Staphylococcus aureus gene expression in a rat model of infective endocarditis

Background: Diabetes mellitus is a frequent underlying comorbidity in patients with Staphylococcus aureus endocarditis, and it represents a risk factor for complications and a negative outcome. The pathogenesis of staphylococcal endocardial infections in diabetic hosts has been poorly characterized, and little is known about S. aureus gene expression in endocardial vegetations. Methods: We utilized a rat model of experimental S. aureus endocarditis to compare the pathogenesis of staphylococcal infection in diabetic and nondiabetic hosts and to study the global S. aureus transcriptome in endocardial vegetations in vivo. Results: Diabetic rats had higher levels of bacteremia and larger endocardial vegetations than nondiabetic control animals. Microarray analyses revealed that 61 S. aureus genes were upregulated in diabetic rats, and the majority of these bacterial genes were involved in amino acid and carbohydrate metabolism. When bacterial gene expression in vivo (diabetic or nondiabetic endocardial vegetations) was compared to in vitro growth conditions, higher in vivo expression of genes encoding toxins and proteases was observed. Additionally, genes involved in the production of adhesins, capsular polysaccharide, and siderophores, as well as in amino acid and carbohydrate transport and metabolism, were upregulated in endocardial vegetations. To test the contribution of selected upregulated genes to the pathogenesis of staphylococcal endocarditis, isogenic deletion mutants were utilized. A mutant defective in production of the siderophore staphyloferrin B was attenuated in the endocarditis model, whereas the virulence of a surface adhesin (ΔsdrCDE) mutant was similar to that of the parental S. aureus strain. Conclusions: Our results emphasize the relevance of diabetes mellitus as a risk factor for infectious endocarditis and provide a basis for understanding gene expression during staphylococcal infections in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0093-3) contains supplementary material, which is available to authorized users

Extensively drug resistant tuberculosis in a high income country: A report of four unrelated cases

<p>Abstract</p> <p>Background</p> <p>Multi drug resistance <it>of Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) remains a major threat to public health, reinforced by recent reports about the clinical course of patients infected with extensively drug resistant (XDR) strains in South Africa. There is little information about the clinical course of XDR tuberculosis patients in industrialised countries.</p> <p>Methods</p> <p>We evaluated all isolates of <it>M. tuberculosis</it>, in which drug susceptibility testing was performed at our institution since 1997, for multi and extensive drug resistance. Clinical courses of patients infected by strains fulfilling the recently revised criteria for XDR tuberculosis were analysed.</p> <p>Results</p> <p>Four XDR <it>M. tuberculosis </it>isolates were identified. All patients had immigrated to Germany from Russia, Georgia, and former Yugoslavia and none were infected by the human immunodeficiency virus. All patients where treated for tuberculosis for 5.5 to 15 years and for XDR tuberculosis for 1.9 to 2.5 years. They received inhospital treatment in Germany for 11 months, 4.5 years and twice for 6 years. Non-compliance was an important factor in all four patients, three patients had to be treated in Germanys only locked facility for tuberculosis treatment. One patient with XDR tuberculosis died, one patient had still open pulmonary tuberculosis at last contact and 2 patients were cured.</p> <p>Conclusion</p> <p>Cases of XDR tuberculosis have been treated in our region for several years. Even in a high income setting, XDR tuberculosis has a tremendous impact on quality of live, outcome and the total cost. All reasonable efforts to prevent the spread of XDR tuberculosis must be made and maintained.</p

Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, <it>C. neoformans </it>causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis.</p> <p>Case Presentation</p> <p>An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with <it>Cryptococcus neoformans</it>, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed.</p> <p>Conclusions</p> <p>Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.</p

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an Infectious Diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52)

Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: Although CD19-targeted agents (blinatumomab or inebilizumab) are not associated with an increased risk of infection, they may cause IgG hypogammaglobulinaemia and neutropenia. The requirement for prolonged intravenous infusion of blinatumomab may increase the risk of catheter-associated bloodstream infections. Infection remains the most common non-haematological adverse effect of anti-CD20 monoclonal antibodies, including severe respiratory tract infection, hepatitis B virus (HBV) reactivation and varicella-zoster virus infection. Screening for chronic or resolved HBV infection is recommended for patients receiving anti-CD20 monoclonal antibodies. Antiviral prophylaxis should be offered for 12\u201318 months to hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/anti-hepatitis B core antibody (HBc)-positive patients. Anti-Pneumocystis prophylaxis should be considered in patients receiving concomitant chemotherapy, particularly steroids. Alemtuzumab (anti-CD52) increases the risk of infections, in particular among leukaemia and solid organ transplant patients. These populations benefit from anti-Pneumocystis prophylaxis, prevention strategies for cytomegalovirus infection, and screening for HBV, hepatitis C virus and tuberculosis. Antiviral prophylaxis for at least 6\u201312 months should be provided for HBsAg-positive patients. Implications: As there are limited clinical data for many of the reviewed agents, special attention must be given to promptly detect and report emerging infectious complication

Influenza pandemic and professional duty: family or patients first? A survey of hospital employees

BACKGROUND: Conflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP). METHODS: We surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic. RESULTS: Of 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients. CONCLUSION: Our results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza

Epidemiology of SARS‑CoV‑2

Purpose SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features. Methods Non-systematic review. Results SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R₀) is between 2 and 3, and the median incubation period is 5.7 (range 2–14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5–10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection’s fatality rate is 0.5–1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries. Conclusions Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures

Increased neutralization of SARS-CoV-2 Delta variant after heterologous ChAdOx1 nCoV-19/BNT162b2 versus homologous BNT162b2 vaccination

Heterologous SARS-CoV-2 vaccine approaches with a second mRNA-based vaccine have been favored in the recommendations of many countries over homologous vector-based ChAdOx1 nCoV-19 vaccination after reports of thromboembolic events and lower efficacy of this regimen. In the middle of 2021, the SARS-CoV-2 Delta variant of concern (VoC) has become predominant in many countries worldwide. Data addressing the neutralization capacity of a heterologous ChAdOx1 nCoV-19/mRNA-based vaccination approach against the Delta VoC in comparison to the widely used homologous mRNA-based vaccine regimen are limited. Here, we compare serological immune responses of a cohort of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants with those of BNT162b2/BNT162b2 vaccinated ones and show that neutralization capacity against the Delta VoC is significantly increased in sera of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants. This overall effect can be attributed to ChAdOx1 nCoV-19/BNT162b2-vaccinated women, especially those with more severe adverse effects leading to sick leave following second immunization

Association between Reactogenicity and Immunogenicity after Vaccination with BNT162b2

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe—defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958–26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC50) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response

Brief report: attitudes towards Covid-19 vaccination among hospital employees in a tertiary care university hospital in Germany in December 2020

Coronavirus disease 2019 (Covid-19) vaccination is essential to fight the pandemic. Health care workers (HCWs) are prioritized to get vaccinated, yet uptake of recommended vaccinations is known to be low in this group. In a tertiary care university hospital with a high number of Covid-19 patients in intensive care, 59.5% of surveyed staff (N = 2454) were willing to get vaccinated, 21.4% were unsure and 18.7% refused. Vaccine hesitancy was higher in female, younger and healthy employees without contact to Covid-19 patients; nurses (53.3%) were much less willing to get vaccinated compared to physicians (82.7%)

Low Adherence to Pneumococcal Vaccination in Lung Cancer Patients in a Tertiary Care University Hospital in Southern Germany

Introduction: The aim of this study was to investigate the adherence to vaccinations, especially pneumococcal vaccinations, in lung cancer patients. Methods: the study was performed at the University Hospital Regensburg, Germany. All patients with a regular appointment scheduled between 1 December 2020 and 29 April 2021 and who provided informed consent were included. Available medical records, vaccination certificates, and a questionnaire were analyzed. Results: we included 136 lung cancer patients (NSCLC n = 113, 83.1%, SCLC n = 23, 16.9%). A correct pneumococcal vaccination according to national recommendations was performed in 9.4% (12/127) of the patients. A correct vaccination was performed for tetanus in 50.4% (66/131), diphtheria in 34.4% (44/128), poliomyelitis in 25.8% (33/128), tick-borne encephalitis in 40.7% (24/59), hepatitis A in 45.5% (7/11), hepatitis B in 38.5% (5/13), shingles in 3.0% (3/101), measles in 50.0% (3/6), pertussis in 47.7% (62/130), influenza in 54.4% (74/136), and meningococcal meningitis in 0% (0/2) of the patients. Conclusion: adherence to pneumococcal vaccinations, as well as to other vaccinations, is low in lung cancer patients