LAURO VIEIRA PERDIGAO NETO
Projetos de Pesquisa
Unidades Organizacionais
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Multidrug-resistant Stenotrophomonas maltophilia: Description of new MLST profiles and resistance and virulence genes using whole-genome sequencing(2018) RIZEK, Camila Fonseca; JONAS, Daniel; PAEZ, Jorge Isaac Garcia; ROSA, Juliana Ferraz; PERDIGAO NETO, Lauro Vieira; MARTINS, Roberta Ruedas; MORENO, Luisa Z.; ROSSI JUNIOR, Alfio; LEVIN, Anna S.; COSTA, Silvia FigueiredoObjectives: Stenotrophomonas maltophilia is an opportunistic pathogen that has high intrinsic and acquired antimicrobial resistance, with great genetic diversity. The aim of this study was to characterise four S. maltophilia clinical isolates displaying different susceptibility profiles using whole-genome sequencing. Methods: The whole genomes of four clinical isolates of S. maltophilia from three patients were sequenced using Ion Torrent (TM) PGM technology. The isolates presented different susceptibilities to trimethoprim/sulfamethoxazole (SXT) and levofloxacin. Results: Three new multilocus sequence typing (MLST) profiles were identified (ST144, ST172 and ST173), differing in virulence and resistance genes. The ST172 isolate had more genes related to toxins than related to motility or adhesion and had different types of efflux pumps than the other isolates. The SXT-resistant strains belonged to ST172 or ST144 and did not harbour the sul1, sul2 or dfrA resistance genes. Strains I and II, from the same patient and belonging to the same ST but differing in resistance to SXT, had all of the resistance genes searched for in common, except for the SmeABC efflux pump complex genes that were only found in the SXT-resistant strain. All strains, including the strain susceptible to levofloxacin, harboured the qnrB gene, which may question the importance of this gene in determining levofloxacin resistance in S. maltophilia. Conclusion: Here we describe three new MLST profiles. Resistance to SXT in these strains appears to be associated with efflux pumps.
- 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.
- 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.
- Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B(2016) RIGATTO, Maria Helena; OLIVEIRA, Maura S.; PERDIGAO-NETO, Lauro V.; LEVIN, Anna S.; CARRILHO, Claudia M.; TANITA, Marcos Toshiyuki; TUON, Felipe F.; CARDOSO, Douglas E.; LOPES, Natane T.; FALCI, Diego R.; ZAVASCKI, Alexandre P.Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for >= 48 h. A multicenter prospective cohort study was performed that included patients aged >= 18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 +/- 1.3 and 2.4 +/- 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P < 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48; P < 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.
- Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem(2019) PERDIGAO NETO, Lauro Vieira; OLIVEIRA, Maura S.; MARTINS, Roberta Cristina Ruedas; MARCHI, Ana Paula; GAUDERETO, Juliana Januario; COSTA, Lucianna Auxi Teixeira Josino da; LIMA, Lia Fernandes Alves de; TAKEDA, Christianne Fernandes Valente; COSTA, Silvia F.; LEVIN, Anna S.Background: In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria. Methods: We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to beta-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS. Results: Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued. Conclusions: Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.
- 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.
- Pharmacokinetic and Pharmacodynamic Characteristics of Vancomycin and Meropenem in Critically Ill Patients Receiving Sustained Low-efficiency Dialysis(2020) OLIVEIRA, Maura Salaroli; MACHADO, Anna Silva; MENDES, Elisa Teixeira; CHAVES, Lucas; PERDIGAO NETO, Lauro Vieira; JR, Carlindo Vieira da Silva; SANTOS, Silvia Regina Cavani Jorge; SANCHES, Cristina; MACEDO, Etienne; LEVIN, Anna S.Purpose: Antibiotic dosing is challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of meropenem and vancomycin in patients undergoing SLED. Methods: Consecutive ICU patients undergoing SLED and receiving meropenem and/or vancomycin were prospectively evaluated. Serial blood samples were collected before, during, and at the end of SLED sessions. Antimicrobial concentrations were determined using a validated HPLC method. Noncompartmental PK analysis was performed. AUC was determined for vancomycin. For meropenem, time above MIC was calculated. Findings: A total of 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations before SLED were 24.5 and 28.0 mu g/mL, respectively; after SLED, 14 and 6 mu g/mL. Mean removal was 42% with vancomycin and 78% with meropenem. With vancomycin, 19 (83%), 16 (70%), and 15 (65%) patients would have achieved the target (AUC(0-24) >400) considering MICs of 1, 2, and 4 mg/L, respectively. With meropenem, 17 (85%), 14 (70%), and 10 (50%) patients would have achieved the target (100% of time above MIC) if infected with isolates with MICs of 1, 4, and 8 mg/L, respectively. (C) 2020 Elsevier Inc.
- Polymyxin-resistant Pseudomonas aeruginosa assigned as ST245: First report in an intensive care unit in Sao Paulo, Brazil(2019) ORSI, Tatiana D'Annibale; PERDIGAO NETO, Lauro Vieira; MARTINS, Roberta Cristina Ruedas; LEVIN, Anna S.; COSTA, Silvia FigueiredoObjectives: Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe infections, especially in hospitalised and immunocompromised patients. Polymyxins are the last therapeutic option to treat infections caused by this micro-organism. Here we describe a polymyxin-resistant P. aeruginosa assigned as sequence type (ST) 245 for the first time in Brazil. Methods: Antimicrobial susceptibility testing of the isolate was performed. In addition, whole-genome sequencing was performed and its virulence and resistance genes were analysed. Results: The P. aeruginosa ST245 isolate was identified for the first time in Brazil in a patient with ventilator-associated pneumonia hospitalised at Hospital das Clinicas, Sao Paulo. Analysis of the genome showed the presence of several resistance and virulence genes. Mutations in beta-lactam resistance genes were found in beta-lactamases, outer membrane proteins, efflux pump and penicillin-binding proteins. Polymorphisms related to pathways leading to polymyxin resistance are also present, such as lipid A or keto-deoxyoctulosonate modification with aminoarabinose as well as activation of lipopolysaccharide (LPS). Conclusion: Such findings may represent an alert for the spread of an unusual profile in the country.