THAIS GUIMARAES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina
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- Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins(2019) GUIMARAES, Thais; NOUER, Simone A.; MARTINS, Roberta C. R.; V, Lauro Perdigao Neto; MARTINS, Willames M. B. S.; BARBOSA, Ana Clara Narciso; FERREIRA, Adriana L. P.; COSTA, Silvia F.; GALES, Ana C.In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 mu g/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 (44%); P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.
- Impact of Discontinuing Levofloxacin Prophylaxis on Bloodstream Infections in Neutropenic Hematopoietic Stem Cell Transplantation Patients(2022) GUIMARAES, Thais; BORGES, Igor Carmo; SPADAO, Fernanda de Souza; MARIANO, Livia; NASCIMENTO, Marina de Mattos; HIGASHINO, Hermes; ROSSI, Flavia; ROCHA, Vanderson; COSTA, Silvia FigueiredoMultidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance pattern could lead to an impact on BSI mortality. This is a quasi-experimental study comparing BSI incidence, resistance patterns of bacteria that cause BSI, and BSI mortality when levofloxacin prophylaxis was routine for neutropenic HSCT patients (2016-2018) to when fluoroquinolone prophylaxis was discontinued in our center (2019). Bivariate comparisons and multivariate logistic regression models were used for analyses. A total of 310 HSCTs (66 (21%) allogeneic and 244 (79%) autologous) were performed during the study period. Sixty (19%) patients had BSIs, 30 in each evaluated period. The discontinuation of levofloxacin prophylaxis was associated with an increase in BSI incidence and a decrease in the resistance rates of causative BSI bacteria and in BSI 30-day mortality. The increase in the rate of resistant bacteria causing BSI and in BSI mortality might outweigh the benefits of a decrease in BSI incidence caused by fluoroquinolone prophylaxis in neutropenic HSCT patients. We suggest that the routine use of fluoroquinolone in this context be revisited.
- Alternative drugs against multiresistant Gram-negative bacteria(2020) PERDIGAO NETO, Lauro Vieira; OLIVEIRA, Maura Salaroli; ORSI, Tatiana D'Annibale; PRADO, Gladys Villas Boas do; MARTINS, Roberta Cristina Ruedas; LEITE, Gleice Cristina; MARCHI, Ana Paula; LIRA, Esther Sant'Ana de; CORTES, Marina Farrel; ESPINOZA, Evelyn Patricia Sanchez; CARRILHO, Claudia Maria Dantas de Maio; BOSZCZOWSKI, Icaro; GUIMARAES, Thais; COSTA, Silvia Figueiredo; LEVIN, Anna S.Objectives: Enterobacterales and other non-fermenting Gram-negative bacteria have become a threat worldwide owing to the frequency of multidrug resistance in these pathogens. On the other hand, efficacious therapeutic options are quickly diminishing. The aims of this study were to describe the susceptibility of 50 multiresistant Gram-negative bacteria, mostly pan-resistant, against old and less-used antimicrobial drugs and to investigate the presence of antimicrobial resistance genes. Methods: A total of 50 genetically distinct isolates were included in this study, including 14 Acinetobacter baumannii (belonging to ST79, ST317, ST835 and ST836), 1 Pseudomonas aeruginosa (ST245), 8 Serratia marcescens and 27 Klebsiella pneumoniae (belonging to STII, ST340, ST258, ST16, ST23, ST25, ST101, ST234, ST437 and ST442). The isolates were submitted to antimicrobial susceptibility testing and whole-genome sequencing to evaluate lineages and resistance genes. Results: Our results showed that some strains harboured carbapenemase genes, e.g. bla(K)(PC-)(2) (28/50; 56%) and bla(OXA-23) (11/50; 22%), and other resistance genes encoding aminoglycoside-modifying enzymes (49/50; 98%). Susceptibility rates to tigecycline (96%) in all species (except P. aeruginosa), to minocycline (100%) and doxycycline (93%) in A. baumannii, to ceftazidime/avibactam in S. marcescens (100%) and K. pneumoniae (96%), and to fosfomycin in S. marcescens (88%) were high. Chloramphenicol and quinolones (6% susceptibility each) did not perform well, making their use in an empirical scenario unlikely. Conclusions: This study involving genetically distinct bacteria showed promising results for tigecycline for all Gram-negative bacteria (except P. aeruginosa), and there was good activity of minocycline against A. baumannii, ceftazidime/avibactam against Enterobacterales, and fosfomycin against S. marcescens. (C) 2020 The Author(s).
- Phenotypic and genotypic characteristics of a carbapenem-resistant Serratia marcescens cohort and outbreak: describing an opportunistic pathogen(2022) PRADO, Gladys; MENDES, Elisa Teixeira; MARTINS, Roberta Cristina Ruedas; PERDIGAO-NETO, Lauro Vieira; FREIRE, Maristela Pinheiro; MARCHI, Ana Paula; CORTES, Marina Farrel; LIMA, Victor Augusto Camarinha de Castro; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; COSTA, Silvia FigueiredoSerratia marcescens is an emerging opportunistic pathogen with high genetic diversity. This article describes the microbiological characteristics of isolates and the risk factors for infections caused by carbapenem-resistant S. marcescens. A retrospective study of patients colonized (n=43) and infected (n= 20) with carbapenem-resistant S. marcescens over a 3-year period was conducted. Polymerase chain reaction for carbapenemase genes and molecular typing of all available strains was performed. Forty-two isolates were analysed, including three environmental samples identified during an outbreak. Thirty-five carbapenem-resistant S. marcescens carried bla KPC-2, one isolate was bla(NDM)-positive and four isolates carried bla(OXA)-101. The genomes were grouped into three clusters with 100% bootstrap; three patterns of mutations on ompC and ompF were found. The strains carried virulence genes related to invasion and haemolysis, and the environmental strains presented fewer mutations on the virulence genes than the clinical strains. Multi-variate analysis showed that previous use of polymyxin (P= 0.008) was an independent risk factor for carbapenem-resistant S. marcescens infection. This study highlighted that bla KPC-2 in association with ompC or ompF mutation was the most common mechanism of resistance in the study hospital, and that previous use of polymyxin was an independent risk factor for carbapenem-resistant S. marcescens. There was a predominant clone, including the environmental isolates, suggesting that crosstransmission was involved in the dissemination of this pathogen.
- Microbiology of Diabetic Foot Infections in a Tertiary Care Hospital in Sao Paulo, Brazil(2022) PALOMO, Amanda Thurler; PIRES, Ana Paula Maia; MATIELO, Marcelo Fernando; SOARES, Rafael de Athayde; PECEGO, Christiano; SACILOTTO, Roberto; PAULA, Alexandre Inacio de; HOSINO, Nair; GAMBA, Cristiano de Melo; FONSECA, Cibele Lefreve; PARASKEVOPOULOS, Daniela K. S.; YAMAGUTI, Augusto; MENDONCA, Joao Silva de; COSTA, Silvia Figueiredo; GUIMARAES, ThaisDiabetic foot infections (DFIs) are one of the causes of hospitalization in diabetic patients and, when this occurs, empirical antibiotic therapy is necessary. We have conducted a retrospective study of patients with DFI that required hospitalization to evaluate microbiologic profile and the susceptibility pattern of these infections. We evaluated 320 patients, of which 223 (69.7%) were male with a media age of 71 years with 276 isolates. Gram-positive bacteria were responsible for 188 (68.1%) of the isolates, while Gram-negative bacilli were responsible for 88 (31.9%). E. faecalis was the most prevalent pathogen, followed by S. aureus and coagulase negative Staphylococci. Among Gram-negative pathogens, P. aeruginosa was the most prevalent agent. Regarding the susceptibility profile, we found ampicillin-sensitive enterococci in 89% of the cases, oxacillin-sensitive S. aureus in 47%, but in coagulase-negative staphylococci, oxacillin was sensible only in 20%. The susceptibility profile of Gram-negatives was very good with 76% susceptibility of P. aeruginosa to ceftazidime and meropenem. The other prevalent Enterobacterales had great susceptibility to ceftazidime, piperacillin-tazobactam and 100% susceptibility to meropenem, with the exception of K. pneumoniae, which had 75% susceptibility to meropenem. Knowledge of microbiological profile and susceptibility patterns of patients with DFIs is useful to guide empirical therapy.
- Virulence and resistance pattern of a novel sequence type of linezolid-resistant Enterococcus faecium identified by whole-genome sequencing(2016) PRADO, Gladys Villas Boas do; MARCHI, Ana Paula; MORENO, Luisa Zanolli; RIZEK, Camila; AMIGO, Ulisses; MORENO, Andrea Micke; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; COSTA, Silvia F.Empirical use of linezolid has been advocated in neutropenic febrile patients colonised by vancomycin-resistant enterococci (VRE) because of the risk of bloodstream infection (BSI). This study aimed to genetically describe a vancomycin-resistant Enterococcus faecium (VREfm) BSI isolate resistant to linezolid (VRLRE) in a patient previously colonised by VREfm and to determine the incidence of colonisation and infection by VREfm in a bone marrow transplant unit over a 10-year period. Data for VREfm colonisation and infection were evaluated. PCR for the vanA and vanB genes, pulsed-field gel electrophoresis (PFGE) and microdilution antimicrobial susceptibility testing (vancomycin, teicoplanin, linezolid and aminoglycosides) were performed. Three isolates, including the VRLRE, were selected for whole-genome sequencing by Ion Torrent (TM), with E. faecium CP006620-Aus0085 used as a reference. Eighty-seven VREfm were analysed; all were linezolid-susceptible and harboured vanA, except for one blood isolate from a febrile neutropenic patient colonised by VREfm who received linezolid for 12 days and developed a BSI by VRLRE (linezolid MIC >= 8 mu g/mL). Linezolid resistance was associated with a G2576T mutation in the 23SrRNA gene. PFGE analysis demonstrated that the 87 isolates belonged to four major clusters; however, the VRLRE presented only 50% similarity. Three sequence types (STs) were identified: ST412 (the predominant clone, which was more virulent compared with the other isolates); ST478 (linezolid-susceptible VREfm); and a novel ST named ST987 (VRLRE). SNP analysis showed a higher similarity between linezolid-susceptible VREfm and the predominant clone compared with VRLRE. VRLRE presented a G2576T mutation and belonged to a novel ST (ST987).
- Metronidazole for Treatment of Clostridioides difficile Infections in Brazil: A Single-Center Experience and Risk Factors for Mortality(2022) ALVES, Joana Darc Freitas; YAMAGUTI, Augusto; MENDONCA, Joao Silva de; GAMBA, Cristiano de Melo; FONSECA, Cibele Lefreve; PARASKEVOPOULOS, Daniela K. S.; PAULA, Alexandre Inacio de; HOSINO, Nair; COSTA, Silvia Figueiredo; GUIMARAES, ThaisWe describe the epidemiology of C. difficile infections (CDIs) focused on treatment and analyze the risk factors for mortality. This is a retrospective cohort study of CDI cases with a positive A/B toxin in the stool in 2017-2018. We analyzed the demographic data, comorbidities, previous use of antimicrobials, severity, and treatment, and we performed multivariate analysis to predict the 30-days mortality. We analyzed 84 patients, 37 (44%) of which were male, where the mean age was 68.1 years and 83 (99%) had comorbidities. The percentage of positivity of the A/B toxin was 11.6%, and the overall incidence density was 1.78/10,000 patient days. Among the patients, 65.4% had previous use of antimicrobials, with third-generation cephalosporins being the class most prescribed, and 22.6% of cases were severe. Treatment was prescribed for 70 (83.3%) patients, and there was no statistically significant difference between the initial treatment with metronidazole and vancomycin even in severe cases. The 30-day mortality was 7/84 (8.3%), and the risk factors associated with mortality was a severity score >= 2 (OR: 6.0; CI: 1.15-31.1; p = 0.03). In this cohort of CDI-affected patients with comorbidities and cancer, metronidazole was shown to be a good option for treating CDIs, and the severity score was the only independent risk factor for death.
- Impact of an Antimicrobial Stewardship Program Intervention Associated with the Rapid Identification of Microorganisms by MALDI-TOF and Detection of Resistance Genes in ICU Patients with Gram-Negative Bacteremia(2022) CAMPOS, Aleia Faustina; ARANTES, Tiago; CAMBIAIS, Amanda Magalhaes Vilas Boas; CURY, Ana Paula; TIROLI, Camila Guimaraes; ROSSI, Flavia; MALBOUISSON, Luiz Marcelo Sa; COSTA, Silvia Figueiredo; GUIMARAES, ThaisCombination of strategies for rapid diagnostics tests (RDT) with real-time intervention could improve patient outcomes. We aimed to assess the impact on clinical outcomes, antimicrobial consumption, and costs in patients with gram-negative bacteremia. We designed a quasi-experimental study among 216 episodes of gram-negative bacteremia using RDT (MALDI-TOF and detection of resistance genes) directly from blood culture bottles combined with real-time communication of results. Our study did not demonstrate impact on 30-day mortality (25% vs. 35%; p = 0.115). Hospital and ICU length of stay were significantly lower in the intervention period ((44 days vs. 39 days; p = 0.005) and (17 days vs. 13 days; p = 0.033)), respectively. The antimicrobial consumption was 1381 DOT/1000 days in the pre-intervention period compared to 1262 DOT/1000 days in the intervention period (p = 0.032). Antimicrobials against gram-positive and carbapenems had a significantly reduced consumption in the intervention period. Our intervention showed no impact on 30 days-mortality, but demonstrated an impact on hospital and ICU length of stay, as well as antimicrobials consumption and costs. Knowledge of resistance genes adds value and information for safe decision making that can result in direct and indirect benefits related to the economic burden of antibiotic overuse and bacterial resistance.
- Virulomic Analysis of Multidrug-Resistant Klebsiella pneumoniae Isolates and Experimental Virulence Model Using Danio rerio (Zebrafish)(2022) DUARTE, Edson Luiz Tarsia; RIZEK, Camila Fonseca; ESPINOZA, Evelyn Sanchez; MARCHI, Ana Paula; NOGUERA, Saidy Vasconez; CORTES, Marina Farrel; FERNANDES, Bianca H. Ventura; GUIMARAES, Thais; CARRILHO, Claudia M. D. de Maio; V, Lauro Perdigao Neto; TRINDADE, Priscila A.; COSTA, Silvia FigueiredoThis study evaluates a possible correlation between multidrug-resistant Klebsiella pneumoniae strains and virulence markers in a Danio rerio (zebrafish) model. Whole-genome sequencing (WGS) was performed on 46 strains from three Brazilian hospitals. All of the isolates were colistin-resistant and harbored bla(KPC-2). Ten different sequence types (STs) were found; 63% belonged to CC258, 22% to ST340, and 11% to ST16. The virulence factors most frequently found were type 3 fimbriae, siderophores, capsule regulators, and RND efflux-pumps. Six strains were selected for a time-kill experiment in zebrafish embryos: infection by ST16 was associated with a significantly higher mortality rate when compared to non-ST16 strains (52% vs. 29%, p = 0.002). Among the STs, the distribution of virulence factors did not differ significantly except for ST23, which harbored a greater variety of factors than other STs but was not related to a higher mortality rate in zebrafish. Although several virulence factors are described in K. pneumoniae, our study found ST16 to be the only significant predictor of a virulent phenotype in an animal model. Further research is needed to fully understand the correlation between virulence and sequence types.
- Synergistic Effect of Ceftazidime-Avibactam with Meropenem against Panresistant, Carbapenemase-Harboring Acinetobacter baumannii and Serratia marcescens Investigated Using Time-Kill and Disk Approximation Assays(2019) GAUDERETO, Juliana Januario; PERDIGAO NETO, Lauro Vieira; LEITE, Gleice Cristina; MARTINS, Roberta Ruedas; PRADO, Gladys Villas Boas do; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; COSTA, Silvia FigueiredoSusceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying bla(KPC-2). Ceftazidime-avibactam was very active and synergistic with meropenem against multiresistant S. marcescens isolates. On the other hand, only the A. baumannii isolates coharboring bla(OXA-23) and bla(OXA-117) displayed synergy. The disk approximation technique presented good sensitivity for synergism in S. marcescens infection.