RESUMO
Polymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients' comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed.
Assuntos
Infecções por Klebsiella , Polimixinas , Humanos , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/genética , Brasil , Genoma Bacteriano , Surtos de Doenças , Carbapenêmicos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , Proteínas de Bactérias/genéticaRESUMO
Stenotrophomonas can survive in a wide range of environments and is considered an opportunistic pathogen. Because of its intrinsic resistance to beta-lactams, this genus is considered irrelevant in studies addressing the environmental spread of antimicrobial resistance genes of medical importance. Consequently, studies on environmental Stenotrophomonas carrying acquired carbapenemase-encoding genes are scarce, though not inexistent. Here, we investigated the frequency and diversity of Stenotrophomonas spp. carrying genes encoding carbapenemases of medical relevance in coastal waters with distinct pollution degrees over one year. Among 319 isolates recovered, 220 (68.9%) showed blaKPC. The frequency of blaKPC-positive Stenotrophomonas spp. was not correlated with thermotolerant counts in coastal waters evaluated. All isolates were susceptible to minocycline, levofloxacin, and trimethoprim-sulfamethoxazole. PFGE typing of 101 blaKPC-positive isolates revealed 55 pulsotypes with 5 subtypes, all of which carried the blaKPC-2 variant. Interspecies differentiation of pulsotypes' representatives revealed 55 isolates belonging to the S. maltophilia complex (91.7%) and 5 S. acidaminiphila (8.3%). The blaKPC-2 gene was more frequently harbored on transposable elements found in enterobacteria of clinical origin, especially Tn4401b. Even though beta-lactams are no therapeutic options to treat Stenotrophomonas infections, the occurrence of a highly relevant antimicrobial resistance determinant harbored on mobile genetic elements in a diverse collection of these ubiquitous microorganisms is noteworthy. Therefore, Stenotrophomonas may act as acceptor, stable reservoirs, and potential vectors of antimicrobial resistance in environmental settings, especially aquatic matrices, and should not be neglected.
Assuntos
Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Humanos , Levofloxacino , Testes de Sensibilidade Microbiana , Stenotrophomonas/genética , Stenotrophomonas maltophilia/genéticaRESUMO
KPC-producing Klebsiella pneumoniae (KPC-Kp) has become an important public health issue. The previous intestinal colonization by KPC-Kp has been an important risk factor associated with the progression to infections. The objective of this study was to assess the genetic characterization of KPC-Kp isolates recovered from human rectal swabs in Brazil. We selected 102 KPC-Kp isolates collected during 2009-2013 in 11 states. Antimicrobial susceptibility was determined by disk diffusion, E-test, and broth microdilution. The resistance and virulence genes were investigated by PCR. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The isolates were mostly resistant to ß-lactams, sulfonamides, chloramphenicol, quinolones, and aminoglycosides but susceptible to fosfomycin/trometamol, polymyxin B, and tigecycline. The blaKPC-2 was mostly associated with Tn4401b. Besides that, the isolates carried blaCTX-M, blaSHV, blaTEM, and aac(6')-Ib in high frequency and aac(3')IIa and qnr genes in moderate frequency. The PFGE revealed 26 pulsotypes and MLST performed in representative strains revealed 23 sequence types, 45% belonging to clonal complex 258 (CC258). Isolates of CC258 were found in all states. Seventy percent of the 102 KPC-Kp isolates belonged to CC258-associated pulsotypes. We describe the dissemination of KPC-2-Kp associated with Tn4401b belonging to CC258 colonizing patients in Brazil, which is also prevalent in infected patients, suggesting a clear colonization-infection correlation.
Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana Múltipla/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Brasil/epidemiologia , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Genes Bacterianos , Humanos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem Molecular , Tipagem de Sequências MultilocusRESUMO
In this study, we describe the genetic features of an XDR KPC-2-producing Klebsiella pneumoniae isolate by using whole-genome sequencing, its clinical-epidemiological context and susceptibility against antimicrobial combinations. The isolate belongs to clonal complex 258 and harbors several acquired genes and mutations associated with antimicrobial resistance.
Assuntos
Compostos Azabicíclicos/farmacologia , Proteínas de Bactérias/genética , Ceftazidima/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Klebsiella pneumoniae/genética , Antibacterianos/farmacologia , Brasil , Cromossomos Bacterianos/genética , Combinação de Medicamentos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Análise de Sequência de DNARESUMO
We characterized NDM-1-producing Klebsiella isolates from Rio de Janeiro, Brazil. PCR was applied for resistance and virulence determinants. The genetic context of blaNDM was determined by S1 nuclease pulsed-field gel electrophoresis (PFGE) and hybridization. Genotyping was performed by PFGE and multilocus sequence typing (MLST). Most isolates carried multiple resistance genes and remained susceptible to amikacin, fosfomycin-trometamol, polymyxin B, and tigecycline. The spread of NDM-1-producing Klebsiella pneumoniae was not associated with clonal expansion and appears to be associated with Tn3000.
Assuntos
Antibacterianos/farmacologia , Elementos de DNA Transponíveis , Farmacorresistência Bacteriana Múltipla/genética , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Amicacina/farmacologia , Técnicas de Tipagem Bacteriana , Brasil/epidemiologia , Células Clonais , Eletroforese em Gel de Campo Pulsado , Fosfomicina/farmacologia , Expressão Gênica , Genótipo , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/transmissão , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Minociclina/análogos & derivados , Minociclina/farmacologia , Tipagem de Sequências Multilocus , Filogenia , Plasmídeos/química , Plasmídeos/metabolismo , Polimixina B/farmacologia , Tigeciclina , beta-Lactamases/metabolismoRESUMO
We aimed to describe an early detection of OXA-370-producing Klebsiella pneumoniae in Brazil. The isolate CCBH10079 belonged to ST17 and the blaOXA-370 was located in a plasmid of â 57kb.
Assuntos
Genótipo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/genética , beta-Lactamases/metabolismo , Brasil , Humanos , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/genética , Tipagem Molecular , Plasmídeos/análiseRESUMO
We aimed to investigate polymyxin B (PMB) resistance and its molecular mechanisms in 126 Klebsiella pneumoniae isolates from rectal swabs in Brazil. Ten isolates exhibited PMB resistance with interruption of mgrB gene by insertion sequences or missense mutations. Most of the PMB-resistant isolates harbored blaKPC-2 (n = 8) and belonged to clonal complex 258 (CC258) (n = 7). These results highlight the importance of monitoring the spread of polymyxin-resistant bacteria in hospitals, since few options remain to treat multidrug-resistant isolates.
Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Polimixina B/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Mutação , Reto/microbiologia , beta-Lactamases/genéticaRESUMO
The emergence of multidrug-resistant Enterobacteriaceae strains producing carbapenemases, such as NDM-1, has become a major public health issue due to a high dissemination capacity and limited treatment options. Here we describe the draft genome of three NDM-1-producing isolates: Providencia rettgeri (CCBH11880), Enterobacter hormaechei subsp. oharae (CCBH10892) and Klebsiella pneumoniae (CCBH13327), isolated in Brazil. Besides blaNDM-1, resistance genes to aminoglycosides [aadA1, aadA2, aac(6')-Ib-cr] and quinolones (qnrA1, qnrB4) were observed which contributed to the multidrug resistance profile. The element ISAba125 was found associated to the blaNDM-1 gene in all strains.
Assuntos
Enterobacter/genética , Genoma Bacteriano/genética , Klebsiella pneumoniae/genética , Providencia/genética , beta-Lactamases/genética , Sequência de Bases , Brasil , Farmacorresistência Bacteriana/genética , Enterobacter/enzimologia , Humanos , Klebsiella pneumoniae/enzimologia , Dados de Sequência Molecular , Providencia/enzimologia , Análise de Sequência de DNARESUMO
In Brazil, since 2009, there has been an ever increasing widespread of the bla(KPC-2) gene, mainly in Klebsiella pneumoniae. This study aims to assess the molecular epidemiology and genetic background of this gene in Enterobacteriaceae (non-K. pneumoniae) species from 9 Brazilian states between 2009 and 2011. Three hundred eighty-seven isolates were analyzed exhibiting nonsusceptibility to carbapenems, in which the bla(KPC-2) gene was detected in 21.4%. By disk diffusion and E-test, these isolates exhibited high rates of resistance to most of the antimicrobials tested, including tigecycline (45.6% nonsusceptible) and polymyxin B (16.5%), the most resistant species being Enterobacter aerogenes and Enterobacter cloacae. We found great clonal diversity and a variety of bla(KPC-2)-carrying plasmids, all of them exhibiting a partial Tn4401 structure. Therefore, this study demonstrates the dissemination of KPC-2 in 9 Enterobacteriaceae species, including species that were not previously described such as Pantoea agglomerans and Providencia stuartii.
Assuntos
Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Tipagem Molecular , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Brasil/epidemiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Variação Genética , Genótipo , Humanos , Epidemiologia Molecular , beta-Lactamases/genéticaRESUMO
Enzymes of the OXA-48 family have become some of the most important beta-lactamases in the world. A new OXA-48 variant (OXA-370) was first described for an Enterobacter hormaechei strain isolated in Rio Grande do Sul (southern region of Brazil) in 2013. Here we report detection of the blaOXA-370 gene in 24 isolates belonging to three Enterobacteriaceae species (22 Klebsiella pneumoniae isolates, 1 Enterobacter cloacae isolate, and 1 Enterobacter aerogenes isolate) collected from five hospitals in Rio de Janeiro, Brazil, in 2013 and 2014. The isolates showed a multidrug resistance profile, and 12.5% were resistant to polymyxin B. Besides blaOXA-370, no other carbapenemase genes were observed by PCR, whereas blaOXA-1 was found in all isolates and 22 isolates (91.6%) possessed blaCTX-M-15. Molecular typing of the K. pneumoniae isolates by pulsed-field gel electrophoresis (PFGE) showed the presence of two clonal groups, i.e., KpA (21 isolates) and KpB (1 isolate). KpA was characterized as sequence type 16 (ST16) and KpB as ST1041 by multilocus sequence typing (MLST). ST16 has been observed for KPC-producing K. pneumoniae in Rio de Janeiro. Plasmid analysis performed with six representative OXA-370-producing isolates showed plasmids harboring the blaOXA-370 gene in all strains, ranging from 25 kb to 150 kb. This study suggests that there is an urgent need to investigate the presence of OXA-370 and dissemination of the K. pneumoniae ST16 clone carrying this gene in Brazil.