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- ItemSomente MetadadadosActivity of daptomycin and selected antimicrobial agents tested against Staphylococcus aureus from patients with bloodstream infections hospitalized in European medical centers(Esift Srl, 2008-02-01) Sader, Helio Silva [UNIFESP]; Watters, A. A.; Fritsche, T. R.; Jones, R. N.; JMI Labs; Universidade Federal de São Paulo (UNIFESP); Tufts UnivDaptomycin is a cyclic lipopeptide with potent bactericidal activity against Gram-positive organisms and has been approved by the United States Food and Drug Administration for the treatment of Staphylococcus aureus bacteremia and infectious endocarditis (right-side). We evaluated the activity of daptomycin against bloodstream infection S. aureus strains from 4,799 patients hospitalized in 32 medical centers (12 European countries, Turkey and Israel) with bloodstream infections (BSI) during a 5-year period (2002-2006). Intravenous catheters were the source of infection in 15% of cases, and those strains were analyzed separately. All strains were susceptibility tested by reference broth microdilution methods utilizing calcium supplementation (50 mg/L) when testing daptomycin. Bactericidal activity of daptomycin and vancomycin were evaluated against a subset of 50 randomly selected strains. Daptomycin (MIC (50/90), 0.25/0.5 mg/L), vancomycin (MIC50/90, 1/1 mg/L), and linezolid (MIC50/90, 2/2 mg/L), were highly active (>99.9% susceptibility) against the strains evaluated; and daptomycin was the most potent (lowest MIC90) among these compounds. Resistance rates to oxacillin and levofloxacin were generally elevated, especially when an intravenous catheter was the source of infection.
- ItemSomente MetadadadosAnalise de desfechos clinicos, adequacao da terapia antimicrobiana e determinacao da farmacodinamica de beta-lactamicos em pacientes com infeccao de corrente sanguinea por pseudomonas aeruginosa(Universidade Federal de São Paulo (UNIFESP), 2014-09-23) Cardinal, Leandro dos Santos Maciel [UNIFESP]; Furtado, Guilherme Henrique Campos Furtado [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To analyze the mortality of patients with bloodstream infection caused by Pseudomonas aeruginosa and to determine the cumulative fraction of response of beta-lactam dosing commonly used in Brazilian hospitals against isolated strains. Methods: A retrospective cohort study was conducted with patients who had P. aeruginosa bloodstream infection during the period January 1, 2010 to December, 31 2012. We analyzed risk factors and correlated antimicrobial therapy used with clinical outcomes. Fifteen-day mortality and 30-day mortality with secondary outcomes, such as clinical failure and microbiological failure were assessed. To determine the cumulative fraction of response of beta-lactams we performed a Monte Carlo simulation model with 5000 patients utilizing the minimum inhibitory concentration of P. aeruginosa strains isolated. Results: Eighty patients were included in the study. The most prevalent site of bacteremia was the respiratory tract (39, 48.8%). In total 47 (60.3%) patients received appropriate empirical antibiotic therapy and the majority (50, 62.5%) received monotherapy. The major antimicrobial drug utilized was meropenem plus polimixin B (32,1%). Regarding targeted antimicrobial therapy, we found that 46 (85.2%) patients received appropriate therapy. The 15-day mortality was lower in patients who used the optimized therapy with beta-lactam, both for empirical therapy (27.3% versus 40%) and for targeted therapy (16.7% versus 60%), but without statistical significance. In multivariate analysis, only clinical failure (OR: 166.25, 95% CI: 17.32 to 1595.42, p <0.0001) was predictor of 15-day mortality. Use of corticosteroids (OR 4.15, 95% CI: 1.11 to 15.42, p = 0.03), use of immunosuppressive drug (OR: 6.18, 95% CI: 1.37 to 27.86; p = 0.01) and use of vasoactive drug (OR: 8.55, 95% CI: 1.73 to 42.10, p <0.01) were predictors of 30-day mortality in the multivariate analysis. The results from Monte Carlo simulation showed that the only antimicrobial regimen and dose which achieved ideal therapeutic target (?90%) was meropenem 2 g every 8 hours in 3-hour infusion (90.1%). Other beta-lactam had a better PK/PD profile as dose and infusion time were increased. Conclusion: This study showed that P. aeruginosa bloodstream infection has a high mortality rate and adequate empirical or directed therapy did not reduce the mortality rate. The use of beta-lactam in high dose and prolonged infusion achieved a higher cumulative fraction of response however among the antimicrobial drugs used only meropenem in high dose and prolonged infusion reached adequate PK/PD target against P. aeruginosa strains.
- ItemSomente MetadadadosAplicação da técnica de pcr em tempo real na identificação microbiana e detecção de genes de resistência a antimicrobianos em episódios de bacteremia de pacientes pediátricos com câncer(Universidade Federal de São Paulo (UNIFESP), 2014-04-11) Carlesse, Fabianne Altruda de Moraes Costa [UNIFESP]; Pignatari, Antonio Carlos Campos Pignatari [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background: Bloodstream infections (BSI) are major cause of infection-related mortality in patients with cancer. Phenotipic methods are utilized to detect and to identify pathogens in blood stream cultures but with slow time for positivity and final results. Molecular techniques have been utilized for a quick ethiologic diagnosis of blood stream infections allowing the institution of an early adequate therapy improving patients survival rates. Aim: To evaluate if the Real Time PCR method used to identify the main pathogens causing blood stream infections and some important antimicrobial resistance genes causing bloodstream infections could improve the early diagnosis and adequate therapy in oncology pediatric patients. Methods: During March 2010 to March 2012 we conducted a retrospective study at the Oncology Pediatric Institute (IOP-GRAACC-Brazil). The blood stream samples were incubated in the automated Bactec® system and the microbal identification and susceptibility tests were done in the automated Phoenix® system. We included 81 blood positive blood stream samples that were submitted to molecular analysis. Polimicrobial infections were excluded, 69 BSI were analysed in 64 patients. Samples from the blood stream bottles were submitted to molecular tests by Real Time PCR with specific Gram probes, 17 specific gender sequences and antimicrobial resistance genes blaSHV, blaTEM, blaCTX, blaKPC, blaIMP, blaSPM, blaVIM, vanA, vanB e mecA.The adequacy of the antimicrobial therapy was evaluated at the time of the Gram stain result from the positive blood bottle (time 1) and in the available final phenotypic result for the assistant physician (time 2). Results: Gram positive bacteria were identified in 61% of the samples, Gram negative bacteria in 32% and fungi in 7%. There was agreement in 82,6% for the initial Gram stain and 78,2% in the final species identification between the phenotipic and molecular methods. The mecA gene was detected in 81,4% of Staphylococcus spp, and was 91,6% concordant with the phenotypic method. Detection of vanA gene was 100% concordant. For Gram negative bacteria the concordance was 71,4% for Enterobacteriacea and 50% for Pseudomonas aeruginosa. Therapy was inadequate particularly in patients who died (5/6). The molecular tests was concordant in 50% of theses cases. Conclusion: Real Time PCR could be useful in the early identification of pathogens and antimicrobial resistance genes in bloodstream infections of pediatric oncologic patients and could contribute to improve the antimicrobial therapy.
- ItemAcesso aberto (Open Access)Clinical and microbiological characteristics of bloodstream infections in a tertiary hospital in Maceió, Alagoas, Brazil(Brazilian Society of Infectious Diseases, 2010-04-01) Tenório, Maria Tereza Freitas [UNIFESP]; Porfírio, Zenaldo [UNIFESP]; Lopes, Antonio Carlos [UNIFESP]; Cendon Filha, Sônia Perez [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de Ciências da Saúde de AlagoasWe observed the clinical and microbiological characteristics of several stages of bloodstream infections (BSI), as well as the mortality attributed to it in a tertiary hospital in the northeast of Brazil (in the city of Maceió, Alagoas). A prospective cohort of 143 patients who had at least one positive blood culture was enrolled in the study. Their clinical evolution was followed up for 30 days from October 2005 to December 2006. The relation among the qualitative variables was verified through Chi-square test. The significance level was 5%. The statistical package adopted was SPSS 15.0 for Windows. Up to the thirtieth day, 30.1% of the patients presented bacteremia and 69.9% developed sepsis.Among these, 20.3% developed severe sepsis and 10.5% septic shock. The mortality attributed to it was 37.8%. In bacteremia, sepsis, severe sepsis, and septic shock conditions, mortality rates were 9.3%, 50%, 65.5%, and 84.6%, respectively. Respiratory (32.2%) and urinary (14%) sources and the ones related to central venous catheter (14%) were prevalent. In the wards 55.12% of the cases developed sepsis, whereas in the intensive care units, the rate was 87.69% (p < 0.05). Chronic renal failure, diabetes melitus, and neuropathy were present in 21.7%, 26.6%, and 29.4% of the cases, respectively. Coagulase-negative Staphylococcus (25.9%), Staphylococcus aureus (21%), and Klebsiella pneumoniae (14%) were the most present microorganism in the sample. The high morbidity and mortality rates in this study are attributed to the lack of knowledge on BSI characteristics and on instituted protocols for detection and treatment in early stages.
- ItemSomente MetadadadosEpidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantion(Edizioni Internazionali Srl, 2007-04-01) Cappellano, Paola [UNIFESP]; Viscoli, Claudio; Bruzzi, Paolo; Van Lint, Maria Teresa; Pereira, Carlos Alberto Pires [UNIFESP]; Bacigalupo, Andrea; Univ Genoa; Universidade Federal de São Paulo (UNIFESP)A total of 315 patients who underwent allogeneic Hematopoietic Stem Cell Transplantation (HSCT) during a 4year period were analysed with the aim of collecting information on bloodstream infections (BSI). Eighty-four patients (27%) developed 112 BSI, with a cumulative risk of 20.6% at 30 days and 27.7% at 180 days. Overall, 127 pathogens were isolated, 95 (75%) gram-positive cocci, 27 (21%) gram-negative rods and 5 (4%) fungi. Enterococcus sp. accounted for 46 of 127 (36%) isolates. In a multivariable analysis only including baseline factors, the type of transplant was the only factor significantly associated with the risk of BSI and the risk was higher for patients receiving transplant from mismatched or unrelated donors.In a case-control study aimed at evaluating the predictive role of additional factors during transplant, the risk appeared to be higher in patients with a positive CMV antigenemia (p=0.03; OR of 4.82; 95% CI, 1.21-19.17), long duration of severe granulocytopenia (p=0.015; OR 7.53; 95% CI, 1.92 - 29.58) and lower platelet count (p<0.001; OR 0.14; 95% CI, 0.05 - 0.40). By day 180 post-transplant, 87 (28%) out of 314 patients had died. The cumulative risk of death was significantly higher among patients with BSI than among other patients.
- ItemSomente MetadadadosEpidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients(Nature Publishing Group, 2007-06-01) Oliveira, A. L.; Souza, M. de; Carvalho-Dias, V. M. H.; Ruiz, M. A.; Silla, L.; Tanaka, P. Yurie; Simoes, B. P.; Trabasso, P.; Seber, Adriana [UNIFESP]; Lotfi, C. J.; Zanichelli, Maria A.; Araujo, V. R.; Godoy, C.; Maiolino, Angelo; Urakawa, P.; Cunha, C. A.; De Souza, C. A.; Pasquini, Ricardo; Nucci, Márcio; Universidade Federal do Rio de Janeiro (UFRJ); Hosp Amaral Carvalho; Univ Fed Parana; Hosp Base; Univ Fed Rio Grande do Sul; Irmandade Santa Casa Misericordia São Paulo; Universidade de São Paulo (USP); Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Hosp AC Camargo Fund Antonio Prudente; Hosp Brigadeiro; Ctr Pesquisas Oncol; Hosp Araujo JorgeThe incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third-or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% con. dence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These. findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.
- ItemSomente MetadadadosFrequency of Occurrence and Daptomycin Susceptibility Rates of Gram-positive Organisms Causing Bloodstream Infections in Cancer Patients(Esift Srl, 2008-10-01) Sader, Helio Silva [UNIFESP]; Fritsche, T. R.; Jones, R. N.; JMI Labs; Universidade Federal de São Paulo (UNIFESP); Tufts UnivWe evaluated the pathogen frequency and the antimicrobial susceptibility patterns of Gram-positive bacteria causing infections in cancer patients. We also compared the antimicrobial susceptibility of isolates from cancer patients to those from non-cancer patients and evaluated the activity of the novel lipopeptide daptomycin against these isolates. A total of 1,222 Gram-positive isolates were collected (one per patient) from bloodstream infections (BSI) in cancer patients at 33 United States (USA) medical centers in 2002-2006 and susceptibility tested by the broth microdilution method. Frequency of occurrence and susceptibility patterns of strains from cancer patients were compared to those from non-cancer patients collected in the same hospitals (10,684 strains). Staphylococcus aureus (39.2%) ranked first among Gram-positive pathogens from cancer patients, followed by Enterococcus spp. (32.2%) and coagulase-negative staphylococci (CoNS; 20.4%). Daptomycin was active against 99.8% of Gram-positive strains collected from patients with cancer at USA hospitals, but vancomycin was only active against 87.6% of strains and showed limited activity against Enterococcus spp. (61.4% susceptible). Only three daptomycin non-susceptible isolates were detected, all with MIC values at one doubling dilution above the susceptible breakpoint. These results indicate that daptomycin has an appropriate spectrum and potency to be used for empirical coverage of Gram-positive infections (especially BSI) in cancer patients in the hospitals surveyed in the USA.
- ItemAcesso aberto (Open Access)Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP(Academia Brasileira de Ciências, 2009-09-01) Colombo, Arnaldo Lopes [UNIFESP]; Janini, Luiz Mário Ramos [UNIFESP]; Salomão, Reinaldo [UNIFESP]; Medeiros, Eduardo Alexandrino Servolo de [UNIFESP]; Wey, Sergio Barsanti [UNIFESP]; Pignatari, Antonio Carlos Campos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.