RESUMO
BACKGROUND: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome of an extensively antibiotic-resistant strain of Enterobater hormaechei, which was isolated from a patient with non-Hodgkin's lymphoma, who had been admitted to a hospital in the city of Manaus, Brazil. METHODS: Phenotypical identification and susceptibility tests were performed in automated equipment. Total DNA extraction was performed using the PureLink genomic DNA mini-Kit. The genomic DNA library was prepared with Illumina Microbial Amplicon Prep and sequenced in the MiSeq Illumina Platform. The assembly of the whole-genome and individual analyses of specific resistance genes extracted were carried out using online tools and the Geneious Prime software. RESULTS: The analyses identified an extensively resistant ST90 clone of E. hormaechei carrying different genes, including blaCTX-M-15, blaGES-2, blaTEM-1A, blaACT-15, blaOXA-1 and blaNDM-1, [aac(3)-IIa, aac(6')-Ian, ant(2â³)-Ia], [aac(6')-Ib-cr, (qnrB1)], dfrA25, sul1 and sul2, catB3, fosA, and qnrB, in addition to resistance to chlorhexidine, which is widely used in patient antisepsis. CONCLUSIONS: These findings highlight the need for actions to control and monitor these pathogens in the hospital environment.
Assuntos
Farmacorresistência Bacteriana Múltipla , Enterobacter , Genoma Bacteriano , Linfoma não Hodgkin , Sequenciamento Completo do Genoma , Humanos , Enterobacter/genética , Enterobacter/efeitos dos fármacos , Enterobacter/isolamento & purificação , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/microbiologia , Linfoma não Hodgkin/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Sequenciamento Completo do Genoma/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/genética , Testes de Sensibilidade Microbiana , BrasilRESUMO
OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Infecções por Bactérias Gram-Negativas , Adulto , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Inibidores de beta-Lactamases/efeitos adversos , Ceftazidima/efeitos adversos , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Estudos ProspectivosRESUMO
The clinical aspects and lineages involved in Extraintestinal pathogenic Escherichia coli (ExPEC) infections in dogs remain largely unknown. In this study, we investigated the antimicrobial resistance and molecular structures of ExPECs isolated from infected dogs in Brazil. Samples were obtained from dogs (n = 42) with suspected extraintestinal bacterial infections. Phylogroup B2 was predominant (65.1%). No association was observed between the site of infection, phylogroups, or virulence factors. Almost half of the isolates (44.2%) were MDR, and 20.9% were extended-spectrum ß-lactamase (ESBL)-positive. E. coli isolates that were resistant to fluoroquinolones (27.9%) were more likely to be MDR. The CTX-M-15 enzyme was predominant among the ESBL-producing strains, and seven sequence types were identified, including the high-risk clones ST44 and ST131. Single SNPs analysis confirmed the presence of two clonal transmissions. The present study showed a high frequency of ExPECs from phylogroup B2 infecting various sites and a high frequency of ESBL-producing strains that included STs frequently associated with human infection. This study also confirmed the nosocomial transmission of ESBL-producing E. coli, highlighting the need for further studies on the prevention and diagnosis of nosocomial infections in veterinary settings.
Assuntos
Doenças do Cão , Infecções por Escherichia coli , Escherichia coli Extraintestinal Patogênica , Cães , Humanos , Animais , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Hospitais Veterinários , Brasil/epidemiologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologiaRESUMO
Vegetables are crucial for a healthy human diet due to their abundance of essential macronutrients and micronutrients. However, there have been increased reports of antimicrobial-resistant Enterobacteriaceae isolated from vegetables. Enterobacteriaceae is a large group of Gram-negative bacteria that can act as commensals, intestinal pathogens, or opportunistic extraintestinal pathogens. Extraintestinal infections caused by Enterobacteriaceae are a clinical concern due to antimicrobial resistance (AMR). ß-lactams have high efficacy against Gram-negative bacteria and low toxicity for eukaryotic cells. These antimicrobials are widely used in the treatment of Enterobacteriaceae extraintestinal infections. This review aimed to conduct a literature survey of the last five years (2018-2023) on the occurrence of ß-lactam-resistant Enterobacteriaceae in vegetables. Research was carried out in PubMed, Web of Science, Scopus, ScienceDirect, and LILACS (Latin American and Caribbean Health Sciences Literature) databases. After a careful evaluation, thirty-seven articles were selected. ß-lactam-resistant Enterobacteriaceae, including extended-spectrum ß-lactamases (ESBLs)-producing, AmpC ß-lactamases, and carbapenemases, have been isolated from a wide variety of vegetables. Vegetables are vectors of ß-lactam-resistant Enterobacteriaceae, contributing to the dissemination of resistance mechanisms previously observed only in the hospital environment.
RESUMO
OBJECTIVES: The aim of this study was to characterise a broad-spectrum cephalosporin-resistant AmpC-positive Enterobacter huaxiensis colonising the skin of a Neotropical frog (Phyllomedusa distincta) inhabiting the Brazilian Atlantic Forest. METHODS: During a genomic surveillance study of antimicrobial resistance, we screened skin samples from P. distincta. Gram-negative bacteria growing on MacConkey agar plates supplemented with 2 µg/mL ceftriaxone were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. A cephalosporin-resistant E. huaxiensis was sequenced using the Illumina NextSeq platform. Genomic data were analysed using bioinformatics tools, whereas AmpC ß-lactamase was characterised in depth by comparative analysis of amino acids, in silico modelling, and analysis of susceptibility to ß-lactam antibiotics and combinations of ß-lactamase inhibitors. RESULTS: Whole-genome sequencing analysis revealed a novel variant of AmpC ß-lactamase belonging to the ACT family, designated ACT-107 by NCBI. This variant contains 12 novel amino acid mutations within the ACT family, 5 in the signal peptide sequence (Ile2, Met14, Tyr16, Gly18 and Thr20), and 7 in the mature protein (Gln22, His43, Cys60, Thr157, Glu225, Ala252 and Asn310). In silico modelling showed that substitutions occurring in the mature chain are localised in the solvent-accessible surface of the protein, where they are not expected to affect the ß-lactamase activity, as observed in the resistance profile. Strikingly, 'not designated' ACT variants from E. huaxiensis were clustered (> 96% identity) with ACT-107. CONCLUSION: Since E. huaxiensis has been isolated from human infection, ACT-107 requires surveillance and the attention of clinicians.
Assuntos
Cefalosporinas , beta-Lactamases , Humanos , Brasil , beta-Lactamases/metabolismoRESUMO
Klebsiella pneumoniae is one of the major nosocomial pathogens responsible for pneumoniae, septicaemia, liver abscesses, and urinary tract infections. Coordinated efforts by antibiotic stewardship and clinicians are underway to curtail the emergence of antibiotic-resistant strains. The objective of the present study is to characterize K. pneumoniae strains through antibiotic resistance screening for production of beta-lactamases (ß-lactamases) such as extended spectrum beta lactamases (ESBLs), AmpC ß-lactamases, and carbapenemases by phenotypic and genotypic methods and genetic fingerprinting by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and repetitive element palindromic PCR (REP-PCR). A total of 85 K. pneumoniae strains isolated from 504 human urinary tract infections (UTI) were used in this study. Only 76 isolates showed positive in phenotypic screening test (PST), while combination disc method (CDM) as phenotypic confirmatory test (PCT) confirmed 72 isolates as ESBL producers. One or more ß-lactamase genes were detected by PCR in 66 isolates (91.66%, 66/72) with blaTEM gene being the most predominant (75.75%, 50/66). AmpC genes could be detected in 21 isolates (31.8%, 21/66) with FOX gene being the predominant (24.24%, 16/66), whereas NDM-I was detected in a single strain (1.51%, 1/66). Genetic fingerprinting using ERIC-PCR and REP-PCR revealed wide heterogeneity among ß-lactamase producing isolates with discriminatory power of 0.9995 and 1, respectively.
Assuntos
Infecções por Klebsiella , Infecções Urinárias , Humanos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Reação em Cadeia da Polimerase , Testes Genéticos , Variação Genética , Infecções por Klebsiella/microbiologiaRESUMO
Introduction: Antimicrobial resistance is a global concern since infections by resistant pathogens are associated with higher mortality and morbidity. Objective: To assess the prevalence of Escherichia coli isolates producing extended-spectrum and AmpC beta-lactamase (ESBL) in urine samples from patients at the Hospital Metropolitano de Santiago in Dominican Republic. Methods: Pathogen identification and antibiogram were carried out by the automated systems BD Phoenix or Microscan®. General information and past medical history were gathered from patients with a positive urine culture for E. coli. Manual ESBL/AmpC screening was performed with the commercial ESBL+AmpC screen disc kit from Liofilchem Laboratory, Italy. Results: One or both of the studied phenotypes were present in 36% of the analyzed isolates. Among the risk factors for the detection of E. coli producing ESBL and/or AmpC in urine were male gender, advanced age, placement of urinary catheter, arterial hypertension, neoplasms, and coexistence of two or more comorbidities. Apart from cephalosporins resistance, isolates producing ESBL and/or AmpC also showed higher resistance to other antibiotics, such as gentamicin (66.7%), ciprofloxacin and levofloxacin (83.3%), and ampicillin (91.7%). Furthermore, 85% of the ESBL/AmpC producing samples were multidrug resistant (resistant to 1 or more drugs in at least 3 different antibiotic categories). Conclusions: The high prevalence of antimicrobial resistance found in this study highlights the importance of implementing national and global measures to tackle the problem, especially in developing countries such as the Dominican Republic, where resources are scarce.
Introducción: La resistencia antimicrobiana es un grave problema global, pues las infecciones causadas por patógenos resistentes están asociadas con una mayor mortalidad y morbilidad. Objetivos: Analizar la prevalencia de aislados de Escherichia coli productores de β-lactamasas de espectro extendido (BLEE) y tipo AmpC procedentes de muestras de orina de pacientes del Hospital Metropolitano de Santiago en la República Dominicana. Métodos: La identificación del patógeno y el antibiograma fueron llevados a cabo mediante los sistemas automáticos BD Phoenix o Microscan®. Se recolectó información general y la historia médica de pacientes con un cultivo de orina positivo para E. coli. La detección de BLEE/AmpC se realizó de manera manual con el estuche comercial ESBL+AmpC de Liofilchem Laboratory, de Italia. Resultados: Un 36 % de las muestras analizadas mostraron uno o ambos fenotipos estudiados. Como factores de riesgo para la detección en orina de E. coli productoras de BLEE o AmpC se encontraron: sexo masculino, edad avanzada, colocación de un catéter urinario, hipertensión, neoplasmas y coexistencia de comorbilidades. Además de resistencia a las cefalosporinas, los aislados productores de BLEE y AmpC revelaron también elevada resistencia a otros antibióticos como gentamicina (66,7 %), ciprofloxacina y levofloxacina (83,3 %), y ampicilina (91,7 %). Un 85,0 % de las muestras productoras de BLEE/AmpC fueron multidrogorresistentes. Conclusiones: La elevada prevalencia de resistencia antimicrobiana encontrada en este estudio refleja la importancia de tomar medidas nacionales y globales para contener el problema, especialmente en países en desarrollo como República Dominicana, donde los recursos son escasos.
Assuntos
HumanosRESUMO
Introduction: The aim of this study was to investigate the prevalence and distribution of AmpC beta-lactamases (BLs) in uropathogens (E. coli and K. pneumoniae) at the University Hospital of the West Indies Jamaica (UHWI). Method: De-duplicated consecutive urine samples, collected from January to March 2020 at the UHWI, were analyzed. Screening and phenotypic confirmatory tests were conducted using resistance to cefoxitin and the Disc Approximation Test (DAT) respectively, for isolates of interest. Multiplex PCR was performed on cefoxitin resistant (CR) isolates for the detection of bla CIT, bla MOX, bla FOX, bla ACC, and bla DHA genes. Whole genome sequencing (WGS) was used to further detect AmpC BL genes in PCR negative isolates with indeterminate phenotypic results. Results: Sixty-four Gram negative isolates were obtained from 61 patients (55% female), aged 18 months to 88 years old. At least 35% (26) had complicated urinary tract infections. Only 7 out of 64 isolates were E. coli or K. pneumoniae, had antibiograms suggestive of possible AmpC BL production and were CR. DATs confirmed AmpC BL in two of these (1 K. pneumoniae; 1 E. coli), one tested negative (E. coli) and four had inconclusive results (K. pneumoniae). PCR detected bla DHA and bla CIT in two CR isolates. WGS further detected bla CMY-42 in one isolate. The prevalence of screened CR isolates with AmpC BL is 57.14% (4 of 7), representing 6.25% of the sample. AmpC BL producers tested had 100% susceptibility to meropenem and nitrofurantoin. Conclusion: AmpC BL prevalence among E. coli and K. pneumoniae, common urinary pathogens, in the studied isolates is low. Although cefoxitin screening is helpful, phenotypic screening using the DAT can yield indeterminate results best clarified by molecular testing.
Assuntos
Escherichia coli , Klebsiella pneumoniae , Humanos , Feminino , Masculino , Klebsiella pneumoniae/genética , Escherichia coli/genética , Cefoxitina/farmacologia , Prevalência , Centros de Atenção Terciária , Antibacterianos/farmacologia , beta-Lactamases/genética , Proteínas de Bactérias/genética , Testes de Sensibilidade MicrobianaRESUMO
The rapid dissemination of colistin resistance mcr-type genes and extended-spectrum ß-lactamase-encoding genes at the human-animal-environment interface has raised concerns worldwide. In this study, we performed a genomic investigation of a multidrug (MDR)- and colistin-resistant Escherichia coli strain recovered from an urban stream strongly affected by pollution and used for recreational purposes in Brazil. E. coli strain EW827 was resistant to clinically significant antimicrobials, including polymyxins, extended-spectrum cephalosporins, and fluoroquinolones. Whole-genome sequencing analysis revealed that EW827 strain belonged to ST1775 and carried the fimH137 allele, clinically relevant antimicrobial resistance genes (e.g., mcr-1.1, blaCTX-M-2, and blaCMY-2), tolerance genes to metals, and biocide resistance genes. Moreover, IncX4 and IncI1-ST12 replicon types were identified carrying mcr-1.1 and blaCMY-2, respectively. A novel genetic environment of the mcr-1.1 gene, in which a 258-bp ∆IS5-like was inserted in the opposite orientation upstream of the mcr-1.1-pap2 element, was also detected. Additionally, the blaCTX-M-2 gene was harbored by a Tn21-like element on the chromosome. The occurrence of MDR E. coli co-harboring mcr-1.1, blaCTX-M-2, and blaCMY-2 in urban water represents a potential risk to humans, animals, and environmental safety. Therefore, epidemiological studies are required to monitoring multidrug-resistant bacteria and their antimicrobial resistance genes in aquatic ecosystems to determine possible routes and fates of these genes.
Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Rios/microbiologia , Brasil , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
INTRODUCCIÓN: La restricción programada (RP) de antimicrobianos puede disminuir selectivamente la tasa de infecciones por determinados microorganismos. En este sentido, los bacilos gramnegativos productores de beta-lactamasas AmpC (BGN-blaAmpC) son seleccionados por el sobreuso de cefalosporinas de tercera generación (C3G). Estas bacterias, también adquieren genes y co-producen otras beta-lactamasas, como las de Nueva Delhi (BGN-blaNDM). OBJETIVOS: Disminuir la tasa de aislamiento de BGN-blaAmpC y BGN-blaNDM en cultivos de pacientes de la UCI luego de una RP de C3G en el marco de un brote nosocomial por estos microrganismos. MATERIALES Y MÉTODOS: Estudio cuasi-experimental, previo (P1= 12 meses) y posterior (P2= 12 meses) a una RP de C3G en un hospital de adultos, donde, en el contexto de brote mencionado, se aplicaron medidas de control de infecciones generales. El uso de antimicrobianos se expresó como "porcentaje de los días de tratamiento (%DDT)"/100 camas ocupadas al día (100-COD). Se compararon las tasas de aislamiento de BGN-blaAmpC y BGN-blaNDM en hemocultivos (HC), mini-lavados bronquio-alveolares (mB) y urocultivos (UC) en la UCI. RESULTADOS: En P2 el consumo de C3G fue 2,5% DDT/100-COD. Hubo un descenso en los aislamientos de BGN-blaAmpC en HC (RR 0,48 [0,2-0,9] p < 0,02) y mB (RR 0,52 [0,3-0,9] p < 0,02), así como también de BGN-blaNDM en HC (RR 8,1 [1,6-39,4] p < 0,00). Conclusiones: La RP de C3G se asoció con la reducción de los BGN-blaAmpC y BGN-blaNDM en HC, así como de los BGN-blaAmpC mB.
BACKGROUND: Programmed restriction (PR) of antimicrobials can selectively decrease the rate of infections by certain microorganisms. In this sense, AmpC beta-lactamase-producing gram-negative bacilli (GNB-blaAmpC) are selected for the overuse of third generation cephalosporins (3GC). These bacteria also acquire genes and co-produce other β-lactamases, such as New Delhi ones (GNB-blaNDM). AIM: To decrease the isolation rate of GNB- blaAmpC and GNB- blaNDM in cultures from ICU patients after a PR of 3GC. METHODS: Quasi-experimental study, before (P1= 12 months) and after (P2= 12 months) a PR of 3GC in an adults' hospital. The use of antibiotics was expressed as "percentage days of treatment (%DOT)" /100 beds occupied per day (100-BOD). The rates of GNB-blaAmpC and GNB-blaNDM were compared in blood cultures (BC), mini-bronchio alveolar lavages (mB) and urine cultures (UC) in the ICU. RESULTS: In P2, 3GC consumption was 2.5% DOT/100-COD. There was a decrease in GNB-blaAmpC from BC (RR 0.48 [0.2-0.9] p < 0.02) and mB (RR 0.52 [0.3-0.9] p < 0.02), as well as of GNB-blaNDM from BC (RR 8.1 [1.6-39.4] p < 0.00). Conclusions: PR of 3GC was linked to the reduction of GNB-blaAmpC and GNB-blaNDM in BC, as well as GNB-blaAmpC in mB from ICU patients.