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1.
Rev Med Inst Mex Seguro Soc ; 60(5): 503-510, 2022 Aug 31.
Artigo em Espanhol | MEDLINE | ID: mdl-36048621

RESUMO

Background: Antimicrobial resistance represents a serious public health problem that has caused an increase in the morbidity and mortality of infections, a greater use of antibiotics and excessive hospitalization costs. Objective: To describe the frequency of Escherichia coli and its pattern of bacterial susceptibility in cultures of blood, urine and other body fluids in a tertiary care hospital. Material and methods: A quantitative and retrospective test was designed to evaluate the sensitivity pattern of the data obtained in the Microbiology Department. Descriptive statistics were obtained from the sensitivity patterns of the microorganism studied in the period of time analyzed. Results: The sensitivity pattern of different samples evaluated in the unit (n = 694) was recovered. In the strains analyzed, it was found that about 50% have a positive phenotype for extended-spectrum beta-lactamases and that the sensitivity pattern shows that penicillins, cephalosporins and fluoroquinolones are not adequate antimicrobials to treat infections derived from this microorganism. Conclusions: The antimicrobial pattern obtained demonstrates the imperative need for rational and well-founded use of antibiotic therapy, highlighted by the great difference with reports in other scientific articles. Investment in mechanisms to confirm these patterns is necessary, which is why no expense should be spared for the identification, typification and classification of disease-causing microorganisms.


Introducción: la resistencia antimicrobiana representa un grave problema de salud pública que ha provocado un aumento en la morbimortalidad de las infecciones, un mayor uso de antibióticos y el exceso en gastos de hospitalización. Objetivo: describir la frecuencia de Escherichia coli y su patrón de susceptibilidad bacteriana en cultivos de sangre, orina y de otros fluidos corporales en un hospital de tercer nivel. Material y métodos: se diseñó un ensayo cuantitativo y retrospectivo para evaluar el patrón de sensibilidad de los datos obtenidos en el departamento de microbiología. Mediante estadística descriptiva se obtuvieron los patrones de sensibilidad del microorganismo estudiado en el periodo de tiempo analizado. Resultados: se recuperó el patrón de sensibilidad de diferentes muestras evaluadas en la unidad (n = 694). En las cepas analizadas, se encontró que cerca del 50% poseen un fenotipo positivo para betalactamasas de expectro extendido y que el patrón de sensibilidad demuestra que penicilinas, cefalosporinas y fluoroquinolonas no son antimicrobianos adecuados para tratar infecciones por este microorganismo. Conclusiones: el patrón antimicrobiano obtenido demuestra la imperiosa necesidad del uso racional y fundamentado de la terapia antibiótica puesto de manifiesto por la gran diferencia con los reportes en otros artículos científicos. Es necesaria la inversión en mecanismos para la confirmación de estos patrones, por lo que no debe escatimarse en gastos para la identificación, tipificación y clasificación de microorganismos causantes de enfermedades.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli/genética , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , beta-Lactamases/genética
2.
Rev Chilena Infectol ; 39(3): 254-259, 2022 06.
Artigo em Espanhol | MEDLINE | ID: mdl-36156686

RESUMO

BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CNS) with virulence and antibiotic sensitivity characteristics which makes it more similar to Staphylococcus aureus than other CNS. AIM: To know the microbiological and clinical characteristics of S. lugdunensis isolates identified from our health sector. METHODS: A retrospective study of S. lugdunensis isolates was carried out between 2017 and 2019 in the Microbiology Service of the San Jorge University Hospital in Huesca (Spain). The clinical records of patients with S. lugdunensis isolation were reviewed, considering the following factors: age, sex, sample type, service and underlying disease. Bacterial identification was performed using MALDI-TOF VITEK MS (BioMérieux, France). The pattern of antibiotic susceptibility was studied by means of plate microdilution. RESULTS: 44 isolates of S. lugdunensis were obtained: 12 corresponded to wounds, 10 were abscesses, 8 ulcers, 7 urine samples, 4 skin smears, 2 otic exudates, and 1 vaginal exudate. Regarding the underlying disease, five patients had a tumor processes and ten had diabetes mellitus. In 17 patients there was a history of recent surgery or trauma. Most of the strains were susceptible to the antibiotics studied. Production of beta-lactamase was observed in 19 of them, two were resistant to macrolides and three to clindamycin. None of the isolates were resistant to oxacillin, gentamicin or cotrimoxazole. CONCLUSIONS: Although S. lugdunensis maintains a good sensitivity to most antibiotics, its tendency to produce abscesses and that it expresses virulence factors more similar to S. aureus than to other CNS requires a correct identification in the laboratory so that its incidence is not underestimated.


Assuntos
Infecções Estafilocócicas , Staphylococcus lugdunensis , Abscesso/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clindamicina , Coagulase , Feminino , Gentamicinas , Humanos , Macrolídeos , Testes de Sensibilidade Microbiana , Oxacilina , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Combinação Trimetoprima e Sulfametoxazol , Fatores de Virulência , beta-Lactamases
3.
Rev Chilena Infectol ; 39(3): 361-363, 2022 06.
Artigo em Espanhol | MEDLINE | ID: mdl-36156701

RESUMO

Enterobacterales co-producing carbapenemases have awakened health alerts in Latin America. Carbapenemase-producing Enterobacterales harboring KPC and NDM-1 are resistant to almost all existing antibiotics. Panama reports KPC since 2010, and NDM since 2011, however, Enterobacterales with double carbapenemase production is new to our hospitals. We present the first two isolates of Enterobacter cloacae complex co-producing KPC and NDM, in a second level hospital in Panama City. Strengthening epidemiological surveillance systems in hospitals allows to carry out timely detection of these new combinations of resistance; to implement outbreak prevention and control measures.


Assuntos
Enterobacter cloacae , Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Proteínas de Bactérias , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/epidemiologia , Hospitais , Humanos , América Latina , Panamá/epidemiologia , beta-Lactamases
4.
Front Cell Infect Microbiol ; 12: 960892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061873

RESUMO

Bacterial infections with the genus Enterobacter are notoriously difficult to treat and often associated with resistance to penicillin, aminoglycosides, fluoroquinolones, and third-generation cephalosporins. Also, Enterobacter species have emerged as the third most common hosts for carbapenemases worldwide, forcing the use of colistin as a "last-resort" antibiotic for the treatment. Studies on the population structure of the genus Enterobacter repeatedly detect E. xiangfangensis as a common clinical species present worldwide. Here, we report on the characteristics of an extreme drug-resistant E. xiangfangensis isolate va18651 (ST88), obtained from a cervical swab of an expectant mother. The isolate was resistant to almost all the classes of antibiotics tested, including ß-lactams (viz., penicillins, carbapenems, cephalosporin, monobactams, and their combinations), quinolone, aminoglycosides, and sulfonamide/dihydrofolate reductase inhibitor, and exhibited heteroresistance towards colistin. Analysis of its complete genome sequence revealed 37 antibiotic resistance genes (ARGs), including mcr-9.1, blaKPC-2 , and blaOXA-48 , encoded on three of the four different plasmids (cumulative plasmidome size 604,632 bp). An unusually high number of plasmid-based heavy metal resistance gene (HRG) clusters towards silver, arsenate, cadmium, copper, mercury, and tellurite were also detected. Virulence genes (VGs) for the lipopolysaccharide and capsular polysaccharide structures, iron acquisition (iroBCDEN, ent/fep/fes, sitABCD, iut, and fur), and a type VI secretion system, together with motility genes and Type IV pili, were encoded chromosomally. Thus, a unique combination of chromosomally encoded VGs, together with plasmid-encoded ARGs and HRGs, converged to result in an extreme drug-resistant, pathogenic isolate with survival potential in environmental settings. The use of a disinfectant, octenidine, led to its eradication; however, the existence of a highly antibiotic-resistant isolate with significant virulence potential is a matter of concern in public health settings and warrants further surveillance for extreme drug-resistant Enterobacter isolates.


Assuntos
Colistina , Farmacorresistência Bacteriana , Aminoglicosídeos , Antibacterianos/farmacologia , Proteínas de Bactérias , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacter/genética , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/genética
5.
Medicina (Kaunas) ; 58(9)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36143821

RESUMO

Background and Objectives. The aim of this study is to determine the prevailing microbiota in samples from pediatric patients with acute appendicitis, as well as evaluate the antibacterial sensitivity of the isolated microorganisms, comparing the data obtained with the clinic's antibacterial therapy guidelines. Materials and Methods. The study group consisted of 93 patients between the ages of 7 and 18. All patients underwent a laparoscopic or conventional appendectomy. The children were hospitalized with signs and symptoms suggestive of acute appendicitis. Microbiological cultures from the appendix and abdominal cavity were collected intraoperatively. Results. E. coli was identified in most cases irrespective of the clinical presentation of acute appendicitis. Most strains were susceptible to ampicillin and amoxicillin/clavulanic acid. Five strains of E. coli produced extended spectrum beta-lactamase (ESBL). Pseudomonas aeruginosa (P. aeruginosa) was the second most commonly isolated causative agent. Furthermore, it was common in cases of acute complex appendicitis. Most strains of P. aeruginosa were resistant to amoxicillin/clavulanic acid, ertapenem, ampicillin and cefotaxime, yet were susceptible to ceftazidime. Regardless of the clinical presentation, the samples yielded mixed isolates. Conclusion. E. coli is the main causative agent of acute appendicitis in the pediatric population displaying susceptibility to various antibiotics. P. aeruginosa was more prevalent in cases of acute complex appendicitis. P. aeruginosa isolates were susceptible to ceftazidime; however, they were resistant to cefotaxime, which should, therefore, be removed from guidelines for empirical antibacterial treatment of acute appendicitis due to phenotypic resistance of P. aeruginosa. We recommend antibiotics with distinct implementation to avoid antibiotic resistance.


Assuntos
Apendicite , Microbiota , Adolescente , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Apendicite/cirurgia , Cefotaxima/uso terapêutico , Ceftazidima/uso terapêutico , Criança , Ertapenem/uso terapêutico , Escherichia coli , Humanos , Pseudomonas aeruginosa , beta-Lactamases/uso terapêutico
6.
Molecules ; 27(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36144666

RESUMO

New Delhi metallo-ß-lactamase-1 (NDM-1), expressed in different Gram-negative bacteria, is a versatile enzyme capable of hydrolyzing ß-lactam rings containing antibiotics such as penicillins, cephalosporins, and even carbapenems. Multidrug resistance in bacteria mediated by NDM-1 is an emerging threat to the public health, with an enormous economic burden. There is a scarcity in the availability of specific NDM-1 inhibitors, and also a lag in the development of new inhibitors in pharmaceutical industries. In order to identify novel inhibitors of NDM-1, we screened a library of more than 20 million compounds, available at the MCULE purchasable database. Virtual screening led to the identification of six potential inhibitors, namely, MCULE-1996250788-0-2, MCULE-8777613195-0-12, MCULE-2896881895-0-14, MCULE-5843881524-0-3, MCULE-4937132985-0-1, and MCULE-7157846117-0-1. Furthermore, analyses by molecular docking and ADME properties showed that MCULE-8777613195-0-12 was the most suitable inhibitor against NDM-1. An analysis of the binding pose revealed that MCULE-8777613195-0-12 formed four hydrogen bonds with the catalytic residues of NDM-1 (His120, His122, His189, and Cys208) and interacted with other key residues. Molecular dynamics simulation and principal component analysis confirmed the stability of the NDM-1 and MCULE-8777613195-0-12 complex. The in vitro enzyme kinetics showed that the catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics decreased significantly in the presence of MCULE-8777613195-0-12, due to poor catalytic proficiency (kcat) and affinity (Km). The IC50 value of MCULE-8777613195-0-12 (54.2 µM) was comparable to that of a known inhibitor, i.e., D-captopril (10.3 µM). In sum, MCULE-8777613195-0-12 may serve as a scaffold to further design/develop more potent inhibitors of NDM-1 and other ß-lactamases.


Assuntos
Captopril , beta-Lactamases , Antibacterianos/química , Carbapenêmicos/farmacologia , Cefalosporinas , Humanos , Simulação de Acoplamento Molecular , Penicilinas , beta-Lactamases/química , beta-Lactamas
7.
Nat Microbiol ; 7(10): 1516-1524, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36109646

RESUMO

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Here, leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n = 46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole-genome sequencing data from CPE isolates (n = 159) helped identify substrain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug-resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Escherichia coli/genética , Humanos , Klebsiella pneumoniae/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
8.
Nat Microbiol ; 7(10): 1593-1604, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36065064

RESUMO

Drug-resistant bacteria of the order Enterobacterales which produce extended-spectrum beta-lactamase enzymes (ESBL-Enterobacterales, ESBL-E) are global priority pathogens. Antimicrobial stewardship interventions proposed to curb their spread include shorter courses of antimicrobials to reduce selection pressure but individual-level acquisition and selection dynamics are poorly understood. We sampled stool of 425 adults (aged 16-76 years) in Blantyre, Malawi, over 6 months and used multistate modelling and whole-genome sequencing to understand colonization dynamics of ESBL-E. Models suggest a prolonged effect of antimicrobials such that truncating an antimicrobial course at 2 days has a limited effect in reducing colonization. Genomic analysis shows largely indistinguishable diversity of healthcare-associated and community-acquired isolates, hence some apparent acquisition of ESBL-E during hospitalization may instead represent selection from a patient's microbiota by antimicrobial exposure. Our approach could help guide stewardship protocols; interventions that aim to review and truncate courses of unneeded antimicrobials may be of limited use in preventing ESBL-E colonization.


Assuntos
Gammaproteobacteria , beta-Lactamases , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Fezes/microbiologia , Humanos , beta-Lactamases/genética
9.
J Photochem Photobiol B ; 235: 112554, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36095975

RESUMO

In this study, we present antimicrobial blue light (aBL) and antimicrobial photoinactivation with green light in the presence of Rose Bengal (aPDI) to modulate the susceptibility of extensively drug-resistant (XDR) Enterobacter cloacae and Klebsiella pneumoniae clinical isolates to antimicrobials. This process can be considered a photodynamic priming tool that influences other therapeutic options, such as antibiotics. The current study evaluated the different environments to estimate the most effective priming conditions by testing a broad spectrum of antimicrobials (including antimicrobials with different targets and mechanisms of action). The susceptibility of the E. cloacae and K. pneumoniae clinical isolates to various antibiotics after aBL and green light (with rose bengal) as aPDI treatment was examined with multiple methods of synergy testing (e.g., diffusion methods, checkerboard assay, postantibiotic effect), and most effective photoinactivation conditions were implemented for each environment. When Enterobacteriaceae were exposed to aBL, the most efficient reduction in survival rate under TSB conditions was observed. Similar results were observed when rose bengal, as a photosensitizer, was present during the exposure to green light in PBS. aBL and aPDI led to an increased susceptibility of K. pneumoniae and E. cloacae isolates to chloramphenicol and colistin or fosfomycin and colistin antibiotics, respectively. However, among the 4 tested isolates, we observed synergies between different antimicrobial agents and photoinactivation conditions. Thus, it may suggest that the sensitization process may be considered a strain dependent priming tool.


Assuntos
Enterobacter cloacae , Fosfomicina , Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Colistina/farmacologia , Fosfomicina/farmacologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/farmacologia , Rosa Bengala/farmacologia , beta-Lactamases/farmacologia
10.
Front Cell Infect Microbiol ; 12: 988236, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159637

RESUMO

Carbapenem-resistant Enterobacterales poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria via horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing Enterobacterales has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring bla OXA-181 in Enterobacterales is currently scarce. In this study, we aimed to determine the phylogeny and evolution of bla OXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring bla OXA-181 in Enterobacterales, we identified 81 bla OXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored bla OXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of bla OXA-181 among the 66 bla OXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring bla OXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in Escherichia coli and Klebsiella pneumoniae. Most of the IncX3 plasmids harboring bla OXA-181 were human origin. Almost all the bla OXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOBP family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both bla OXA-181 and qnrS1 in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS26 in the same orientation. Our findings provide important insights into the phylogeny and evolution of bla OXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading bla OXA-181 genes in Enterobacterales.


Assuntos
Elementos de DNA Transponíveis , Sistemas de Secreção Tipo IV , Antibacterianos/farmacologia , Carbapenêmicos , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
11.
BMJ Open ; 12(9): e061463, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36153019

RESUMO

INTRODUCTION: Data regarding the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in neonates at the community level are scarce in low-income and middle-income countries (LMICs), where the burden of neonatal sepsis is high.Our study aims at identifying and quantifying the role of the different routes of ESBL-PE transmission for neonates, which are still undefined in the community in LMICs. METHODS AND ANALYSIS: In a semirural community in Madagascar, 60 mothers and their neonates will be recruited at delivery, during which a maternal stool sample and meconium of the newborn will be collected. Home visits will be planned the day of the delivery and next at days 3, 7, 14, 21 and 28. Stool samples from the newborn, the mother and every other household member will be collected at each visit, as well as samples from the environment in contact with the newborn (food, surfaces and objects). Sociodemographic data and factors which might drive ESBL-PE acquisition will also be collected.We will analyse the isolated ESBL-PE using DNA sequencing methods to characterise clones, resistance genes and plasmids of ESBL-PE. To analyse these data globally, we will develop novel analytical approaches combining mathematical modelling and statistics. Finally, mathematical simulations will be performed to test different strategies of control of ESBL-PE transmission to neonates.In complement, we will conduct an anthropological investigation to understand local environments and practices that would contribute to neonatal ESBL-PE acquisition. In-depth interviews with members of 16 households will be conducted and 4 mother-newborn pairs will be followed by a participants' observations methodology. ETHICS AND DISSEMINATION: The study was approved by the ethical committee in Madagascar and by the institutional review board of Institut Pasteur, Paris, France.Findings will be reported to participating families, collaborators and local government; presented at national and international conferences and disseminated by peer-review publications.


Assuntos
Infecções por Enterobacteriaceae , beta-Lactamases , Antibacterianos/uso terapêutico , Estudos de Coortes , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Recém-Nascido , Madagáscar/epidemiologia , beta-Lactamases/genética
12.
Gut Microbes ; 14(1): 2121577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36154446

RESUMO

Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) by Escherichia coli, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection of E. coli genomes from EnteroBase, enriched in clinical isolates of worldwide origins, suggest the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene, cnf1, is preferentially distributed in four common sequence types (ST) encompassing the pandemic E. coli MDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment, with known enhanced capacities to colonize the gastrointestinal tract. Statistical projections based on this dataset point to a global expansion of cnf1-positive multidrug-resistant ST131 strains from subclade H30Rx/C2, accounting for a rising prevalence of cnf1-positive strains in ST131. Despite the absence of phylogeographical signals, cnf1-positive isolates segregated into clusters in the ST131-H30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the same cnf1 allele. The suggested dominant expansion of cnf1-positive strains in ST131-H30Rx/C2 led us to uncover the competitive advantage conferred by cnf1 for gut colonization to the clinical strain EC131GY ST131-H30Rx/C2 versus cnf1-deleted isogenic strain. Complementation experiments showed that colon tissue invasion was compromised in the absence of deamidase activity on Rho GTPases by CNF1. Hence, gut colonization factor function of cnf1 was confirmed for another clinical strain ST131-H30Rx/C2. In addition, functional analysis of the cnf1-positive clinical strain EC131GY ST131-H30Rx/C2 and a cnf1-deleted isogenic strain showed no detectable impact of the CNF1 gene on bacterial fitness and inflammation during the acute phase of bladder monoinfection. Together these data argue for an absence of role of CNF1 in virulence during UTI, while enhancing gut colonization capacities of ST131-H30Rx/C2 and suggested expansion of cnf1-positive MDR isolates in subclade ST131-H30Rx/C2.


Assuntos
Infecções por Escherichia coli , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli , Infecções por Escherichia coli/microbiologia , Humanos , Fatores de Virulência/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Proteínas rho de Ligação ao GTP
14.
Sci Rep ; 12(1): 15083, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36065056

RESUMO

Selection and spread of Extended Spectrum Beta-Lactamase (ESBL) -producing Enterobacteriaceae within animal production systems and potential spillover to humans is a major concern. Intramammary treatment of dairy cows with first-generation cephalosporins is a common practice and potentially selects for ESBL-producing Enterobacteriaceae, although it is unknown whether this really occurs in the bovine fecal environment. We aimed to study the potential effects of intramammary application of cephapirin (CP) and cefalonium (CL) to select for ESBL-producing Escherichia coli in the intestinal content of treated dairy cows and in manure slurry, using in vitro competition experiments with ESBL and non-ESBL E. coli isolates. No selection of ESBL-producing E. coli was observed at or below concentrations of 0.8 µg/ml and 4.0 µg/ml in bovine feces for CP and CL, respectively, and at or below 8.0 µg/ml and 4.0 µg/ml, respectively, in manure slurry. We calculated that the maximum concentration of CP and CL after intramammary treatment with commercial products will not exceed 0.29 µg/ml in feces and 0.03 µg/ml in manure slurry. Therefore, the results of this study did not find evidence supporting the selection of ESBL-producing E. coli in bovine feces or in manure slurry after intramammary use of commercial CP or CL-containing products.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Antibacterianos/farmacologia , Bovinos , Cefalosporinas/farmacologia , Enterobacteriaceae , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Fezes , Feminino , Humanos , Esterco , Testes de Sensibilidade Microbiana , beta-Lactamases
15.
Int J Food Microbiol ; 380: 109885, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36057242

RESUMO

Resistant Enterobacterales of avian intestinal origin can contaminate carcasses during broiler processing and thereby spread through the human food chain. This study aimed at assessing the prevalence, diversity and genomic characteristics of ESBL/AmpC Enterobacterales in poultry flocks from different farms and cities in the state of Paraná, Brazil. Enterobacterales isolated from cloacal samples were subjected to antimicrobial susceptibility testing (AST). ESBL/AmpC isolates were whole-genome sequenced and subjected to S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) followed by Southern blotting to determine the location of resistant genes on plasmids. A surprisingly high proportion of E. coli (40.6 %) collected on non-selective plates presented an ESBL/AmpC phenotype. Multidrug resistance was statistically not higher in ESBL/AmpC E. coli having the potential to be Avian Pathogenic (APEC-like) compared to non-APEC-like ESBL/AmpC E. coli isolates. Resistance to antibiotics not authorized for use in poultry in the State of Paraná was observed, suggesting that antimicrobial resistance (AMR) is co-selected by the use of veterinary-licensed antibiotics. Phylogenetic analyzes revealed the presence of identical or highly similar ESBL/AmpC E. coli clones on farms distant up to 100 km of each other; this strongly suggests that the centralization and verticalization of the poultry industry can facilitate the spread of resistant bacteria among different farms, companies, and cities. The molecular characterization of clones and plasmids proved the dominance of the ST224 E. coli lineage and the IncF/blaCTX-M-55 plasmid, possibly indicating the emergence of successful clones and plasmids adapted to the chicken host. Our data contribute to the epidemiological tracking of resistance mechanisms in Enterobacterales from poultry and to knowledge for further One Health studies to control the spread of resistant bacteria from food animals to humans.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Brasil , Cefalosporinas , Galinhas/microbiologia , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Humanos , Filogenia , Plasmídeos/genética , Aves Domésticas/microbiologia , beta-Lactamases/genética
16.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077146

RESUMO

The EPIC consortium brings together experts from a wide range of fields that include clinical, molecular and basic microbiology, infectious diseases, computational biology and chemistry, drug discovery and design, bioinformatics, biochemistry, biophysics, pharmacology, toxicology, veterinary sciences, environmental sciences, and epidemiology. The main question to be answered by the EPIC alliance is the following: "What is the best approach for data mining on carbapenemase inhibitors and how to translate this data into experiments?" From this forum, we propose that the scientific community think up new strategies to be followed for the discovery of new carbapenemase inhibitors, so that this process is efficient and capable of providing results in the shortest possible time and within acceptable time and economic costs.


Assuntos
Biologia Computacional , beta-Lactamases , Proteínas de Bactérias , Biologia Computacional/métodos , Simulação por Computador
17.
Saudi Med J ; 43(9): 991-999, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36104060

RESUMO

OBJECTIVES: To assess the prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) isolates from tertiary care centers in Southern Thailand. METHODS: The prevalence of carbapenemase genes in P. aeruginosa isolates collected from patients hospitalized between 2015-2017 in 2 tertiary care hospitals in Songkhla Province, Southern Thailand, was investigated. Standard laboratory procedures were followed and disk diffusion test was used for bacterial identification and susceptibility evaluations. Carbapenemase genes were detected using multiplex polymerase chain reaction (PCR) and genotyping by pulsed field gel electrophoresis. RESULTS: Among the 289 P. aeruginosa isolates, 55% was from sputum, 19.4% was from urine, and 8% was from secretions. The prevalence was 55.7% in carbapenem-resistant multidrug-resistant P. aeruginosa (CR-MDR-PA) and 39.4% in multidrug-resistant P. aeruginosa (MDR-PA). Resistance to imipenem, meropenem, gentamicin, and ceftazidime ranged from 50-60%, and amikacin was the most effective antibiotic (38.4%). The carbapenemase genes bla VIM (27.7%), bla IMP (23.9%), and bla OXA48 (4.8%) were detected; however, bla SPM and bla BIC were not detected in any of the isolates. Pulsed field gel electrophoresis analysis revealed clonal diversity among 17 CR-MDR-PA strains. CONCLUSION: A high percentage of CR-MDR-PA carries carbapenemase genes in our area; therefore, more emphasis on and application of molecular techniques for infection prevention and control may provide useful insights on disease epidemiology.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Proteínas de Bactérias , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Centros de Atenção Terciária , Tailândia/epidemiologia , beta-Lactamases
18.
PLoS One ; 17(9): e0272806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36054112

RESUMO

Surface waters, especially those receiving wastewater flows, can disseminate antimicrobial resistant bacteria (ARB), antimicrobial resistance genes (ARG), and antibiotics. In the Scioto River of central Ohio, United States, we evaluated fishes as potential sentinels of ARB and antimicrobial contamination and investigated the influence of antimicrobial exposure on the fish intestinal resistome. Seventy-seven fish were collected from river reaches receiving inputs from two wastewater treatment plants that serve the greater Columbus Metropolitan Area. Fish were screened for the presence of cephalosporin-resistant (CeRO) and carbapenem-resistant (CRO) organisms, epidemic carbapenemase genes, and antibiotic drugs and metabolites using culture methods, droplet digital PCR, and ultra-high performance liquid chromatography tandem mass spectroscopy (UHPLC-MS/MS). Nearly 21% of fish harbored a CeRO in their resistome, with 19.4% exhibiting bacteria expressing an AmpC genotype encoded by blaCMY, and 7.7% with bacteria expressing an extended-spectrum ß-lactamase phenotype encoded by blaCTX-M. blaKPC and blaNDM were present in 87.7% (57/65) and 80.4% (37/46) of the intestinal samples at an average abundance of 104 copies. Three antibiotics-lincomycin (19.5%), azithromycin (31.2%) and sulfamethoxazole (3.9%)-were found in hepatic samples at average concentrations between 25-31 ng/g. Fish harboring blaCTX-M and those exposed to azithromycin were at greater odds of being downstream of a wastewater treatment plant. Fish that bioconcentrated antibiotics in their liver were not at greater odds of harboring CeRO, CRO, or epidemic carbapenemase gene copies in their resistome. Our findings confirm that fishes can be effective bioindicators of surface waters contaminated with ARB, ARG, and antibiotics. Moreover, our findings highlight the varying importance of different mechanisms that facilitate establishment of ARB in aquatic ecosystems.


Assuntos
Antibacterianos , Anti-Infecciosos , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Azitromicina/farmacologia , Bactérias/genética , Proteínas de Bactérias , Cefalosporinas/farmacologia , Ecossistema , Peixes/genética , Espectrometria de Massas em Tandem , Águas Residuárias/microbiologia , Água/farmacologia , beta-Lactamases/genética , beta-Lactamases/farmacologia
19.
Cells ; 11(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36078157

RESUMO

Serine beta-lactamase-like protein (LACTB) is the only mammalian mitochondrial homolog evolved from penicillin-binding proteins and ß-lactamases (PBP-ßLs) in bacteria. LACTB, an active-site serine protease, polymerizes into stable filaments, which are localized to the intermembrane space (IMS) of mitochondrion and involved in the submitochondrial organization, modulating mitochondrial lipid metabolism. Cancer pathogenesis and progression are relevant to the alterations in mitochondrial metabolism. Metabolic reprogramming contributes to cancer cell behavior. This article (1) evidences the clinical implications of LACTB on neoplastic cell proliferation and migration and tumor growth and metastasis as well as LACTB's involvement in chemotherapeutic and immunotherapeutic responses; (2) sketches the structural basis for LACTB activity and function; and (3) highlights the relevant regulatory mechanisms to LACTB. The abnormal expression of LACTB has been associated with clinicopathological features of cancer tissues and outcomes of anticancer therapies. With the current pioneer researches on the tumor-suppressed function, structural basis, and regulatory mechanism of LACTB, the perspective hints at a great appeal of enzymic property, polymerization, mutation, and epigenetic and post-translational modifications in investigating LACTB's role in cancer pathogenesis. This perspective provides novel insights for LACTB as a metabolic regulator with potential to develop targeted cancer therapies or neoadjuvant therapeutic interventions.


Assuntos
Proteínas Mitocondriais , Neoplasias , Animais , Mamíferos/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo
20.
Antimicrob Resist Infect Control ; 11(1): 117, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36117231

RESUMO

BACKGROUND: Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW). METHODS: A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed. RESULTS: The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained. CONCLUSIONS: Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries.


Assuntos
Infecção Hospitalar , Proteínas de Bactérias , Análise Custo-Benefício , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Hospitais , Humanos , beta-Lactamases
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