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Purpose The incidence of bone and joint infections is increasing while their treatment remains a challenge. Although guidelines and recommendations exist, evidence is often lacking and treatment complicated by complex clinical presentations and therapeutic options. Interdisciplinary boards shown to improve management of other diseases, seem potentially helpful. We describe the establishment of an osteomyelitis board to show the existing demand for such a platform. Methods All patients discussed in the board for bone and joint infections between October 2014 and September 2020 were included in this retrospective study. Data were extracted from patient records and analyzed descriptively. Results A total of 851 requests related to 563 patients were discussed in the board during the study period. After a run-in period of 3 years, a stable number of cases (> 170/year) were discussed, submitted by nearly all hospital departments (22 of 25). Recommendations were mainly related to antibiotic treatment (43%) and to diagnostics (24%). Periprosthetic joint infections were the most frequent entity (33%), followed by native vertebral osteomyelitis and other osteomyelitis. In 3% of requests, suspected infection could be excluded, in 7% further diagnostics were recommended to confirm or rule out infection. Conclusions A multidisciplinary board for bone and joint infections was successfully established, potentially serving as a template for further boards. Recommendations were mainly related to antibiotic treatment and further diagnostics, highlighting the need for interdisciplinary discussion to individualize and optimize treatment plans based on guidelines. Further research in needed to evaluate impact on morbidity, mortality and costs.

Echinococcus multilocularis is endemic in Germany. However, alveolar echinococcosis is a rare disease. Most commonly the parasite affects the liver, behaving like a malignant tumor. Bones are only affected in less than 2% of cases. We report a case of vertebral osteomyelitis accompanied by recurrent cutaneous fistula formation.

Staphylococcus aureus (SA) and Streptococcus species (SS) show different clinical manifestations in infective endocarditis (IE), but the impact on the complexity of surgical treatment remains unclear. All patients with surgically treated IE due to SA or SS between July 2013 and December 2016 were extracted from a prospectively collected, single-center registry. Data on patient characteristics, surgical procedures, and postprocedural outcomes were collected. SA-IE was more common with prosthetic valves (26.3% vs. 7.3%, p = 0.04), cardiac devices (14.3% vs. 0%, p = 0.03), previous cardiac surgery (28.6% vs. 9.8%, p = 0.03), intravenous drug abuse (14.3% vs. 0%, p = 0.03), and embolic events (57.1% vs. 26.8%, p = 0.007). Preoperative CRP was significantly higher in SA-IE (median 96.1 mg/L vs. 42.4 mg/L, p = 0.002). Otherwise, SS-IE affected more cusps/leaflets (mean 2.4 vs. 1.8, p = 0.03) and led to more valve dysfunction (83.8% vs. 54.3%, p = 0.007). Surgery times did not differ between the groups, though patients with SA spent more time in the intensive care unit (median 7 vs. 4.5 days, p = 0.04). Hospital mortality did not differ, but patients with SA-IE had unfavorable long-term survival (p = 0.001). Future studies need to be larger and focus on the mechanism behind the reduced long-term survival to mitigate the deleterious effect of SA in surgically treated patients with IE.

Background With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. Methods The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. Results Plasma IP-10 levels were found to be significantly increased (p

Although vertebral osteomyelitis (VO) has a major impact on morbidity, functional status, and quality of life, data concerning the influence on the patient’s ability to work (ATW) are lacking. Therefore, the aim of this study was to analyze the work status after VO-treatment as well as risk factors associated with loss of the ATW. We conducted a post-hoc analysis of data from a prospective VO-registry (2008–2019) supplemented by workforce data. Primary endpoint was the work status after one year (T1). Univariate analysis comparing patients’ characteristics “at-work” versus “not-at-work” at T1 was performed. Of a total of 335 VO-patients, n = 52 (16%) were part of the workforce at time of diagnosis (T0), of which 22 (42%) failed to be part of the workforce at T1. A higher number of comorbidities and a body mass index (BMI) < 25 kg/m2 were associated with a reduced ATW. VO in working age patients is a debilitating condition and associated with reduced patients’ ATW. Patients engaged in heavy physical work mostly had a BMI < 25 kg/m2 and therefore were more severely affected and no longer able to keep their workforce. More support in retraining should be offered after successful treatment to maintain ATW and reduce the socio-economic burden.

Background There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. Methods Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3–5, 6–11, 40–56, and 63–142. Results The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3–5 days post-OP, and 6–11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6–11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37–0.79), p Conclusion The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP. Trial registration ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these “elite neutralizers” also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19., Graphical abstract, Vanshylla et al. report longitudinal antibody kinetics in a mainly mild COVID-19 convalescent cohort of 963 individuals. There is broad variation in the initial response with older age and disease severity predicting higher SARS-CoV-2 neutralizing activity. Neutralizing IgG antibodies are detectable for up to 10 months in the majority of individuals.

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 85 years: aOR 2.38, 95% CI 1.49–3.81, p 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.

Background The objective of this study was to identify clinical risk factors for COVID-19 in a German outpatient fever clinic that allow distinction of SARS-CoV-2 infected patients from other patients with flu-like symptoms. Methods This is a retrospective, single-centre cohort study. Patients were included visiting the fever clinic from 4th of April 2020 to 15th of May 2020. Symptoms, comorbidities, and socio-demographic factors were recorded in a standardized fashion. Multivariate logistic regression was used to identify risk factors of COVID-19, on the bases of those a model discrimination was assessed using area under the receiver operation curves (AUROC). Results The final analysis included 930 patients, of which 74 (8%) had COVID-19. Anosmia (OR 10.71; CI 6.07–18.9) and ageusia (OR 9.3; CI 5.36–16.12) were strongly associated with COVID-19. High-risk exposure (OR 12.20; CI 6.80–21.90), especially in the same household (OR 4.14; CI 1.28–13.33), was also correlated; the more household members, especially with flu-like symptoms, the higher the risk of COVID-19. Working in an essential workplace was also associated with COVID-19 (OR 2.35; CI 1.40–3.96), whereas smoking was inversely correlated (OR 0.19; CI 0.08–0.44). A model that considered risk factors like anosmia, ageusia, concomitant of symptomatic household members and smoking well discriminated COVID-19 patients from other patients with flu-like symptoms (AUROC 0.84). Conclusions We report a set of four readily available clinical parameters that allow the identification of high-risk individuals of COVID-19. Our study will not replace molecular testing but will help guide containment efforts while waiting for test results.

COVID-19 is a life threatening disease, caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with undergoing treatment for hematologic malignancies including hematopoietic stem cell transplantation are considered to be at particular risk for fatal outcomes [1, 2]. This report describes for the first time the detection of SARS-CoV-2 viremia prior to the onset of symptoms and diagnosis of COVID-19 in a 51-year-old patient with acute myeloid leukemia (AML) and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notably, we illustrate that SARS-CoV-2 viremia inversely correlates with anti-SARS-CoV-2 antibody production, which predates negativity in respiratory samples for 4 weeks. A 51-year-old female patient was admitted to the University Hospital of Cologne on March 9, 2020, with herpes zoster involving C8/Th1 and Enterococcus faecalis bloodstream infection in the context of a third relapse of a FLT-3 mutated AML after an allo-HSCT from her HLA-identical brother in 2017. At this point, she presented with CTC (Common Toxicity Criteria) grade IV neutropenia and thrombocytopenia. Antibiotic and antiviral treatment was initiated. The patient received Midostaurin and Gemtuzumab ozogamicin as treatment for the relapsed AML. Under this therapy, the general condition of the patient improved, with symptoms and inflammatory parameters retreating. However, on March 21, 2020, 11 days after admission, the patient developed fever with temperatures up to 38.4 °C combined with a dry cough and fatigue. SARS-CoV-2 infection was confirmed in a PCR analysis of a pharyngeal swab on March 23, 2020. Laboratory results showed an increase in inflammatory parameters such as ferritin, C-reactive protein (CRP) and interleukin (IL)-6 (Fig. 1). A computed tomography (CT) scan showed infiltrates characteristic of COVID-19 pneumonia (see Supplementary Fig. 1). The patient rapidly developed dyspnea, peripheral blood oxygen saturation decreased and non-invasive oxygen supplementation was required (Fig. 1). Following, IL-6 and ferritin levels increased fast correlating with clinical decline. Under the assumption of a hyperinflammatory syndrome, the patient received Tocilizumab twice in a 7 days interval due to not satisfactory recovery after the first dose. After anti-IL6 treatment, symptoms decreased as well as inflammatory parameters (Fig. 1). The patient recovered slowly in the following 6 weeks: fever subsided with the exception of a new catheter-associated soft-tissue infection after 6 weeks. Oxygen supplementation could be slowly reduced and a progressive decrease of inflammatory parameters was observed. The patient was finally discharged seven weeks after admission and referred to our outpatient clinic for further treatment of her AML. a Real-time PCR Cycle threshold (RT-PCR Ct) values for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood samples and IgG antibody ratios. The dotted horizontal line marks the detection line of RNA, as well as the threshold for antibody seroconversion. Onset of symptoms defined as day 0, presented with grey vertical dotted line. Onset and end of viremia presented with red vertical dotted lines. Negative RT-PCR test results are displayed as Ct (Cycle threshold) values of 42. b RT-PCR Ct values for SARS-CoV-2 RNA in respiratory samples and corresponding IgG antibody ratios. c Maximum Temperature measured on each day in °C and maximum oxygen supply in l/min on each day over the course of disease. Fever is defined as a temperature >38.0 °C. d Levels of CRP (C-reactive protein) in mg/l, ferritin in μg/l and interleukin (IL)-6 in ng/l over the course of disease. Respiratory and plasma specimens were collected routinely for SARS-CoV-2 real-time PCR (RT-PCR) and antibody testing (detailed information is reported in Supplementary Materials). The publication of this data was approved by the Institutional Review Board of the University of Cologne (20-1254) and the patient’s written informed consent obtained. SARS-CoV-2 viremia was first detected on March 19, 2020, 2 days before the first symptoms (fever and dry cough) occurred and inflammatory parameters began to rise. Thus, we confirmed the presence of SARS-CoV-2 viremia 4 days before the detection of SARS-CoV-2 RNA in pharyngeal swab (Fig. 1). Analyzing the virus-related molecular and serological parameters throughout the course of disease, the progressive increase of detected SARS-CoV-2 RNA in the evaluated plasma samples reached a peak 8 days after the first detection in blood, whereas the last positive evidence of SARS-CoV-2 RNA in plasma was observed on April 14, 2020. On the same date, corresponding to 24 days after initial symptoms, SARS-CoV-2 specific IgA and IgG antibodies were detected (above threshold of 1.1). Along the course, the increase of specific SARS-CoV-2 antibody levels correlated with viral clearance from the blood (Fig. 1). However, SARS-CoV-2 RT-PCR from respiratory samples remained positive for three more weeks (7 weeks in total), despite occurrence of seroconversion, disappearance of COVID-19 related symptoms, and normalized inflammatory markers. Finally, 51 days after the onset of symptoms, the patient was tested SARS-CoV-2 negative in respiratory specimen (Fig. 1). The present report describes a case of SARS-CoV-2 viremia, preceding COVID-19 symptoms for 2 days, indicating a clear link between the observed SARS-CoV-2 viremia and beginning of COVID-19 symptoms. Consecutively, this suggests that SARS-CoV-2 viremia might play a more crucial role in COVID-19 than previously assumed because viremia before onset of symptoms is possible at least in a portion of cases. So far, SARS-CoV-2 RNA detected in blood has been considered a bystander effect, assuming that it is an avital virus component [3]. However, the detection of viremia prior to the onset of clinical symptoms suggests a systemic infection with...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4–3.2) vs. 11.8 (IQR, 9.9–13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3–12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = −3.3, 95% CI (−5.8; 0.8), p = 0.024 and ß = −4.4, 95% CI (−7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.

The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.

Background The volume of joint replacement surgery has risen steadily in recent years, because the population is aging and increasingly wishes to reserve a high functional status onward into old age. Infection is among the more common complications of joint replacement surgery, arising in 0.2% to 2% of patients, or as many as 9% in special situations such as the implantation of megaprostheses. The associated morbidity and mortality are high. It is thus very important to minimize risk factors for infection and to optimize the relevant diagnostic and therapeutic strategies. Methods This review is based on pertinent publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations. Results The crucial diagnostic step is joint biopsy for the identification of the pathogenic organism, which succeeds with over 90% sensitivity and specificity. If the prosthesis is firmly anchored in bone, the pathogen is of a type that responds well to treatment, and symptomatic infection has been present only for a short time, then rapidly initiated treatment can save the prosthesis in 35-90% of cases. The pillars of treatment are thorough surgical care (radical debridement) and targeted antibiotic therapy. On the other hand, if the prosthesis is loose or the pathogen is of a poorly treatable type, the infection can generally only be cured by a change of the prosthesis. This can be performed in either one or two procedures, always in conjunction with systemic antibiotic therapy tailored to the specific sensitivity and resistance pattern of the pathogen. Conclusion The risk of infection of an artificial joint is low, but the overall prevalence of such infections is significant, as the number of implanted joints is steadily rising. Artificial joint infections should be treated by a standardized algorithm oriented toward the recommendations of current guidelines. Many of these recommendations, however, are based only on expert opinion, as informative studies providing high-grade evidence are lacking. Thus, for any particular clinical situation, there may now be multiple therapeutic approaches with apparently comparable efficacy. Randomized trials are urgently needed.

Background Rapid initiation of appropriate antimicrobial therapy is crucial in managing severe infections, including bloodstream infections. Timely availability of microbiological results is essential to enable early de-escalation of empiric therapy, which is one of the key components of an effective antimicrobial stewardship program. The Accelerate Pheno™ system (AXDX) is a novel technology for rapid identification and phenotypic antimicrobial susceptibility testing with promising results. Yet the impact of this technology on the clinical management and patient outcome still is unclear. Methods The University Hospital Cologne is a 1,464-bed tertiary care hospital. We conducted a retrospective before and after observational study and analyzed three groups with different diagnostic and therapeutic pathways following a change in the standard of care and recent integration of AXDX: conventional microbiological diagnostics with and without antimicrobial stewardship program (ASP) intervention from January 2015 to July 2015, rapid diagnostics (AXDX in addition to conventional standard) with ASP intervention from January 2017 to March 2018. Results n = 280 patients met inclusion criteria and n = 225 (conventional microbiological diagnostics n = 74/conventional diagnostics + ASP intervention n = 79/rapid diagnostics + ASP intervention n = 72) were included in the final analysis during the two study periods. There was no difference in clinical and demographic characteristics among the three groups. The use of AXDX significantly decreased time from positive blood culture to microorganism identification (ID) (median: 25 hours vs. 12.5 hours, P < 0,001) and susceptibility testing (AST) (median: 43.8 hours vs. 17.6 hours, P < 0.001) and improved time from Gram stain to optimal therapy (median: 20.1 hours vs. 7 hours, P < 0.01). ASP intervention alone without AXDX improved the proportion of patients on optimal therapy within 48 hours after Gram stain (62.2% vs. 77.2%, P < 0.05). Conclusion Use of AXDX significantly reduced time to ID and AST by 12.5/26.2 hours. In combination with ASP intervention AXDX significantly reduced time to optimal therapy by 13.1 hours, ASP intervention alone also improved the proportion of patients on optimal therapy within 48 hours. Disclosures K. Ehren, Accelerate Diagnostics Inc.: Research Contractor, Research support. A. Meißner, Accelerate Diagnostics Inc.: Research Contractor, Research support. J. Ertel, Accelerate Diagnostics Inc.: Research Contractor, Research grant. H. Seifert, Accelerate Diagnostics Inc.: Research Contractor, Research grant.