Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.857
Filtrar
1.
Euro Surveill ; 25(3)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31992391

RESUMO

From September to October 2019, seven patients colonised or infected with a ceftazidime-avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae were detected in two intensive care units of a Greek general hospital. The outbreak strain was sequence type (ST)147 and co-produced KPC-2 and the novel plasmid-borne Vietnamese extended-spectrum ß-lactamase (VEB)-25 harbouring a K234R substitution associated with CZA resistance. Epidemiological investigations revealed that the resistance was probably acquired by horizontal transmission independently from previous CZA exposure.


Assuntos
Antibacterianos/farmacologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Compostos Azabicíclicos , Ceftazidima , Surtos de Doenças , Combinação de Medicamentos , Farmacorresistência Bacteriana , Feminino , Genoma Bacteriano , Grécia , Humanos , Unidades de Terapia Intensiva , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação/genética , Sequenciamento Completo do Genoma
2.
J Med Microbiol ; 69(1): 82-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31904319

RESUMO

In recent years, Serratia marcescens has emerged as an important agent of hospital-acquired infections, such as pneumonia, urinary tract infection, septicaemia and meningitis, particularly in vulnerable patients. Compared to Klebsiella pneumoniae and Escherichia coli, S. marcescens is less commonly associated with bla KPC genes, yet few cases of plasmid transmission at the gastrointestinal level from K. pneumoniae carbapenemase (KPC)-producing Enterobacterales to S. marcescens have been described. Here we report a case of in vivo acquisition, during a 3-month period of hospitalization in the intensive care unit, of a bla KPC-3 gene carried by a pKpQIL-IT plasmid, and its probable transmission at the bronchial level among different species of Enterobacterales, including K. pneumoniae and S. marcescens. By using whole genome sequence analyses we were able provide insight into the dynamics of carbapenem-resistance determinants acquisition in the lower respiratory tract, a novel anatomical region for such plasmid transmission events, that usually involve the gastrointestinal tract. The co-presence at the same time of both wild-type and resistant Enterobacterales could have been the critical factor leading to the spread of plasmids harbouring carbapenem-resistance genes, of particular importance during surveillance screenings. The possibility of such an event may have significant consequences in terms of antimicrobial treatment, with a potential limitation of therapeutic options, thereby further complicating the clinical management of high-risk critically ill patients.


Assuntos
Proteínas de Bactérias/genética , Transferência Genética Horizontal , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Plasmídeos , Serratia marcescens/enzimologia , Serratia marcescens/genética , beta-Lactamases/genética , Adulto , Infecção Hospitalar/microbiologia , Humanos , Unidades de Terapia Intensiva , Infecções por Klebsiella/microbiologia , Masculino , Infecções Respiratórias/microbiologia , Infecções por Serratia/microbiologia , Sequenciamento Completo do Genoma
3.
BMC Infect Dis ; 19(1): 928, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684890

RESUMO

BACKGROUND: Endemic presence of Klebsiella pneumoniae resistant to carbapenem in Italy has been due principally to the clonal expansion of CC258 isolates; however, recent studies suggest an ongoing epidemiological change in this geographical area. METHODS: 50 K. pneumoniae strains, 25 carbapenem-resistant (CR-Kp) and 25 susceptible (CS-Kp), collected from march 2014 to march 2016 at the Laboratory of Bacteriology of the Paolo Giaccone Polyclinic University hospital of Palermo, Italy, were characterized for antibiotic susceptibility and fully sequenced by next generation sequencing (NGS) for the in silico analysis of resistome, virulome, multi-locus sequence typing (MLST) and core single nucleotide polymorphism (SNP) genotypes RESULTS: MLST in silico analysis of CR-Kp showed that 52% of isolates belonged to CC258, followed by ST395 (12%), ST307 (12%), ST392 (8%), ST348 (8%), ST405 (4%) and ST101 (4%). In the CS-Kp group, the most represented isolate was ST405 (20%), followed by ST392 and ST15 (12%), ST395, ST307 and ST1727 (8%). The in silico ß-lactamase analysis of the CR-Kp group showed that the most detected gene was blaSHV (100%), followed by blaTEM (92%), blaKPC (88%), blaOXA (88%) and blaCTX-M (32%). The virulome analysis detected mrk operon in all studied isolates, and wzi-2 was found in three CR-Kp isolates (12%). Furthermore, the distribution of virulence genes encoding for the yersiniabactin system, its receptor fyuA and the aerobactin system did not show significant distribution differences between CR-Kp and CS-Kp, whereas the Klebsiella ferrous iron uptake system (kfuA, kfuB and kfuC genes), the two-component system kvgAS and the microcin E495 were significantly (p < 0.05) prevalent in the CS-Kp group compared to the CR-Kp group. Core SNP genotyping, correlating with the MLST data, allowed greater strain tracking and discrimination than MLST analysis. CONCLUSIONS: Our data support the idea that an epidemiological change is ongoing in the Palermo area (Sicily, Italy). In addition, our analysis revealed the co-existence of antibiotic resistance and virulence factors in CR-Kp isolates; this characteristic should be considered for future genomic surveillance studies.


Assuntos
Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Fatores de Virulência/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Genótipo , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogenia , Polimorfismo de Nucleotídeo Único , Sicília , beta-Lactamases/genética
4.
Anal Bioanal Chem ; 411(27): 7315-7325, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637462

RESUMO

Biofilms are communities of bacteria living embedded in a highly hydrated matrix composed of polysaccharides, proteins, and extracellular DNA. This life style confers numerous advantages to bacteria including protection against external threats. However, they also contribute to increase bacterial resistance against antimicrobials, an issue particularly relevant in dangerous infections. Due to the complexity of the matrix, few information is present in the literature on details of its architecture including the spatial distribution of the macromolecular components which might give hints on the way the biofilm scaffold is built up by bacteria. In this study, we investigated the possibility to combine well-established microbiological procedures with advanced microscopies to get information on composition and distribution of the macromolecular components of biofilm matrices. To this, confocal microscopy, diffraction-limited infrared (IR) spectral imaging, and atomic force microscopy (AFM) were used to explore biofilm produced by a clinical strain of Klebsiella pneumoniae. IR imaging permitted to have clues on how the biofilm grows and spreads on surfaces, and the local distribution of the components within it. Through the analysis of the pure component spectra, it was possible to assess the chemical and structural composition of the saccaridic matrix, confirming the data obtained by NMR. It was also possible to follow the time course of biofilm from 6 up to 48 h when the biofilm grew into a 3-dimensional multi-layered structure, characteristic of colonies of bacteria linked together by a complex matrix. In addition, nanoFTIR and AFM investigations allowed the estimation of biofilm growth in the vertical direction and the morphological analysis of bacterial colonies at different time points and the evaluation of the chemical composition at the nanoscale.


Assuntos
Biofilmes/crescimento & desenvolvimento , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/fisiologia , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/ultraestrutura , Humanos , Klebsiella pneumoniae/química , Klebsiella pneumoniae/ultraestrutura , Microscopia de Força Atômica , Microscopia Confocal , Espectrofotometria Infravermelho
5.
New Microbiol ; 42(4): 197-204, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31609454

RESUMO

Klebsiella pneumoniae due to the presence of multiple antibiotic resistance mechanisms is one of the most threatening human pathogens nowadays. The aim of the study was to characterize antimicrobial susceptibility, presence of resistance mechanisms and the prevalence of selected genes encoding ESBLs in 170 K. pneumoniae isolates recovered from children and adults hospitalized in two Polish medical centers from 2008 to 2015. The phenotypic identification of strains was confirmed by amplification of mdh gene. ESBLs, metallo-beta- lactamases, Klebsiella pneumoniae carbapenemases and OXA-48 were detected using phenotypic tests. The blaCTX-M-1, blaTEM and blaSHV ESBL genes were amplified by PCR. Pediatric K. pneumoniae isolates displayed significantly higher resistance to piperacillin/tazobactam, cefoxitin, imipenem, amikacin and ciprofloxacin than strains obtained from adults (P<0.05). The presence of ESBLs, OXA-48, KPC and MBL was confirmed in 80.6%, 21.8%, 8.2% and 2.4%, respectively, of the tested strains. The CTX-M-1 enzymes were predominant (91.2%), followed by TEM (63.5%) and SHV (11.8%). The blaTEM was significantly more common in adults than in children (P<0.05). Dual or triple bla genes were observed in 55.9% and 8.2% of K. pneumoniae isolates. Further local epidemiological studies are required to monitor the dissemination of multidrug-resistant K. pneumoniae strains.


Assuntos
Anti-Infecciosos , Infecções por Klebsiella , Klebsiella pneumoniae , beta-Lactamases , Adulto , Anti-Infecciosos/farmacologia , Criança , Hospitais/estatística & dados numéricos , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Polônia/epidemiologia , Prevalência , beta-Lactamases/metabolismo
6.
Medicine (Baltimore) ; 98(39): e17362, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574882

RESUMO

RATIONALE: Klebsiella pneumoniae infection can induce multiple invasive abscesses, and the invasive infection is severe and life-threatening. PATIENT CONCERNS: A 69-year-old previously healthy Chinese male presented with fever, chill, backache, and ocular pain. DIAGNOSIS: The blood culture results indicated Klebsiella pneumoniae of the K1 serotype. Multiple invasive abscesses in liver, lung, eye, soft tissue, and central nervous system were identified by imaging examination. Subsequently, the patient experienced right ocular pain accompanied by visual disturbance. Tyndall sign was strongly positive, and lens opacity was observed by the ophthalmologist. INTERVENTIONS: Full-dose and long-term treatment with meropenem was performed. Intraventricular injection of glass and anterior chamber puncture with antibiotics were performed twice. The patient also underwent an evacuation of the brain abscess. OUTCOMES: The patient's headache and lumbar backache were relieved, his ophthalmodynia disappeared, and his vision recovered after nearly 3 months of treatment. LESSONS: Imaging examination is very important for severe Klebsiella pneumoniae infection. The choice of antibiotics is complex, and the antimicrobial regimen should be adjusted according to the assessment of illness and the therapeutic effect. Surgical intervention must be considered for patients with multiple invasive abscesses.


Assuntos
Abscesso/microbiologia , Antibacterianos/uso terapêutico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Meropeném/uso terapêutico , Idoso , Humanos , Masculino
7.
Medicine (Baltimore) ; 98(38): e17215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567977

RESUMO

The aim of the study is to explore whether monocyte-to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41-104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.


Assuntos
Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae , Contagem de Leucócitos , Contagem de Linfócitos , Monócitos , Pneumonia Bacteriana/diagnóstico , Idoso , Feminino , Humanos , Infecções por Klebsiella/sangue , Infecções por Klebsiella/microbiologia , Masculino , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/microbiologia , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença
9.
Turk J Pediatr ; 61(1): 40-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31559720

RESUMO

Zhu Y, Xu F. The pathogens and curative effects analysis of perianal abscess of infants under 3 months. Turk J Pediatr 2019; 61: 40-43. In order to guide clinical treatment for perianal abscess of young infants, the characteristics of pathogens and curative effects analysis were conducted. Bacterial culture results, antibiotics susceptibility tests and curative effects of abscess incision were retrospectively analyzed in 66 cases of perianal abscess of infants under 3 months. There were 48 cases of Klebsiella pneumoniae, 7 cases of Staphylococcus, 6 cases of Escherichia coli, 5 cases of Proteus in the pathogen culture results. Klebsiella pneumoniae, the predominant pathogen, was susceptible to most antibiotics, especially to imipenem, cefoperazonesulbactam and amikacin with low drug resistance rates. However, high drug resistance rates were found to ampicillin and nitrofurantion. After abscess incision, the complication rate of anal fistula was 6.6% in infants under 3 months and 60.3% in the adult group. There was significant difference P<0.01. In conclusion, Klebsiella pneumoniae was the most common pathogen in perianal abscess of infants under 3 months and was commonly resistant to ampicillin and nitrofurantion. Since perianal abscess of infants under 3 months is a self-limited disorder, simple surgical intervention and synchronous sensitive antibiotic administration are suggested as the optimal management.


Assuntos
Abscesso , Doenças do Ânus , Infecções por Escherichia coli , Infecções por Klebsiella , Klebsiella pneumoniae/isolamento & purificação , Infecções Estafilocócicas , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Abscesso/cirurgia , Adulto , Antibacterianos/uso terapêutico , Doenças do Ânus/diagnóstico , Doenças do Ânus/tratamento farmacológico , Doenças do Ânus/microbiologia , Doenças do Ânus/cirurgia , Terapia Combinada , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/cirurgia , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Resultado do Tratamento
10.
Lett Appl Microbiol ; 69(5): 333-338, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536642

RESUMO

Due to increasing antibiotic resistance Klebsiella pneumoniae is a serious threat for the hospitalized patients. The aim of this study was the assessment of radiant catalytic ionization (RCI) efficacy on K. pneumoniae reduction in the air and on selected surfaces. Four K. pneumoniae NDM and ESBLs-producing strains were included in the study. Three types of surface were tested: cotton-polyester, terry and PVC. It was found that RCI significantly reduced the number of bacteria from all types of surface (terry: 0·56-1·22 log CFU m2 , cotton-polyester: 2·15-3·71 log CFU per m2 , PVC: 4·45-4·92 log CFU per m2 ) as well as from the air (1·80 log CFU per m3 ). The RCI technology may be a useful disinfection method in hospitals. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contamination of air and surfaces in hospitals play an important role in healthcare-associated infections. The aim was the assessment of Klebsiella pneumoniae elimination using radiant catalytic ionization (RCI). K. pneumoniae are aetiological agent of nosocomial infections, such as: pneumonia, infections of urinary tract, blood, e.t.c. The strains producing the New Delhi metallo-ß-lactamases are one of the greatest epidemiological threat. The use of RCI eliminate the tested bacteria from the hospital environment, but can also be effective in food processing plants or public facilities, ensuring the safety of people and products. This research is scarce in references and has a large innovation and application potential.


Assuntos
Proteínas de Bactérias/metabolismo , Infecção Hospitalar/prevenção & controle , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/efeitos da radiação , beta-Lactamases/metabolismo , Microbiologia do Ar , Proteínas de Bactérias/genética , Infecção Hospitalar/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos da radiação , Radiação Ionizante
11.
Nat Commun ; 10(1): 3957, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477712

RESUMO

Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggests that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost.


Assuntos
Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Porinas/genética , Sequência de Aminoácidos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mutação , Porinas/química , Porinas/metabolismo , Homologia de Sequência de Aminoácidos , Virulência/genética
12.
BMC Surg ; 19(1): 111, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412850

RESUMO

BACKGROUND: Bacteraemia of the donor is not considered to be contraindication of organ procurement. On the other hand, infection of solid organ transplant recipients remains to be a major cause of their morbidity and mortality. When using organs from bacteraemic donors, individual risks need to be assessed and the appropriate antibiotic treatment applied. CASE PRESENTATION: In this case series we report several serious donor-derived infectious complications in four out of five recipients of different organs from one single donor in the early posttransplant period. Donor-transmitted multi-drug resistant strains of Escherichia coli and Klebsiella pneumonia was confirmed by both serologic and molecular testing. CONCLUSIONS: To prevent donor-derived infections, careful microbiological screening followed by targeted antibiotic treatment is essential. Although such complications can never by completely prevented, a high index for potential bacterial infection in organ donors and transplant recipients should be routinely employed.


Assuntos
Bacteriemia , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/microbiologia , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/microbiologia , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Adulto , Antibacterianos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos , Transplantados
13.
Indian J Med Res ; 149(4): 528-538, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411177

RESUMO

Background & objectives: The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is an emerging clinical problem. Hence, in this study, the plausible role of extended-spectrum beta-lactamases (ESBLs)/carbapenemases, OmpC/Ompk36, acrB and their combinations was explored among CRE. Methods: The minimum inhibitory concentration (MIC) of meropenem, enzyme-phenotypes (ESBLs/IR and metallo-beta-lactamase (MBL)/non-MBL carbapenemase), genotypes (blaTEM, blaSHV and blaCTX-M; blaNDM and blaVIM; blaKPC and blaOXA-48-like variants), acrB and outer membrane protein (OMP) expressions were analyzed with a total of 101 non-duplicate clinical isolates, obtained from various samples of patients visiting two tertiary care units of Eastern India during May 2013 - October 2016. This included Escherichia coli (n=36) and Klebsiella pneumoniae (n=65), categorized into two groups, namely Group I (resistant to all carbapenems; n=93; E. coli=34 and Klebsiella spp.=59) and Group II (non-resistant to all the carbapenems; n=8; E. coli=2 and Klebsiella spp.=6). Results: Though 88.17 per cent of Group I isolates exhibited ESBL property, the presence of carbapenemase activity (70.96%) and that of blaNDM gene (42/66: 63.63%) indicated their contributions towards the emergence of CRE. Further, porin loss and/or efflux pump activation among ESBL/carbapenemase-producing isolates heightened the MIC of meropenem from 64 to 256 mg/l (range exhibited by only ESBL/carbapenemase-producing isolates) to >256 mg/l. Interpretation & conclusions: These findings implied the major contribution of porin loss and/or efflux pump activation over the presence of ESBLs/carbapenemases in imparting carbapenem resistance in pathogenic bacteria.


Assuntos
Proteínas de Bactérias/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Porinas/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , beta-Lactamases/genética
14.
Int J Antimicrob Agents ; 54(4): 381-399, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369812

RESUMO

Carbapenem-resistant Enterobacteriaceae infections have spread globally, leaving polymyxins, including colistin, as 'last-resort treatments'. Emerging colistin resistance raises the spectre of untreatable infections. Despite this threat, data remain limited for much of the world, including Southeast Asia where only 3 of 11 nations submitted data on carbapenem and colistin resistance for recent World Health Organization (WHO) reports. To improve our understanding of the challenge, we utilised broad strategies to search for and analyse data on carbapenem and colistin resistance among Escherichia coli and Klebsiella in Southeast Asia. We found 258 studies containing 526 unique reports and document carbapenem-resistant E. coli and Klebsiella in 8 and 9 of 11 nations, respectively. We estimated carbapenem resistance proportions through meta-analysis of extracted data for nations with ≥100 representative isolates. Estimated resistance among Klebsiella was high (>5%) in four nations (Indonesia, Philippines, Thailand and Vietnam), moderate (1-5%) in two nations (Malaysia and Singapore) and low (<1%) in two nations (Cambodia and Brunei). For E. coli, resistance was generally lower but was high in two of seven nations with ≥100 isolates (Indonesia and Myanmar). The most common carbapenemases were NDM metallo-ß-lactamases and OXA ß-lactamases. Despite sparse data, polymyxin resistance was documented in 8 of 11 nations, with mcr-1 being the predominant genotype. Widespread presence of carbapenem and polymyxin resistance, including their overlap in eight nations, represents a continuing risk and increases the threat of infections resistant to both classes. These findings, and remaining data gaps, highlight the urgent need for sufficiently-resourced robust antimicrobial resistance surveillance.


Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Infecções por Escherichia coli/epidemiologia , Infecções por Klebsiella/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia Sudeste/epidemiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Criança , Pré-Escolar , Infecções por Escherichia coli/microbiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
PLoS Pathog ; 15(8): e1008010, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31449551

RESUMO

Klebsiella pneumoniae (Kp), one of the most common causes of healthcare-associated infections, increases patient morbidity, mortality, and hospitalization costs. Kp must acquire nutrients from the host for successful infection; however, the host is able to prevent bacterial nutrient acquisition through multiple systems. This includes the innate immune protein lipocalin 2 (Lcn2), which prevents Kp iron acquisition. To identify novel Lcn2-dependent Kp factors that mediate evasion of nutritional immunity during lung infection, we undertook an InSeq study using a pool of >20,000 transposon mutants administered to Lcn2+/+ and Lcn2-/- mice. Comparing transposon mutant frequencies between mouse genotypes, we identified the Kp citrate synthase, GltA, as potentially interacting with Lcn2, and this novel finding was independently validated. Interestingly, in vitro studies suggest that this interaction is not direct. Given that GltA is involved in oxidative metabolism, we screened the ability of this mutant to use a variety of carbon and nitrogen sources. The results indicated that the gltA mutant has a distinct amino acid auxotrophy rendering it reliant upon glutamate family amino acids for growth. Deletion of Lcn2 from the host leads to increased amino acid levels in bronchioloalveolar lavage fluid, corresponding to increased fitness of the gltA mutant in vivo and ex vivo. Accordingly, addition of glutamate family amino acids to Lcn2+/+ bronchioloalveolar lavage fluid rescued growth of the gltA mutant. Using a variety of mouse models of infection, we show that GltA is an organ-specific fitness factor required for complete fitness in the spleen, liver, and gut, but dispensable in the bloodstream. Similar to bronchioloalveolar lavage fluid, addition of glutamate family amino acids to Lcn2+/+ organ lysates was sufficient to rescue the loss of gltA. Together, this study describes a critical role for GltA in Kp infection and provides unique insight into how metabolic flexibility impacts bacterial fitness during infection.


Assuntos
Citrato (si)-Sintase/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Lipocalina-2/metabolismo , Lipocalina-2/fisiologia , Animais , Citrato (si)-Sintase/genética , Modelos Animais de Doenças , Humanos , Infecções por Klebsiella/metabolismo , Klebsiella pneumoniae/enzimologia , Lipocalina-2/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Emerg Infect Dis ; 25(9): 1632-1638, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31441424

RESUMO

We aimed to provide updated epidemiologic data on carbapenem-resistant Klebsiella pneumoniae in Portugal by characterizing all isolates (N = 46) recovered during 2013-2018 in a 123-bed hospital in Lisbon. We identified blaKPC-3 (n = 36), blaOXA-181 (n = 9), and blaGES-5 (n = 8) carbapenemase genes and observed co-occurrence of blaKPC-3 and blaGES-5 in 7 isolates. A single GES-5-producing isolate co-produced the extended-spectrum ß-lactamase BEL-1; both corresponding genes were co-located on the same ColE1-like plasmid. The blaOXA-181 gene was always located on an IncX3 plasmid, whereas blaKPC-3 was carried on IncN, IncFII, IncFIB, and IncFIIA plasmid types. The 46 isolates were distributed into 13 pulsotypes and 9 sequence types. All isolates remained susceptible to ceftazidime/avibactam, but some exhibited reduced antimicrobial susceptibility (MIC = 3 mg/L).


Assuntos
Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Hospitais , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Portugal/epidemiologia , beta-Lactamases/metabolismo
17.
Biomed Res Int ; 2019: 6736897, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467906

RESUMO

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6')-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The bla NDM-1 gene was always identified on a 70-kb plasmid, whereas the bla VIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6']-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Arábia Saudita/epidemiologia
18.
Acta Microbiol Immunol Hung ; 66(3): 367-376, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31438725

RESUMO

The aim of the study was to find out the carbapenem resistance rate and prevalence of different carbapenemase genes in Klebsiella pneumoniae and Escherichia coli from a North Indian corporate hospital that receives both Indian and international patients. A total of 528 clinical isolates of E. coli and K. pneumoniae were included in the study. All isolates that were found resistant to carbapenems by MIC testing (Vitek II Compact®) were screened for NDM, OXA-48, VIM, and KPC genes by PCR. Sequencing of NDM gene and transmissibility by conjugation assay were checked on 22 randomly selected NDM-positive isolates. One hundred and fifty-six isolates (29.54%) were carbapenem-resistant. The rate of carbapenem resistance was significantly higher in K. pneumoniae as compared to E. coli (53.9% vs. 15.6%; p < 0.05). The NDM gene was found in 34.6% (54/156), OXA-48 in 31.4% (49/156), co-expression of NDM + OXA-48 in 15.3% (24/156) of the carbapenem-resistant isolates. VIM and KPC were absent in all isolates. NDM gene was significantly more prevalent in E. coli than K. pneumoniae (p < 0.05). All the tested isolates formed transconjugants and NDM-5 was the most common variant in both species (15/22). The presence of plasmid-based NDM calls for stricter surveillance measures in our hospital settings.


Assuntos
Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/genética , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Carbapenêmicos/farmacologia , Conjugação Genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Plasmídeos/análise , Prevalência , Análise de Sequência de DNA
19.
Nat Commun ; 10(1): 3517, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388008

RESUMO

New Delhi metallo-ß-lactamase-1 (NDM-1) is the most prevalent type of metallo-ß-lactamase and hydrolyzes almost all clinically used ß-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin's dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Parede Celular/efeitos dos fármacos , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/metabolismo , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Carbapenêmicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração Inibidora 50 , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Zinco/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA