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.
- 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.
- 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).
- Colistin-resistant Klebsiella pneumoniae co-harboring KPC and MCR-1 in a Hematopoietic Stem Cell Transplantation Unit(2019) HIGASHINO, Hermes Ryoiti; MARCHI, Ana Paula; MARTINS, Roberta Cristina Ruedas; BATISTA, Marjorie Vieira; PERDIGAO NETO, Lauro Vieira; LIMA, Victor Augusto Camarinha de Castro; ROSSI, Flavia; GUIMARAES, Thais; LEVIN, Anna Sara; ROCHA, Vanderson; COSTA, Silvia Figueiredo
- Vancomycin-resistant enterococci isolates colonizing and infecting haematology patients: clonality, and virulence and resistance profile(2018) MARCHI, A. P.; PERDIGAO NETO, L. V.; MARTINS, R. C. R.; RIZEK, C. F.; CAMARGO, C. H.; MORENO, L. Z.; MORENO, A. M.; BATISTA, M. V.; BASQUEIRA, M. S.; ROSSI, F.; AMIGO, U.; GUIMARAES, T.; LEVIN, A. S.; COSTA, S. F.Background: Vancomycin-resistant enterococci (VRE) are an important agent of colonization and infection in haematology patients. However, the role of virulence on VRE colonization and infection is controversial. Aim: To characterize the lineage, virulence and resistance profile of VRE infection and colonization isolates; as well as their impact on outcome of haematology patients using a regression logistic model. Methods: Eighty-six isolates (80 Enterococcus faecium and six E. faecalis) from 76 patients were evaluated. Polymerase chain reaction for resistance and virulence genes, and pulsed-field gel electrophoresis and whole genome sequencing of the major clusters, were performed. Bivariate and multivariate analyses were carried out to evaluate the role of virulence genes on outcome. Findings: All isolates harboured the vanA gene. Regarding the virulence genes, 96.5% of isolates were positive for esp, 69.8% for gelE and asa1 genes. VRE infection isolates were more virulent than colonization isolates and harboured more often the gelE gene (P = 0.008). Infections caused by VRE carrying asal gene resulted more frequently in death (P = 0.004), but only the predominant clone remained as protector in the multivariate model. The E. faecium strains were assigned to seven STs (ST78, ST412, ST478, ST792, ST896, ST987, ST963) that belonged to CC17. The E. faecalis sequenced belonged to ST9 (CC9). Conclusion: E. faecium was predominant, and infection isolates were more virulent than colonization isolates and harboured more often the gene gelE. Infections caused by VRE carrying the asal gene appeared to be associated with a fatal outcome.
- 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.
- Multidrug-resistant Klebsiella pneumoniae: genetic diversity, mechanisms of resistance to polymyxins and clinical outcomes in a tertiary teaching hospital in Brazil(2019) BOSZCZOWSKI, Icaro; SALOMAO, Matias Chiarastelli; MOURA, Maria Luisa; FREIRE, Maristela Pinheiro; GUIMARAES, Thais; CURY, Ana Paula; ROSSI, Flavia; RIZEK, Camila Fonseca; MARTINS, Roberta Cristina Ruedas; COSTA, Silvia FigueiredoIncreased resistance to polymyxin in Klebsiella pneumoniae (ColRKP) has been observed. Molecular epidemiology, as well as the clinical impact of these difficult to treat pathogens need to be better characterized. We present the clinical outcomes of 28 patients infected by ColRKP in a tertiary hospital. Isolates with MIC >2 by Vitek 2 were confirmed by the microdilution broth test. Polymerase chain reaction (PCR) was performed for bla(KPC), bla(NDM), bla(OXA-48), and bla(mcr-1) genes in the isolates, and Whole Genome Sequencing (WGS) was performed in six isolates. Seventeen (61%) patients were female and the mean age was 50 years old. In-hospital and 30-day mortality were 64% (18/28) and 53% (15/28), respectively. Central line-associated bloodstream infection in addition to bacteremia episodes due to other sources were the most frequent (61%). Mean APACHE and Charlson comorbidity index were 16 and 5, respectively. Twenty patients (71%) received at least one active drug and ten (35%) received two drugs: tigecycline 46% (13/28); amikacin 21% (6/28) and fosfomycin 3% (1 case). Twenty-six out of 28 tested cases were positive for bla(KPC) Eight different clusters were identified. Four STs were detected (ST1, ST23, ST340, and ST437). Mutations on pmrA, arnB udg, and yciM genes were present in all six isolates submitted to WGS; /pxMand mgrB mutations were also detected in all but one isolate. In conclusion, we observed resistance to polymyxin in severely ill patients mostly from intensive care units and/or immunosuppressed patients with high mortality rates in whom a diversity of ColRKP clusters was identified and might indicate selective pressure.
- Carbapenem-resistant Serratia marcescens bloodstream infection in hematopoietic stem cell transplantation patients: Will it be the next challenge?(2021) PRADO, G. V. B. do; MENDES, E. T.; MARTINS, R. C. R.; PERDIGãO-NETO, L. V.; FREIRE, M. P.; SPADãO, F.; LIMA, V. A. C. de Castro; ROSSI, F.; GUIMARãES, T.; LEVIN, A. S.; ROCHA, V.; COSTA, S. F.Surveillance programs have been reporting decreasing rates of carbapenem-sensitivity in Serratia marcescens, leading to a concern regarding the few remaining therapeutic options to treat these multidrug-resistant (MDR) organisms. Here, we describe a case series of 11 stem cell hematopoietic transplantation patients infected (N = 6) or colonized (N = 5) by carbapenem-resistant S marcescens (CrSm) from 2010 to 2013. The comorbidities found were acute renal insufficiency (3/11), neutropenia (7/11), and mucositis (8/11), and the mortality rate was 64%. KPC was the most prevalent carbapenemase detected (8/11) and tigecycline and gentamicin were the antimicrobials used as treatment. © 2021 Wiley Periodicals LLC