load in transplant recipients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 3.4.1. EBV viral load to predict diagnose or monitor PTLD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 3.4.2. EBV viral load to guide immunosuppression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 3.5. EBV viral load in HIV or AIDS patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 3.6. EBV viral load in neurological disorders of immunocompetent and 4. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .