Absence of Type I Interferon Autoantibodies or Significant Interferon Signature Alterations in Adults With Post-COVID-19 Syndrome.

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-ß, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS.

Antibiotic use in pediatric acute care hospitals: an analysis of antibiotic consumption data from Germany, 2013-2020.

BACKGROUND: Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. METHOD: We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013-2020. RESULTS: In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1-79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p < 0.0001). The highest use densities were seen on oncology wards and intensive care units at university hospitals (67.3 vs. 38.4 DDD/100 pd). During 2013-2020, overall ACD declined (- 10%) and cephalosporin prescriptions also decreased (- 36%). In 2020, cephalosporins nevertheless remained the most commonly dispensed class of antibiotics. Interhospital variability in cephalosporin/penicillin ratio was substantial. Antibiotics belonging to WHO AWaRe "Watch" and "Reserve" categories, including broad-spectrum penicillins (+ 31%), linezolid (+ 121%), and glycopeptides (+ 43%), increased over time. CONCLUSION: Significant heterogeneity in ACD and prescription of different antibiotic classes as well as high prescription rates for cephalosporins and an increased use of reserve antibiotics indicate improvable antibiotic prescribing quality. AMS programs should urgently prioritize these issues to reduce antimicrobial resistance.

[Development and validation of potential structure indicators for clinical infectious disease (ID) care in German hospitals during the COVID-19 pandemic]. / Entwicklung und Validierung potenzieller Strukturindikatoren zur Evaluierung des klinisch-infektiologischen Versorgungsangebots in deutschen Krankenhäusern während der COVID-19-Pandemie.

INTRODUCTION: This study describes the development and validation of structure indicators for clinical infectious disease (ID) care in German hospitals, which is important to adequately face the future challenges in ID medicine. METHODS: A team of experts developed the structure indicators in a three-stage, multicriteria decision-making process: (1) identification of potential structure indicators based on a literature review, (2) written assessment process, and (3) face-to-face discussion to reach consensus and final selection of appropriate structure indicators. A field study was conducted to assess the developed structure indicators. A score based on the structure indicators was determined for each hospital and validated via receiver operator characteristic (ROC) curves using externally validated ID expertise (German Society of ID (DGI) Centre). RESULTS: Based on a list of 45 potential structure indicators, 18 suitable indicators were developed for clinical ID care structures in German hospitals. Out of these, ten key indicators were defined for the general and coronavirus disease 2019- (COVID-19-) specific clinical ID care structures. In the field survey of clinical ID care provision for COVID-19 patients in 40 German hospitals, the participating facilities achieved 0 to 9 points (median 4) in the determined score. The area under the ROC curve was 0.893 (95% CI: 0.797, 0.988; p < 0.001). DISCUSSION/CONCLUSION: The structure indicators developed within the framework of a transparent and established development process can be used in the future to both capture the current state and future developments of ID care quality in Germany and enable comparisons.

Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections.

PURPOSE: This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. METHODS: In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and "Sniffin' Sticks" extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. RESULTS: C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. CONCLUSIONS: Patients with C19 and non-C19 URTI exhibit a similar improvement over 3-4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses.

The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss.

Individual HLA-A, -B, -C, and -DRB1 Genotypes Are No Major Factors Which Determine COVID-19 Severity.

HLA molecules are key restrictive elements to present intracellular antigens at the crossroads of an effective T-cell response against SARS-CoV-2. To determine the impact of the HLA genotype on the severity of SARS-CoV-2 courses, we investigated data from 6,919 infected individuals. HLA-A, -B, and -DRB1 allotypes grouped into HLA supertypes by functional or predicted structural similarities of the peptide-binding grooves did not predict COVID-19 severity. Further, we did not observe a heterozygote advantage or a benefit from HLA diplotypes with more divergent physicochemical peptide-binding properties. Finally, numbers of in silico predicted viral T-cell epitopes did not correlate with the severity of SARS-CoV-2 infections. These findings suggest that the HLA genotype is no major factor determining COVID-19 severity. Moreover, our data suggest that the spike glycoprotein alone may allow for abundant T-cell epitopes to mount robust T-cell responses not limited by the HLA genotype.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

Association of history of cerebrovascular disease with severity of COVID-19.

OBJECTIVE: To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). METHODS: In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran's Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. RESULTS: Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52-2.81; p < 0.0001]. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22-1.71; p < 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83-4.24; p < 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75-2.7; p < 0.0001). CONCLUSION: A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19  suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Impact of safety warnings for fluoroquinolones on prescribing behaviour. Results of a cohort study with outpatient routine data.

PURPOSE: The need for drug-related safety warnings is undisputed, but their impact on prescribing behaviour is not always clear. Safety warnings usually do not contain therapeutic alternatives. Based on German outpatient routine healthcare data, our cohort study investigated the impact of three warnings for fluoroquinolones on prescribing behaviour. METHODS: Structural breaks were estimated in a time-series analysis (2005-2014) of 184,134 first antibiotic prescriptions for patients (≥ 18 years) diagnosed with community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), or acute exacerbation of chronic bronchitis (AECB). Subsequently, risk factors for patients' before/after safety warnings presented as risk ratios (RR) were estimated by Poisson regression. RESULTS: Following the 2008 warning for moxifloxacin, the RR of being prescribed moxifloxacin was reduced by 56% (95% CI 0.41-0.47; p < 0.001) for CAP, by 65% (95% CI 0.32-0.39; p < 0.001) for ABS, by 57% (95% CI 0.41-0.45; p < 0.001) for AECB. After the 2012 warning for levofloxacin, the RR of being prescribed levofloxacin was reduced by 31% (95% CI 0.64-0.74; p < 0.001) for CAP, by 14% (95% CI 0.77-0.96; p = 0.007) for ABS, by 27% (95% CI 0.69-0.77; p < 0.001) for AECB. We noticed a prescription-switch to other antibiotics which was not in line with the national guideline recommendations. The warning for moxifloxacin 2009 had no impact on prescribing behaviour. CONCLUSION: This study observed an impact on prescribing behaviour in response to regulatory safety warnings for two out of three warnings. Information on therapeutic alternatives should be a part of any safety warning to encourage the intended changes in prescribing behaviour.

Mathematical basis for the assessment of antibiotic resistance and administrative counter-strategies.

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden (cf. supplement "DiebnerEtAl_Data-Supplement"). Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic.

OBJECTIVE: Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. METHODS: Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. RESULTS: During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). CONCLUSIONS: Universal laboratory testing for SARS-CoV-2 provided useful information on patients' infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Predictive Value of Sudden Olfactory Loss in the Diagnosis of COVID-19.

INTRODUCTION: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an outpatient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom "sudden smell loss" for screening procedures. METHODS: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria completed a standardized diagnostic questionnaire which included the patients' main symptoms, time course, and an additional self-assessment of the patients' current smell, taste function, and nasal breathing compared to the level before the onset of symptoms. RESULTS: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only 12 out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom "sudden smell loss" in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom "sudden smell loss" can be attested a high specificity (97%) and a sensitivity of 65% with a positive predictive value of 63% and negative predictive value of 97% for COVID-19. CONCLUSION: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be recognized as an early symptom of the disease and should be tested for on a regular basis. In contrast to other acute viral smell impairment, COVID-19-associated smell loss seems to be only rarely accompanied by a severely blocked nose.

Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

Cerebral Abscess by Fonsecaea monophora-The First Case Reported in Germany.

We report the first case of cerebral Fonsecaea monophora infection in a German woman without immunodeficiency or travel history. F. monophora infection is a rare differential diagnosis of cerebral tumors; it was previously considered a tropical fungus. This case adds to the scarce reports in nontropical regions.

Serum vancomycin concentrations after oral and intracolonic vancomycin administration in a patient with colonic discontinuity and severe Clostridium difficile infection.

PURPOSE: A case of detectable systemic vancomycin levels after oral vancomycin administration but not after intracolonic administration in a patient with colonic discontinuity and severe Clostridium difficile infection (CDI) is reported. SUMMARY: A 63-year-old woman who had recently undergone pancreas-kidney transplantation developed severe CDI after 13 days of meropenem therapy for presumed urosepsis. Meropenem was stopped immediately, and treatment with oral vancomycin (250 mg every 6 hours) was started. Due to fulminant C. difficile colitis with signs of toxic megacolon and abdominal compartment syndrome, an emergency left hemicolectomy (Hartmann's procedure) was performed. Ten days after initiation of oral vancomycin therapy, the serum vancomycin concentration was 16.7 mg/L. After oral dose reduction to 125 mg every 6 hours, the measured serum vancomycin concentrations stayed above 10 mg/L. CDI therapy was terminated after 16 days. Eight days later, as sigmoidoscopy of the Hartmann rectal stump still showed pseudomembranes, intracolonic vancomycin application in the Hartmann rectal stump was started; 7-9 days after initiation of intracolonic therapy, the serum vancomycin concentration remained undetectable. The observed patterns of vancomycin exposure and absorption in this case suggest that the sigmoid colon is not the site of resorption of intracolonically applied vancomycin. CONCLUSION: A patient with severe CDI and Hartmann rectal stump after hemicolectomy was treated with vancomycin. After oral vancomycin therapy, significant enteral absorption was observed, while levels stayed undetectable during intracolonic administration alone.

Management of bloodstream infections by infection specialists in France and Germany: a cross-sectional survey.

INTRODUCTION: Bloodstream infections (BSI) are frequent infections worldwide. Our objective was to explore variation in the management of patients with BSI by infection specialists in France and Germany. METHODS: This work is part of an international ESCMID cross-sectional internet-based questionnaire survey that was opened from December 2016 to February 2017. All hospital-based infection specialists, senior or trainees, giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting an uncomplicated BSI due to different pathogens. RESULTS: A hundred and ninety-six professionals (125 from Germany and 71 from France) participated. Systematic expert advice for positive blood cultures was more often available in Germany as compared with France (73 vs. 56%, p = 0.004). In Germany, the professional providing the expert advice was more often a microbiologist or a pharmacist as compared with France (p = 0.001 and p = 0.037, respectively) where it was more often an infectious diseases specialist. Fewer German respondents reported to advise systematic IV-oral switch of antibiotic therapy. German respondents also recommended less often combination therapy: for example for Enterococcus faecalis (64 vs. 43%, p = 0.015), ESBL E. coli (94 vs. 67%, p < 0.001) and Pseudomonas aeruginosa (76 vs. 37%, p < 0.001). Overall, management of candidaemia was more often compliant with the IDSA guidelines in France as compared with Germany, but no difference was noted for MRSA bacteraemia. CONCLUSION: Our survey shows that wide variations exist between two neighboring countries in the recommendations by infection specialists for the management of BSI. International guidelines are needed.