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1.
Antimicrob Agents Chemother ; 65(12): e0076821, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34606337

RESUMO

Staphylococcus aureus bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective, due to insufficient penetration into the infectious site. In an osteomyelitis model, the single local administration of nanoparticle-encapsulated daptomycin allows sterilization of the infectious sites after 4 and 14 days of treatment, while daily systemic daptomycin treatment for 4 days was not effective. These results demonstrate the great potential of this local antibiotic treatment.


Assuntos
Artrite Infecciosa , Daptomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Daptomicina/uso terapêutico , Humanos , Infecções Estafilocócicas/tratamento farmacológico
2.
Artigo em Inglês | MEDLINE | ID: mdl-30858223

RESUMO

Impeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum ß-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone ß-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of ß-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the in vivo efficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepime in vivo The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused by Enterobacteriaceae expressing ESBLs.


Assuntos
Compostos Azabicíclicos/farmacologia , Cefepima/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Combinação Piperacilina e Tazobactam/farmacologia , Sulbactam/farmacologia , Triazóis/farmacologia , Inibidores de beta-Lactamases/farmacologia , Espectrometria de Massas por Ionização por Electrospray
3.
Ann Emerg Med ; 74(4): 580-591, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30982631

RESUMO

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pró-Calcitonina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Esquema de Medicação , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Procedimentos Desnecessários , Adulto Jovem
4.
Can J Microbiol ; 63(6): 475-492, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28257583

RESUMO

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.


Assuntos
Neoplasias do Sistema Digestório/microbiologia , Microbiota , Boca/microbiologia , Microbioma Gastrointestinal , Humanos , Doenças da Boca/microbiologia
5.
BMC Emerg Med ; 17(1): 27, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854874

RESUMO

BACKGROUND: Sepsis management in the Emergency Department remains a daily challenge. The Surviving Sepsis Campaign (SSC) has released three-hour bundle. The implementation of these bundles in European Emergency Departments remains poorly described. The main objective was to assess the compliance with the Severe Sepsis Campaign 3-h bundle (blood culture, lactate dosage, first dose of antibiotics and 30 ml/kg fluid challenge). Secondary objectives were the analysis of the delay of severe sepsis recognition and description of the population. METHODS: In accordance with STROBE statement, we performed a retrospective study in two French University Hospital Emergency Departments from February to August 2015. Patients admitted during the study period were screened using the electronic files of the hospital databases. Patient's files were reviewed and included in the study if they met severe sepsis criteria. Demographics, comorbities, treatments were recorded. Delays from admission to severe sepsis diagnosis, fluid loading onset and antibiotics administration were calculated. RESULTS: One hundred thirty patients were included (76 men, mean age 71 ± 14 years). Blood culture, lactate dosage, antibiotics and 30 ml/kg fluid loading were performed within 3 hours in % [95% confidence interval] 100% [96-100%], 62% [54-70%], 49% [41-58%] and 19% [13-27%], respectively. 25 patients out of 130 (19% [13-27%]) fulfilled each criteria of the 3-h bundle. The mean fluid loading volume was 18 ± 11 ml/kg. Mean delay between presentation and severe sepsis diagnosis was 200 ± 263 min, from diagnosis to fluid challenge and first antibiotic dose, 10 ± 27 min and 20 ± 55 min, respectively. CONCLUSION: Compliance with SSC 3-h bundle and delay between admission and sepsis recognition have to be improved. If confirmed by other studies, an improvement program might be deployed.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Sepse/diagnóstico , Sepse/terapia , Adulto , Idoso , Feminino , França , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tempo para o Tratamento , Triagem
6.
Infection ; 43(6): 681-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25998004

RESUMO

OBJECTIVE: Fluoroquinolones and 3rd-generation cephalosporins that are prescribed for pneumonia may be avoided and replaced by a penicillin in some cases. We aimed to determine if the proportion of patients treated for pneumonia with a cephalosporin, a fluoroquinolone or both varies among Emergency Departments (EDs), and to estimate the proportion of avoidable prescriptions. METHODS: This was a retrospective study of patients treated for pneumonia in eight French EDs, and subsequently hospitalized in non-ICU wards. Third-generation cephalosporins or respiratory fluoroquinolones were presumed unavoidable if they met both criteria: (1) age ≥65 years or comorbid condition; and (2) allergy or intolerance to penicillin, or failure of penicillin, or previous treatment with penicillin, or for fluoroquinolones only, suspected legionellosis. RESULTS: We included 832 patients. Thirty-four percent (95 % CI, 31-38 %) of patients were treated with a cephalosporin, a respiratory fluoroquinolone or both (range among EDs 19-44 %). Four EDs were independent risk factors for prescription of a cephalosporin, a fluoroquinolone or both [adjusted OR, 2.27 (1.64-3.15)], as were immune compromise [aOR 2.54 (1.56-4.14)], antibacterial therapy started before arrival in the ED [aOR 3.32 (2.30-4.81)], REA-ICU class III or IV [aOR 1.93 (1.15-3.23)], PSI class V [aOR 1.49 (1.00-2.20)], fluid resuscitation [aOR 3.98 (2.49-6.43)] and non-invasive ventilation in the ED [aOR, 7.18 (1.7-50.1)]. Treatment with a cephalosporin, a fluoroquinolone or both was avoidable in 67 % (62-73 %) of patients. CONCLUSION: Cephalosporins and fluoroquinolones use in pneumonia is highly variable among EDs. The majority of these prescriptions are avoidable. Antibiotic stewardship programs should be implemented to restrict their use in EDs.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Uso de Medicamentos , Serviço Hospitalar de Emergência , Feminino , França , Humanos , Masculino , Penicilinas/uso terapêutico , Proibitinas , Estudos Retrospectivos , Resultado do Tratamento
7.
Crit Care ; 19: 303, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26306393

RESUMO

INTRODUCTION: Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. METHODS: Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. RESULTS: One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. CONCLUSIONS: We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.


Assuntos
Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Meningites Bacterianas/tratamento farmacológico , Rifampina/uso terapêutico , Infecções Comunitárias Adquiridas , Feminino , França/epidemiologia , Escala de Resultado de Glasgow , Mortalidade Hospitalar , Humanos , Masculino , Meningites Bacterianas/mortalidade , Meningite Meningocócica/tratamento farmacológico , Meningite Meningocócica/mortalidade , Meningite Pneumocócica/tratamento farmacológico , Pessoa de Meia-Idade , Neisseria meningitidis , Estudos Retrospectivos , Resultado do Tratamento
8.
Palliat Med ; 29(6): 564-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25739966

RESUMO

BACKGROUND: Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase of cancer. CASES PRESENTATION: Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases. Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3 analgesics had not been tolerated. CASES MANAGEMENT: Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the right motor cortex. CASES OUTCOME: Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal level of consciousness and lucidity. Patient 2's pain was also markedly decreased over the days following these five consecutive sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patient's anxiety and mood. CONCLUSION: In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patient's quality of life.


Assuntos
Analgesia/métodos , Córtex Motor/fisiologia , Neoplasias/complicações , Dor Intratável/terapia , Cuidados Paliativos/métodos , Estimulação Magnética Transcraniana/métodos , Idoso , Feminino , Humanos , Manejo da Dor/métodos , Resultado do Tratamento , Adulto Jovem
9.
Prehosp Emerg Care ; 19(2): 254-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25295382

RESUMO

OBJECTIVE: It has been proved that emergency medical dispatch centers (EMDC) save lives by promoting an appropriate allocation of emergency medical service resources. Indeed, optimal dispatcher call duration is pivotal to reduce the time gap between the time a call is placed and the delivery of medical care. However, little is known about the impact of work shift configurations (i.e., work shift duration and work shift rotation throughout the day) and dispatcher call duration. Thus, the objective of our study was to assess the effect of work shift configurations on dispatcher call duration. METHODS: During a 1-year study period, we analyzed the dispatcher call durations for medical and trauma calls during the 4 different work shift rotations (day, morning, evening, and night) and during the 10-hour work shift of each dispatcher in the EMDC of Nantes. We extracted dispatcher call durations from our advanced telephone system, configured with CC Pulse + (Genesys, Alcatel Lucent), and collected them in a custom designed database (Excel, Microsoft). Afterward, we analyzed these data using linear mixed effects models. RESULTS: During the study period, our EMDC received 408,077 calls. Globally, the mean dispatcher call duration was 107 ± 45 seconds. Based on multivariate linear mixed effects models, the dispatcher call duration was affected by night work shift and work shift duration greater than 8 hours, increasing it by about 10 ± 1 seconds and 4 ± 1 seconds, respectively (both p < 0.001). CONCLUSION: Our study showed that there was a statistically significant difference in dispatcher call duration over work shift rotation and duration, with longer durations seen over night shifts and shifts over 8 hours. While these differences are small and may not have clinical significance, they may have implications for EMDC efficiency.


Assuntos
Serviços Médicos de Emergência , Socorristas , Tolerância ao Trabalho Programado , Carga de Trabalho , Sistemas de Comunicação entre Serviços de Emergência , Humanos , Fatores de Tempo
10.
J Infect Dis ; 210(5): 814-23, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24620024

RESUMO

BACKGROUND: Linezolid is considered as a therapeutic alternative to the use of glycopeptides for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Clinical studies reported a potent survival advantage conferred by the oxazolidinone and called into question the use of glycopeptides as first-line therapy. METHODS: In a mouse model of MRSA-induced pneumonia, quantitative bacteriology, proinflammatory cytokine concentrations in lung, myeloperoxidase activity, Ly6G immunohistochemistry, and endothelial permeability were assessed to compare therapeutic efficacy and immunomodulative properties of linezolid and vancomycin administered subcutaneously every 12 hours. RESULTS: Significant antibacterial activity was achieved after 48 hours of treatment for linezolid and vancomycin. Levels of interleukin 1ß, a major proinflammatory cytokine, and macrophage inflammatory protein 2, a chemokine involved in the recruitment of neutrophils, were decreased by both antimicrobials. Only linezolid was able to dramatically reduce the production of tumor necrosis factor α. Analysis of myeloperoxidase activity and Ly6G immunostaining showed a dramatic decrease of neutrophil infiltration in infected lung tissues for linezolid-treated animals. A time-dependent increase of endothelial permeability was observed for the control and vancomycin regimens. Of interest, in the linezolid group, decreased endothelial permeability was detected 48 hours after infection. CONCLUSIONS: Our results indicate that linezolid could be superior to vancomycin for the management of MRSA pneumonia by attenuating an excessive inflammatory reaction and protecting the lung from pathogen-associated damages.


Assuntos
Acetamidas/administração & dosagem , Antibacterianos/administração & dosagem , Fatores Imunológicos/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Neutrófilos/efeitos dos fármacos , Oxazolidinonas/administração & dosagem , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/patologia , Animais , Antígenos Ly/análise , Carga Bacteriana , Citocinas/análise , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Injeções Subcutâneas , Linezolida , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Neutrófilos/imunologia , Peroxidase/análise , Pneumonia Estafilocócica/imunologia , Vancomicina/administração & dosagem
11.
Crit Care Med ; 42(6): e441-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24732238

RESUMO

OBJECTIVES: Pseudomonas aeruginosa infection is a clinically relevant infection involved in pneumonia in ICUs. Understanding the type of immune response initiated by the host during pneumonia would help defining new strategies to interfere with the bacteria pathogenicity. In this setting, the role of natural killer cells remains controversial. We assessed the role of systemic natural killer cells in a Pseudomonas aeruginosa mouse pneumonia model. DESIGN: Experimental study. SETTING: Research laboratory from a university hospital. SUBJECTS: RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g). INTERVENTIONS: Lung injuries were assessed by bacterial load, myeloperoxidase activity, endothelial permeability (pulmonary edema), immune cell infiltrate (histological analysis), proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads were assessed in the lungs and spleen. Natural killer cell number and status were assessed in spleen (flow cytometry and quantitative polymerase chain reaction). Depletion of natural killer cells was achieved through an IV anti-asialo-GM1 antibody injection. MEASUREMENTS AND MAIN RESULTS: Pseudomonas aeruginosa tracheal instillation led to an acute pneumonia with a rapid decrease of bacterial load in lungs and with an increase of endothelial permeability, proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß), and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs. Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation and maturation (CD69 and KLRG1 molecules) were increased in splenic natural killer cells during Pseudomonas aeruginosa infection. Splenic natural killer cells activated upon Pseudomonas aeruginosa infection produced interferon-γ but not interleukin-10. Ultimately, mice depleted of natural killer cells displayed an increased neutrophil numbers in the lungs and an increased mortality rate without bacterial load modifications in the lungs, indicating that mice depleted of natural killer cells were much more susceptible to infection compared with control animals. CONCLUSIONS: We report for the first time that natural killer cells play a major role in the mice susceptibility toward a Pseudomonas aeruginosa-induced acute pneumonia model.


Assuntos
Suscetibilidade a Doenças/imunologia , Células Matadoras Naturais/imunologia , Pulmão/imunologia , Neutrófilos/metabolismo , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa , Baço/imunologia , Animais , Separação Celular , Modelos Animais de Doenças , Suscetibilidade a Doenças/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interferon gama/análise , Interleucina-10/análise , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos , Peroxidase/análise , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade , Fator de Necrose Tumoral alfa/análise
12.
Microb Ecol ; 67(3): 690-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24402367

RESUMO

Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota.


Assuntos
Antineoplásicos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/genética , Transplante de Medula Óssea , DNA Bacteriano/genética , Fezes/microbiologia , Linfoma não Hodgkin/terapia , Microbiota/efeitos dos fármacos , RNA Ribossômico 16S/genética , Adulto , Bactérias/isolamento & purificação , Cromatografia Líquida de Alta Pressão , DNA Bacteriano/isolamento & purificação , Eletroforese em Gel de Gradiente Desnaturante , Feminino , França , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Análise de Sequência de RNA
15.
J Emerg Med ; 46(6): 857-64, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24565882

RESUMO

BACKGROUND: Many adverse drug events (ADEs) are not identified by emergency physicians. Research has been done to study risk factors for ADEs and help emergency physicians diagnose ADEs. However, no research has specifically examined the causes underlying a lack of attribution of ADEs to medications in emergency department (ED) patients. OBJECTIVE: We conducted an exploratory study in a medical ED to search for the factors associated with ADE nonrecognition that are related to ED patients and ADEs. METHODS: We conducted an observational study in the medical ED of a French tertiary care hospital between January and December 2009. The study focused on all ADEs, whether or not they were related to the patient's chief complaint. ADEs were identified by an expert physician and pharmacist based on National Electronic Injury Surveillance System criteria. An ADE was considered "attributed" if any evidence of ADE suspicion, ADE diagnosis, or ADE management was documented on ED charts. Factors associated with ADE nonrecognition were identified using multiple logistic regression analysis. RESULTS: Of the 465 included patients, 90 experienced an ADE at ED visit (19.4%; 95% confidence interval [CI] 15.9%-23.2%). Emergency physicians correctly recognized 36 of these cases (40.0%; 95% CI 29.8%-50.9%). On multivariate analysis, ADE nonrecognition was significantly associated with the following variables: nonrelation between the ADE and the patient's chief complaint; daily prescription of four drugs or more; and hospitalization ADE severity category. CONCLUSIONS: Our results emphasize the importance of searching for ADEs in patients with daily polypharmacy or whose chief complaint does not seem to be drug related.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Serviço Hospitalar de Emergência , Polimedicação , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Consciência/induzido quimicamente , Constipação Intestinal/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Infecções/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Desequilíbrio Hidroeletrolítico/induzido quimicamente
16.
J Antimicrob Chemother ; 68(1): 177-83, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22941899

RESUMO

OBJECTIVES: To assess the activity of ceftolozane, a novel oxyimino-cephalosporin, in comparison with ceftazidime and piperacillin/tazobactam against a multidrug-resistant Pseudomonas aeruginosa strain using a murine model of pneumonia. METHODS: Quantitative bacteriology, survival, histological examination, myeloperoxidase activity, proinflammatory cytokine levels in lungs and endothelial permeability were evaluated to determine the effects of ceftolozane and comparators on P. aeruginosa-induced pneumonia. RESULTS: After 48 h of treatment, ceftolozane reduced the bacterial load by 3-4 log(10) cfu/g of lung. Systemic dissemination of the pulmonary infection and development of lung damage were inhibited in all ß-lactam-treated animals. P. aeruginosa-induced pneumonia led to elevated concentrations of tumour necrosis factor-α, interleukin (IL)-1ß and macrophage inflammatory protein (MIP)-2 in the lungs. While the levels of proinflammatory cytokines decreased following ceftazidime and piperacillin/tazobactam therapy, ceftolozane exhibited increased concentrations of IL-1ß and MIP-2 after 24 h of infection, resulted in significantly increased levels of recruited neutrophils within the infected lung without increasing lung endothelial permeability. CONCLUSIONS: These data strongly support ceftolozane as an effective option for the treatment of severe P. aeruginosa respiratory infections by improving the early pulmonary inflammatory response without impairing 48 h post-infection homeostasis.


Assuntos
Anti-Infecciosos/farmacologia , Cefalosporinas/farmacologia , Modelos Animais de Doenças , Pneumonia Bacteriana/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Doença Aguda , Animais , Anti-Infecciosos/uso terapêutico , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/patologia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Pneumonia Bacteriana/patologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Resultado do Tratamento
17.
Pharmacoepidemiol Drug Saf ; 22(2): 151-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23124864

RESUMO

PURPOSE: To develop the first questionnaire to obtain a complete medication history by documenting self-medication history in adult patients admitted to a medical emergency department (ED). METHODS: A Questionnaire to document Self-Medicating Behaviours (QSMB) was developed between January and September 2008 (reference period), tested and refined between October and December 2008, and used routinely between January and December 2009 (routine period) in a tertiary care medical ED. The rate of SMBs measured with QSMB during the routine period was compared to the SMB rate measured with a spontaneous reporting method during the reference period. As survey teams changed every trimester, we also analysed the evolution of SMB rate over time. RESULTS: QSMB is divided into two parts. The first part consists of 20 closed-ended questions exploring all indications and dimensions of self-medication. The second part assesses the characteristics of each medication mentioned by the patient in the first 20 questions. The patients interviewed during reference and routine periods did not significantly differ. The routine period patients reported a third more SMBs (89.8% vs 57.6%, respectively; p < 0.0001) and twice more self-medication drugs than the reference period patients. SMB rate was significantly different between the survey teams during the reference period (p < 0.0001), but not during the routine period (p = 0.078). CONCLUSIONS: This questionnaire complements the traditional tools that are already available to collect medication histories of prescribed drugs. It may improve the recognition of iatrogenic conditions related to self-medication, and provide support to public health efforts and research programs on self-medication.


Assuntos
Serviço Hospitalar de Emergência , Automedicação , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Serviços Médicos de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Automedicação/estatística & dados numéricos
18.
J Emerg Med ; 44(5): 970-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23478183

RESUMO

BACKGROUND: Transient ischemic attack (TIA) is common and precedes 15% of strokes. TIA should be managed as a time-sensitive illness to prevent a subsequent stroke. However, management of TIA is heterogeneous, with little consensus about its optimal assessment. OBJECTIVE: The objective of this study was to determine the outcome of patients with TIA evaluated in the Emergency Department (ED) and managed as outpatients within a 90-day period after discharge. METHODS: All patients with symptoms of TIA admitted to the ED were eligible for inclusion. Patients were evaluated by an Emergency Physician who followed a decision algorithm used in the selection of patients for discharge. The main outcome variable was the occurrence of stroke during the 90 days after discharge from the ED. RESULTS: During a 1-year period, a total of 118 patients were evaluated for TIA in the ED, representing 1.4% of ED medical admissions: 56 (47.5%) were hospitalized and 62 (52.5%) were discharged and enrolled in the outpatient TIA management. Two (3.2%) of the discharged patients could not be contacted for follow-up. Among the patients managed as outpatients, one (1.7%) presented with an ischemic stroke and 3 (5%) experienced a subsequent TIA within a period of 90 days after discharge from the ED. The rate of stroke predicted from the ABCD2 score was 9.7% at 90 days. CONCLUSION: The results of our study suggest that outpatient management of TIA, as described in our institution's guidelines, may be a safe and effective strategy, but further confirmatory studies should be performed.


Assuntos
Assistência Ambulatorial , Ataque Isquêmico Transitório/epidemiologia , Idoso , Algoritmos , Estenose das Carótidas/diagnóstico por imagem , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Encaminhamento e Consulta , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Ultrassonografia
19.
J Emerg Med ; 44(2): 406-12, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23103064

RESUMO

BACKGROUND: Our emergency medical service developed a telephone (phone)-assisted cardiopulmonary resuscitation (PACPR) procedure. OBJECTIVES: To describe this procedure and study the factors modulating its implementation. METHODS: We conducted a single-center prospective study of telephone calls to our emergency medical communication center for cardiac arrest, for which PACPR was initiated. RESULTS: Thirty-eight patients were included in the study. In six cases, cardiopulmonary resuscitation (CPR) had been started before the call. When PACPR was initiated, CPR was performed until the rescue team arrived in 27 cases. One-third (n = 9) of the bystanders in these cases knew first-aid interventions, and all of these bystanders continued CPR until the rescue team arrived. The absence of a familial relationship between bystander and patient facilitated the continuation of CPR (100% vs. 37% with family ties, p = 0.01). CPR was continued more often if the bystander immediately agreed to PACPR than when he or she did not agree at first (88% vs. 45%, respectively, p = 0.01). When an obstacle to performing CPR was encountered, CPR was then performed in 57% of cases vs. 100% of cases with no obstacle (p = 0.003). These obstacles were associated with either the bystander (panic, apprehension, feelings of inadequacy, physical inability, indirect witness, tiredness) or the victim (morphotype, physical position). The presence of an obstacle, compared to no obstacle, associated with the bystander lowered the CPR performance rate (58% vs. 94%, respectively, p = 0.01). The presence of an obstacle, compared to no obstacle, associated with the victim also lowered CPR performance rate (50% vs. 85%, respectively, p = 0.04). CONCLUSION: Our study demonstrates the feasibility of PACPR. The results may lead to a better understanding of facilitating factors and obstacles to telephone-assisted CPR, with the goal of improving its implementation. Good command of communication tools, identification of an appropriate bystander, and appropriate victim positioning are three fundamental factors of success.


Assuntos
Reanimação Cardiopulmonar , Sistemas de Comunicação entre Serviços de Emergência , Parada Cardíaca Extra-Hospitalar/terapia , Ensino/métodos , Telefone , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Serviços Médicos de Emergência , Feminino , França , Humanos , Lactente , Recém-Nascido , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Postura , Estudos Prospectivos , Adulto Jovem
20.
Emerg Med J ; 30(1): 63-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22366041

RESUMO

OBJECTIVES: The frequency and the severity of drug-related visits in emergency department (ED) make the improvement of adverse drug event (ADE) recognition a crucial issue. As part of a research project aiming to improve the diagnosis and the management of ADEs in ED, the authors conducted a pilot study whose primary objective was to assess ADE recognition by emergency physicians. METHODS: The patients presenting to the ED were included at randomised time periods between 1 October 2007 and 31 March 2008 in this prospective cross-sectional study. The primary outcome was the frequency of ADEs that were attributed to a medication-related problem by the emergency physician. RESULTS: A total of 423 patients met the inclusion criteria, of which 95 experienced an ADE (22.5%; 95% CI 18.6% to 26.7%). Emergency physicians correctly attributed 33 of these cases (34.7%; 95% CI 25.3% to 45.2%) to a medication-related problem. Of the 28 cases in which the ADE was considered as a 'direct drug effect' (29.5%; 95% CI 20.6% to 39.7%), 16 were correctly identified by emergency physicians (57.1%; 95% CI 37.2% to 75.5%). Of the 67 cases in which the ADE was considered as a 'drug involvement in a multifactorial pathological condition' (70.5%; 95% CI 60.3% to 79.4%), 17 were correctly attributed (25.4%; 95% CI 15.5% to 37.5%). CONCLUSIONS: ADEs are frequent in EDs and are not well recognised by emergency physicians, especially when the drug is involved in a multifactorial pathological condition.


Assuntos
Competência Clínica/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Medicina de Emergência/normas , Serviço Hospitalar de Emergência/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , França , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
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