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1.
Clin Infect Dis ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31323088

RESUMO

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Though beta-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers), including hospitalized patients with P . aeruginosa bacteremia treated with beta-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate analyses, including propensity adjusted analysis, were conducted introducing monotherapy type as an independent variable. RESULTS: We included 767 patients. Thirty-day mortality was 37/213 (17.4%) in the ceftazidime group; 42/210 (20%) in the carbapenem group, and 55/344 (16%) in the piperacillin-tazobactam group. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate or propensity adjusted analyses (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.52-2.46 for ceftazidime, OR 1.3, 95% CI 0.67-2.51 for piperacillin-tazobactam with carbapenems as reference in propensity adjusted multivariate analysis, 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequently with carbapenems (36/206, 17.5% versus ceftazidime 25/201, 12.4% and piperacillin-tazobactam 28/332, 8.4%, p=0.007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.

2.
J Glob Antimicrob Resist ; 18: 37-44, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154007

RESUMO

BACKGROUND: Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option. OBJECTIVES: This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015). METHODS: Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates. RESULTS: In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection. CONCLUSIONS: These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial.

3.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(2): 82-88, feb. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-181146

RESUMO

Introduction: To characterize OXA-48 carbapenemase-producing Klebsiella pneumoniae strains isolated after an increase in carbapenem resistance in Catalonia. Methodology: K. pneumoniae identification, antimicrobial susceptibility studies, the Modified Hodge Test method, amplification of antimicrobial resistance genes (against β-lactamases, quinolones and aminoglycosides), molecular typing (by PFGE and MLST), conjugation assays, plasmid characterization (PBRT-PCR and Southern blot), a description of mobile genetic elements and statistical analysis were done. Results: OXA-48 was the only carbapenemase detected, with a prevalence of 1.9%. The blaOXA-48 gene was located in an IncL conjugative plasmid of 62 kb and integrated into the transposons Tn1999.2 (91.7%) or Tn1999.1. Five PFGE profiles (A to E) were found, which exactly matched the MLST: ST101, ST17, ST1233, ST14 and ST405, respectively. ST1233 is described here for the first time. K. pneumoniae OXA-48-producing strains were also CTX-M-15 carriers, some producing OXA-1 and TEM-1 penicillinases. The acquired qnrB66 and qnrB1 and aac(3′)-IIa, aac(6′)-Ib genes were also identified. Conclusion: The K. pneumoniae ST405 clone has played an important role in the growing prevalence of OXA-48 in Catalonia. All clones described preserved the blaOXA-48 genetic environment and mobile genetic elements (Tn1999). Notably, the three strains with minor sequence types in this study are not multiresistant strains. These strains are expanding in elderly patients (average age of 76 years) with serious underlying diseases, mainly women (61.2%)


Introducción: El objetivo de este estudio fue caracterizar las cepas de Klebsiella pneumoniae productoras de carbapenemasa OXA-48 aisladas tras observar un aumento de estos aislados resistentes a los carbapenémicos en Cataluña. Métodos: Se realizó la identificación de K. pneumoniae, estudios de sensibilidad antimicrobiana, el test de Hodge modificado, amplificación de genes de resistencia antimicrobiana (contra β-lactamasas, quinolonas y aminoglucósidos), tipificación molecular (por PFGE y MLST), ensayos de conjugación, caracterización de plásmidos (PBRT-PCR y Southern blot), descripción de los elementos genéticos móviles y el análisis estadístico. Resultados: OXA-48 fue la única carbapenemasa presente, con una prevalencia del 1,9%. El gen blaOXA-48 se localizó en un plásmido conjugativo IncL de 62kb e integrado en los transposones Tn1999.2 (91,7%) o Tn1999.1. Se encontraron 5 perfiles diferentes de PFGE (A a E), que tenían una concordancia exacta con el MLST: ST101, ST17, ST1233, ST14 y ST405, respectivamente. El ST1233 se describe aquí por primera vez. Las cepas productoras de K. pneumoniae OXA-48 también fueron portadoras de CTX-M-15 y algunas de ellas productoras también de penicilinasas OXA-1 y TEM-1. Los genes adquiridos qnrB66 y qnrB1 y aac(3’)-IIa, aac(6’)-Ib también se identificaron. Conclusión: El clon K. pneumoniae ST405 tiene un papel importante en la creciente prevalencia de OXA-48 en Cataluña. Todos los clones descritos preservaron el entorno genético de blaOXA-48, así como los elementos genéticos móviles (Tn1999). Notablemente, las 3 cepas con tipos de secuencia menos prevalentes en este estudio no son cepas multirresistentes. Además, la expansión de estas cepas con blaOXA-48 se está produciendo en pacientes de edad avanzada (promedio de edad de 76 años), la mayoría mujeres (61,2%) con enfermedades subyacentes graves


Assuntos
Humanos , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Conjugação Genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação
4.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29631930

RESUMO

INTRODUCTION: To characterize OXA-48 carbapenemase-producing Klebsiella pneumoniae strains isolated after an increase in carbapenem resistance in Catalonia. METHODOLOGY: K. pneumoniae identification, antimicrobial susceptibility studies, the Modified Hodge Test method, amplification of antimicrobial resistance genes (against ß-lactamases, quinolones and aminoglycosides), molecular typing (by PFGE and MLST), conjugation assays, plasmid characterization (PBRT-PCR and Southern blot), a description of mobile genetic elements and statistical analysis were done. RESULTS: OXA-48 was the only carbapenemase detected, with a prevalence of 1.9%. The blaOXA-48 gene was located in an IncL conjugative plasmid of 62kb and integrated into the transposons Tn1999.2 (91.7%) or Tn1999.1. Five PFGE profiles (A to E) were found, which exactly matched the MLST: ST101, ST17, ST1233, ST14 and ST405, respectively. ST1233 is described here for the first time. K. pneumoniae OXA-48-producing strains were also CTX-M-15 carriers, some producing OXA-1 and TEM-1 penicillinases. The acquired qnrB66 and qnrB1 and aac(3')-IIa, aac(6')-Ib genes were also identified. CONCLUSION: The K. pneumoniae ST405 clone has played an important role in the growing prevalence of OXA-48 in Catalonia. All clones described preserved the blaOXA-48 genetic environment and mobile genetic elements (Tn1999). Notably, the three strains with minor sequence types in this study are not multiresistant strains. These strains are expanding in elderly patients (average age of 76 years) with serious underlying diseases, mainly women (61.2%).

7.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(8): 499-504, oct. 2017. graf, tab
Artigo em Inglês | IBECS | ID: ibc-167837

RESUMO

Introduction: Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of Beta -lactam agents is compromised by microorganisms harboring extended-spectrum Beta -lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non Beta -lactam agent that inhibits clinically relevant Beta -lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms. Methods: The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extended-spectrum Beta -lactamases (ESBLs) and acquired AmpC Beta -lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated. Results: The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime. Conclusion: CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceaeproducing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins (AU)


Introducción: La resistencia antibiótica en enterobacterias está en aumento y el tratamiento de infecciones producidas por enterobacterias multirresistentes supone un reto terapéutico. El uso de betalactámicos se afecta con la producción de betalactamasas de espectro extendido (BLEE) y otros mecanismos de resistencia. Avibactam es un compuesto no betalactámico que inhibe betalactamasas como BLEE o AmpC. La combinación ceftazidima-avibactam (CAZ-AVI) ha sido aprobada recientemente para el tratamiento de infecciones complicadas y puede ser una alternativa terapéutica en estas infecciones. Métodos: La actividad in vitro de CAZ y CAZ-AVI (AVI, concentración fija de 4mg/mL) fue determinada en 250 aislamientos clínicos de enterobacterias mediante microdilución en caldo. Los puntos de corte de EUCAST fueron utilizados para CAZ, y los criterios de FDA se utilizaron para CAZ-AVI. Las enterobacterias estudiadas producían BLEE y/o AmpC adquiridas (BLAA). El papel de la pérdida de porinas en Klebsiella pneumoniae también fue evaluado. Resultados: CAZ-AVI demostró una excelente actividad en Escherichia coli y Klebsiella pneumoniaeproductoras de BLEE, devolviendo la sensibilidad a CAZ en todos los aislamientos resistentes a CAZ. CAZ-AVI mantuvo su actividad en aislamientos de K. pneumoniae deficientes en porinas productoras de BLEE y/o BLAA, aunque los valores de CMI fueron más altos comparados con las cepas que expresaban porinas. En todas las enterobacterias resistentes a ceftazidima productoras de BLAA analizadas en este estudio CAZ-AVI devolvió la sensibilidad a ceftazidima. Conclusión: CAZ-AVI demostró una potente actividad in vitro en aislamientos clínicos de enterobacterias productoras de BLEE y/o BLAA, incluyendo K. pneumoniae con pérdida de porinas (AU)


Assuntos
Resistência a Múltiplos Medicamentos , Enterobacteriaceae , beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Técnicas In Vitro/métodos , Porinas/isolamento & purificação , Klebsiella pneumoniae , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana/instrumentação
8.
Artigo em Inglês | MEDLINE | ID: mdl-28874376

RESUMO

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the ß-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in ß-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Aminoglicosídeos/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , Fluoroquinolonas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Polimixinas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Espanha/epidemiologia , Tazobactam , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
9.
J Infect ; 75(6): 493-498, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28919348

RESUMO

OBJECTIVES: The objectives were to determine the prevalence of colistin resistance in clinical isolates of Enterobacteriaceae, and to gain knowledge on the epidemiological and clinical features of the patients. METHODS: All colistin-resistant Enterobacteriaceae consecutively isolated from clinical samples in our institution from 2012 to 2015, were included in this cross-sectional study. Intrinsic-resistant species were excluded. Minimum inhibitory concentration was performed by gradient diffusion. Detection of plasmid-encoded colistin resistance genes mcr-1 and mcr-2 was performed by amplification. Epidemiological and clinical features were reviewed. RESULTS: Of 13579 Enterobacteriaceae isolates, 91 were colistin-resistant. The overall prevalence of colistin resistance was 0.67%. The rates were higher in Enterobacter cloacae (4.2%) than Escherichia coli (0.5%) and Klebsiella pneumoniae (0.4%). One third of the isolates were multi-drug resistant (MDR). While mcr-2 was not detected, mcr-1 was detected only in E. coli. Regarding these infections, 23% were community-acquired. 89% of the patients had not received colistin previously. There were no significant differences between infections caused by mcr-1 and non-mcr-1-carrying isolates. CONCLUSIONS: Colistin resistance was not restricted to MDR isolates and to clinical settings. Most patients had no record of previous administration of colistin.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antibacterianos/uso terapêutico , Criança , Colistina/uso terapêutico , Estudos Transversais , Enterobacteriaceae/isolamento & purificação , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Espanha/epidemiologia , Centros de Atenção Terciária , Adulto Jovem
10.
Methods Mol Biol ; 1615: 311-320, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28667623

RESUMO

Pili are widespread among bacteria. Type IVa pili (T4aP) are associated with a variety of bacterial functions, including adhesion, motility, natural transformation, biofilm formation, and force-dependent signaling. In pathogenic bacteria, T4aP play a crucial role during infection and have been the subject of hundreds of studies. Methods for the isolation and purification of T4aP were first described in the 1970s. Purified pili have been used for studies of filament protein content, morphology, immunogenicity, post-translational modifications, and X-ray crystallography. We detail a tried-and-true method of isolating large amounts of native T4aP from bacterial surfaces. The method requires supplies and equipment that are available in most microbiology labs.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Fímbrias Bacterianas/metabolismo , Proteínas de Bactérias/isolamento & purificação , Fracionamento Celular , Pseudomonas aeruginosa/metabolismo , Fluxo de Trabalho
12.
Microb Drug Resist ; 23(7): 833-837, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28304213

RESUMO

Proteus mirabilis is the second most common cause of urinary tract infections and is also an important cause of nosocomial infections. TEM-type and CTX-M-type extended-spectrum ß-lactamases (ESBLs) are the most widely distributed in this bacterial species, but minor ESBLs such as the VEB-type have also been identified. The aim of this study was to analyze the genetic environment of the blaVEB-4 gene found in a P. mirabilis clinical isolate recovered in Spain. P. mirabilis N2231 showed resistance to penicillins, cephalosporins, and aminoglycosides, remaining susceptible to imipenem, cefoxitin, ß-lactamases inhibitors, and quinolones. Southern blot analysis revealed that blaVEB-4 was located in the chromosome. Analysis of the blaVEB-4 genetic context revealed a 15 kb segment 98% identical to the multidrug resistance (MDR) region of a Salmonella genomic island 1 (SGI1), which included a class 1 integron belonging to the In104 family, previously described in blaVEB-6-producing P. mirabilis VB1248. blaVEB-4 was surrounded by repeat elements, transposon Tn1721, and located on a class 1 integron containing aacA4-aadB-dfrA1-orfC genes. The blaVEB-4 gene was inserted in a complex structure of a class 1 integron, which is part of an MDR region of an SGI1, possibly involved in the mobilization of the gene and homologous recombination.


Assuntos
Cromossomos Bacterianos/química , Farmacorresistência Bacteriana Múltipla/genética , Integrons , Proteus mirabilis/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Mapeamento Cromossômico , Cromossomos Bacterianos/metabolismo , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Elementos de DNA Transponíveis , Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Repetições de Microssatélites , Infecções por Proteus/tratamento farmacológico , Infecções por Proteus/microbiologia , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/enzimologia , Proteus mirabilis/isolamento & purificação , Espanha , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , beta-Lactamases/metabolismo
13.
Enferm Infecc Microbiol Clin ; 35(8): 499-504, 2017 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27887765

RESUMO

INTRODUCTION: Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of ß-lactam agents is compromised by microorganisms harboring extended-spectrum ß-lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non ß-lactam agent that inhibits clinically relevant ß-lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms. METHODS: The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extended-spectrum ß-lactamases (ESBLs) and acquired AmpC ß-lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated. RESULTS: The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime. CONCLUSION: CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins.

14.
Euro Surveill ; 21(13)2016.
Artigo em Inglês | MEDLINE | ID: mdl-27055477

RESUMO

Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012-15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Eletroforese em Gel de Campo Pulsado , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Espanha/epidemiologia , Adulto Jovem
15.
Int J Antimicrob Agents ; 47(1): 62-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26607336

RESUMO

Escherichia coli recovered from three hospitals in Barcelona (Spain) were studied to determine the prevalence of isolates with acquired AmpC (ac-AmpC) and/or overproduced chromosomal AmpC (c-AmpC). Mechanisms involved in blac-AmpC overexpression, blaac-AmpC and the plasmids associated with their distribution as well as the prevalence of plasmid-mediated quinolone resistance (PMQR) in AmpC-producing isolates were also determined. Isolates were selected according to their resistance phenotype. blaac-AmpC, alterations in the blac-AmpC promoter/attenuator, and PMQR genes [qnrA, qnrB, qnrS, aac(6')-Ib-cr and qepA] were characterised by PCR and sequencing. blac-AmpC expression was determined by qRT-PCR. Population structure analysis was performed using PFGE, MLST and phylogenetic group PCR. Plasmids carrying blaac-AmpC were characterised by PCR-based replicon typing and S1-PFGE. IncI1 and IncF plasmids were also analysed by plasmid MLST and replicon sequence typing, respectively. Among 21563 E. coli isolates, 240 (1.1%) overproduced AmpC ß-lactamases, including 180 (75.0%) harbouring ac-AmpC (132 CMY-2 variants and 48 DHA-1) and 60 (25.0%) c-AmpC enzymes. Three mutation profiles in the blac-AmpC promoter/attenuator were associated with a 72.5-, 19.9- and 5.8-fold increased expression, respectively. Moreover, 63.3% of ac-AmpC and 43.3% of c-AmpC isolates belonged to B2, D, E or F phylogenetic groups. PMQR was found in 31% of ac-AmpC isolates [38 qnrB4, 8 aac(6')-Ib-cr, 6 qnrS1 and 3 qnrB19] and in 10% of c-AmpC isolates [5 aac(6')-Ib-cr and 1 qnrS1]. IncI1-ST12 and IncF were associated with blaCMY-2 and blaDHA-1, respectively. These results suggest that ac-AmpC ß-lactamases were the main mechanism of AmpC production. Isolates and plasmids both showed high genetic diversity.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Escherichia coli/microbiologia , Escherichia coli/enzimologia , Escherichia coli/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Cromossomos Bacterianos , Impressões Digitais de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Escherichia coli/classificação , Expressão Gênica , Transferência Genética Horizontal , Genes Bacterianos , Variação Genética , Humanos , Tipagem de Sequências Multilocus , Mutação , Plasmídeos , Reação em Cadeia da Polimerase , Quinolonas/metabolismo , Análise de Sequência de DNA , Espanha
17.
Nature ; 520(7549): 633-9, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25896325

RESUMO

Natural events present multiple types of sensory cues, each detected by a specialized sensory modality. Combining information from several modalities is essential for the selection of appropriate actions. Key to understanding multimodal computations is determining the structural patterns of multimodal convergence and how these patterns contribute to behaviour. Modalities could converge early, late or at multiple levels in the sensory processing hierarchy. Here we show that combining mechanosensory and nociceptive cues synergistically enhances the selection of the fastest mode of escape locomotion in Drosophila larvae. In an electron microscopy volume that spans the entire insect nervous system, we reconstructed the multisensory circuit supporting the synergy, spanning multiple levels of the sensory processing hierarchy. The wiring diagram revealed a complex multilevel multimodal convergence architecture. Using behavioural and physiological studies, we identified functionally connected circuit nodes that trigger the fastest locomotor mode, and others that facilitate it, and we provide evidence that multiple levels of multimodal integration contribute to escape mode selection. We propose that the multilevel multimodal convergence architecture may be a general feature of multisensory circuits enabling complex input-output functions and selective tuning to ecologically relevant combinations of cues.


Assuntos
Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Locomoção , Vias Neurais/fisiologia , Animais , Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Sinais (Psicologia) , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Interneurônios/metabolismo , Larva/citologia , Larva/fisiologia , Neurônios Motores/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais , Sinapses/metabolismo
18.
J Antimicrob Chemother ; 70(3): 899-904, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25468902

RESUMO

OBJECTIVES: To describe the prevalence and risk factors for infection due to AmpC ß-lactamase-producing Escherichia coli (AmpC-EC). METHODS: For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. RESULTS: We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P < 0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P < 0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P = 0.008] was independently associated with AmpC-EC in the multivariate analysis. CONCLUSIONS: Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor.


Assuntos
Proteínas de Bactérias/biossíntese , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/enzimologia , beta-Lactamases/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , Estudos de Casos e Controles , Estudos Transversais , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Regiões Promotoras Genéticas , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Análise de Sequência de DNA , beta-Lactamases/genética
19.
Enferm Infecc Microbiol Clin ; 32 Suppl 1: 30-6, 2014 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-24630581

RESUMO

ß-lactam antimicrobial agents are frequently used to treat infections caused by Enterobacteriaceae. The main mechanism of resistance to these antibiotics is the production of certain enzymes, collectively named ß-lactamases. Due to their substrate profile and their epidemiological implications, the most clinically important ß-lactamases are extended-spectrum ß-lactamases, class C ß-lactamases and carbapenemases. Phenotypic detection of these enzymes may be complicated and is based on the use of specific inhibitors of each ß-lactamase and on the loss of activity on some ß-lactam indicators. Various international committees postulate that it is no longer necessary to interpret the susceptibility results or determine the mechanism of resistance. Several critics disagree, however, and consider that susceptibility results should be interpreted until more data are available on the clinical efficacy of treatment with ß-lactams. Given these methodological difficulties and constant changes in the interpretation criteria, we consider that training and external quality controls are essential to keep updated in this field. For learning purposes, these external quality controls should always be accompanied by a review of the results and methodology used, and the analysis of errors. In this paper we review and contextualize all the aspects related to the detection and interpretation of these ß-lactamases.


Assuntos
Enterobacteriaceae/efeitos dos fármacos , Controle de Qualidade , Resistência beta-Lactâmica , Humanos , Testes de Sensibilidade Microbiana/normas
20.
Curr Biol ; 24(3): R109-10, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24502781

RESUMO

The placement of neuronal cell bodies relative to the neuropile differs among species and brain areas. Cell bodies can be either embedded as in mammalian cortex or segregated as in invertebrates and some other vertebrate brain areas. Why are there such different arrangements? Here we suggest that the observed arrangements may simply be a reflection of wiring economy, a general principle that tends to reduce the total volume of the neuropile and hence the volume of the inclusions in it. Specifically, we suggest that the choice of embedded versus segregated arrangement is determined by which neuronal component - the cell body or the neurite connecting the cell body to the arbor - has a smaller volume. Our quantitative predictions are in agreement with existing and new measurements.


Assuntos
Sistema Nervoso Central/citologia , Neurônios/citologia , Neurópilo/citologia , Especificidade da Espécie , Animais , Humanos
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