RESUMEN
Cybersecurity is currently a major issue. Large hospitals are no longer the only main targets of attacks, but all healthcare organizations and establishments, without distinction of size or activities. The information system is defined as all the resources needed to collect images, store and process them with general distribution of multiple information within an organization. Systems are therefore crucial for the functioning of a medical department. Radiation oncology is one of the specialties most dependent on digital resources, for imaging, data transfer, dosimetry, treatment and so on.. Radiation oncology departments are therefore a prime target for ransomware attacks, which have increased significantly in recent years. Cybersecurity can be likened to a viral or bacterial attack. It is based on the two usual pillars of antimicrobial protection : hygiene and prophylaxis. In this article, we will detail by analogy the three classic levels of prevention of a bacillary attack: "primary prevention", which acts upstream of the infection; "secondary prevention", which acts at an early stage of its evolution; and "tertiary prevention", which acts on complications and risks of recurrence. This article is the result of an interprofessional group on behalf of SFRO, the French society of radiation oncology, with the aim of helping all teams to implement safety adapted to the specificities of a radiation oncology department in France.
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Oncología por Radiación , Humanos , Hospitales , FranciaRESUMEN
PURPOSE: Depleted uranium (DU) has several civilian and military applications. The effects of this emerging environmental pollutant on human health raise some concerns. Previous experimental studies have shown that uranium (U) exposure can disturb the central nervous system. A small quantity of U reaches the brain via the blood, but the effects on the blood-brain barrier (BBB) remain unclear. MATERIALS AND METHODS: In the present work, two cell culture models were exposed to DU for different times to study its cytotoxicity, paracellular permeability and extracellular concentration of U. The well-known immortalized human cerebral microvascular endothelial cells, hCMEC/D3, were cultured on the filter in the first model. In the second model, human primary cells of pericytes were cultured under the filter to understand the influence of cell environment after U exposure. RESULTS: The results show that U is not cytotoxic to hCMEC/D3 cells or pericytes until 500 µM (1.6 Bq.L-1). In addition, acute or chronic low-dose exposure of U did not disturb permeability and was conserved in both cell culture models. However, U is able to reach the brain compartment. During the first hours of exposure, the passage of U to the abluminal compartment was significantly reduced in the presence of pericytes. Electronic microscopy studies evidenced the formation of needlelike structures, like urchin-shaped precipitates, from 1 h of exposure. Analytical microscopy confirmed the U composition of these precipitates. Interestingly, precipitated U was detected only in endothelial cells and not in pericytes. U was localized in multilamellar or multivesicular bodies along the endo-lysosomal pathway, suggesting the involvement of these traffic vesicles in U sequestration and/or elimination. CONCLUSIONS: We show for the first time the in vitro passage of U across a human cerebral microvascular endothelial cells, and the intracellular localization of U precipitates without any cytotoxicity or modification of paracellular permeability. The difference between the results obtained with monolayers and co-culture models with pericytes illustrates the need to use complex in vitro models in order to mimic the neurovascular unit. Further in vivo studies should be performed to better understand the passage of U across the blood-brain barrier potentially involved in behavioral consequences.
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Encéfalo/irrigación sanguínea , Células Endoteliales/metabolismo , Microvasos/citología , Uranio/metabolismo , Barrera Hematoencefálica/metabolismo , Línea Celular , Técnicas de Cocultivo , Células Endoteliales/efectos de la radiación , Espacio Extracelular/metabolismo , Espacio Extracelular/efectos de la radiación , Humanos , Permeabilidad , Factores de TiempoRESUMEN
Evaluation of the consequences of low to moderate doses of ionizing radiation (IR) remains a societal challenge, especially for children exposed to CT scans. Appropriate experimental models are needed to improve scientific understanding of how exposure of the postnatal brain to IR affects behavioral functions and their related pathophysiological mechanisms, considering brain complex functional organization. In the brain, the dorsal and ventral hippocampal dentate gyrus can be involved in distinct major behavioral functions. To study the long term behavioral effects of brain exposure at low to moderate doses of IR (doses range 0.25-1 Gy), we developed three new experimental models in 10-day-old mice: a model of brain irradiation and two targeted irradiation models of the dorsal and ventral dentate gyrus. We used the technological properties of the SARRP coupled with MR imaging. Our irradiation strategy has been twofold endorsed. The millimetric ballistic specificity of our models was first validated by measuring gamma-H2AX increase after irradiation. We then demonstrated higher anxiety/depressive-like behavior, preferentially mediate by the ventral part of the dentate gyrus, in mice after brain and ventral dentate gyrus IR exposure. This work provides new tools to enhance scientific understanding of how to protect children exposed to IR.
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Conducta Animal/efectos de la radiación , Encéfalo/diagnóstico por imagen , Giro Dentado/diagnóstico por imagen , Histonas/metabolismo , Animales , Animales Recién Nacidos , Ansiedad/etiología , Ansiedad/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Giro Dentado/metabolismo , Giro Dentado/efectos de la radiación , Depresión/etiología , Depresión/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de la radiación , Imagen por Resonancia Magnética , Masculino , Ratones , Modelos Animales , Dosis de RadiaciónRESUMEN
Localization of uranium within cells is mandatory for the comprehension of its cellular mechanism of toxicity. Secondary Ion Mass Spectrometry (SIMS) has recently shown its interest to detect and localize uranium at very low levels within the cells. This technique requires a specific sample preparation similar to the one used for Transmission Electronic Microscopy, achieved by implementing different chemical treatments to preserve as much as possible the living configuration uranium distribution into the observed sample. This study aims to compare the bioaccumulation sites of uranium within liver or kidney cells after chemical fixation and cryomethods preparations of the samples: SIMS analysis of theses samples show the localization of uranium soluble forms in the cell cytoplasm and nucleus with a more homogenous distribution when using cryopreparation probably due to the diffusible portion of uranium inside the cytoplasm.
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Células Epiteliales/química , Hepatocitos/química , Fijación del Tejido/métodos , Uranio/análisis , Línea Celular , Humanos , Espectrometría de Masa de Ion SecundarioRESUMEN
Multiple direct-acting antiviral (DAA)-based regimens are now available for all hepatitis C virus (HCV) genotypes (GTs). Because HCV GT 4, 5 and 6 are less common in the United States (US) and worldwide, relatively small numbers of participants with these GTs were evaluated in individual clinical trials. To provide a comprehensive description of subtype diversity and treatment outcomes in clinical trials for these less common GTs, we analysed data from 744 participants with HCV GT4 (n = 573), GT5 (n = 81), or GT6 (n = 90) across 18 clinical trials of DAA regimens. These data are from US New Drug Applications submitted between 2014 and 2017, and our analyses included only approved regimens. Excluding unresolved or mixed subtypes, the distribution of reported GT4 subtypes was 49% 4a, 31% 4d and 16% for one of 14 other subtypes. The distribution of GT6 subtypes was 39% 6a, 27% 6e, 8% 6 L and 23% for one of 11 other subtypes. Across approved regimens, sustained virologic response rates 12 weeks post-treatment (SVR12) for GT 4, 5 and 6 ranged from 91% to 100%, 93% to 97% and 96% to 100%, respectively. SVR12 by GT4 subtype ranged from 96% to 100% for 4a and 81% to 100% for 4d. Virologic failures occurred in GT 4a, 4b, 4d and 4r. For GT6, SVR12 was 100% for all subtypes except 6 L, for which 1 of 7 participants experienced virologic failure. To our knowledge, this is the largest compilation of HCV GT 4, 5 or 6 clinical trial data. These analyses may be useful for clinicians treating HCV GT 4, 5 or 6.
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Antivirales/administración & dosificación , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Respuesta Virológica Sostenida , Ensayos Clínicos como Asunto , Hepacivirus/aislamiento & purificación , Humanos , Resultado del Tratamiento , Estados UnidosRESUMEN
Populations living in radiation-contaminated territories, such as Chernobyl and Fukushima, are chronically exposed to external gamma radiation and internal radionuclide contamination due to the large amount of 137Cs released in the environment. The effect of chronic low-dose exposure on the development of cardiovascular diseases remains unclear. Previously reported studies have shown that low-dose radiation exposure could lead to discrepancies according to dose rate. In this study, we examined the effect of very low-dose and dose-rate chronic external exposure on atherosclerosis development. ApoE-/- mice were chronically irradiated with a gamma source for 8 months at two different dose rates, 12 and 28 µGy/h, equivalent to dose rates measured in contaminated territories, with a cumulative dose of 67 and 157 mGy, respectively. We evaluated plaque size and phenotype, inflammatory profile and oxidative stress status. The results of this study showed a decrease in plaque sizes and an increase in collagen content in ApoE-/- mice exposed to 28 µGy/h for 8 months compared to nonexposed animals. The plaque phenotype was associated with an increase in anti-inflammatory and anti-oxidative gene expression. These results suggest that chronic low-dose gamma irradiation induces an upregulation of organism defenses leading to a decrease in inflammation and plaque size. To our knowledge, this is the first study to describe the possible effect of chronic external very low-dose ionizing radiation exposure for 8 months. This work could help to identify the potential existence of a dose threshold, below that which harmful effects are not exhibited and beneficial effects are potentially observed. Furthermore, these findings permit consideration of the importance of dose rate in radiation protection.
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Antioxidantes/metabolismo , Apolipoproteínas E/deficiencia , Rayos gamma/efectos adversos , Placa Aterosclerótica/metabolismo , Animales , Relación Dosis-Respuesta en la Radiación , Inflamación/complicaciones , Masculino , Ratones , Oxidación-Reducción/efectos de la radiación , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/patología , Factores de TiempoRESUMEN
INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial roles associated with the development of several diseases. OBJECTIVE: The current work investigates the epigenetic effect of chronic exposure to low doses of uranium and its inheritance across generations. Materials and Methods To test this proposition, a rodent multigenerational model, males and females, were exposed to a non-toxic concentration of uranium (40mgL-1 drinking water) for nine months. The uranium effects on were evaluated over three generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT genes expression in ovaries and testes tissues. RESULTS: Here we report a significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was significantly maintained across generations F0, F1 and F2. Furthermore, qPCR results of both tissues imply a significant change in the expression of DNA methyltransferase genes (DNMT 1 and DNMT3a/b) as well. CONCLUSION: Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context.
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Metilación de ADN/efectos de la radiación , Epigénesis Genética/efectos de la radiación , Ovario/efectos de la radiación , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Testículo/efectos de la radiación , Uranio/toxicidad , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de la radiación , Masculino , Ovario/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Ratas , Caracteres Sexuales , Testículo/metabolismoRESUMEN
90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL-1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure.
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Daño del ADN/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Radioisótopos de Estroncio/farmacología , Análisis de Varianza , Animales , Muerte Celular , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Citocinas/metabolismo , Roturas del ADN de Doble Cadena/efectos de los fármacos , Reparación del ADN , Histonas/metabolismo , Humanos , Oxidación-Reducción/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L(-1) for male rats and 40 mg·L(-1) for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L(-1) NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L(-1) NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.
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Líquido Cefalorraquídeo/metabolismo , Locomoción/fisiología , Aprendizaje por Laberinto/fisiología , Metaboloma/fisiología , Uranio/toxicidad , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Líquido Cefalorraquídeo/efectos de los fármacos , Femenino , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Metaboloma/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Uranio/administración & dosificaciónRESUMEN
The ubiquitous use of phthalate esters in plastics, building material, medical devices, personal care products and food packaging materials results in a widespread exposure of general population. This study reports measurement of urinary concentration of phthalate metabolites in France and provides a first assessment of the exposure of French pregnant women to this chemical class. For the majority of the phthalate metabolites, concentrations measured in urine were similar to those reported in previous studies except for two phthalates that were characterized by high concentrations of metabolites if compared to previous European and American studies: DiNP (Di-iso-nonylphthalate) and DEHP (Di(2-ethylhexyl)phthalate). In a second part of the study, a pharmacokinetic model was used in order to gain understanding on exposure to DEHP. A high concentration of the primary metabolite of DEHP, MEHP (Mono(2-ethylhexyl)phthalate), was thus identified probably because of a very recent exposure to perfusion materials at the hospital. Pharmacokinetics modelling highlighted that gathering data on the time gap between exposure and biomonitoring is an essential information requirement for reconstructing the dose of non persistent pollutants. Information about exposure pathway is also crucial for conducting effective reverse dosimetry.
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Contaminantes Ambientales/orina , Ácidos Ftálicos/orina , Embarazo/orina , Monitoreo del Ambiente , Contaminantes Ambientales/sangre , Contaminantes Ambientales/farmacocinética , Femenino , Francia , Humanos , Modelos Biológicos , Ácidos Ftálicos/sangre , Ácidos Ftálicos/farmacocinética , Proyectos PilotoRESUMEN
This study investigated the potential of the novel systemic pleuromutilin antibiotic BC-3781 to treat patients with an acute bacterial skin and skin structure infection (ABSSSI) caused by a Gram-positive pathogen. Patients were randomized to intravenous BC-3781 100 mg, BC-3781 150 mg, or vancomycin 1 g every 12 h. Response to treatment was assessed daily and at test of cure (TOC). The primary endpoint was the clinical success rate at TOC in the modified intent-to-treat (MITT) and clinically evaluable (CE) analysis populations. Baseline characteristics, including the frequency of methicillin-resistant Staphylococcus aureus (MRSA), were comparable between the different treatment groups. Of 210 patients randomized, 186 (88.6%) patients completed the study. Clinical success at TOC in the CE population occurred in 54 (90.0%) patients in the BC-3781 100-mg group, 48 (88.9%) in the BC-3781 150-mg group, and 47 (92.2%) in the vancomycin group. At day 3, the clinical response rate was similar across the three treatment groups. Six patients discontinued study medication following an adverse event. The incidence rate for drug-related adverse events was lower for patients receiving BC-3781 (34.3% and 39.4% in the 100-mg and 150-mg groups, respectively) than those receiving vancomycin (53.0%). When BC-3781 was used to treat ABSSSIs caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin. BC-3781 was generally well tolerated. These results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs.
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Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Piel/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Enfermedad Aguda , Adulto , Diterpenos/farmacología , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Compuestos Policíclicos , Piel/microbiología , Piel/patología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/patología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Resultado del Tratamiento , Vancomicina/farmacología , PleuromutilinasRESUMEN
OBJECTIVES: To compare the efficacy and safety of linezolid and vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan. METHODS: Patients with nosocomial pneumonia, complicated skin and soft-tissue infections or sepsis caused by MRSA were randomized to receive linezolid (600 mg every 12 h) or vancomycin (1 g every 12 h). RESULTS: One hundred patients received linezolid and 51 received vancomycin with outcomes evaluated at the end of therapy (EOT) and at the follow-up (FU), 7-14 days later. At EOT, clinical success rates in the MRSA microbiologically evaluable population were 62.9% and 50.0% for the linezolid and vancomycin groups, respectively; and microbiological eradication rates were 79.0% and 30.0% in the two groups, respectively (P < 0.0001). At FU, the clinical success rates were 36.7% for both groups and the microbiological eradication rates were 46.8% and 36.7%, respectively. Reversible anaemia (13%) and thrombocytopenia (19%) were reported more frequently in linezolid patients; laboratory analysis showed mild decrease in platelet counts with full recovery by FU. The mean platelet count in linezolid patients with thrombocytopenia was 101,000/mm(3). Significantly low platelet counts (<50,000/mm(3)) were observed more frequently in patients receiving vancomycin than in linezolid patients (6% versus 3%). Mean changes in haemoglobin levels between the two groups were not different. CONCLUSIONS: Linezolid is as effective as vancomycin for the treatment of MRSA infections and may be more effective than vancomycin in achieving microbiological eradication. Haematological adverse events were reported more frequently in linezolid-treated patients; analysis of laboratory data showed a mild reversible trend towards lower platelet counts.
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Acetamidas/uso terapéutico , Antiinfecciosos/uso terapéutico , Resistencia a la Meticilina , Oxazolidinonas/uso terapéutico , Staphylococcus aureus/efectos de los fármacos , Vancomicina/uso terapéutico , Acetamidas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/administración & dosificación , Femenino , Humanos , Japón , Linezolid , Masculino , Persona de Mediana Edad , Oxazolidinonas/efectos adversos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/administración & dosificaciónRESUMEN
In an open-label emergency-use study, 23 patients with bacterial infections caused by multiply drug resistant pathogens were treated with clinafloxacin. Efficacy and safety were evaluated by tabulating investigators' assessments at the end of treatment, treatment discontinuations and adverse event data. Most of the patients were seriously ill and had multi-organ infections, primarily respiratory tract infections such as nosocomial pneumonia and gastrointestinal infections. Eleven patients were successfully treated, two had treatment failure and 10 were not evaluable because the patients died of their underlying disease. Considering that most of the patients had several infections caused by multiply resistant pathogens, clinafloxacin may be useful for the treatment of such life-threatening episodes.
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Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Enfermedad Crítica/terapia , Farmacorresistencia Bacteriana Múltiple , Fluoroquinolonas , Adulto , Antiinfecciosos/efectos adversos , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/microbiología , Humanos , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: To assess the efficacy and safety of clinafloxacin as a single agent for the empirical treatment of febrile episodes and bacterial infections in neutropenic cancer patients. METHODS: An open label, active-controlled, randomized, parallel treatment, multicenter study was conducted where clinafloxacin monotherapy was compared to the combination of ceftazidime plus amikacin (plus optional vancomycin or teicoplanin). Four hundred and nineteen patients were randomized to receive either intravenous clinafloxacin 200 mg every 12 h or intravenous ceftazidime (2 g) iv every 8 h plus intravenous amikacin (15 mg/kg) per day in divided doses. All randomized patients were to receive a minimum of 48 h of primary study drug treatment, after which the primary treatment could be modified. Clinical and microbiological responses were evaluated at 7-21 days post-treatment after study treatment and long term (maximum 28 days), in intent-to-treat and modified intent-to-treat populations. RESULTS: Clinafloxacin and ceftazidime-amikacin were statistically equivalent for the 72-h defervescence rate, overall defervescence rate, time to defervescence, clinical success rate, by-pathogen microbiological eradication rate, and survival rate. Clinical cure was achieved in 84% (59/70) of patients who received clinafloxacin monotherapy. There were no significant differences between treatments in rates of adverse events or treatment discontinuation rates due to adverse events. CONCLUSIONS: Clinafloxacin appears to be an appropriate agent for empirical treatment in febrile neutropenic cancer patients.
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Amicacina/uso terapéutico , Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Ceftazidima/uso terapéutico , Fluoroquinolonas , Neoplasias/complicaciones , Neutropenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Amicacina/efectos adversos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Antiinfecciosos/efectos adversos , Infecciones Bacterianas/etiología , Ceftazidima/efectos adversos , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada/efectos adversos , Femenino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Teicoplanina/efectos adversos , Teicoplanina/uso terapéutico , Resultado del Tratamiento , Vancomicina/efectos adversos , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: The emergence of antibiotic-resistant organisms is of great concern in the medical community. Antibiotic sensitivity patterns were studied at a large university hospital. METHODS: From 1992 through 1999, susceptibility testing was done and results recorded for all isolates of Streptococcus pneumoniae, Enterococcus sp, Staphylococcus aureus, coagulase-negative Staphylococcus, Eshcherichia coli, Haemophilus influenzae, and Pseudomonas aeruginosa. Microbiologic and sensitivity data were reviewed and compiled. RESULTS: Over the 8-year period, several common bacterial pathogens declined in susceptibility to various antimicrobial agents. Most notable were the decreased sensitivities of S pneumoniae to penicillin (96% to 63%), coagulase-negative Staphylococcus to oxacillin (50% to 38%), and P aeruginosa to aminoglycosides [(gentamicin (85% to 64%), tobramycin (96% to 83%), amikacin (92% to 74%)] and ciprofloxacin (85% to 69%). CONCLUSIONS: These decreased antibiotic sensitivities reflect increased bacterial selection pressure as a result of widespread antibiotic use. A combined approach involving infection-control specialists, infectious disease physicians, and hospital administrators is necessary to address this increasingly difficult problem.
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Farmacorresistencia Microbiana , Hospitales Universitarios , Pruebas de Sensibilidad Microbiana , MissouriRESUMEN
An elderly woman came to our emergency room for evaluation of a syncopal episode. While climbing a flight of stairs, she had turned her head to the left and abruptly passed out. Positive physical findings included blood pressure of 141/65 mm Hg (right arm) and 80/43 mm Hg (left arm), as well as nonpalpable left radial and brachial pulses that were detectable only by Doppler ultrasonography. Carotid duplex ultrasonography showed reverse flow in the left vertebral artery and an abnormal, stenotic distal left subclavian artery. Magnetic resonance angiography confirmed complete occlusion of the left subclavian artery with classic subclavian steal. The patient had percutaneous transluminal angioplasty with stenting of the left subclavian artery and has remained asymptomatic through 2 years of follow-up with aggressive risk-factor modification.
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Síndrome del Robo de la Subclavia/complicaciones , Síndrome del Robo de la Subclavia/diagnóstico , Síncope/etiología , Anciano , Angioplastia de Balón , Femenino , Movimientos de la Cabeza , Humanos , Hipertensión/complicaciones , Hipertensión/prevención & control , Angiografía por Resonancia Magnética , Factores de Riesgo , Fumar/efectos adversos , Prevención del Hábito de Fumar , Stents , Síndrome del Robo de la Subclavia/terapia , Ultrasonografía DopplerRESUMEN
BACKGROUND: Influenza and pneumococcal infections are the most vaccine-preventable infectious diseases among the elderly population. Elderly patients (65 years and older) with chronic diseases derive substantial benefit from having current immunization status due to their high risk for respiratory diseases. However, immunization levels for influenza and pneumococcus remain suboptimal. This study sought to determine the immunization rates in a high-risk geriatric population. METHODS: Charts of consecutive patients seen in a geriatric clinic from November 1999 to February 2000 were obtained. Medical records were reviewed to assess their influenza and pneumococcal immunization status. RESULTS: Of 200 patients who qualified for the study, all had at least two indications for vaccination, yet only 34% were current with influenza immunization, and 26% were current with pneumococcus immunization. CONCLUSIONS: In a high-risk elderly population, influenza and pneumococcal immunization rates were low. Patients who received pneumococcus vaccination were more likely to receive influenza immunization as well.
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Vacunas contra la Influenza , Vacunas Neumococicas , Anciano , Anciano de 80 o más Años , Humanos , Gripe Humana/prevención & control , Missouri , Infecciones Neumocócicas/prevención & control , Factores de Riesgo , Vacunación/estadística & datos numéricosRESUMEN
In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients.
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Agranulocitosis/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Imipenem/uso terapéutico , Tienamicinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Agranulocitosis/microbiología , Antiinfecciosos/efectos adversos , Recuento de Células Sanguíneas , Canadá , Método Doble Ciego , Femenino , Humanos , Imipenem/efectos adversos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tienamicinas/efectos adversos , Resultado del Tratamiento , Estados UnidosRESUMEN
Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P = 0.001). The clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P = 0.577) in the two treatment groups. Drug-associated adverse events (P = 0.050) and treatment discontinuations (P = 0.052) were marginally more frequent in the clinafloxacin group, primarily due to phototoxicity in outpatients receiving clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs.
Asunto(s)
Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Fluoroquinolonas , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Penicilinas/uso terapéutico , Piperacilina/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Inhibidores de beta-Lactamasas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/efectos adversos , Infecciones Bacterianas/microbiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/uso terapéutico , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Penicilánico/efectos adversos , Penicilinas/efectos adversos , Piperacilina/efectos adversos , Enfermedades Cutáneas Infecciosas/microbiología , TazobactamRESUMEN
OBJECTIVE: Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy. SUMMARY BACKGROUND DATA: Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity. METHODS: This prospective, randomized, double-blind trial was conducted to compare clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections. RESULTS: Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin. CONCLUSIONS: The results of this study clearly demonstrate the safety and efficacy of clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances.