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1.
Clin Microbiol Infect ; 25(1): 108.e1-108.e7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29705558

RESUMO

OBJECTIVES: Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia. METHODS: We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%). RESULTS: A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68-0.89, optimism-corrected AUCs 0.63-0.85) and pathogen-guided (12 models, AUCs 0.75-0.98, optimism-corrected AUCs 0.64-0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy. CONCLUSIONS: Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires further prospective evaluation. SUMMARY: Readily available epidemiologic risk factors can be used to predict susceptibility of Gram-negative organisms among patients with bacteraemia, using automated decision-making models.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Técnicas de Apoio para a Decisão , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Criança , Pré-Escolar , Tomada de Decisão Clínica , Farmacorresistência Bacteriana Múltipla , Registros Eletrônicos de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
2.
Clin Microbiol Infect ; 24(5): 493-499, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28811241

RESUMO

OBJECTIVES: Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. METHODS: We conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015. RESULTS: Among 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91-0.93), and positive predictive value was 0.66 (95% CI 0.61-0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five. CONCLUSIONS: In patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.


Assuntos
Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Hemocultura , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Hemocultura/métodos , Hemocultura/normas , Criança , Pré-Escolar , Tomada de Decisão Clínica , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Gerenciamento Clínico , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Illinois/epidemiologia , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Razão de Chances , Ontário/epidemiologia , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
4.
Antimicrob Agents Chemother ; 50(8): 2872-4, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16870791

RESUMO

We screened 313 ceftazidime-resistant Enterobacteriaceae isolates obtained in the United States from 1999 to 2004 for all three known qnr genes. A qnr gene was present in 20% of Klebsiella pneumoniae isolates, 31% of Enterobacter sp. isolates, and 4% of Escherichia coli isolates. qnrA and qnrB occurred with equivalent frequencies and, except for qnrB in enterobacters, were stable over time. qnrS was absent.


Assuntos
Antibacterianos/farmacologia , Ceftazidima/farmacologia , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Genes Bacterianos , Prevalência , Distribuição por Idade , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/epidemiologia , Escherichia coli , Feminino , Humanos , Pacientes Internados , Klebsiella pneumoniae , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Dados de Sequência Molecular , Estudos Retrospectivos , Salmonella enterica/classificação , Salmonella enterica/genética , Homologia de Sequência de Aminoácidos , Estados Unidos/epidemiologia
5.
Antimicrob Agents Chemother ; 49(7): 3001-3, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15980384

RESUMO

The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains in the United States.


Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Plasmídeos/genética , Quinolonas/farmacologia , Proteínas de Bactérias/genética , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Estados Unidos/epidemiologia
6.
J Appl Physiol (1985) ; 89(6): 2258-62, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11090576

RESUMO

We have previously shown that raising arterial PCO(2) (Pa(CO(2))) by small increments in dogs ventilated below the apneic threshold (AT) results in almost complete tracheal constriction before the return of phrenic activity (Dickstein JA, Greenberg A, Kruger J, Robicsek A, Silverman J, Sommer L, Sommer D, Volgyesi G, Iscoe S, and Fisher JA. J Appl Physiol 81: 1844-1849, 1996). We hypothesized that, if increasing chemical drive above the AT mediates increasing constrictor drive to tracheal smooth muscle, then pulmonary slowly adapting receptor input should elicit more tracheal dilation below the AT than above. In six methohexital sodium-anesthetized, paralyzed, and ventilated dogs, we measured changes in tracheal diameter in response to step increases in tidal volume (VT) or respiratory frequency (f) below and above the AT at constant Pa(CO(2)) ( approximately 40 and 67 Torr, respectively). Increases in VT (400-1,200 ml) caused significantly more (P = 0.005) tracheal dilation below than above AT (7.0 +/- 2.2 vs. 2.8 +/- 1.0 mm, respectively). In contrast, increases in f (14-22 breaths/min) caused similar (P = 0.93) tracheal dilations below and above (1.0 +/- 1.3 and 1.0 +/- 0.8 mm, respectively) AT. The greater effectiveness of dilator stimuli below compared with above the AT is consistent with the hypothesis that drive to tracheal smooth muscle increases even after attainment of maximal constriction. Our results emphasize the importance of controlling PCO(2) with respect to the AT when tracheal smooth muscle tone is experimentally altered.


Assuntos
Apneia/fisiopatologia , Traqueia/fisiopatologia , Animais , Artérias , Dióxido de Carbono/sangue , Limiar Diferencial , Cães , Contração Muscular , Relaxamento Muscular , Músculo Liso/fisiopatologia , Pressão Parcial , Fenômenos Fisiológicos Respiratórios , Volume de Ventilação Pulmonar
7.
Eur Respir J ; 12(3): 698-701, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9762802

RESUMO

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.


Assuntos
Hiperventilação/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Respiração , Adulto , Análise de Variância , Animais , Dióxido de Carbono/sangue , Modelos Animais de Doenças , Cães , Feminino , Humanos , Masculino , Alvéolos Pulmonares/fisiologia , Valores de Referência , Mecânica Respiratória/fisiologia
8.
J Appl Physiol (1985) ; 81(3): 1184-9, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8889752

RESUMO

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.


Assuntos
Apneia/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Ventilação Pulmonar/fisiologia , Traqueia/fisiopatologia , Animais , Cães , Feminino , Masculino
9.
J Appl Physiol (1985) ; 78(2): 388-93, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7759406

RESUMO

We describe and validate a new minimally invasive method for continuous measurement of tracheal diameter in anesthetized dogs. The method is based on measuring displacement of water into and out of a modified endotracheal tube cuff placed in the trachea. The system was calibrated to allow tracheal diameter to be calculated from known cuff volume. The resolution of the method in measuring changes in tracheal diameter is 0.1 mm over a range of approximately 10-25 mm. The apparatus was tested in five dogs by observing the response of the trachea to four stimuli previously shown to alter tracheal tone: stimulation of nasal mucosa, hyperinflation of the lungs, induction of hypocapnea, and infusion of atropine. The observed changes in tracheal diameter were generally consistent with those of previous studies. The direction and extent of changes in tracheal diameter in response to the test conditions were confirmed by fluoroscopy. We conclude that continuous measurement of volume changes in the cuff reflects corresponding changes in tracheal diameter.


Assuntos
Traqueia/fisiologia , Animais , Atropina/farmacologia , Cães , Intubação Intratraqueal , Medidas de Volume Pulmonar , Cavidade Nasal/fisiologia , Estimulação Física , Radiografia , Músculos Respiratórios/anatomia & histologia , Músculos Respiratórios/fisiologia , Traqueia/anatomia & histologia , Traqueia/diagnóstico por imagem
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