SILVIA FIGUEIREDO COSTA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?(2014) MASSARO, K. S. R.; MACEDO, R.; CASTRO, B. S. de; DULLEY, F.; OLIVEIRA, M. S.; YASUDA, M. A. S.; LEVIN, A. S.; COSTA, S. F.The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73 %) autologous and 80 (20 %) allogeneic were assessed. One hundred and ninety (64.2 %) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4 %). Twenty-three cases (7.8 %) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 > 140 pg/mL and CRP a parts per thousand yen120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH a parts per thousand yen390 UI/L, urea a parts per thousand yen25 mg/dL and CRP a parts per thousand yen120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP a parts per thousand yen120 mg/L for allogeneic HSCT, however, CRP a parts per thousand yen120 mg/L did not remain in the model when urea a parts per thousand yen25 mg/L was included. No independent risk factor was found for autologous patients. Out of the biomarkers assessed, only CRP a parts per thousand yen120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH a parts per thousand yen390 UI/L and urea a parts per thousand yen25 mg/dL. For allogeneic patients only CRP a parts per thousand yen120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea a parts per thousand yen25 mg/L was included.
- Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury(2014) HEIJDEN, Karin M. van der; HEIJDEN, Inneke M. van der; GALVAO, Flavio H.; LOPES, Camila G.; COSTA, Silvia F.; ABDALA, Edson; D'ALBUQUERQUE, Luiz A.; LEVIN, Anna S.The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results - The best inocula were: VRE: 2.4x10(10) cfu and ESBL-E. coli: 1.12x10(10) cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 mu mg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p: 0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761x13.804 EU/mL-p:0.01). No differences for endotoxin occurred in portal blood. Conclusion - e developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups. Systemic blood endotoxin levels were higher in the group with complete hepatic ischemia.
- Polymyxin use as a risk factor for colonization or infection with polymyxin-resistant Acinetobacter baumannii after liver transplantation(2014) FREIRE, M. P.; HEIJDEN, I. M. Van Der; PRADO, G. V. B.; CAVALCANTE, L. S.; BOSZCZOWSKI, I.; BONAZZI, P. R.; ROSSI, F.; GUIMARAES, T.; D'ALBUQUERQUE, L. A. C.; COSTA, S. F.; ABDALA, E.Introduction Acinetobacter baumannii is a leading agent of healthcare-associated infection. The objective of this study was to evaluate cases of colonization or infection with polymyxin-resistant A.baumannii (PRAB) in liver transplant recipients and to identify the risk factors for the acquisition of PRAB. Methods We evaluated all patients undergoing liver transplantation (LT) between January and November of 2011. The exclusion criterion was death within the first 72h after transplant. Patients were screened for PRAB through weekly rectal and inguinal swabs during their stay in the intensive care unit (ICU) and at ICU discharge. Patients who came from other hospitals or had been treated in the emergency room for >72h were screened at ICU admission. The minimum inhibitory concentrations (MICs) for polymyxins were determined by broth microdilution, and clonality was determined by pulsed-field gel electrophoresis. The stepwise logistic regression was used to identify risk factors related to acquisition of PRAB, and Cox forward regression used to identify risk factors for 60-day mortality. Results We evaluated 65 patients submitted to LT, among whom PRAB was isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged from 16 to 128mg/mL. All patients with PRAB required dialysis. The median time of polymyxin use before PRAB isolation was 21days. These 4 included 1 case of primary bloodstream infection (BSI), which was treated with the carbapenem-polymyxin combination; 1 case of surgical site infection, which was treated with gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of pneumonia, treated with the combination of carbapenem-polymyxin. In the case of BSI and in 1 of the cases of pneumonia, the treatment was considered successful. Mortality was 71% among the cases, compared with 33% among the non-cases. Conclusion In the final model of the survival analysis, PRAB colonization or infection after LT was independently associated with mortality. One predominant clone was identified. The only risk factor identified in the multivariate analysis was polymyxin use. PRAB was an agent with high mortality, and the most important risk factor associated with colonization or infection for such bacterium was polymyxin use.
- Non-Multidrug-Resistant, Methicillin-Resistant Staphylococcus aureus in a Neonatal Unit(2014) GARCIA, Cilmara P.; ROSA, Juliana F.; CURSINO, Maria A.; LOBO, Renata D.; MOLLACO, Carla H.; GOBARA, Satiko; MALIENO, Paula B.; RAYMUNDO, Gabriela F.; SOARES, Robson E.; KEIL, Kleiste G.; TOMA, Edi; SALOMAO, Matias C.; MATTE, M. Helena; KREBS, Vera L.; GIBELLI, M. Augusta; KONDO, Mario M.; ZUGAIB, Marcelo; COSTA, Silvia F.; LEVIN, Anna S.Background: In the last decade, non-multiresistant methicillin-resistant Staphylococcus aureus (NM-MRSA) has been described as an important agent in bloodstream infections in our hospital. Methods: This prospective cohort study, conducted from February 2009 through January 2010 in the neonatal unit, evaluated 403 newborns (NB), their 382 mothers and 148 health care workers (HCW). Results: Approximately 217 NB (54%), 187 mothers (48%) and 87 HCW (59%) were colonized by S. aureus (SA). MRSA colonization was greater among NB (15%) than mothers (4.7%) and HCW (3.4%). Although mother-to-NB transmission occurred, in most cases mothers were not responsible for NB colonization. There were 2 predominant PFGE patterns among the NB and some mothers and HCW became colonized by them. Factors significantly associated with MRSA carriage by NB were lower level of maternal schooling (risk factor: odds ratio: 2.99; 95% confidence interval: 1.10-8.07) and maternal rhinosinusitis (protective factor: odds ratio: 0.33; 95% confidence interval: 0.12-0.88). Among NB who remained hospitalized for more than 72 hours, breast feeding was protective (odds ratio: 0.22; 95% confidence interval: 0.05-0.98). All the isolates were NM-MRSA, carried few virulence factors and SCCmec types IVa and type IVd predominated. Conclusions: Although there were no cases of infection, nosocomial transmission of MRSA clearly occurred in the neonatal unit, and this highlights the need for infection control practices such as hand hygiene to prevent cross-dissemination. Other healthcare practices, which are very basic but also ample in scope, may play a role, such as general education of women and breast feeding.
- POLYCLONAL OUTBREAK OF BLOODSTREAM INFECTIONS CAUSED BY Burkholderia cepacia COMPLEX IN HEMATOLOGY AND BONE MARROW TRANSPLANT OUTPATIENT UNITS(2014) BOSZCZOWSKI, Icaro; PRADO, Gladys Villas Boas do; DALBEN, Mirian F.; TELLES, Roberto C. P.; FREIRE, Maristela Pinheiro; GUIMARAES, Thais; OLIVEIRA, Maura S.; ROSA, Juliana F.; SOARES, Robson E.; LLACER, Pedro Enrique Dorlhiac; DULLEY, Frederico Luiz; COSTA, Silvia F.; LEVIN, Anna S.Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients. Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units. Findings: 14 patients had B. multivorans (one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred. Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials.
- Susceptibility of Multiresistant Gram-Negative Bacteria to Fosfomycin and Performance of Different Susceptibility Testing Methods(2014) PERDIGAO-NETO, L. V.; OLIVEIRA, M. S.; RIZEK, C. F.; CARRILHO, C. M. D. M.; COSTA, S. F.; LEVIN, A. S.Fosfomycin may be a treatment option for multiresistant Gram-negative bacteria. This study compared susceptibility methods using 94 multiresistant clinical isolates. With agar dilution (AD), susceptibilities were 81%, 7%, 96%, and 100% (CLSI) and 0%, 0%, 96%, and 30% (EUCAST), respectively, for Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter spp. Categorical agreement between Etest and AD for Enterobacteriaceae and A. baumannii was >= 80%. Disk diffusion was adequate only for Enterobacter. CLSI criteria for urine may be adequate for systemic infections.
- Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients(2014) MARQUES, Heloisa Helena de Sousa; SHIKANAI-YASUDA, Maria Aparecida; AZEVEDO, Luiz Sergio Fonseca de; CAIAFFA-FILHO, Helio Helh; PIERROTTI, Ligia Camera; AQUINO, Maria Zilda de; LOPES, Marta Heloisa; MALUF, Natalya Zaidan; CAMPOS, Silvia Vidal; COSTA, Silvia FigueiredoEpstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.
- Characterization of carbapenem-resistant Pseudomonas aeruginosa clinical isolates, carrying multiple genes coding for this antibiotic resistance(2014) RIZEK, Camila; FU, Liang; SANTOS, Leticia Cavalcanti dos; LEITE, Gleice; RAMOS, Jessica; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna S.; COSTA, Silvia FigueiredoBackground: Carbapenemase genes are one of the most frequent mechanisms reported in carbapenem-resistant P. aeruginosa; however, description of P. aeruginosa co-harbouring two or more carbapenemases is unusual. Methods: In this study we evaluated the presence of carbapenemase genes and the clonality of P. aeruginosa isolates obtained from a hospital over a 12-year period. A total of 127 isolates of carbapenem-resistant P. aeruginosa recovered from 109 patients feces (four samples), rectal swab (three samples), nasal swab (one sample) and anal abscess (one sample), were evaluated. Minimum inhibitory concentrations of the following antibiotics imipenem, meropenem and polymyxin E were determined by broth microdilution. The molecular profile of isolates was evaluated by pulsed field gel electrophoresis (PFGE). PCR for the following carbapenemase genes bla(IMP); bla(SPM); bla(VIM); bla(SIM); bla(NDM); bla(KPC); bla(GES) and nucleotide sequencing to confirm the enzyme gene types were performed and compared with the database available on the Internet (BLAST-http://www.ncbi.nlm.nhi.gov/blast/). Results: All isolates were carbapenem-resistant, their MIC50 and MIC90 were respectively 64 mu g/mL and 256 mu g/mL to imipenem and 32 mu g/mL and 256 mu g/mL to meropenem, all isolates except one (MIC = 8 mg/L) were susceptible to polymyxin E. The most frequent carbapenemase genes identified were bla(SPM) identified in 41 isolates (32%), followed by 10 with bla(kpc) and 5 with bla(VIM) (3.9%). All belonged to the class SPM-1 and VIM-2. In 2011, one isolate harbouring three carbapenemase genes (SPM-1, VIM-2 and KPC-2) that belonged to a new clone was identified in a hematopoietic stem cell transplanted patient. Then, 19 carbapenem-resistant P. aeruginosa were identified in an outbreak that occurred in the bone marrow transplant unit, all positive for SPM-1 gene, and 9 (47.3%) harbored both SPM-1 and KPC. Conclusion: Our findings showed that PCR for KPC gene should be performed to evaluate carbapenem resistance in P. aeruginosa and that this agent can harbor more than one carbapenemase gene. Attention should be focused on the possible rapid spread of KPC in P. aeruginosa isolates and for the fact that P. aeruginosa may become a reservoir of this transmissible resistance mechanism.
- INCIDENCE OF DIARRHEA BY Clostridium difficile IN HEMATOLOGIC PATIENTS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS: RISK FACTORS FOR SEVERE FORMS AND DEATH(2014) SPADAO, Fernanda; GERHARDT, Juliana; GUIMARAES, Thais; DULLEY, Frederico; ALMEIDA JUNIOR, Joao Nobrega de; BATISTA, Marjorie Vieira; SHIKANAI-YASUDA, Maria Aparecida; LEVIN, Anna Sara; COSTA, Silvia FigueiredoWe describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.