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1.
J Child Neurol ; : 883073821989154, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33543660

RESUMEN

Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement Therapy (ERT) in CLN2 Disease." Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.

2.
Int J Hyg Environ Health ; 232: 113671, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33338782

RESUMEN

We sequentially assessed the presence of SARS-CoV-2 IgG antibodies in 1253 hospital workers including 1026 HCWs at the University Medical Center Hamburg-Eppendorf at three time points during the early phase of the epidemic. By the end of the study in July 2020, the overall seroprevalence was 1.8% (n = 22), indicating the overall effectiveness of infection control interventions in mitigating coronavirus disease 2019 (COVID-19) in hospital workers.


Asunto(s)
Anticuerpos Antivirales/sangre , Personal de Salud/estadística & datos numéricos , Inmunoglobulina G/sangre , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , /inmunología , Femenino , Alemania , Humanos , Control de Infecciones , Masculino , Persona de Mediana Edad , Seroconversión , Estudios Seroepidemiológicos
3.
Artículo en Inglés | MEDLINE | ID: mdl-33007476

RESUMEN

OBJECTIVES: Investigation whether in depth characterization of virus variant patterns can be used for epidemiological analysis of the first SARS-CoV-2 infection clusters in Hamburg, Germany. METHODS: Metagenomic RNA- and amplicon-sequencing and subsequent variant calling in 25 respiratory samples from SARS-CoV-2 infected patients involved in the earliest infection clusters in Hamburg. RESULTS: Amplikon sequencing and cluster analyses of these SARS-CoV-2 sequences allowed the identification of the first infection cluster and five non-related infection clusters occurring at the beginning of the viral entry of SARS-CoV-2 in the Hamburg metropolitan region. Viral genomics together with epidemiological analyses revealed that the index patient acquired the infection in Northern Italy and transmitted it to two out of 134 contacts. Single nucleotide polymorphisms clearly distinguished the virus variants of the index and other clusters and allowed to track in which sequences worldwide these mutations were first described. Minor variant analyses identified the transmission of intra-host variants in the index cluster and household clusters. CONCLUSIONS: SARS-CoV-2 variant tracing allows the identification of infection clusters and the follow up of infection chains occurring in the population. Furthermore, the follow up of minor viral variants in infection cluster can provide further resolution on transmission events indistinguishable on consensus sequence level.

4.
Oncol Res Treat ; 43(6): 307-313, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32380501

RESUMEN

With the outbreak of the COVID-19 pandemia, routine clinical work was immediately, deeply, and sustainably impacted in Germany and worldwide. The infrastructure of almost all hospitals is currently redirected to provide a maximum of intensive care resources, including the necessary staff. In parallel, routine as well as emergency clinical care for all patients in need has to be secured. This challenge becomes particularly evident in cancer care. In order to maintain adequate oncological care at all levels of provision and to conduct especially curative and intensive treatments with a maximum of safety, continuous adaption of the oncology care system has to be ensured. Intensive communication with colleagues and patients is needed as is consequent expert networking and continuous reflection of the own developed strategies. In parallel, it is of high importance to actively avoid cessation of innovation in order not to endanger the continuous improvement in prognosis of cancer patients. This includes sustained conduction of clinical trials as well as ongoing translational research. Here, we describe measures taken at the University Cancer Center Hamburg (UCCH) - a recognized comprehensive oncology center of excellence - during the COVID-19 crisis. We aim to provide support and potential perspectives to generate a discussion basis on how to maintain high-end cancer care during such a crisis and how to conduct patients safely into the future.


Asunto(s)
Betacoronavirus , Instituciones Oncológicas/organización & administración , Infecciones por Coronavirus/prevención & control , Hospitales Universitarios/organización & administración , Pandemias/prevención & control , Neumonía Viral/prevención & control , Atención Ambulatoria , Instituciones Oncológicas/economía , Infecciones por Coronavirus/economía , Infecciones por Coronavirus/virología , Alemania , Hospitales Universitarios/economía , Humanos , Control de Infecciones/métodos , Pacientes Internos , Pandemias/economía , Seguridad del Paciente , Neumonía Viral/economía , Neumonía Viral/virología
5.
J Microbiol Immunol Infect ; 53(2): 240-249, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30146415

RESUMEN

BACKGROUND: Coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis are highly prevalent pathogens for sepsis in neonates. The interaction between host, environment and pathogenic factors of S. epidermidis are still poorly understood. Our objective was to address the role of several pathogenic factors of S. epidermidis on neonatal cytokine responses and to characterize the influence of three immunomodulatory drugs. METHODS: We performed an ex-vivo model of S. epidermidis sepsis by assessment of blood cytokine production in neonatal whole blood stimulation assays (ELISA). S. epidermidis strains with different characteristics were added as full pathogen to umbilical cord blood cultures and the influence of indomethacin, ibuprofen and furosemide on neonatal immune response to S. epidermidis was evaluated (Flow cytometry). RESULTS: Stimulation with S. epidermidis sepsis strains induced higher IL-6 and IL-10 expression than stimulation with colonization strains. Biofilm formation in clinical isolates was associated with increased IL-10 but not IL-6 levels. In contrast, stimulation with mutant strains for biofilm formation and extracellular virulence factors had no major effect on cytokine expression. Notably, addition of ibuprofen or indomethacin to S. epidermidis inoculated whole blood resulted in mildly increased expression of TNF-α but not IL-6, while frusemide decreased the production of pro-inflammatory cytokines, i.e. IL-6 and IL-8. CONCLUSIONS: The virulence of sepsis strains is coherent with increased cytokine production in our whole-blood in-vitro sepsis model. Biofilm formation and expression of extracellular virulence factors had no major influence on readouts in our setting. It is important to acknowledge that several drugs used in neonatal care have immunomodulatory potential.


Asunto(s)
Inmunidad Innata , Sepsis/inmunología , Sepsis/microbiología , Infecciones Estafilocócicas/inmunología , Staphylococcus epidermidis/inmunología , Amidohidrolasas/genética , Proteínas Bacterianas/genética , Citocinas/metabolismo , Humanos , Inmunomodulación , Recién Nacido , Interleucinas/metabolismo , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/aislamiento & purificación , Factores de Virulencia/inmunología
6.
Artículo en Inglés | MEDLINE | ID: mdl-30603083

RESUMEN

Background: Infections caused by third generation cephalosporin-resistant Enterobacteriaceae (3GCREB) are an increasing healthcare problem. We aim to describe the 3GCREB infection incidence and compare it to prevalence upon admission. In addition, we aim to describe infections caused by 3GCREB, which are also carbapenem resistant (CRE). Methods: In 2014-2015, we performed prospective 3GCREB surveillance in clinically relevant patient specimens (screening specimens excluded). Infections counted as hospital-acquired (HAI) when the 3GCREB was detected after the third day following admission, otherwise as community-acquired infection (CAI). Results: Of 578,420 hospitalized patients under surveillance, 3367 had a 3GCREB infection (0.58%). We observed a similar 3GCREB CAI and HAI incidence (0.28 and 0.31 per 100 patients, respectively). The most frequent pathogen was 3GCR E. coli, in CAI and HAI (0.15 and 0.12 per 100 patients). We observed a CRE CAI incidence of 0.006 and a HAI incidence of 0.008 per 100 patients (0.014 per 1000 patient days). Conclusions: Comparing the known 3GCREB admission prevalence of the participating hospitals (9.5%) with the percentage of patients with a 3GCREB infection (0.58%), we conclude the prevalence of 3GCREB in university hospitals to be about 16 times higher than suggested when only patients with 3GCREB infections are considered. Moreover, we find the HAI and CAI incidence caused by CRE in Germany to be relatively low.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Infecciones por Enterobacteriaceae/epidemiología , Anciano , Cefalosporinas , Farmacorresistencia Bacteriana , Enterobacteriaceae/aislamiento & purificación , Femenino , Alemania/epidemiología , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Admisión del Paciente , Estudios Prospectivos
7.
Transfus Med Hemother ; 43(1): 37-43, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27022321

RESUMEN

OBJECTIVE: Testing for antibodies against hepatitis B core antigen (anti-HBc) was introduced to detect blood donors suffering from occult hepatitis B infection. Confirmation of specification of reactive results in the anti-HBc screening assay is still a challenge for blood donation services. METHODS: Two different test strategies for confirmation of specification of reactive anti-HBc tests, one performed in our institute and one suggested by the German authority (Paul-Ehrlich-Institut (PEI)), were compared. The first strategy is based on one supplemental anti-HBc test, the other requires two supplemental anti-HBc tests. RESULTS: 389 samples from 242 donors were considered. Both test strategies yielded concordant results in 117 reactive samples termed 'true-positive' or 'specificity confirmed', in 156 reactive samples termed 'false-positive' or 'specificity not confirmed', and in 99 negative samples. In 17 samples obtained from 11 donors, both test strategies gave discrepant results ('false-positive' but 'specificity confirmed'). In 10 of 11 donors, a real HBV infection was very unlikely, one remained unclear. 30 donors considered 'false-positive' became negative in all anti-HBc tests after follow-up testing and thus eligible for donor re-entry. CONCLUSIONS: The test strategy suggested by the PEI yielded no additional information but induced an overestimation of HBV infections and unnecessary look-back procedures. Many anti-HBc-reactive donors can be regained after follow-up testing.

8.
Nephrol Dial Transplant ; 31(1): 95-103, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26180049

RESUMEN

BACKGROUND: Shiga toxin-producing, enteroaggregative Escherichia coli was responsible for the 2011 outbreak of haemolytic uraemic syndrome (HUS). The present single-centre, observational study describes the 1-year course of the disease with an emphasis on kidney function. Outcome data after 1 year are associated with treatment and patient characteristics at onset of HUS. METHODS: Patients were treated according to a standardized approach of supportive care, including a limited number of plasmapheresis. On top of this treatment, patients with severe HUS (n = 35) received eculizumab, a humanized anti-C5 monoclonal antibody inhibiting terminal complement activation. The per-protocol decision--to start or omit an extended therapy with eculizumab accompanied by azithromycin--separated the patients into two groups and marked Day 0 of the prospective study. Standardized visits assessed the patients' well-being, kidney function, neurological symptoms, haematological changes and blood pressure. RESULTS: Fifty-six patients were regularly seen during the follow-up. All patients had survived without end-stage renal disease. Young(er) age alleviated restoring kidney function after acute kidney injury even in severe HUS. After 1 year, kidney function was affected with proteinuria [26.7%; 95% confidence interval (CI) 13.8-39.6], increased serum creatinine (4.4%, CI 0.0-10.4), increased cystatin C (46.7%, CI 32.1-61.3) and reduced (<90 mL/min) estimated glomerular filtration rate (46.7%, CI 32.1-61.3). Nine of the 36 patients without previous hypertension developed de novo hypertension (25%, CI 10.9-39.1). All these patients had severe HUS. CONCLUSIONS: Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy.


Asunto(s)
Escherichia coli Enterohemorrágica , Infecciones por Escherichia coli/complicaciones , Síndrome Hemolítico-Urémico/complicaciones , Hipertensión/microbiología , Insuficiencia Renal Crónica/microbiología , Adulto , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azitromicina/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Quimioterapia Combinada , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Síndrome Hemolítico-Urémico/microbiología , Humanos , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/prevención & control , Resultado del Tratamiento
9.
Int J Antimicrob Agents ; 44(4): 363-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25182711

RESUMEN

Discovered in 1949, the antibiotic colistin was initially used for therapeutic purposes. Parenteral use of colistin was gradually abandoned because of its side-effect profile, especially its nephrotoxicity and neurotoxicity. Despite the risk of these potentially serious adverse effects, increasing resistance of Gram-negative bacteria has led to a renaissance of intravenous use of colistin in the last few years. Local administration of colistin is an alternative method to minimise the risk of systemic toxicity. We present a case of extensively drug-resistant Pseudomonas aeruginosa osteomyelitis treated successfully with high-dose colistin- and tobramycin-impregnated bone cement as a drug delivery vehicle. For the first time, local colistin concentrations in drainage and synovial fluid were quantified in order to determine the optimal dose and to minimise serious side effects. Insertion of a bone cement spacer loaded with a high dose of tobramycin and colistin resulted in local colistin levels at the infection site that exceeded the minimum inhibitory concentration (MIC) of colistin against the isolated P. aeruginosa five-fold on Day 4. Thus, the treatment may be expected to exert a prolonged effect. Whereas systemic administration of colistin alone was not sufficient to treat the infection, combined local and parenteral therapy led to eradication of P. aeruginosa in this patient. Plasma colistin levels remained in the therapeutic range, which confirms the systemic safety of the method.


Asunto(s)
Colistina/administración & dosificación , Farmacorresistencia Bacteriana Múltiple , Osteomielitis/tratamiento farmacológico , Polimetil Metacrilato/administración & dosificación , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Colistina/farmacocinética , Portadores de Fármacos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/microbiología , Plasma/química , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Líquido Sinovial/química , Tobramicina/farmacocinética , Resultado del Tratamiento
10.
Invest Ophthalmol Vis Sci ; 55(8): 4759-67, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24985479

RESUMEN

PURPOSE: To investigate the effects of Bruch's membrane (BrM) neutral lipid deposition in mouse models and its significance to aging and age-related macular degeneration, it is essential to reliably detect small quantities of neutral lipids including esterified cholesterol (EC). In chorioretinal sections and BrM wholemounts, we tested a novel fluorescent cholesterol marker based on the bacterial toxin perfringolysin O (PFO) and compared results with those obtained with the classic cholesterol dye filipin. METHODS: An engineered plasmid containing the specific cholesterol binding domain (D4) of PFO fused to green fluorescent protein (GFP) was expressed in cultured E. coli, isolated, purified, and concentrated. A total of 150 BrM-choroid wholemounts and chorioretinal sections of 11- to 13-month-old ApoE(null) mice were prepared and stained with PFO/D4-GFP or filipin for EC. Samples were examined by epifluorescence microscopy. RESULTS: The fluorescence intensity of PFO/D4-GFP was strong, stable, and, if small quantities of EC were present, superior to filipin. In all specimens, we could sharply locate the PFO/D4-GFP signal to BrM. A semiquantitative evaluation of BrM lipid deposition is possible by measuring PFO/D4-GFP fluorescence intensity. CONCLUSIONS: The use of PFO/D4-GFP allowed a robust and direct detection of EC in aged murine BrM. In wholemount samples, its strong and stable fluorescence facilitated a semiquantitative evaluation of BrM-EC content over a large area. The patterns of EC deposition in murine BrM wholemounts are comparable with findings in human BrM wholemounts. Perfringolysin O/D4-GFP could be an important tool for investigating the effects of BrM lipid deposition in mouse models.


Asunto(s)
Envejecimiento/metabolismo , Lámina Basal de la Coroides/metabolismo , Ésteres del Colesterol/metabolismo , Proteínas Hemolisinas , Degeneración Macular/diagnóstico , Envejecimiento/patología , Animales , Toxinas Bacterianas , Lámina Basal de la Coroides/ultraestructura , Células Cultivadas , Clostridium perfringens , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Degeneración Macular/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión
12.
Clin Infect Dis ; 56(8): 1132-40, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23300241

RESUMEN

BACKGROUND: In May-July 2011, Germany experienced a large food-borne outbreak of Shiga toxin 2-producing Escherichia coli (STEC O104:H4) with 3842 cases, including 855 cases with hemolytic uremic syndrome (HUS) and 53 deaths. METHODS: A multicenter study was initiated in 5 university hospitals to determine pathogen shedding duration. Diagnostics comprised culture on selective media, toxin enzyme-linked immunosorbent assay, and polymerase chain reaction. Results were correlated with clinical and epidemiologic findings. Testing for pathogen excretion was continued after discharge of the patient. RESULTS: A total of 321 patients (104 male, 217 female) were included (median age, 40 years [range, 1-89 days]). Median delay from onset of symptoms to hospitalization was 4 days (range, 0-17 days). Two hundred nine patients presented with HUS. The estimate for the median duration of shedding was 17-18 days. Some patients remained STEC O104:H4 positive until the end of the observation time (maximum observed shedding duration: 157 days). There was no significant influence of sex on shedding duration. Patients presenting with HUS had a significantly shortened shedding duration (median, 13-14 days) compared to non-HUS patients (median, 33-34 days). Antimicrobial treatment was also significantly associated with reduced shedding duration. Children (age≤15 years) had longer shedding durations than adults (median, 35-41 vs 14-15 days). CONCLUSIONS: STEC O104:H4 is usually eliminated from the human gut after 1 month, but may sometimes be excreted for several months. Proper follow-up of infected patients is important to avoid further pathogen spread.


Asunto(s)
Derrame de Bacterias , Brotes de Enfermedades , Escherichia coli Enterohemorrágica , Infecciones por Escherichia coli/epidemiología , Heces/microbiología , Síndrome Hemolítico-Urémico/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Infecciones por Escherichia coli/microbiología , Femenino , Alemania/epidemiología , Síndrome Hemolítico-Urémico/microbiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores Sexuales , Estadísticas no Paramétricas , Adulto Joven
13.
PLoS One ; 8(1): e53440, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23301072

RESUMEN

The acute disease antigen A (adaA) gene is believed to be associated with Coxiella burnetii strains causing acute Q fever. The detailed analysis of the adaA genomic region of 23 human- and 86 animal-derived C. burnetii isolates presented in this study reveals a much more polymorphic appearance and distribution of the adaA gene, resulting in a classification of C. burnetii strains of better differentiation than previously anticipated. Three different genomic variants of the adaA gene were identified which could be detected in isolates from acute and chronic patients, rendering the association of adaA positive strains with acute Q fever disease disputable. In addition, all adaA positive strains in humans and animals showed the occurrence of the QpH1 plasmid. All adaA positive isolates of acute human patients except one showed a distinct SNP variation at position 431, also predominant in sheep strains, which correlates well with the observation that sheep are a major source of human infection. Furthermore, the phylogenetic analysis of the adaA gene revealed three deletion events and supported the hypothesis that strain Dugway 5J108-111 might be the ancestor of all known C. burnetii strains. Based on our findings, we could confirm the QpDV group and we were able to define a new genotypic cluster. The adaA gene polymorphisms shown here improve molecular typing of Q fever, and give new insights into microevolutionary adaption processes in C. burnetii.


Asunto(s)
Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Cromosomas Bacterianos/ultraestructura , Coxiella burnetii/genética , Coxiella burnetii/metabolismo , Evolución Molecular , Fiebre Q/microbiología , Antígenos Bacterianos/fisiología , Proteínas de la Membrana Bacteriana Externa , Proteínas Bacterianas/fisiología , Cartilla de ADN/genética , ADN Bacteriano/genética , Eliminación de Gen , Marcadores Genéticos , Genotipo , Humanos , Tipificación Molecular , Filogenia , Polimorfismo Genético , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
Curr Infect Dis Rep ; 15(1): 4-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23212721

RESUMEN

In 2011, a large outbreak caused by a Shiga toxin producing E. coli (STEC) occurred in Northern Germany, with a satellite outbreak in Western France, including the highest number of hemolytic uremic syndrome (HUS) cases ever encountered during a STEC outbreak. The outbreak strain was characterized as an enteroaggregative E. coli of serotype O104:H4 expressing a phage-encoded Shiga toxin 2. The majority of STEC infections and HUS cases were observed in adults, with a preponderance of the female gender. The outbreak imposed huge challenges on clinicians, microbiologists, and epidemiologists but also provided important new insight for the understanding of STEC infection. Thus, novel therapeutic strategies in the treatment of HUS in adults and for decolonization of long-term STEC carriers were evaluated. This review highlights the unusual features of the recent O104:H4 outbreak and focuses on emerging new strategies in diagnostics and treatment of acute STEC-related disease, as well as STEC long-term carriage.

15.
JAMA ; 307(10): 1046-52, 2012 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-22416100

RESUMEN

CONTEXT: An outbreak of Shiga toxin-producing enteroaggregative Escherichia coli (STEC O104:H4) infection with a high incidence of hemolytic uremic syndrome (HUS) occurred in Germany in May 2011. Antibiotic treatment of STEC infection is discouraged because it might increase the risk of HUS development. However, antibiotic therapy is widely used to treat enteroaggregative E coli infection. In the German outbreak, a substantial number of patients received prophylactic azithromycin treatment as part of a therapeutic regimen with the C5 antibody eculizumab. OBJECTIVE: To analyze the duration of bacterial shedding in patients with STEC infection who did and did not receive oral azithromycin therapy. DESIGN, SETTING, AND PATIENTS: At a single center in Lübeck, Germany, 65 patients with STEC infection, including patients with HUS as well as STEC-infected outpatients without manifestation of HUS, were investigated between May 15 and July 26, 2011, and were monitored for a mean of 39.3 days after onset of clinical symptoms. MAIN OUTCOME MEASURE: Carriage of STEC after azithromycin therapy. RESULTS: Twenty-two patients received oral azithromycin and 43 patients did not receive antibiotic treatment. Among antibiotic-treated patients, long-term STEC carriage (>28 days) was observed in 1 of 22 patients (4.5%; 95% CI, 0%-13.3%) compared with 35 of 43 patients (81.4%; 95% CI, 69.8%-93.0%) who were not treated with antibiotics (P < .001). All 22 patients receiving azithromycin treatment had at least 3 STEC-negative stool specimens after the completion of treatment, and no recurrence of STEC was observed in these patients. As proof of principle, 15 patients who initially were not treated with antibiotics and were long-term STEC carriers were treated with oral azithromycin given for 3 days and subsequently had negative stool specimens. CONCLUSION: Treatment with azithromycin was associated with a lower frequency of long-term STEC O104:H4 carriage.


Asunto(s)
Antibacterianos/administración & dosificación , Azitromicina/administración & dosificación , Derrame de Bacterias/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Escherichia coli Shiga-Toxigénica/patogenicidad , Adulto , Anciano , Portador Sano/tratamiento farmacológico , Brotes de Enfermedades , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Femenino , Alemania/epidemiología , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/microbiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escherichia coli Shiga-Toxigénica/aislamiento & purificación
16.
Int J Artif Organs ; 32(9): 584-91, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19856270

RESUMEN

Biofilm formation is a major pathogenetic factor of Staphylococcus epidermidis. In S. epidermidis the alternative sigma factor sigma B was identified to regulate biofilm formation in S. epidermidis 1457. In S. aureus sigma B dependent regulation plays a minor role, whereas sarA (Staphylococcus accessory regulator) is an essential regulator. Therefore, we investigated the impact of sigma B on sarA transcription and biofilm formation in three independent S. epidermidis isolates. Mutants with dysfunctional sigma B displayed a strongly reduced biofilm formation, whereas in mutants with constitutive sigma B activity biofilm formation was increased. Transcriptional analysis revealed that icaA transcription was down-regulated in all sigma B negative mutants while icaR transcription was up-regulated. However, transcriptional differences varied between individual strains, indicating that additional sigma B-dependent regulators are involved in biofilm expression. Interestingly, despite the presence of a sigma B promoter beside two sigma A promoters no differences, or only minor ones, were observed in sarA transcription, indicating that sigma B-dependent sarA transcript has no influence on the phenotypic changes. The data observed in independent clinical S. epidermidis isolates suggests that, in contrast to S. aureus, regulation of biofilm formation by sigma B is a general feature in S. epidermidis. Additionally, we were able to demonstrate that the sarA- dependent regulation is not involved in this regulatory pathway.


Asunto(s)
Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas , Factor sigma/metabolismo , Staphylococcus epidermidis/metabolismo , Transactivadores/genética , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica , Genes Reguladores , Genotipo , Meticilina/farmacología , Resistencia a la Meticilina , Mutación , Fenotipo , Polisacáridos Bacterianos/metabolismo , Regiones Promotoras Genéticas , Factor sigma/genética , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/crecimiento & desarrollo , Staphylococcus epidermidis/patogenicidad , Transcripción Genética
17.
Top Curr Chem ; 288: 157-82, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-22328030

RESUMEN

Medical device-associated infections, most frequently caused by Staphylococcus epidermidis and Staphylococcus aureus, are of increasing importance in modern medicine. The formation of adherent, multilayered bacterial biofilms is crucial in the pathogenesis of these infections. Polysaccharide intercellular adhesin (PIA), a homoglycan of ß-1,6-linked 2-acetamido-2-deoxy-D: -glucopyranosyl residues, of which about 15% are non-N-acetylated, is central to biofilm accumulation in staphylococci. It transpires that polysaccharides - structurally very similar to PIA - are also key to biofilm formation in a number of other organisms including the important human pathogens Escherichia coli, Aggregatibacter (Actinobacillus) actinomycetemcomitans, Yersinia pestis, and Bordetella spp. Apparently, synthesis of PIA and related polysaccharides is a general feature important for biofilm formation in diverse bacterial genera. Current knowledge about the structure and biosynthesis of PIA and related polysaccharides is reviewed. Additionally, information on their role in pathogenesis of biomaterial-related and other type of infections and the potential use of PIA and related compounds for prevention of infection is evaluated.

18.
Microbiology (Reading) ; 154(Pt 9): 2827-2836, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18757816

RESUMEN

Staphylococcal biofilm formation depends on the transcription factor sigma(B). We further investigated the role of sigma(B) in biofilm formation and persistence in vitro and in vivo in a subcutaneous rat model. As expected, expression of all sigma(B) operon genes was transiently higher in the first 6 h of biofilm formation compared to planktonic bacteria, concurrent with a temporary upregulation of icaA and aap expression. However, we also observed a second upregulation of sigB expression in biofilm more than 2 days old without upregulation of icaA or aap. Biofilm formation by Staphylococcus epidermidis strains 8400 and 1457 was compared to that of isogenic mutants with inactivation of rsbU, of rsbUVW and of the entire sigma(B) operon. Both wild-type strains and the constitutively sigB-expressing rsbUVW mutant showed a strong biofilm-positive phenotype. The rsbUVW mutant biofilm was, however, thinner and more evenly spread than the wild-type biofilm. Inactivation of SigB in the rsbUVWsigB mutant or mutation of the positive regulator RsbU reduced both the number of sessile bacteria and polysaccharide intercellular adhesin (PIA) synthesis. These differences between the wild-types and their respective mutants appeared after 6 h in in vitro biofilms but only after 4 days in in vivo biofilms. Our results provide additional evidence for a role for sigma(B) in biofilm formation. They also suggest a role for sigma(B) in biofilm maturation and stability that is independent of PIA or accumulation-associated protein (Aap) and point to significant differences in the temporal development between in vitro and in vivo biofilms.


Asunto(s)
Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , Factor sigma/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/metabolismo , Análisis de Varianza , Animales , Proteínas Bacterianas/genética , Catéteres de Permanencia/microbiología , ADN Bacteriano/genética , Reacción a Cuerpo Extraño/microbiología , Regulación Bacteriana de la Expresión Génica , Microscopía Confocal , Microscopía Electrónica de Rastreo , Mutación , Operón , Fenotipo , Polisacáridos Bacterianos/biosíntesis , ARN Bacteriano/genética , Ratas , Ratas Endogámicas F344 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor sigma/genética , Staphylococcus epidermidis/genética , Factores de Tiempo , Regulación hacia Arriba
19.
Biomaterials ; 28(9): 1711-20, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17187854

RESUMEN

Nosocomial staphylococcal foreign-body infections related to biofilm formation are a serious threat, demanding new therapeutic and preventive strategies. As the use of biofilm-associated factors as vaccines is critically restricted by their prevalence in natural staphylococcal populations we studied the distribution of genes involved in biofilm formation, the biofilm phenotype and production of polysaccharide intercellular adhesin (PIA) in clonally independent Staphylococcus aureus and Staphylococcus epidermidis strains isolated from prosthetic joint infections after total hip or total knee arthroplasty. Biofilm formation was detected in all S. aureus and 69.2% of S. epidermidis strains. Importantly, 27% of biofilm-positive S. epidermidis produced PIA-independent biofilms, in part mediated by the accumulation associated protein (Aap). Protein-dependent biofilms were exclusively found in S. epidermidis strains from total hip arthroplasty (THA). In S. aureus PIA and proteins act cooperatively in biofilm formation regardless of the infection site. PIA and protein factors like Aap are of differential importance for the pathogenesis of S. epidermidis in prosthetic joint infections (PJI) after THA and total knee arthroplasty (TKA), implicating that icaADBC cannot serve as a general virulence marker in this species. In S. aureus biofilm formation proteins are of overall importance and future work should focus on the identification of functionally active molecules.


Asunto(s)
Adhesinas Bacterianas/metabolismo , Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/aislamiento & purificación , Staphylococcus epidermidis/aislamiento & purificación , Prótesis de Cadera/efectos adversos , Humanos , Prótesis de la Rodilla/efectos adversos , Polisacáridos Bacterianos/metabolismo , Infecciones Relacionadas con Prótesis/etiología
20.
Anal Bioanal Chem ; 387(2): 399-408, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16955256

RESUMEN

Medical device-associated infections, most frequently caused by coagulase-negative staphylococci, especially Staphylococcus epidermidis, are of increasing importance in modern medicine. The formation of adherent, multilayered bacterial biofilms is the most important factor in the pathogenesis of these infections, which regularly fail to respond to appropriate antimicrobial therapy. Progress in elucidating the factors functional in elaboration of S. epidermidis biofilms and the regulation of their expression with a special emphasis on the role of quorum sensing are reviewed. Significant progress has been made in recent years, which provides the rationale for developing better preventive, therapeutic and diagnostic measures.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Percepción de Quorum , Staphylococcus epidermidis/citología , Fenómenos Fisiológicos Bacterianos , Comunicación Celular/fisiología , Staphylococcus epidermidis/fisiología
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