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1.
Ann Pharmacother ; 47(2): 170-80, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23341160

RESUMO

BACKGROUND: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.


Assuntos
Antibacterianos/administração & dosagem , Infecção Hospitalar/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , beta-Lactamas/administração & dosagem , Idoso , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/administração & dosagem , Cefalosporinas/uso terapêutico , Estudos de Coortes , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Esquema de Medicação , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Hospitais de Ensino , Hospitais Urbanos , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Meropeném , Pessoa de Meia-Idade , Missouri/epidemiologia , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Projetos Piloto , Piperacilina/administração & dosagem , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tienamicinas/administração & dosagem , Tienamicinas/uso terapêutico , beta-Lactamas/uso terapêutico
2.
Crit Care Med ; 40(7): 2016-21, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22584765

RESUMO

OBJECTIVE: To identify the determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. DESIGN: A retrospective cohort study of hospitalized patients with blood culture positive septic shock (January 2002-December 2007). SETTING: Barnes-Jewish Hospital, a 1,250-bed urban teaching hospital. PATIENTS: Four hundred thirty-six consecutive patients with septic shock and a positive blood culture. INTERVENTIONS: Data abstraction from computerized medical records. MEASUREMENTS AND MAIN RESULTS: Septic shock was associated with bloodstream infection due to Gram-negative bacteria (59.2%) and Gram-positive bacteria (40.8%). Two hundred twenty-four patients (51.4%) died during their hospitalization. The presence of infection attributed to antibiotic-resistant bacteria was similar for patients who survived and expired (22.6% vs. 20.1%; p = .516). Multivariate logistic regression analysis demonstrated that infection acquired in the intensive care unit (adjusted odds ratio 1.99; 95% confidence interval 1.52-2.60; p = .011) and increasing Acute Physiology and Chronic Health Evaluation II scores (one-point increments) (adjusted odds ratio 1.11; 95% confidence interval 1.09-1.14; p < .001) were independently associated with a greater risk of hospital mortality, whereas infection with methicillin-susceptible Staphylococcus aureus (adjusted odds ratio 0.32; 95% confidence interval 0.20-0.52; p = .017) was independently associated with a lower risk of hospital mortality. Patients infected with methicillin-susceptible Staphylococcus aureus infections were statistically younger and had lower Charlson comorbidity and Acute Physiology and Chronic Health Evaluation II scores compared to patients with non-methicillin-susceptible Staphylococcus aureus infections. CONCLUSIONS: Among patients with septic shock who receive appropriate initial antibiotic treatment, acquisition of infection in the intensive care unit and severity of illness appear to be the most important determinants of clinical outcome.


Assuntos
Mortalidade Hospitalar , Choque Séptico/mortalidade , APACHE , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Estudos de Coortes , Comorbidade , Infecção Hospitalar/mortalidade , Transfusão de Eritrócitos , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Missouri/epidemiologia , Análise Multivariada , Respiração Artificial , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia , Adulto Jovem
3.
Arthroscopy ; 23(9): 923-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17868830

RESUMO

PURPOSE: The purpose of this study was to determine the depth of penetration from mechanical chondroplasty and metabolic consequences of this procedure on the remaining articular cartilage. METHODS: Mechanical chondroplasty was performed in vitro on a portion of fresh grade I or II articular cartilage from 8 human knee arthroplasty specimens. Treated and control (untreated) explants (approximately 30 mg) were cut from the cartilage. The explants were divided into 2 groups, day 1 and day 4, placed separately in a 48-well plate containing media, and incubated at 37 degrees C for 24 hours. After the 24-hour incubation, the explants were weighed on day 1 and day 4, and explant media were removed and tested for total proteoglycan synthesis and aggrecan synthesis. At time 0, 2 sets (2.6 mm each) of treated and control cartilage slices were cut with a precision saw. One set was stained for confocal laser microscopy via a cytotoxicity stain to determine cell viability. The second set was stained with H&E to determine depth of penetration. RESULTS: The mean depth of penetration was 252.8 +/- 78 microm. There was no significant difference (P > .25) between total proteoglycan synthesis for control versus treatment groups on day 1 or 4. Aggrecan synthesis was significantly reduced on day 1 when normalized for tissue weight (P = .019) and double-stranded deoxyribonucleic acid (P = .004). On day 4, no significant difference was detected. Confocal laser microscopy did not show cell death below the zone of treatment. CONCLUSIONS: There was no significant metabolic consequence caused by chondroplasty to the remaining articular cartilage, and the zone of injury was limited to the treatment area. CLINICAL RELEVANCE: Mechanical chondroplasty causes no significant metabolic consequences to articular cartilage under these conditions.


Assuntos
Agrecanas/biossíntese , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Proteoglicanas/biossíntese , Artroplastia , Artroscopia , Cartilagem Articular/cirurgia , Humanos , Técnicas In Vitro , Articulação do Joelho/cirurgia , Microscopia Confocal
4.
Surg Infect (Larchmt) ; 15(3): 283-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24801126

RESUMO

BACKGROUND: Macrolide-based treatment has been associated with survival benefit in patients hospitalized with community-acquired pneumonia (CAP). However, the influence of macrolide therapy in all patients hospitalized with pneumonia, including healthcare-associated pneumonia (HCAP), is unclear. METHODS: Analysis of a retrospective single-center cohort. RESULTS: Community-acquired pneumonia was present in 220 (22.5%) of all patients with pneumonia admitted through the emergency department of Barnes-Jewish Hospital, and HCAP was present in 757. Macrolide-based treatment was administered to 411 patients (42.1%). These patients were more likely to have CAP than were patients not receiving macrolide-based therapy (35.3% vs. 13.3%; p<0.001) and had lower scores on the CURB-65 tool, a measure of the severity of illness (2.4±1.5 vs. 3.1±1.3; p<0.001). Patients receiving macrolides also had a lower hospital mortality rate in univariable analysis (12.7% vs. 27.2%; p<0.001). A propensity score analysis showed that macrolide-based treatment was associated with a lower in-hospital mortality rate (adjusted odds ratio [AOR] 0.67; 95% confidence interval [CI] 0.54-0.81; p=0.043). Separate propensity score analyses of patients with CAP (AOR 0.20; 95% CI 0.11-0.34; p=0.003) and HCAP (AOR 0.81; 95% CI 0.65-1.01; p=0.337) produced discordant findings. CONCLUSIONS: Macrolide-based treatment was associated with better survival in patients hospitalized with pneumonia. The survival advantage appeared predominantly among patients with CAP.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Macrolídeos/uso terapêutico , Pneumonia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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