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1.
BMC Infect Dis ; 20(1): 676, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938420

RESUMO

BACKGROUND: Raoultella planticola(R.planticola) is a very rare opportunistic pathogen and sometimes even associated with fatal infection in pediatric cases. Recently,the emergence of carbapenem resistance strains are constantly being reported and a growing source of concern for pediatricians. CASE PRESENTATION: We reported 4 cases of neonatal septicemia caused by Raoultella planticola. Their gestational age was 211 to 269 days, and their birth weight was 1490 to 3000 g.The R. planticola infections were detected on the 9th to 27th day after hospitalization and occured between May and June. They clinically manifested as poor mental response, recurrent cyanosis, apnea, decreased heart rate and blood oxygen, recurrent jaundice, fever or nonelevation of body temperature. The C-reactive protein and procalcitonin were elevated at significantly in the initial phase of the infection,and they had leukocytosis or leukopenia. Prior to R.planticola infection,all of them recevied at least one broad-spectrum antibiotic for 7-27d.All the R.planticola strains detected were only sensitive to amikacin, but resistant to other groups of drugs: cephalosporins (such as cefazolin, ceftetan,etc) and penicillins (such as ampicillin-sulbactam,piperacillin,etc),and even developed resistance to carbapenem. All the infants were clinically cured and discharged with overall good prognosis. CONCLUSION: Neonatal septicemia caused by Raoultella planticola mostly occured in hot and humid summer, which lack specific clinical manifestations. Pediatricians should keep in mind that R. planticola can be a potential source of neonatal sepsis and even has the potential to acquire carbapenem-resistance. Preventing outbreaks of epidemics requires early detection, timely diagnosis and treatment, and active isolation.


Assuntos
Infecções por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/isolamento & purificação , Sepse Neonatal/diagnóstico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peso ao Nascer , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Piperacilina/farmacologia , Piperacilina/uso terapêutico
2.
BMC Infect Dis ; 20(1): 557, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736605

RESUMO

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Fezes/microbiologia , beta-Lactamases/biossíntese , Adolescente , Adulto , Antibacterianos/uso terapêutico , Ceftazidima , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Tanzânia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
3.
PLoS Comput Biol ; 16(8): e1008106, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797079

RESUMO

Antibiotic resistance is rising and we urgently need to gain a better quantitative understanding of how antibiotics act, which in turn would also speed up the development of new antibiotics. Here, we describe a computational model (COMBAT-COmputational Model of Bacterial Antibiotic Target-binding) that can quantitatively predict antibiotic dose-response relationships. Our goal is dual: We address a fundamental biological question and investigate how drug-target binding shapes antibiotic action. We also create a tool that can predict antibiotic efficacy a priori. COMBAT requires measurable biochemical parameters of drug-target interaction and can be directly fitted to time-kill curves. As a proof-of-concept, we first investigate the utility of COMBAT with antibiotics belonging to the widely used quinolone class. COMBAT can predict antibiotic efficacy in clinical isolates for quinolones from drug affinity (R2>0.9). To further challenge our approach, we also do the reverse: estimate the magnitude of changes in drug-target binding based on antibiotic dose-response curves. We overexpress target molecules to infer changes in antibiotic-target binding from changes in antimicrobial efficacy of ciprofloxacin with 92-94% accuracy. To test the generality of our approach, we use the beta-lactam ampicillin to predict target molecule occupancy at MIC from antimicrobial action with 90% accuracy. Finally, we apply COMBAT to predict antibiotic concentrations that can select for resistance due to novel resistance mutations. Using ciprofloxacin and ampicillin as well defined test cases, our work demonstrates that drug-target binding is a major predictor of bacterial responses to antibiotics. This is surprising because antibiotic action involves many additional effects downstream of drug-target binding. In addition, COMBAT provides a framework to inform optimal antibiotic dose levels that maximize efficacy and minimize the rise of resistant mutants.


Assuntos
Antibacterianos , Biologia Computacional/métodos , Desenvolvimento de Medicamentos/métodos , Quinolonas , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Quinolonas/administração & dosagem , Quinolonas/química , Quinolonas/metabolismo , Quinolonas/farmacologia
4.
Proc Natl Acad Sci U S A ; 117(33): 20202-20210, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32747578

RESUMO

In biology, it is often critical to determine the identity of an organism and phenotypic traits of interest. Whole-genome sequencing can be useful for this but has limited power for trait prediction. However, we can take advantage of the inherent information content of phenotypes to bypass these limitations. We demonstrate, in clinical and environmental bacterial isolates, that growth dynamics in standardized conditions can differentiate between genotypes, even among strains from the same species. We find that for pairs of isolates, there is little correlation between genetic distance, according to phylogenetic analysis, and phenotypic distance, as determined by growth dynamics. This absence of correlation underscores the challenge in using genomics to infer phenotypes and vice versa. Bypassing this complexity, we show that growth dynamics alone can robustly predict antibiotic responses. These findings are a foundation for a method to identify traits not easily traced to a genetic mechanism.


Assuntos
Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/genética , Antibacterianos/farmacologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Microbiologia Ambiental , Regulação Bacteriana da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Especificidade da Espécie , Fatores de Tempo
5.
PLoS One ; 15(6): e0230652, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603331

RESUMO

Toxin-antitoxin systems (TAS) are commonly found on bacterial plasmids and are generally involved in plasmid maintenance. In addition to plasmid maintenance, several plasmid-mediated TAS are also involved in bacterial stress response and virulence. Even though the same TAS are present in a variety of plasmid types and bacterial species, differences in their sequences, expression and functions are not well defined. Here, we aimed to identify commonly occurring plasmid TAS in Escherichia coli and Klebsiella pneumoniae and compare the sequence, expression and plasmid stability function of their variants. 27 putative type II TAS were identified from 1063 plasmids of Klebsiella pneumoniae in GenBank. Among these, ccdAB and pemIK were found to be most common, also occurring in plasmids of E. coli. Comparisons of ccdAB variants, taken from E. coli and K. pneumoniae, revealed sequence differences, while pemIK variants from IncF and IncL/M plasmids were almost identical. Similarly, the expression and plasmid stability functions of ccdAB variants varied according to the host strain and species, whereas the expression and functions of pemIK variants were consistent among host strains. The specialised functions of some TAS may determine the host specificity and epidemiology of major antibiotic resistance plasmids.


Assuntos
Enterobacteriaceae/genética , Plasmídeos/genética , Sistemas Toxina-Antitoxina/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência Conservada , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica
6.
BMC Infect Dis ; 20(1): 452, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600270

RESUMO

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Neoplasias/microbiologia , Idoso , Antibacterianos/farmacologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
7.
Mikrobiyol Bul ; 54(2): 191-202, 2020 Apr.
Artigo em Turco | MEDLINE | ID: mdl-32723275

RESUMO

Carbapenems are used in the treatment of infections caused by multidrug-resistant bacteria and colistin (polymyxin E) is used as the last choice of antimicrobial agent in those resistant to carbapenems. The worldwide and increased use of colistin, which causes cell death by disrupting the permeability of the cytoplasmic membrane of gram-negative bacteria, raised the problem of resistance. The transferable colistin resistance enzyme mcr, is a phosphoethanolamine transferase that adds phosphoethanolamine to lipid A and modifies lipopolysaccharides, leading to polymyxin resistance. The aim of this study was to investigate some of the most prevalent plasmid mediated colistin and carbapenemase resistance genes in colistin resistant Enterobacterales isolates. Enterobacterales isolates which were isolated in the samples of patients treated in the clinical units between October 2016 and September 2018 in the Karadeniz Technical University Faculty of Medicine Farabi Hospital Medical Microbiology Laboratory were included in the study. In addition to conventional methods, isolates were identified to the species level by MALDI-TOF MS (Bruker Daltonics, Germany). The antibiotic susceptibilities of Enterobacterales isolates were studied by an automated microbiology system (Phoenix, Becton Dickinson, USA) and evaluated according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. In isolates that are resistant to colistin, and the isolates that are found to be sensitive but should be included in the patient report of the colistin susceptibility test, colistin susceptibility tests were repeated with liquid microdilution method in accordance with EUCAST standards. The presence of extended spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase were determined by phenotypic methods according to EUCAST recommendations in colistin resistant Enterobacterales isolates. Furthermore, resistance genes of mcr-1-5, blaOXA-48, blaKPC, blaNDM, blaVIM, blaIMP were detected by polymerase chain reaction (PCR) method, followed by nucleotide sequence analysis of the amplified products. In our study, 14657 Enterobacterales isolates belonging to 7535 patients treated in different clinical units were examined retrospectively. Escherichia coli 61.2% (n= 8968), Klebsiella pneumoniae 22.7% (n= 3334) and Enterobacter cloacae 6.9% (n= 1005) were the most prevalent isolates. Carbapenem resistance was detected in 894 isolates, and 5.8% (n= 412) of 7135 isolates isolated between October 2016 and September 2017; 6.4% (n= 482) of 7522 isolates between October 2017 and September 2018 were found to be resistant. Considering all isolates, colistin resistant isolates were 65 (0.9%) between October 2016 and September 2017 and 97 (1.3%) between October 2017 and September 2018. By including only the first isolates in the study for the same agent growths in different samples of the same patient, 46 colistin resistant isolates were selected. Six isolates which could not be cultivated from stock cultures were excluded from the study material. Thirteen (32.5%) of the 40 colistin resistant Enterobacterales isolates were isolated in 2017 and 27 (67.5%) were isolated in 2018. ESBL was detected in 22, AmpC beta-lactamase was detected in 6, carbapenem resistance was detected in 15 of them by phenotypic methods. As a result of PCR analysis, mcr-1 gene detected in 2 isolates, blaOXA-48 in 2 isolates, blaVIM in 1 isolate, blaKPC and blaOXA-48 in 1 isolate, blaNDM and blaOXA-48 in 5 isolates. These results were confirmed by sequencing of the PCR products. The mcr-1 genes were found in E.coli isolates grown in urine culture samples of 2 women over 65 years of age treated in our hospital. Among the antibiotics tested, only ampicillin resistance was observed in 1 of the patients, whereas ampicillin, amoxicillin-clavulanate and ciprofloxacin resistance were detected in the other. In conclusion, as far as we can reach in the literature our publication is the first study showing the presence of mcr-1 gene in clinical samples in our country and confirmed by DNA sequence analysis. The detection of mcr gene in isolates without multidrug resistance showed once again the importance of colistin susceptibility testing in the laboratories. In addition, the presence of isolates containing more than one resistance genes in our study, suggests that the spread of carbapenem and colistin resistance may be faster than expected.


Assuntos
Colistina , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae , Plasmídeos , Idoso , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Alemanha , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Estudos Retrospectivos
8.
Int J Food Microbiol ; 331: 108750, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32559710

RESUMO

For the first time, this study evaluates consumer exposure via poultry meat to Enterobacteriaceae with capacity to develop severe extraintestinal infections by either bacterial virulence and/or antibiotic resistance traits. The characterization of 256 isolates and the assessment of five parameters, showed that 96 of 100 poultry meat samples from supermarkets of northwest Spain posed ≥ one potential risk: i) 96% carried Enterobacteriaceae resistant to antimicrobials of categories A (64% to monobactams) or B (95% to cephalosporins 3rd and 4rd- generation, quinolones and/or polymixins) of the new categorization of EMA. ii) More than one extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae species were recovered from 28% of poultry meat. iii) High-risk lineages of E. coli, including multidrug-resistant ST131-H22, were present in 62% of samples. iv) E. coli recovered from 25% of samples conformed the ExPEC status. v) E. coli from 17% of samples satisfied the UPEC status. Of note, the recovery from different samples of two E. coli CC10-A (CH11-54) carrying mcr-1.1-bearing IncX4 plasmids, and four E. coli CC10-A (eae-beta1) of the hybrid pathotype aEPEC/ExPEC. (ESBL)-producing K. pneumoniae were isolated from 27% of samples. In summary, poultry meat microbiota is a source of genetically diverse Enterobacteriaceae, resistant to relevant antimicrobials and potentially pathogenic for consumers.


Assuntos
Exposição Dietética/estatística & dados numéricos , Resistência a Múltiplos Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Microbiologia de Alimentos/estatística & dados numéricos , Carne/microbiologia , Animais , Antibacterianos/farmacologia , Galinhas/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Plasmídeos/genética , Espanha/epidemiologia , Perus , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/isolamento & purificação
9.
Int J Infect Dis ; 97: 11-18, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32473388

RESUMO

OBJECTIVES: To study the molecular epidemiology of clinical metallo-ß-lactamase (MBL)-producing Enterobacteriaceae isolates in China and to evaluate the antimicrobial susceptibility of MBL-Enterobacteriaceae isolates to aztreonam-avibactam. METHODS: Bacterial speciation was determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PCR was used to screen for common carbapenemase genes. Antimicrobial susceptibility testing of common clinical antibiotics and aztreonam-avibactam was performed using the standard broth microdilution method. RESULTS: A total of 161 MBL-Enterobacteriaceae isolates were included, with Klebsiella pneumoniae (n = 73, 45.4%) and Escherichia coli (n = 53, 32.9%) being the most common species. Among the 161 isolates, blaNDM (n = 151), blaIMP (n = 13), and blaVIM (n = 2) were detected, including five strains (3.1%) co-harboring two MBLs. MBL-Enterobacteriaceae isolates frequently contained two (n = 55, 34.2%) or more (n = 89, 55.3%) additional serine ß-lactamase genes (blaKPC, blaCTX-M, blaTEM, or blaSHV). Antimicrobial susceptibility testing showed that 81.4% of isolates (n = 131) were resistant to aztreonam. The rates of resistance to cefazolin, ceftazidime, ceftriaxone, cefotaxime, ampicillin-sulbactam, amoxicillin-clavulanic acid, and piperacillin-tazobactam were all over 90%. The addition of avibactam (4 µg/ml) significantly reduced the minimum inhibitory concentrations (MICs) of the aztreonam-resistant isolates by more than 8-fold (range ≤0.125 to 4 µg/ml), with a MIC50/MIC90 of ≤0.125/1 µg/ml among the 131 isolates. Overall, 96.9% (n = 156) of the total isolates were inhibited at an aztreonam-avibactam concentration of ≤1 µg/ml. Univariate and multivariate logistic regression analysis found that in patients with MBL-Enterobacteriaceae infections, the presence of pre-existing lung disease (adjusted odds ratio 8.267, 95% confidence interval 1.925-28.297; p = 0.004) was associated with a hazard effect on worse disease outcomes. CONCLUSIONS: The combined use of aztreonam-avibactam is highly potent against MBL-Enterobacteriaceae and may serve as a new candidate for the treatment of infections caused by MBL-Enterobacteriaceae in China.


Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Aztreonam/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , China , Farmacorresistência Bacteriana , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , beta-Lactamases/biossíntese , beta-Lactamases/genética
11.
J Infect Public Health ; 13(9): 1330-1335, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32439355

RESUMO

BACKGROUND: Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) and carbapenem-resistant Enterobacteriaceae (CRE) are disseminated worldwide posing a serious public health concern. Although, the presence of ESBL-PE and CRE in Sri Lanka has been reported, the prevalence is unknown. This study aimed to provide up-to-date epidemiological data on multidrug-resistant Enterobacteriaceae and to characterize the molecular determinants of carbapenemase-producing Enterobacteriaceae (CPE) in Sri Lanka. METHODS: A prospective cross-sectional study was conducted at a tertiary care hospital in Sri Lanka between December 2017 and February 2018. ESBL-PE and CRE were identified by disc diffusion method. Carbapenemase production was determined by carbapenem inactivation method and the presence of selected carbapenemase genes were detected by PCR. RESULTS: Five hundred and ninety three Enterobacteriaceae were isolated from variety of clinical samples. Overall prevalence of ESBL-PE and CRE were 26.0% (n = 154) and 9.6% (n = 57), respectively. The highest rate of ESBL-PE (30.8%) was found in urine samples, while the highest occurrence of CRE (20.8%) was seen in respiratory specimens. The most common CRE species identified was K. pneumoniae (n = 46, 80.7%), followed by C. freundii (n = 4, 7.0%), E. coli (n = 3, 5.3%), P. rettgeri (n = 2, 3.5%), E. cloacae (n = 1, 1.7%), and K. aerogenes (n = 1, 1.7%). Carbapenemase production was observed in 54 (94.7%) of CRE isolates. Fifty eight carbapenemase encoding genes were identified in 54 CPE. The most prevalent carbapenemase gene was blaOXA-48-like (n = 48, 88.9%), followed by blaNDM (n = 8, 14.8%), and blaKPC (n = 2, 3.7%). CONCLUSION: This study reports an alarming rate of CRE and the emergence of blaKPC harboring K. pneumoniae in Sri Lanka. The need for preventive measures is highlighted to limit the spread of these difficult-to-treat bacteria in the country.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Klebsiella pneumoniae/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Criança , Pré-Escolar , Estudos Transversais , Enterobacteriaceae/efeitos dos fármacos , Feminino , Humanos , Lactente , Recém-Nascido , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Sri Lanka/epidemiologia , Adulto Jovem , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
12.
PLoS One ; 15(4): e0231146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287306

RESUMO

Extended Spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are of major concern as they are implicated in multidrug resistant nosocomial infections. They are listed on a recently published global priority list of antibiotic-resistant bacteria by the World Health Organization which raises concern in both healthcare and community settings. This study aimed at determining the frequency of ESBL genes in multidrug resistant human clinical Enterobacteriaceae isolates from Edo state Nigeria and to characterize the resistance mechanisms using whole genome sequencing. A total of 217 consecutive clinical isolates of Enterobacteriaceae, selection based on inclusion criteria, were collected from March-May 2015 from three medical microbiology laboratories of hospitals in Edo state Nigeria. All isolates were analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Antibiotic susceptibility testing was performed by Kirby-Bauer method and minimum inhibitory concentration (MIC) determination by E-test method. Double disc synergy test was used to screen for the production of ESBL. Whole genome sequencing (WGS) was performed for isolate characterization and identification of resistance determinants. Out of 217 consecutive clinical Enterobacteriaceae isolates, 148 (68.2%) were multi-drug resistant. Of these multi-drug resistant isolates, 60 (40.5%) were positive for the ESBL phenotypic test and carried ESBL genes. CTX-M-15 was the predominant ESBL found, among 93.3% (n = 56/60). Thirty-two plasmid incompatibility groups and 28 known and two new sequence types were identified among the ESBL isolates. The high occurrence of CTX-M-15 with associated resistant determinants in multidrug resistant Enterobacteriaceae harboring different plasmid incompatibility groups and sequence types calls for the need of continuous monitoring of this resistance threat to reduce its public health impact. To our knowledge, this study presents the first genomic characterization of ESBL production mediated by blaCTX-M-15 in human clinical isolates of Enterobacter hormaechei, Citrobacter werkmanii and Atlantibacter hermannii from Nigeria.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/enzimologia , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Genoma Bacteriano/genética , Humanos , Testes de Sensibilidade Microbiana , Nigéria , Sequenciamento Completo do Genoma
13.
Acta Vet Scand ; 62(1): 18, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334616

RESUMO

Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3-2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.


Assuntos
Doenças do Cão/microbiologia , Cães/microbiologia , Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae/veterinária , Enterobacteriaceae/isolamento & purificação , Animais , Antibacterianos/farmacologia , Cefalosporinase/metabolismo , Doenças do Cão/epidemiologia , Enterobacteriaceae/classificação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Genótipo , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Suécia/epidemiologia
15.
N Engl J Med ; 382(14): 1309-1319, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32242356

RESUMO

BACKGROUND: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. METHODS: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa. RESULTS: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases. CONCLUSIONS: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.).


Assuntos
Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana Múltipla , Acinetobacter/efeitos dos fármacos , Adolescente , Adulto , Idoso , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Carbapenêmicos/farmacologia , Resistência às Cefalosporinas , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Inquéritos Epidemiológicos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Pacientes Internados , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Pseudomonas aeruginosa/efeitos dos fármacos , Estados Unidos/epidemiologia , Resistência a Vancomicina , Adulto Jovem
16.
PLoS One ; 15(3): e0229451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130234

RESUMO

In many countries, emission of insufficiently treated wastewater into water bodies appears to be an important factor in spreading clinically relevant antimicrobial resistant bacteria. In this study, we looked for the presence of Enterobacteriaceae strains with resistance to 3rd generation cephalosporin antibiotics in four urban wetlands in southwestern Nigeria by isolation, whole genome sequencing and qPCR enumeration of marker genes. Genome analysis of multi-drug resistant and potentially pathogenic Escherichia coli isolates (members of the widely distributed ST10 complex) revealed the presence of the extended spectrum beta-lactamase gene blaCTX-M-15 on self-transmissible IncF plasmids. The gene was also present together with a blaTEM-1B gene on self-transmissible IncH plasmids in multi-drug resistant Enterobacter cloacae isolates. A Citrobacter freundii isolate carried blaTEM-1B on an IncR-type plasmid without discernable conjugation apparatus. All strains were isolated from a wetland for which previous qPCR enumeration of marker genes, in particular the ratio of intI1 to 16S rRNA gene copy numbers, had indicated a strong anthropogenic impact. Consistent with the isolation origin, qPCR analysis in this study showed that the blaCTX-M gene was present at an abundance of 1x10-4 relative to bacterial 16S rRNA gene copy numbers. The results indicate that contamination of these urban aquatic ecosystems with clinically relevant antibiotic resistant bacteria is substantial in some areas. Measures should therefore be put in place to mitigate the propagation of clinically relevant antimicrobial resistance within the Nigerian aquatic ecosystems.


Assuntos
Cidades , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Inquéritos e Questionários , Áreas Alagadas , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/genética , Genes Bacterianos/genética , Testes de Sensibilidade Microbiana , Nigéria , Prevalência
17.
Emerg Microbes Infect ; 9(1): 508-516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116151

RESUMO

Mobile colistin resistance (mcr) genes represent an emerging challenge. Here we describe a novel mcr gene, mcr-10, on an IncFIA plasmid of an Enterobacter roggenkampii clinical strain. mcr-10 has the highest nucleotide identity (79.69%) with mcr-9 and encodes MCR-10 with 82.93% amino acids identical to MCR-9. mcr-10 confers 4-fold increase in colistin MIC (from 1 to 4 mg/L) when cloned into a colistin-susceptible E. roggenkampii strain. By screening GenBank, mcr-10 was found in various Enterobacteriaceae species of countries in four continents, suggesting that this gene has widely spread. MCR-10 shows 79.04% to 83.67% amino acid identity and highly conserved predicted protein structures with chromosomally encoded MCR-like phosphoethanolamine transferases (designated MCR-B here) of various Buttiauxella species. MCR-10, MCR-9 and MCR-B proteins may, therefore, originate from a common ancestor. mcr-10 was adjacent to a site-specific recombinase-encoding gene and was bracketed by IS903 and may be mobilized by site-specific recombination or composite transposon. Our results indicate that mcr-10 is a novel plasmid-borne colistin resistance gene and warrants immediate monitoring and further studies.


Assuntos
Proteínas de Bactérias/genética , Enterobacteriaceae/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Colistina/farmacologia , Bases de Dados Genéticas , Farmacorresistência Bacteriana , Enterobacteriaceae/química , Enterobacteriaceae/efeitos dos fármacos , Modelos Moleculares , Plasmídeos , Estrutura Terciária de Proteína , Análise de Sequência de Proteína
18.
Nat Rev Microbiol ; 18(5): 286-298, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32152509

RESUMO

The antibacterial agents currently in clinical development are predominantly derivatives of well-established antibiotic classes and were selected to address the class-specific resistance mechanisms and determinants that were known at the time of their discovery. Many of these agents aim to target the antibiotic-resistant priority pathogens listed by the WHO, including Gram-negative bacteria in the critical priority category, such as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales. Although some current compounds in the pipeline have exhibited increased susceptibility rates in surveillance studies that depend on geography, pre-existing cross-resistance both within and across antibacterial classes limits the activity of many of the new agents against the most extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens. In particular, cross-resistance to unrelated classes may occur by co-selection of resistant strains, thus leading to the rapid emergence and subsequent spread of resistance. There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria.


Assuntos
Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Desenvolvimento de Medicamentos/tendências , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Pseudomonas/efeitos dos fármacos , Infecções por Acinetobacter/microbiologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Infecções por Pseudomonas/microbiologia
19.
PLoS Biol ; 18(3): e3000652, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32191697

RESUMO

The rise in carbapenem-resistant Enterobacteriaceae (CRE) infections has created a global health emergency, underlining the critical need to develop faster diagnostics to treat swiftly and correctly. Although rapid pathogen-identification (ID) tests are being developed, gold-standard antibiotic susceptibility testing (AST) remains unacceptably slow (1-2 d), and innovative approaches for rapid phenotypic ASTs for CREs are urgently needed. Motivated by this need, in this manuscript we tested the hypothesis that upon treatment with ß-lactam antibiotics, susceptible Enterobacteriaceae isolates would become sufficiently permeabilized, making some of their DNA accessible to added polymerase and primers. Further, we hypothesized that this accessible DNA would be detectable directly by isothermal amplification methods that do not fully lyse bacterial cells. We build on these results to develop the polymerase-accessibility AST (pol-aAST), a new phenotypic approach for ß-lactams, the major antibiotic class for gram-negative infections. We test isolates of the 3 causative pathogens of CRE infections using ceftriaxone (CRO), ertapenem (ETP), and meropenem (MEM) and demonstrate agreement with gold-standard AST. Importantly, pol-aAST correctly categorized resistant isolates that are undetectable by current genotypic methods (negative for ß-lactamase genes or lacking predictive genotypes). We also test contrived and clinical urine samples. We show that the pol-aAST can be performed in 30 min sample-to-answer using contrived urine samples and has the potential to be performed directly on clinical urine specimens.


Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , DNA Bacteriano/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , beta-Lactamas/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/urina , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Reprodutibilidade dos Testes , Fatores de Tempo , beta-Lactamases/genética
20.
Poult Sci ; 99(3): 1571-1580, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115034

RESUMO

The effects of 3 ethanol levels (30, 50, and 70%) with and without thiamine dilaurylsulfate (TDS; 1,000 ppm) were evaluated for the reduction of natural mesophilic aerobic bacteria (MAB), coliforms, and inoculated Salmonella Typhimurium (S. Typhimurium) in chicken skin. The chicken skin was inoculated with a 7 log cfu/mL suspension of S. Typhimurium. Loosely, intermediately, and tightly attached cells were recovered from chicken skin through shaking at 200 rpm for 5 min, stomaching for 1 min, and blending for 1 min, respectively. Increasing the ethanol concentration reduced the number of MAB, coliforms, and S. Typhimurium on the chicken skin, whereas TDS treatment without ethanol was not effective. Intermediately and tightly attached microorganisms (total MAB, coliforms, and S. Typhimurium) were more resistant to chemical disinfectants than loosely attached microorganisms. The combination of 70% ethanol with TDS was most effective than the combination of TDS with lower concentrations of ethanol in reducing populations of loosely, intermediately, and tightly attached MAB (by 1.88 log cfu/g, 1.21 log cfu/g, and 0.84 log cfu/g, respectively), coliforms (by 1.14 log cfu/g, 1.04 log cfu/g, and 0.67 log cfu/g, respectively), and S. Typhimurium (by 1.62 log cfu/g, 1.72 log cfu/g, and 1.27 log cfu/g, respectively). However, the chicken skin treated with higher concentrations of ethanol was tougher (P < 0.05) and more yellow and less red (P < 0.05) than that treated with lower concentrations of ethanol or with water (control). On the other hand, a combination of 30% ethanol and TDS yielded the best results, showing the reduction greater than 0.5 log cfu/g in S. Typhimurium, with no negative effect on chicken skin color or texture. Thus, a combination of 30% ethanol and TDS appears to be the optimal treatment for reducing microbial contamination of skin-on chicken products to enhance poultry safety without decreasing food quality, and this treatment could be applied in the poultry industry.


Assuntos
Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Etanol/farmacologia , Manipulação de Alimentos , Microbiologia de Alimentos , Tiamina/farmacologia , Animais , Antibacterianos/administração & dosagem , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Aeróbias/fisiologia , Galinhas , Relação Dose-Resposta a Droga , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/fisiologia , Etanol/administração & dosagem , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/fisiologia , Pele/microbiologia , Tiamina/administração & dosagem
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