THAIS GUIMARAES
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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.
- Prevalence of Clostridioides difficile associated diarrhea in hospitalized patients in five Brazilian centers: A multicenter, prospective study(2020) GIRAO, Evelyne Santana; TAVARES, Bruno de Melo; SANTOS, Sania Alves dos; GAMARRA, Gessica Lorena; RIZEK, Camila; MARTINS, Roberta Cristina; NETO, Lauro Vieira Perdigao; DIOGO, Constancia; ORSI, Tatiana D'Annibale; ESPINOZA, Evelyn Patricia Sanchez; MORALES, Hugo Manuel Paz; NOGUEIRA, Keite da Silva; MAESTRI, Adriane Ceshin; BOSZCZOWSKI, Icaro; PIASTRELLI, Filipe; COSTA, Cecilia Leite; COSTA, Daniely Viana; MACIEL, Geovania; ROMAO, Janete; GUIMARAES, Thais; BRITO, Gerly Anne de Castro; COSTA, Silvia FigueiredoEpidemiological data on CD infection (CDI) in Latin American are scarce. CDI prevalence and strains characterization were prospectively evaluated in 5 Brazilian hospitals from different regions. Prevalence rates of CDI were 15%, ranging from 0 to 37%. ST42 was the most common Sequence Type and hyper virulent strains were not identified.
- Clinical outcome from hematopoietic cell transplant patients with bloodstream infection caused by carbapenem-resistant P. aeruginosa and the impact of antimicrobial combination in vitro(2022) RAMOS, Jessica Fernandes; LEITE, Gleice; MARTINS, Roberta Cristina Ruedas; RIZEK, Camila; SANABANI, Sabri Saeed Al; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; ROCHA, Vanderson; COSTA, Silvia FigueiredoBloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored bla(SPM-1) and Tn4371 and belonged to ST277. The synergistic effect in vitro with meropenem with colistin appeared to be a better therapeutic option.
- Comparison of methods for the detection of in vitro synergy in multidrug-resistant gram-negative bacteria(2020) GAUDERETO, Juliana Januario; PERDIGAO NETO, Lauro Vieira; LEITE, Gleice Cristina; SANCHEZ, Evelyn; MARTINS, Roberta Cristina Ruedas; PRADO, Gladys Villas Boas; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; COSTA, Silvia FigueiredoBackground The use of combined antibiotic therapy has become an option for infections caused by multidrug-resistant (MDR) bacteria. The time-kill (TK) assay is considered the gold standard method for the evaluation of in vitro synergy, but it is a time-consuming and expensive method. The purpose of this study was to evaluate two methods for testing in vitro antimicrobial combinations: the disk diffusion method through disk approximation (DA) and the agar gradient diffusion method via the MIC:MIC ratio. The TK assay was included as the gold standard. MDR Gram-negative clinical isolates (n = 62; 28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii, and 14 Serratia marcescens) were submitted to TK, DA, and MIC:MIC ratio synergy methods. Results Overall, the agreement between the DA and TK assays ranged from 20 to 93%. The isolates of A. baumannii showed variable results of synergism according to TK, and the calculated agreement was statistically significant in this species against fosfomycin with meropenem including colistin-resistant isolates. The MIC:MIC ratiometric agreed from 35 to 71% with TK assays. The kappa test showed good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates. Conclusions The DA and MIC:MIC ratiometric methods are easier to perform and might be a more viable tool for clinical microbiology laboratories.
- High mortality of bloodstream infection outbreak caused by carbapenem-resistant P. aeruginosa producing SPM-1 in a bone marrow transplant unit(2017) CHAVES, Lucas; TOMICH, Lisia Moura; SALOMAO, Matias; LEITE, Gleice Cristina; RAMOS, Jessica; MARTINS, Roberta Ruedas; RIZEK, Camila; NEVES, Patricia; BATISTA, Marjorie Vieira; AMIGO, Ulysses; GUIMARAES, Thais; LEVIN, Anna Sara; COSTA, Silvia FigueiredoPurpose. Carbapenem resistance in P. aeruginosa is increasing worldwide. In Brazil, SPM-1 is the main P. aeruginosa carbapenemase identified. Little is known about the virulence factor in SPM-1 clones. Methodolgy. We describe a carbapenem-resistant P. aeruginosa bloodstream infection (CRPa-BSI) outbreak in a bone marrow transplant Unit (BMT). Twenty-nine CRPa-BSI cases were compared to 58 controls. Microbiological characteristics of isolates, such as sensitivity, carbapenemase gene PCR for P. aeruginosa, and PFGE are described, as well as the whole-genome sequence (WGS) of three strains. Results/Key findings. The cultures from environmental and healthcare workers were negative. Some isolates harboured KPC and SPM. The WGS showed that the 03 strains belonged to ST277, presented the same mutations in outer membrane protein, efflux pump, and virulence genes such as those involved in adhesion, biofilm, quorum-sensing and the type III secretion system, but differ regarding the carbapenemase profile. A predominant clone-producing SPM harbouring Tn 4371 was identified and showed cross-transmission; no common source was found. Overall mortality rate among cases was 79 %. The first multivariate analysis model showed that neutropenia (P=0.018), GVHD prophylaxis (P=0.016) and prior use of carbapenems (P=0.0089) were associated with CRPa-BSI. However, when MASCC >= 21 points and platelets were added in the final multivariate analysis, only prior use of carbapenems remained as an independent risk factor for CRPa-BSI (P=0.043). Conclusions. The predominant clone belonging to ST277 showed high mortality. Carbapenem use was the only risk factor associated with CRPa-BSI. This finding is a wake-up call for the need to improve management in BMT units.
- Bloodstream Infections caused by Klebsiella pneumoniae and Serratia marcescens isolates co-harboring NDM-1 and KPC-2(2021) BES, Taniela; NAGANO, Debora; MARTINS, Roberta; MARCHI, Ana Paula; PERDIGAO-NETO, Lauro; HIGASHINO, Hermes; PRADO, Gladys; GUIMARAES, Thais; LEVIN, Anna S.; COSTA, SilviaCarbapenem-resistant Enterobacteriaceae are a worldwide health problem and isolates carrying both bla(KPC-2) and bla(NDM-1) are unusual. Here we describe the microbiological and clinical characteristics of five cases of bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens having both bla(KPC-2) and bla(NDM-1). Of the five blood samples, three are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a surgical patient. All patients lived in low-income neighbourhoods and had no travel history. Despite antibiotic treatment, four out of five patients died. The phenotypic susceptibility assays showed that meropenem with the addition of either EDTA, phenylboronic acid (PBA), or both, increased the zone of inhibition in comparison to meropenem alone. Molecular tests showed the presence of bla(KPC-2) and bla(NDM-1) genes. K. pneumoniae isolates were assigned to ST258 or ST340 by whole genome sequencing. This case-series showed a high mortality among patients with BSI caused by Enterobacteriae harbouring both carbapenemases. The detection of carbapenemase-producing isolates carrying both bla(KPC-2) and bla(NDM-1) remains a challenge when using only phenotypic assays. Microbiology laboratories must be alert for K. pneumoniae isolates producing both KPC-2 and NDM-1.
- 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.
- Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool? (vol 101, 115344, 2021)(2022) CORTES, Marina Farrel; ALMEIDA, Bianca Leal de; ESPINOZA, Evelyn Patricia Sanchez; CAMPOS, Aleia Faustina; MOURA, Maria Luiza do Nascimento; SALOMAO, Matias C.; BOSZCZOWSKI, Icaro; FREIRE, Maristela Pinheiro; CARVALHO, Laina Bubach de; PARANHOS-BACCALA, Glaucia; COSTA, Silvia Figueiredo; GUIMARAES, Thais
- Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing(2021) HIGASHINO, Hermes Ryoiti; MARCHI, Ana Paula; MARTINS, Roberta Cristina Ruedas; CARVALHO, Laina Bubach; PERDIGAO NETO, Lauro Vieira; CORTES, Marina Farrel; OLIVEIRA, Fernando Nivaldo de; DUARTE, Edson Luiz Tarsia; GUIMARAES, Thais; ROSSI, Flavia; FERREIRA, Aliana M.; ROCHA, Vanderson; COSTA, Silvia FigueiredoCarbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 mu g ml(-1). Demographic and clinical data were retrieved from the patients' charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4% in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.
- Clonality, outer-membrane proteins profile and efflux pump in KPC- producing Enterobacter sp. in Brazil(2017) ROSA, Juliana Ferraz; RIZEK, Camila; MARCHI, Ana Paula; GUIMARAES, Thais; MIRANDA, Lourdes; CARRILHO, Claudia; LEVIN, Anna S.; COSTA, Silvia F.Background: Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year. Methods: Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates. Outer-membrane protein (OMP) was evaluated based on PFGE profile. Results: A total of 130 isolates of Enterobacter spp were analyzed, 44/105 (41, 9%) E. aerogenes and 8/25 (32,0%) E. cloacae were resistant to carbapenems. All isolates were susceptible to fosfomycin, polymyxin B and tigecycline. KPC was present in 88.6% of E. aerogenes and in all E. cloacae resistant to carbapenems. The carbapenems-resistant E. aerogenes identified in hospital A belonged to six clones, however, a predominant clone was identified in this hospital over the study period. There is a predominant clone in Hospital B and Hospital C as well. The mechanisms of resistance to carbapenems differ among subtypes. Most of the isolates co-harbored blaKPC, blaTEM and /or blaCTX associated with decreased or lost of 35-36KDa and or 39 KDa OMP. The efflux pump AcrAB-TolC gene was only identified in carbapenems-resistant E. cloacae. Conclusions: There was a predominant clone in each hospital suggesting that cross-transmission of carbapenems-resistant Enterobacter spp. was frequent. The isolates presented multiple mechanisms of resistance to carbapenems including OMP alteration.