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1.
BMC Infect Dis ; 24(1): 561, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840122

RESUMO

BACKGROUND: Treatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy. METHODS: We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy. RESULTS: We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0-52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873). CONCLUSION: In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.


Assuntos
Antibacterianos , Bacteriemia , Enterobacteriáceas Resistentes a Carbapenêmicos , Colistina , Infecções por Enterobacteriaceae , Humanos , Colistina/uso terapêutico , Colistina/farmacologia , Estudos Transversais , Masculino , África do Sul/epidemiologia , Feminino , Pessoa de Meia-Idade , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Adulto Jovem , Adolescente , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/mortalidade , Infecções por Enterobacteriaceae/microbiologia , Pré-Escolar , Lactente , Criança , Recém-Nascido , Mortalidade Hospitalar , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Hospitais
2.
BMC Microbiol ; 24(1): 202, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851699

RESUMO

BACKGROUND: Bacteroides fragilis group (BFG) species are the most significant anaerobic pathogens and are also the most antibiotic-resistant anaerobic species. Therefore, surveying their antimicrobial resistance levels and investigating their antibiotic resistance mechanisms is recommended. Since their infections are endogenous and they are important constituents of the intestinal microbiota, the properties of the intestinal strains are also important to follow. The aim of this study was to investigate the main antibiotic gene content of microbiota isolates from healthy people and compare them with the gene carriage of strains isolated from infections. RESULTS: We detected 13, mainly antibiotic resistance determinants of 184 intestinal BFG strains that were isolated in 5 European countries (Belgium, Germany, Hungary, Slovenia and Turkey) and compared these with values obtained earlier for European clinical strains. Differences were found between the values of this study and an earlier one for antibiotic resistance genes that are considered to be mobile, with higher degrees for cfxA, erm(F) and tet(Q) and with lower degrees for msrSA, erm(B) and erm(G). In addition, a different gene prevalence was found depending on the taxonomical groups, e.g., B. fragilis and NBFB. Some strains with both the cepA and cfiA ß-lactamase genes were also detected, which is thought to be exceptional since until now, the B. fragilis genetic divisions were defined by the mutual exclusion of these two genes. CONCLUSIONS: Our study detected the prevalences of a series of antibiotic resistance genes in intestinal Bacteroides strains which is a novelty. In addition, based on the current and some previous data we hypothesized that prevalence of some antibiotic resistance genes detected in the clinical and intestinal BFG strains were different, which could be accounted with the differential composition of the Bacteroides microbiota and/or the MGE mobilities at the luminal vs. mucosal sites of the intestine.


Assuntos
Antibacterianos , Infecções por Bacteroides , Bacteroides , Carbapenêmicos , Humanos , Europa (Continente) , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecções por Bacteroides/microbiologia , Bacteroides/genética , Bacteroides/efeitos dos fármacos , Bacteroides/isolamento & purificação , Farmacorresistência Bacteriana/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Testes de Sensibilidade Microbiana , Genes Bacterianos/genética , Intestinos/microbiologia , Proteínas de Bactérias/genética
3.
Med Sci Monit ; 30: e943596, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831571

RESUMO

BACKGROUND In China, the most prevalent type of CRKP is ST11, but the high-risk clone ST15 has grown in popularity in recent years, posing a serious public health risk. Therefore, we investigated the molecular prevalence characteristics of ST15 CRKP detected in a tertiary hospital in Ningbo to understand the current potential regional risk of ST15 CRKP outbreak. MATERIAL AND METHODS We collected and evaluated 18 non-duplicated CRKP strains of ST15 type for antibiotic resistance. Their integrons, virulence genes, and resistance genes were identified using polymerase chain reaction (PCR), and their homology was determined using MALDI-TOF MS. RESULTS The predominant serotype of 18 ST15 CRKP strains was K5. ST15 CRKP exhibited the lowest antimicrobial resistance to Cefoperazone/sulbactam (11.1%), followed by trimethoprim/sulfamethoxazole (22.2%). Resistance gene testing revealed that 14 out of 18 ST15 CRKP strains (77.8%) carried Klebsiella pneumoniae carbapenemase 2 (KPC-2), whereas all ST15 CRKP integrons were of the intI1 type. Furthermore, virulence gene testing revealed that all 18 ST15 CRKP strains carried ybtS, kfu, irp-1, and fyuA genes, followed by the irp-2 gene (17 strains) and entB (16 strains). The homology analysis report showed that 2 clusters had closer affinity, which was mainly concentrated in classes C and D. CONCLUSIONS The ST15 CRKP antibiotic resistance rates demonstrate clear geographical differences in Ningbo. Additionally, some strains carried highly virulent genes, indicating a possible evolution towards carbapenem-resistant highly virulent strains. To reduce the spread of ST15 CRKP, we must rationalize the clinical use of antibiotics and strengthen resistance monitoring to control nosocomial infections.


Assuntos
Antibacterianos , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , China/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Prevalência , Integrons/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Farmacorresistência Bacteriana/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos
4.
Commun Biol ; 7(1): 695, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844513

RESUMO

Infection caused by KPC and NDM carbapenemases co-producing Klebsiella pneumoniae (KPC_NDM_CRKP) poses serious public health concerns. Here, we elucidate the prevalence of a hypertransmissible lncM1 plasmid, pKPC_NDM, co-carrying blaKPC-2 and blaNDM-1 genes in sequence type 1049 K_locus 5 (ST1049-KL5) KPC_NDM_CRKP isolates. Genetic and clonal relatedness analyses using pulsed-field gel electrophoresis, single nucleotide polymorphism analysis and core genome multilocus sequence typing suggested clonal dissemination of ST1049-KL5 KPC_NDM_CRKP strains in our hospital. Whole genome sequencing identified an identical 76,517 bp- blaKPC-2 and blaNDM-1 genes co-carrying IncM1 plasmid pKPC_NDM and a pLVPK-like hypervirulent plasmid in all ST1049-KL5 KPC_NDM_CRKP isolates. pKPC_NDM shared 100% identity with a previously sequenced plasmid CRKP35_unnamed4, demonstrating high transferability in conjugation assay, with conjugation frequencies reaching 10-4 and 10-5 in Escherichia coli and K. pneumoniae recipients, respectively. It also maintained favorable stability and flexible compatibility, with retention rates exceeding 80% after 10 days of continuous passage, and could be compatible with pre-existing blaKPC- or blaNDM-carrying plasmids in recipient strains. This study summarizes the characteristics of KPC_NDM_CRKP outbreaks and highlights the importance of ongoing surveillance and infection control strategies to address the challenges posed by ST1049 K. pneumoniae strains.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Plasmídeos , beta-Lactamases , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/genética , beta-Lactamases/metabolismo , Plasmídeos/genética , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Humanos , Prevalência , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Sequenciamento Completo do Genoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade Microbiana
5.
Yakugaku Zasshi ; 144(6): 627-631, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38825471

RESUMO

Cefiderocol is a novel siderophore-conjugated cephalosporin with a catechol residue acting as an iron chelator. Cefiderocol forms a chelating complex with ferric iron and is transported rapidly into bacterial cells through iron-uptake systems. As a result, cefiderocol shows good activity against Gram-negative bacteria, including carbapenem-resistant isolates that are causing significant global health issues. Cefiderocol has been approved for clinical use in the United States and Europe, where it is being used to treat infection caused by carbapenem-resistant Gram-negative pathogens.


Assuntos
Antibacterianos , Cefiderocol , Cefalosporinas , Bactérias Gram-Negativas , Sideróforos , Cefalosporinas/farmacologia , Cefalosporinas/química , Sideróforos/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Farmacorresistência Bacteriana , Descoberta de Drogas , Carbapenêmicos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
6.
Front Cell Infect Microbiol ; 14: 1380678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817445

RESUMO

Introduction: The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China. Methods: A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups. Results: The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics. Conclusion: Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.


Assuntos
Antibacterianos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Humanos , China/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Masculino , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização , Adulto , Carbapenêmicos/farmacologia
7.
Front Cell Infect Microbiol ; 14: 1382145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736748

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenêmicos , Genoma Viral , Terapia por Fagos , Filogenia , Esgotos , Acinetobacter baumannii/virologia , Acinetobacter baumannii/efeitos dos fármacos , Esgotos/virologia , Esgotos/microbiologia , Animais , Carbapenêmicos/farmacologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Infecções por Acinetobacter/microbiologia , Camundongos , Antibacterianos/farmacologia , Fases de Leitura Aberta , Modelos Animais de Doenças , Mariposas/virologia , Mariposas/microbiologia , Composição de Bases
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(5): 649-655, 2024 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-38715505

RESUMO

Objective: To evaluate the virulence levels of carbapenem-resistant Acinetobacter baumannii ST191, ST195, and ST208, and to analyze the differences in virulence factors among these epidemic clones. Methods: The study involved the genomic sequencing of 233 Acinetobacter baumannii strains that were isolated from the Fifth Medical Center of the Chinese People's Liberation Army General Hospital (North Hospital) between 2011 and 2019. The genomic data was cross-referenced with the Virulence Factor Database (VFDB) to examine the presence of virulence genes in the strains. Furthermore, a Galleria mellonella infection survival model was used to evaluate the virulence levels of the strains, and the association between virulence levels and virulence genes was analyzed. Results: The study included 38 strains of the ST191 clone, 104 strains of the ST195 clone, and 91 strains of the ST208 clone. In the Galleria mellonella infection survival experiment, the average mortality rate for ST191 was 23.0%, with 3 (7.9%) highly virulent strains. For ST195, the average mortality rate was 53.0%, with 34 (32.7%) highly virulent strains. For ST208, the average mortality rate was 47.0%, with 20 (21.9%) highly virulent strains. There was a significant statistical difference in mortality rates between ST191 and ST195 (χ2=13.9, P<0.001) as well as between ST191 and ST208 (χ2=15.2, P<0.001). A comparison of the strains with the VFDB revealed significant differences in the virulence genes carried by the clones. Specifically, the type Ⅵ secretion system-related genes (clpV/tssH, hcp/tssD, tagX, tssA, tssB, tssC, tssE, tssF, tssG, tssK, ssL, tssM) and the sugar transferase gene ACICU_RS00475 were found to be universally absent in ST191 strains (0%) while being prevalent in ST195 (100.0%) and ST208 (>82.0%) strains. Statistical analysis revealed an association between the mortality rate of the clones and the presence of virulence genes(clpV/tssH P<0.001, hcp/tssD P=0.001, tagX P<0.001, tssA P<0.001, tssB P=0.001, tssC P=0.001, tssE P=0.001, tssF P=0.001, tssG P<0.001, tssK P<0.001, tssL P<0.001, tssM P=0.001, ACICU_RS00475 P=0.001). Conclusion: Among the carbapenem-resistant epidemic clones of Acinetobacter baumannii, the ST191 clone shows lower mortality rates in Galleria mellonella, possibly because of the lack of type Ⅵ secretion system and sugar transferase genes.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Carbapenêmicos , Fatores de Virulência , Acinetobacter baumannii/genética , Acinetobacter baumannii/patogenicidade , Carbapenêmicos/farmacologia , Virulência/genética , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Fatores de Virulência/genética , Animais , Mariposas/microbiologia , Antibacterianos/farmacologia , Humanos , Farmacorresistência Bacteriana
9.
Exp Clin Transplant ; 22(4): 300-306, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742321

RESUMO

OBJECTIVES: In this study, we analyzed the effects of carbapenem-resistant Pseudomonas aeruginosa infection and mixed infection on the perioperative prognosis of lung transplant recipients and studied statistics on antibiotic resistance in P aeruginosa. MATERIALS AND METHODS: This was a retrospective casecontrol study. We collected data on lung transplant recipients with combined lower respiratory tract P aeruginosa infection within 48 hours after lung transplant at the China-Japan Friendship Hospital from August 2018 to April 2022. We grouped recipients according to P aeruginosa resistance to carbapenem antibiotics and summarized the clinical characteristics of carbapenem-resistant P aeruginosa infection. We analyzed the effects of carbapenemresistant P aeruginosa infection and mixed infections on all-cause mortality 30 days after lung transplant by Cox regression. We used the Kaplan-Meier method to plot survival curves. RESULTS: Patients in the carbapenem-resistant P aeruginosa group had a higher all-cause mortality rate than those in the carbapenem-sensitive P aeruginosa group at both 7 days (6 patients [22.3%] vs 2 patients [4.5%]; P = .022) and 30 days (12 patients [44.4%] vs 7 patients [15.9%]; P = .003) after lung transplant. In multivariate analysis, both carbapenemresistant P aeruginosa infection and P aeruginosa combined with bacterial infection were independent risk factors for death 30 days after transplant in lung transplant recipients (P < .05). In subgroup analysis, carbapenem-resistant P aeruginosa combined with bacterial infection increased the risk of death 30 days after transplant in lung transplant recipients compared with carbapenem-sensitive P aeruginosa combined with bacterial infection (12 patients [60%] vs 6 patients [19.4%]; P < .001). CONCLUSIONS: Combined lower respiratory tract carbapenem-resistant P aeruginosa infection and P aeruginosa combined with bacterial infection early after lung transplant increased the risk of 30-day mortality after lung transplant.


Assuntos
Antibacterianos , Carbapenêmicos , Coinfecção , Transplante de Pulmão , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Infecções por Pseudomonas/mortalidade , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Fatores de Risco , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Carbapenêmicos/farmacologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Antibacterianos/uso terapêutico , Adulto , Resultado do Tratamento , Medição de Risco , Resistência beta-Lactâmica
10.
J Mol Biol ; 436(12): 168603, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38729259

RESUMO

OXA-66 is a member of the OXA-51 subfamily of class D ß-lactamases native to the Acinetobacter genus that includes Acinetobacter baumannii, one of the ESKAPE pathogens and a major cause of drug-resistant nosocomial infections. Although both wild type OXA-66 and OXA-51 have low catalytic activity, they are ubiquitous in the Acinetobacter genomes. OXA-51 is also remarkably thermostable. In addition, newly emerging, single and double amino acid variants show increased activity against carbapenems, indicating that the OXA-51 subfamily is growing and gaining clinical significance. In this study, we used molecular dynamics simulations, X-ray crystallography, and thermal denaturation data to examine and compare the dynamics of OXA-66 wt and its gain-of-function variants: I129L (OXA-83), L167V (OXA-82), P130Q (OXA-109), P130A, and W222L (OXA-234). Our data indicate that OXA-66 wt also has a high melting temperature, and its remarkable stability is due to an extensive and rigid hydrophobic bridge formed by a number of residues around the active site and harbored by the three loops, P, Ω, and ß5-ß6. Compared to the WT enzyme, the mutants exhibit higher flexibility only in the loop regions, and are more stable than other robust carbapenemases, such as OXA-23 and OXA-24/40. All the mutants show increased rotational flexibility of residues I129 and W222, which allows carbapenems to bind. Overall, our data support the hypothesis that structural features in OXA-51 and OXA-66 promote evolution of multiple highly stable variants with increased clinical relevance in A. baumannii.


Assuntos
Acinetobacter baumannii , Simulação de Dinâmica Molecular , beta-Lactamases , Acinetobacter baumannii/genética , Acinetobacter baumannii/enzimologia , beta-Lactamases/química , beta-Lactamases/genética , beta-Lactamases/metabolismo , Cristalografia por Raios X , Estabilidade Enzimática , Conformação Proteica , Carbapenêmicos/farmacologia , Carbapenêmicos/metabolismo , Evolução Molecular , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico
11.
Emerg Microbes Infect ; 13(1): 2352432, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38712634

RESUMO

This study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 µg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 µg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.


Assuntos
Antibacterianos , Proteínas de Escherichia coli , Escherichia coli , Testes de Sensibilidade Microbiana , Plasmídeos , Porinas , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Plasmídeos/genética , Antibacterianos/farmacologia , Porinas/genética , Porinas/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Carbapenêmicos/farmacologia , Meropeném/farmacologia , Mutação , Evolução Molecular , Conjugação Genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Sequenciamento Completo do Genoma , Dosagem de Genes , beta-Lactamases/genética
12.
Front Public Health ; 12: 1385118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784576

RESUMO

Background: This study aimed to explore the risk factors for failed treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia (CRAB-VAP) with tigecycline and to establish a predictive model to predict the incidence of failed treatment and the prognosis of CRAB-VAP. Methods: A total of 189 CRAB-VAP patients were included in the safety analysis set from two Grade 3 A national-level hospitals between 1 January 2022 and 31 December 2022. The risk factors for failed treatment with CRAB-VAP were identified using univariate analysis, multivariate logistic analysis, and an independent nomogram to show the results. Results: Of the 189 patients, 106 (56.1%) patients were in the successful treatment group, and 83 (43.9%) patients were in the failed treatment group. The multivariate logistic model analysis showed that age (OR = 1.04, 95% CI: 1.02, 1.07, p = 0.001), yes. of hypoproteinemia (OR = 2.43, 95% CI: 1.20, 4.90, p = 0.013), the daily dose of 200 mg (OR = 2.31, 95% CI: 1.07, 5.00, p = 0.034), yes. of medication within 14 days prior to surgical intervention (OR = 2.98, 95% CI: 1.19, 7.44, p = 0.019), and no. of microbial clearance (OR = 0.31, 95% CI: 0.14, 0.70, p = 0.005) were risk factors for the failure of tigecycline treatment. Receiver operating characteristic (ROC) analysis showed that the AUC area of the prediction model was 0.745 (0.675-0.815), and the decision curve analysis (DCA) showed that the model was effective in clinical practice. Conclusion: Age, hypoproteinemia, daily dose, medication within 14 days prior to surgical intervention, and microbial clearance are all significant risk factors for failed treatment with CRAB-VAP, with the nomogram model indicating that high age was the most important factor. Because the failure rate of CRAB-VAP treatment with tigecycline was high, this prediction model can help doctors correct or avoid risk factors during clinical treatment.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenêmicos , Pneumonia Associada à Ventilação Mecânica , Tigeciclina , Falha de Tratamento , Humanos , Acinetobacter baumannii/efeitos dos fármacos , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Carbapenêmicos/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Antibacterianos/uso terapêutico , Idoso , Modelos Logísticos , Infecções por Acinetobacter/tratamento farmacológico , Tigeciclina/uso terapêutico , Adulto , Estudos Retrospectivos , China , Farmacorresistência Bacteriana
13.
Front Cell Infect Microbiol ; 14: 1404404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779560

RESUMO

Background: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. Methods: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. Results: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. Conclusion: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Carbapenêmicos , Ceftazidima , Combinação de Medicamentos , Infecções por Bactérias Gram-Negativas , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Ceftazidima/uso terapêutico , Ceftazidima/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Compostos Azabicíclicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Adulto , Bactérias Gram-Negativas/efeitos dos fármacos , Resultado do Tratamento , Idoso , Transplantados
14.
BMC Infect Dis ; 24(1): 522, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783175

RESUMO

BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CR-GNB) are a critical public health threat globally; however, there are inadequate surveillance data, especially in intensive care units (ICU), to inform infection prevention and control in many resource-constrained settings. Here, we assessed the prevalence of CR-GNB infections and risk factors for acquisition in a Kenyan ICU. METHODS: A hospital-based cross-sectional study design was adopted, recruiting 162 patients clinically presenting with bacterial infection after 48 h of ICU admission, from January to October 2022 at the Nairobi West Hospital, Kenya. Demographics and clinical data were collected by case report form. The type of sample collected, including blood, tracheal aspirate, ascitic tap, urine, stool, and sputum depended on the patient's clinical presentation and were transported to the hospital Microbiology laboratory in a cool box for processing within 2 h. The samples were analyzed by cultured and BD Phoenix system used for isolates' identity and antimicrobial susceptibility. RESULTS: CR-GNB infections prevalence was 25.9% (42/162), with Klebsiella pneumoniae (35.7%, 15/42) and Pseudomonas aeruginosa (26.2%, 11/42) predominating. All isolates were multidrug-resistant (MDR). P. aeruginosa and A. baumannii were 100% colistin-resistant, while K. pneumoniae (33.3%) was tigecycline-resistant. History of antibiotics (aOR = 3.40, p = 0.005) and nasogastric tube (NGT) use (aOR = 5.84, p = < 0.001) were the risk factors for infection. CONCLUSION: Our study highlights high MDR- and CR-GNB infections in ICU, with prior antibiotic exposure and NGT use as risk factors, and diminishing clinical value of colistin and tigecycline. In this study setting and beyond, strict implementation of antimicrobial stewardship programs and adherence to infection prevention and control through monitoring, evaluation and feedback are warranted to curb CR-GNB infections, especially among the risk groups.


Assuntos
Antibacterianos , Carbapenêmicos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Unidades de Terapia Intensiva , Humanos , Quênia/epidemiologia , Masculino , Fatores de Risco , Feminino , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Transversais , Pessoa de Meia-Idade , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Adulto , Prevalência , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Idoso , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Adulto Jovem
15.
Diagn Microbiol Infect Dis ; 109(3): 116324, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733752

RESUMO

We aimed to determine the epidemiology and resistance patterns of Gram-negative bacteria, the risk factors and outcome of bloodstream infection (BSI). In all, 412 episodes in children who were hospitalized with the diagnosis of bacteremia were analyzed. The most common microorganisms were Klebsiella spp. (43.9%), Escherichia coli (13.5 %) and Acinetobacter spp. (10.6 %). Among isolates, 41.2 % were multidrug-resistant, 13.5 % were extensively drug-resistant and 0.4 % were pan-drug-resistant. Carbapenem resistance was revealed in 27.6 % of isolates. Carbapenem and colistin resistance increased over the years. The most common risk factors were the presence of a central-venous catheter and pediatric intensive care unit admission. Clinical response and infection-related mortality were significantly different in cases infected with carbapenem-resistant gram-negative (CRGN) vs carbapenem-susceptible gram-negative bacteria. The increase in multi-resistant Klebsiella spp. seems to be the biggest obstacles in fight against nosocomial infections. The increasing number of CRGN infections over the years affects both the clinical response and mortality rate of BSI.


Assuntos
Antibacterianos , Bacteriemia , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Humanos , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Bacteriemia/tratamento farmacológico , Fatores de Risco , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Criança , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/classificação , Masculino , Pré-Escolar , Feminino , Lactente , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Adolescente , Recém-Nascido , Resultado do Tratamento , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/tratamento farmacológico , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico
16.
PLoS Pathog ; 20(5): e1012187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718038

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Klebsiella pneumoniae , RNA Bacteriano , Pequeno RNA não Traduzido , beta-Lactamases , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Regulação Bacteriana da Expressão Gênica , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética
17.
Virulence ; 15(1): 2349768, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736039

RESUMO

ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the "mcsw" morphotype. Two distinct morphotypes ("ntrd" and "msdw") were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (wza, wzc, and wbaP), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.


Assuntos
Antibacterianos , Biofilmes , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Virulência , Infecções por Klebsiella/microbiologia , Humanos , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Carbapenêmicos/farmacologia , Animais , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Camundongos , Mutação , Sequenciamento Completo do Genoma , Plasmídeos/genética , Farmacorresistência Bacteriana
18.
BMC Med Inform Decis Mak ; 24(1): 123, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745177

RESUMO

BACKGROUND: Predicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2-5 days conventionally to return the results from doctor's order. METHODS: It is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture. RESULTS: There were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively. CONCLUSIONS: The machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.


Assuntos
Bacteriemia , Carbapenêmicos , Infecções por Bactérias Gram-Negativas , Unidades de Terapia Intensiva , Aprendizado de Máquina , Humanos , Carbapenêmicos/farmacologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Adulto , Antibacterianos/farmacologia , Farmacorresistência Bacteriana
19.
J Microbiol Methods ; 221: 106940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702032

RESUMO

Bloodstream infections (BSI) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) are a subject of major clinical concern, mainly those associated with carbapenemase-producing isolates. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed to detect specific ß-lactamases, including KPC. We aimed to detect KPC enzyme directly from positive blood cultures using MALDI-TOF MS. Overall, 146 clinical Gram-negative bacilli (46 CR-GNB) recovered from consecutive blood cultures were evaluated. Proteins were extracted using formic acid, isopropyl alcohol, and water and spotted onto a steel target plate using the double-layer sinapinic acid method. The relative ions intensity ≥120 arbitrary units (a.u.) of a peak close to 28,700 m/z indicated the presence of KPC. The results were compared to HRM-qPCR methodology. This specific peak was observed in 11/14 blood bottles with blaKPC positive isolates (78.6% sensitivity), with 3 false-positive results (97.7% specificity). Analysis from colonies reached identical sensitivity (78.6%), but higher specificity (100%). The detection of KPC peaks directly from positive blood cultures using MALDI-TOF MS is feasible and rapid. It's excellent specificity indicates that positive results are consistently associated with the presence of a KPC producer in positive blood culture.


Assuntos
Proteínas de Bactérias , Hemocultura , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , beta-Lactamases , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Humanos , beta-Lactamases/genética , Hemocultura/métodos , Proteínas de Bactérias/genética , Sensibilidade e Especificidade , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/genética , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/sangue , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia
20.
Sci Total Environ ; 931: 172873, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38692330

RESUMO

Carbapenem resistance's global proliferation poses a significant public health challenge. The primary resistance mechanism is carbapenemase production. In this study, we discovered a novel carbapenemase, RATA, located on the chromosome of Riemerella anatipestifer isolates. This enzyme shares ≤52 % amino acid sequence identity with other known ß-lactamases. Antimicrobial susceptibility tests and kinetic assays demonstrated that RATA could hydrolyze not only penicillins and extended-spectrum cephalosporins but also monobactams, cephamycins, and carbapenems. Furthermore, its activity was readily inhibited by ß-lactamase inhibitors. Bioinformatic analysis revealed 46 blaRATA-like genes encoding 27 variants in the NCBI database, involving 21 different species, including pathogens, host-associated bacteria, and environmental isolates. Notably, blaRATA-positive strains were globally distributed and primarily collected from marine environments. Concurrently, taxonomic analysis and GC content analysis indicated that blaRATA orthologue genes were predominantly located on the chromosomes of Flavobacteriaceae and shared a similar GC content as Flavobacteriaceae. Although no explicit mobile genetic elements were identified by genetic environment analysis, blaRATA-2 possessed the ability of horizontal transfer in R. anatipestifer via natural transformation. This work's data suggest that RATA is a new chromosome-encoded class A carbapenemase, and Flavobacteriaceae from marine environments could be the primary reservoir of the blaRATA gene.


Assuntos
Proteínas de Bactérias , beta-Lactamases , beta-Lactamases/genética , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Carbapenêmicos/farmacologia
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