First report of invasive liver abscess syndrome with endophthalmitis caused by a K2 serotype ST2398 hypervirulent Klebsiella pneumoniae in Germany, 2016

We report a case of severe infection with liver abscess and endophthalmitis caused by a hypervirulent Klebsiella pneumoniae strain in an immunocompetent German male patient without travel history to Asia. Phenotypic and molecular characterization showed high similarity to the reference genome NTUH-K2044 isolated in Asia. The isolate was assigned as ST2398 (clonal complex 66). The findings underline global spread of hypervirulent Klebsiella pneumoniae strains to Europe

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation

Kryptokokkose: Kasuistiken, Epidemiologie und Therapiestrategien

Die Kryptokokkose ist eine Pilzinfektion, die meist durch Cryptococcus neoformans verursacht wird. Neben den seltener werdenden Erkrankungen bei HIV-Infizierten werden zunehmend Fälle bei anderen Patientenkollektiven wie Organtransplantierten, Patienten mit chronischen Organerkrankungen oder auch bei Patienten ohne Immundefekt diagnostiziert. Das Krankheitsbild reicht von lokalisierten Infektionen der Atemwege oder der Haut bis hin zur typischen Meningoenzephalitis nach hämatogener Dissemination. Da aber auch alle anderen Organe beteiligt sein können, resultiert eine vielgestaltige Präsentation der Erkrankung. Daher muss die Kryptokokkose oft in die differenzialdiagnostischen Überlegungen einbezogen werden. Aufgrund sensitiver Labortests kann die Erkrankung bei disseminierter Infektion rasch gesichert werden. Für therapeutische Entscheidungen sind Patientenfaktoren und die jeweilige Organbeteiligung ausschlaggebend. Während in der ersten Therapiephase bei disseminierten oder schweren lokalen Erkrankungen in der Regel Amphotericin B-Derivate und 5-Flucytosin in Kombination eingesetzt werden, ist nach dieser Induktionstherapie oder bei leichten lokalisierten Infektionen eine Therapie mit Fluconazol indiziert. Echinocandine sind bei der Kryptokokkose nicht wirksam.Cryptococcosis is a fungal infection that is usually caused by Cryptococcus neoformans. Given the decreasing number of cases in HIV-infected patients in developed countries, infections in other patient populations, such as solid organ transplant recipients, patients with chronic organ diseases or even patients without immunodeficiency gain more attention. Due to a possible involvement of many organs, the clinical presentation varies from localized infections of the respiratory tract and the skin, to the characteristic meningoencephalitis or other organs after hematogenous dissemination. Sensitive laboratory tests allow a rapid diagnosis in patients with disseminated infection. Crucial therapeutic decisions depend on the underlying patient condition and the particular organ involvement. The induction therapy of disseminated infections or severe localised infections is based on amphotericin B in combination with 5-flucytosine. In non-severe localised infections and after induction therapy, antifungal treatment with fluconazole is indicated. Echinocandins are not effective in cryptococcosis

Kryptokokkose: Kasuistiken, Epidemiologie und Therapiestrategien

Die Kryptokokkose ist eine Pilzinfektion, die meist durch Cryptococcus neoformans verursacht wird. Neben den seltener werdenden Erkrankungen bei HIV-Infizierten werden zunehmend Fälle bei anderen Patientenkollektiven wie Organtransplantierten, Patienten mit chronischen Organerkrankungen oder auch bei Patienten ohne Immundefekt diagnostiziert. Das Krankheitsbild reicht von lokalisierten Infektionen der Atemwege oder der Haut bis hin zur typischen Meningoenzephalitis nach hämatogener Dissemination. Da aber auch alle anderen Organe beteiligt sein können, resultiert eine vielgestaltige Präsentation der Erkrankung. Daher muss die Kryptokokkose oft in die differenzialdiagnostischen Überlegungen einbezogen werden. Aufgrund sensitiver Labortests kann die Erkrankung bei disseminierter Infektion rasch gesichert werden. Für therapeutische Entscheidungen sind Patientenfaktoren und die jeweilige Organbeteiligung ausschlaggebend. Während in der ersten Therapiephase bei disseminierten oder schweren lokalen Erkrankungen in der Regel Amphotericin B-Derivate und 5-Flucytosin in Kombination eingesetzt werden, ist nach dieser Induktionstherapie oder bei leichten lokalisierten Infektionen eine Therapie mit Fluconazol indiziert. Echinocandine sind bei der Kryptokokkose nicht wirksam.Cryptococcosis is a fungal infection that is usually caused by Cryptococcus neoformans. Given the decreasing number of cases in HIV-infected patients in developed countries, infections in other patient populations, such as solid organ transplant recipients, patients with chronic organ diseases or even patients without immunodeficiency gain more attention. Due to a possible involvement of many organs, the clinical presentation varies from localized infections of the respiratory tract and the skin, to the characteristic meningoencephalitis or other organs after hematogenous dissemination. Sensitive laboratory tests allow a rapid diagnosis in patients with disseminated infection. Crucial therapeutic decisions depend on the underlying patient condition and the particular organ involvement. The induction therapy of disseminated infections or severe localised infections is based on amphotericin B in combination with 5-flucytosine. In non-severe localised infections and after induction therapy, antifungal treatment with fluconazole is indicated. Echinocandins are not effective in cryptococcosis

Detection of a cfr(B) variant in German Enterococcus faecium clinical isolates and the impact on Linezolid resistance in Enterococcus spp

The National Reference Centre for Staphylococci and Enterococci in Germany has received an increasing number of clinical linezolid-resistant E. faecium isolates in recent years. Five isolates harbored a cfr(B) variant gene locus the product of which is capable of conferring linezolid resistance. The cfr(B)-like methyltransferase gene was also detected in Clostridium difficile. Antimicrobial susceptibility was determined for cfr(B)-positive and linezolid-resistant E. faecium isolates and two isogenic C. difficile strains. All strains were subjected to whole genome sequencing and analyzed with respect to mutations in the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B) variant locus. To evaluate methyltransferase function, the cfr(B) variant of Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp. Ribosomal target site mutations were detected in E. faecium strains but absent in clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218 which was present in C. difficile Ox3196, truncated in some E. faecium and absent in C. difficile Ox3206. The latter finding explains the lack of linezolid and chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first time a direct correlation of elevated linezolid MICs in C. difficile upon cfr acquisition. Tn6218 insertion sites revealed novel target loci for integration, both within the bacterial chromosome and as an integral part of plasmids. Importantly, the very first plasmid-association of a cfr(B) variant was observed. Although we failed to measure cfr(B)-mediated resistance in transformed laboratory strains the occurrence of the multidrug resistance gene cfr on putatively highly mobile and/or extrachromosomal DNA in clinical isolates is worrisome with respect to dissemination of antibiotic resistances