LAURO VIEIRA PERDIGAO NETO
Projetos de Pesquisa
Unidades Organizacionais
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina
8 resultados
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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.
- 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
- Genetic and virulence characterization of colistin-resistant and colistin-sensitive A. baumannii clinical isolates(2019) LEITE, Gleice Cristina; STABLER, Richard A.; NEVES, Patricia; PERDIGAO NETO, Lauro V.; MARTINS, Roberta C. Ruedas; RIZEK, Camila; ROSSI, Flavia; LEVIN, Anna S.; COSTA, Silvia FigueiredoTreatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital.
- 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.
- 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.
- Simultaneous colonization by Escherichia coli and Klebsiella pneumoniae harboring mcr-1 in Brazil(2019) PERDIGAO NETO, Lauro Vieira; CORSCADDEN, Louise; MARTINS, Roberta Cristina Ruedas; NAGANO, Debora Satie; CUNHA, Marcos Paulo Vieira; NEVES, Patricia Regina; FRANCO, Lucas Augusto Moyses; MOURA, Maria Luisa Nascimento; RIZEK, Camila Fonseca; GUIMARAES, Thais; BOSZCZOWSKI, Icaro; ROSSI, Flavia; LEVIN, Anna S.; STABLER, Richard A.; COSTA, Silvia F.Case presentationWe present a case report of a woman, concurrently colonized by polymyxin-resistant E. coli and K. pneumoniae. A Brazilian female patient, in her mid-fifties, was hospitalized with schistosomiasis. During hospitalization, polymyxin-resistant E. coli and K. pneumoniae were isolated from surveillance cultures.MethodsIdentification, antimicrobial susceptibility testings, PCR for mcr-1, plasmid transfer by conjugation and whole genome sequencing were performed.ResultsE. coli ST744 and K. pneumoniae ST101 carrying mcr-1 gene were described. Transconjugant E. coli was positive for mcr-1 and IncX4 by PCR. The plasmid is a 33,304-base pair plasmid, and the mcr-1 gene was the only antimicrobial resistance gene present in the plasmid.ConclusionsThis study presents a case report of a hospitalized woman, concurrently colonized by mcr-1-harboring E. coli ST744, a different ST from previously described in Brazil, and a K. pneumoniae ST101.
- 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.
- Carbapenem-resistant Pseudomonas aeruginosa carrying bla(VIM-36) assigned to ST308: Indicated non-virulence in a Galleria mellonella model(2019) NEVES, Patricia R.; PERDIGAO NETO, Lauro Vieira; MARTINS, Roberta Cristina Ruedas; RAMOS, Jessica F.; LEITE, Gleice; ROSSI, Flavia; SANABANI, Sabri Saeed; ROCHA, Vanderson; BATISTA, Marjorie Vieira; GUIMARAES, Thais; LEVIN, Anna S.; COSTA, Silvia F.Objectives: Based on pulsed-field gel electrophoresis (PFGE) profile, whole-genome sequencing (WGS) of eight carbapenem-resistant Pseudomonas aeruginosa isolates from a bone marrow transplant unit in Sao Paulo, Brazil, was performed to investigate the presence of resistance and virulence genes as well as to determine the sequence type (ST) by multilocus sequence typing (MLST). Methods: The initial phenotypic susceptibility pattern of the isolates was determined by VITEK (R) 2. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method for amikacin, meropenem and colistin. WGS was performed using an Illumina MiSeq system. A Galleria mellonella infection model was used to evaluate the virulence of the strains. Results: WGS demonstrated that mutations in genes encoding outer membrane proteins and efflux pumps in an isolate harbouring bla(VIM-36) (ST308) differed from those in isolates harbouring bla(SPM)(ST277). The mexTgene harboured a mutation resulting in a frameshift in all isolates; in addition, the oprD gene of the bla(VIM-36)-carrying isolate had an insertion leading to a frameshift. Virulence genes did not differ between ST277 and ST308 strains. Moreover, only two isolates harbouring bla(SPM) showed virulence in the G. mellonella model, killing 100% of larvae after 18-24 h. Conclusions: P. aeruginosa carrying bla(VIM-36) belonging to ST308 was identified for the first time in our hospital. Although the virulence gene profiles were similar in isolates carrying bla(SPM )and the isolate carrying bla(VIM-36), only two isolates harbouring bla(SPM )showed virulence in the G. mellonella model.