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1.
Eur Rev Med Pharmacol Sci ; 28(4): 1272-1281, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436160

RESUMO

OBJECTIVE: Recently, Klebsiella pneumoniae strains causing bacteremia and showing significant antibiotic resistance have raised serious health concerns. Especially carbapenem-resistant K. pneumoniae has spread worldwide and caused an increase in mortality rates. In this study, we aimed to present information about KPC-2 carriage and molecular characteristics of K. pneumoniae strains showing multiple antibiotic resistance among patients in our hospital. PATIENTS AND METHODS: Blood samples were collected from patients hospitalized in the intensive care units (ICU) of Van Regional Training and Research Hospital between 2020-2021. Culture, biochemical tests, antibiotic susceptibility tests, and molecular tests were performed to identify K. pneumoniae strains isolated from blood culture samples. RESULTS: Two hundred and sixteen K. pneumoniae were isolated from patients with positive blood cultures. Twenty-seven of these isolates showed multidrug resistance. Carbapenem, ß-lactam, and quinolone resistance were particularly high. On the contrary, almost all of these isolates were susceptible to Amikacin (AK), Gentamicin (CN), Colistin (CT) and Tigecycline (TGC). Molecular analysis revealed that all of these isolates were KPC-2-positive and ST11 variants. CONCLUSIONS: It was observed that KPC-2- positive K. pneumoniae strains with multi-drug resistance may pose a serious risk in patients hospitalized in ICU in our hospital. It was concluded that surveillance and personnel training regarding the hospital and community-acquired infections due to these isolates that show pandemic spread would be important.


Assuntos
Hemocultura , Klebsiella pneumoniae , Humanos , Turquia/epidemiologia , Klebsiella pneumoniae/genética , Carbapenêmicos , Resistência Microbiana a Medicamentos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38468632

RESUMO

Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis. Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360-57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112-65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037-1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006-1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%). Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient's condition more seriously and significantly increases the risk of death.


Assuntos
Infecções por Klebsiella , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Klebsiella pneumoniae , Estudos Retrospectivos , Estudos de Casos e Controles , Antibacterianos/uso terapêutico , Klebsiella , Prognóstico , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonia/tratamento farmacológico , Fatores de Risco , Farmacorresistência Bacteriana
3.
Mol Genet Genomics ; 299(1): 29, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472486

RESUMO

Pseudomonas aeruginosa (PA) is an important opportunistic pathogen that causes different infections on immunocompromised patients. Within PA accessory genome, differences in virulence, antibiotic resistance and biofilm formation have been described between strains, leading to the emergence of multidrug-resistant strains. The genome sequences of 17 strains isolated from patients with healthcare-associated infections in a Mexican hospital were genomically and phylogenetically analyzed and antibiotic resistance genes, virulence genes, and biofilm formation genes were detected. Fifteen of the 17 strains were resistant to at least two of the carbapenems meropenem, imipenem, and the monobactam aztreonam. The antibiotic resistance (mexA, mexB, and oprM) and the biofilm formation (pslA and pslD) genes were detected in all strains. Differences were found between strains in accessory genome size. The strains had different sequence types, and seven strains had sequence types associated with global high risk epidemic PA clones. All strains were represented in two groups among PA global strains. In the 17 strains, horizontally acquired resistance genes to aminoglycosides and beta-lactams were found, mainly, and between 230 and 240 genes that encode virulence factors. The strains under study were variable in terms of their accessory genome, antibiotic resistance, and virulence genes. With these characteristics, we provide information about the genomic diversity of clinically relevant PA strains.


Assuntos
Carbapenêmicos , Infecções por Pseudomonas , Humanos , Aztreonam , Pseudomonas aeruginosa/genética , Antibacterianos , Hospitais , Genômica , Atenção à Saúde , Testes de Sensibilidade Microbiana
4.
Sci Rep ; 14(1): 5215, 2024 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433246

RESUMO

Tigecycline has been regarded as one of the most important last-resort antibiotics for the treatment of infections caused by extensively drug-resistant (XDR) bacteria, particularly carbapenem- and colistin-resistant Klebsiella pneumoniae (C-C-RKP). However, reports on tigecycline resistance have been growing. Overall, ~ 4000 K. pneumoniae clinical isolates were collected over a five-year period (2017-2021), in which 240 isolates of C-C-RKP were investigated. Most of these isolates (91.7%) were resistant to tigecycline. Notably, a high-risk clone of ST16 was predominantly identified, which was associated with the co-harboring of blaNDM-1 and blaOXA-232 genes. Their major mechanism of tigecycline resistance was the overexpression of efflux pump acrB gene and its regulator RamA, which was caused by mutations in RamR (M184V, Y59C, I141T, A28T, C99/C100 insertion), in RamR binding site (PI) of ramA gene (C139T), in MarR (S82G), and/or in AcrR (L154R, R13Q). Interestingly, four isolates of ST147 carried the mutated tet(A) efflux pump gene. To our knowledge, this is the first report on the prevalence and mechanisms of tigecycline resistance in C-C-RKP isolated from Thailand. The high incidence of tigecycline resistance observed among C-C-RKP in this study reflects an ongoing evolution of XDR bacteria against the last-resort antibiotics, which demands urgent action.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Colistina , Tigeciclina/farmacologia , Colistina/farmacologia , Klebsiella pneumoniae/genética , Tailândia/epidemiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia
5.
Microbiologyopen ; 13(2): e1403, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38488803

RESUMO

This study investigates extended-spectrum beta-lactamase-producing and carbapenem-resistant Escherichia coli isolates from Sydney's wastewater. These isolates exhibit resistance to critical antibiotics and harbor novel resistance mechanisms. The findings highlight the importance of wastewater-based surveillance in monitoring resistance beyond the clinical setting.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Escherichia coli , Humanos , Águas Residuárias , beta-Lactamases/genética , Escherichia coli/genética , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Testes de Sensibilidade Microbiana , Carbapenêmicos/farmacologia , Genômica
6.
Antonie Van Leeuwenhoek ; 117(1): 57, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491220

RESUMO

Carbapenem resistant Klebsiella pneumoniae causing severe infection resulting in morbidity and mortality have become a global health concern. K. pneumoniae with sequence type ST147 is an international high-risk clonal lineage, genomic studies have been done on K. pneumoniae ST147 isolated from clinical origin but genomic data for environmental K. pneumoniae ST147 is very scarce. Herein, K. pneumoniae IITR008, an extensively drug resistant and potentially hypervirulent bacterium, was isolated from Triveni Sangam, the confluence of three rivers where religious congregations are organized. Phenotypic, genomic and comparative genomic analysis of strain IITR008 was performed. Antibiotic susceptibility profiling revealed resistance to 9 different classes of antibiotics including ß-lactams, ß-lactam combination agents, carbapenem, aminoglycoside, macrolide, quinolones, cephams, phenicol, and folate pathway antagonists and was found to be susceptible to only tetracycline. The strain IITR008 possesses hypervirulence genes namely, iutA and iroN in addition to numerous virulence factors coding for adherence, regulation, iron uptake, secretion system and toxin. Both the IITR008 chromosome and plasmid pIITR008_75 possess a plethora of clinically relevant antibiotic-resistant genes (ARGs) including blaCTX-M-15, blaTEM-1, and blaSHV-11, corroborating the phenotypic resistance. Comparative genomic analysis with other ST147 K. pneumoniae provided insights on the phylogenetic clustering of IITR008 with a clinical strain isolated from a patient in Czech with recent travel history in India and other clinical strains isolated from India and Pakistan. According to the 'One Health' perspective, surveillance of antibiotic resistance in the environment is crucial to impede its accelerated development in diverse ecological niches.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Filogenia , Rios , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Plasmídeos , Genômica , Ferro , Água , beta-Lactamases/genética , Testes de Sensibilidade Microbiana
7.
Sci Rep ; 14(1): 6538, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503805

RESUMO

Klebsiella aerogenes is an emergent pathogen associated with outbreaks of carbapenem-resistant strains. To date, studies focusing on K. aerogenes have been small-scale and/or geographically restricted. Here, we analyzed the epidemiology, resistome, virulome, and plasmidome of this species based on 561 genomes, spanning all continents. Furthermore, we sequenced four new strains from Brazil (mostly from the Amazon region). Dozens of STs occur worldwide, but the pandemic clones ST93 and ST4 have prevailed in several countries. Almost all genomes were clinical, however, most of them did not carry ESBL or carbapenemases, instead, they carried chromosomal alterations (omp36, ampD, ampG, ampR) associated with resistance to ß-lactams. Integrons were also identified, presenting gene cassettes not yet reported in this species (blaIMP, blaVIM, blaGES). Considering the virulence loci, the yersiniabactin and colibactin operons were found in the ICEKp10 element, which is disseminated in genomes of several STs, as well as an incomplete salmochelin cluster. In contrast, the aerobactin hypervirulence trait was observed only in one ST432 genome. Plasmids were common, mainly from the ColRNAI replicon, with some carrying resistance genes (mcr, blaTEM, blaNDM, blaIMP, blaKPC, blaVIM) and virulence genes (EAST1, senB). Interestingly, 172 genomes of different STs presented putative plasmids containing the colicin gene.


Assuntos
Enterobacter aerogenes , Infecções por Klebsiella , Humanos , Enterobacter aerogenes/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Carbapenêmicos , Plasmídeos/genética , beta-Lactamas , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológico , Testes de Sensibilidade Microbiana
8.
Antimicrob Resist Infect Control ; 13(1): 28, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433212

RESUMO

BACKGROUND: Aeromonas hydrophila infections can cause gastrointestinal symptoms such as diarrhea; however, deep infections are rarely reported. Outbreaks of A. hydrophila are reported more frequently in fish, poultry, and snakes than in humans. This study aimed to track clonal relatedness of deep infections caused by A. hydrophila using whole genome sequencing (WGS). METHODS: We collected three isolates of A. hydrophila in July 19 to August 29, 2019, from patients that underwent spine surgery. Accurate species identification was performed using whole-genome average nucleotide identity (ANI). Antimicrobial susceptibility testing was performed using a VITEK 2 automated AST-N334 Gram-negative susceptibility card system. Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database and Virulence Factor Database VFanalyzer. RESULTS: All three isolates were identified as A. hydrophila based on ANI and multilocus sequence typing analysis revealed that A. hydrophila belonged to a novel sequence type (ST1172). All three isolates were susceptible to amikacin and levofloxacin; however, they were resistant to piperacillin/tazobactam, ceftriaxone, cefuroxime, cefoxitin, and imipenem. Isolate 19W05620 (patient 3) showed increased ceftazidime resistance (minimum inhibitory concentration ≥ 64 µg/mL). All three isolates possessed the same chromosomally encoded ß-lactamases, including blaOXA-724 (ß-lactamase), imiH (metallo-ß-lactamase), and blaMOX-13 (AmpC) in plasmids. CONCLUSIONS: Our study validated the transmission of a novel carbapenem-resistant A. hydrophila sequence type (ST1172) in patients that underwent spine surgery. Control measures should be developed to prevent dissemination of A. hydrophila in the hospital setting.


Assuntos
Aeromonas hydrophila , Anti-Infecciosos , Animais , Humanos , Aeromonas hydrophila/genética , Amicacina , Carbapenêmicos , beta-Lactamases
9.
Ann Med ; 56(1): 2314236, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38442299

RESUMO

BACKGROUND: The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients. METHODS: This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023. RESULTS: A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization. CONCLUSION: Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.


Assuntos
Doença Hepática Terminal , Transplante de Órgãos , Adulto , Humanos , Índice de Gravidade de Doença , Bactérias Gram-Negativas , Carbapenêmicos/uso terapêutico , Transplante de Órgãos/efeitos adversos , Estudos Observacionais como Assunto
10.
Biol Res ; 57(1): 7, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475927

RESUMO

BACKGROUND: The convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide. Here, within the carbapenemase production Enterobacterales surveillance system headed by the Chilean Public Health Institute, we describe the isolation in Chile of a high-risk ST23 dual-carbapenemase-producing hvKp strain, which carbapenemase genes are encoded in a single conjugative plasmid. RESULTS: Phenotypic and molecular tests of this strain revealed an extensive resistance to at least 15 antibiotic classes and the production of KPC-2 and VIM-1 carbapenemases. Unexpectedly, this isolate lacked hypermucoviscosity, challenging this commonly used hvKp identification criteria. Complete genome sequencing and analysis confirmed the K1 capsular type, the KpVP-1 virulence plasmid, and the GIE492 and ICEKp10 genomic islands carrying virulence factors strongly associated with hvKp. Although this isolate belonged to the globally disseminated hvKp clonal group CG23-I, it is unique, as it formed a clade apart from a previously reported Chilean ST23 hvKp isolate and acquired an IncN KPC-2 plasmid highly disseminated in South America (absent in other hvKp genomes), but now including a class-I integron carrying blaVIM-1 and other resistance genes. Notably, this isolate was able to conjugate the double carbapenemase plasmid to an E. coli recipient, conferring resistance to 1st -5th generation cephalosporins (including combinations with beta-lactamase inhibitors), penicillins, monobactams, and carbapenems. CONCLUSIONS: We reported the isolation in Chile of high-risk carbapenem-resistant hvKp carrying a highly transmissible conjugative plasmid encoding KPC-2 and VIM-1 carbapenemases, conferring resistance to most beta-lactams. Furthermore, the lack of hypermucoviscosity argues against this trait as a reliable hvKp marker. These findings highlight the rapid evolution towards multi-drug resistance of hvKp in Chile and globally, as well as the importance of conjugative plasmids and other mobile genetic elements in this convergence. In this regard, genomic approaches provide valuable support to monitor and obtain essential information on these priority pathogens and mobile elements.


Assuntos
Proteínas de Bactérias , Infecções por Klebsiella , Klebsiella pneumoniae , beta-Lactamases , Humanos , Klebsiella pneumoniae/genética , Chile , Escherichia coli , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Plasmídeos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia
11.
BMC Infect Dis ; 24(1): 161, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317132

RESUMO

BACKGROUND: Bloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP. METHODS: Electronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis. RESULTS: Following the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62-2.97, P = 0.45, Tau2 = 0.00, I2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27-2.45, P = 0.71, Tau2 = 0.00, I2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34-7.04, P = 0.008, Tau2 = 0.00, I2 = 0%) and 0.98 (95%CI = 0.29-3.31, P = 0.98, Tau2 = 0.00, I2 = 0% ), respectively. CONCLUSIONS: Colistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects. TRIAL REGISTRATION: retrospectively registered.


Assuntos
Infecções por Klebsiella , Sepse , Humanos , Colistina/uso terapêutico , Antibacterianos/uso terapêutico , Tigeciclina/uso terapêutico , Klebsiella pneumoniae , Carbapenêmicos/uso terapêutico , Sepse/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Testes de Sensibilidade Microbiana
12.
Sci Rep ; 14(1): 3022, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321071

RESUMO

The numbers of infections caused by Gram-negative bacteria (GNB) that produce extended-spectrum beta-lactamases (ESBLs) and those that are carbapenem resistant, especially Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are increasing, and these infections are becoming a global public health problem. The aim of this study was to assess the prevalence of infections caused by ESBL-producing and carbapenem-resistant Gram-negative bacilli in patients hospitalized at An-Najah National University Hospital in Nablus, Palestine, and to provide healthcare workers with valuable information on the treatment of these infections. A retrospective cross-sectional investigation was conducted at a large tertiary care teaching hospital. The study included patients admitted to the hospital between January and December 2021, from whom ESBL-producing and carbapenem-resistant Gram-negative bacilli were isolated. The patients' clinical and demographic information was obtained from the hospital information system. In addition, information regarding the bacterial isolates and antibiotic resistance was obtained from the hospital's microbiology laboratory. This study included a total of 188 patients-91 males (48.4%) and 97 females (51.6%). The general surgical ward accounted for the highest proportion of infections (30.9%), followed by the surgical ICU (12.2%). The most common infections were caused by ESBL-producing E. coli, which accounted for 62.8% of the cases. Among them, urinary tract infections caused by this microorganism were the most prevalent (44.7% of patients). Over 50% of the patients (54.2%) had a history of antibiotic use, and 77.8% had been hospitalized within the past three months. ESBL-producing E. coli was significantly isolated from blood cultures (p-value = 0.000), and CR-K. pneumoniae was significantly isolated from endotracheal isolates (p-value = 0.001). This study emphasizes the concerning frequency of healthcare-acquired infections caused by ESBL-producing and carbapenem-resistant GNB in a tertiary care hospital. The substantial prevalence of antibiotic resistance presents considerable obstacles to the successful administration of routinely employed antibiotics. The results highlight the immediate need for improved antimicrobial stewardship and the implementation of infection control strategies to reduce the effects of multidrug-resistant GNB on patient well-being and public health.


Assuntos
Escherichia coli , beta-Lactamases , Masculino , Feminino , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária , Estudos Transversais , beta-Lactamases/farmacologia , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae , Atenção à Saúde , Testes de Sensibilidade Microbiana
13.
BMC Microbiol ; 24(1): 67, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413891

RESUMO

BACKGROUND: Carbapenems represent the first line treatment of serious infections caused by drug-resistant Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) is one of the urgent threats to human health worldwide. The current study aims to evaluate the carbapenemase inhibitory potential of coumarin and to test its ability to restore meropenem activity against CRKP. Disk diffusion method was used to test the antimicrobial susceptibility of K. pneumoniae clinical isolates to various antibiotics. Carbapenemase genes (NDM-1, VIM-2, and OXA-9) were detected using PCR. The effect of sub-MIC of coumarin on CRKP isolates was performed using combined disk assay, enzyme inhibition assay, and checkerboard assay. In addition, qRT-PCR was used to estimate the coumarin effect on expression of carbapenemase genes. Molecular docking was used to confirm the interaction between coumarin and binding sites within three carbapenemases. RESULTS: K. pneumoniae clinical isolates were found to be multi-drug resistant and showed high resistance to meropenem. All bacterial isolates harbor at least one carbapenemase-encoding gene. Coumarin significantly inhibited carbapenemases in the crude periplasmic extract of CRKP. The checkerboard assay indicated that coumarin-meropenem combination was synergistic exhibiting a fractional inhibitory concentration index ≤ 0.5. In addition, qRT-PCR results revealed that coumarin significantly decreased carbapenemase-genes expression. Molecular docking revealed that the binding energies of coumarin to NDM1, VIM-2, OXA-48 and OXA-9 showed a free binding energy of -7.8757, -7.1532, -6.2064 and - 7.4331 Kcal/mol, respectively. CONCLUSION: Coumarin rendered CRKP sensitive to meropenem as evidenced by its inhibitory action on hydrolytic activity and expression of carbapenemases. The current findings suggest that coumarin could be a possible solution to overcome carbapenems resistance in CRKP.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Meropeném/farmacologia , Simulação de Acoplamento Molecular , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Cumarínicos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/tratamento farmacológico
14.
Sci Rep ; 14(1): 2749, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302510

RESUMO

The emergence and dissemination of carbapenem-resistant species of Acinetobacter and Pseudomonas have become a serious health concern. Routine antimicrobial disk susceptibility tests in clinical laboratories cannot distinguish between isolates that are highly carbapenem-resistant and those that are moderately carbapenem-resistant. The present study describes antimicrobial susceptibility tests using disks containing high doses (1000 µg) of meropenem. The diameters of inhibition zones were significantly negatively correlated with the MICs of Pseudomonas and Acinetobacter species for meropenem (R2: 0.93 and 0.91, respectively) and imipenem (R2: 0.75 and 0.84, respectively). Double disk synergy tests using clavulanic acid or sodium mercaptoacetate can detect ESBL or MBL producers. Susceptibility tests using disks containing high doses of meropenem can easily detect highly carbapenem-resistant isolates in a quantitative manner. These disks may be useful in bacteriological laboratories because of their technical ease, stability, and relatively low cost.


Assuntos
Acinetobacter , Anti-Infecciosos , Meropeném/farmacologia , Pseudomonas , Tienamicinas/farmacologia , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , beta-Lactamases
15.
Sci Total Environ ; 920: 170635, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340846

RESUMO

Considerable attention is given to intensive care unit-acquired infections; however, research on the transmission dynamics of multichain carbapenemase-resistant Enterobacter cloacae complex (CRECC) outbreaks remains elusive. A total of 118 non-duplicated CRECC strains were isolated from the clinical, intestinal, and hospital sewage samples collected from Zhejiang province of China during 2022-2023. A total of 64 CRECC strains were isolated from the hospital sewage samples, and their prevalence increased from 10.0 % (95 % confidence interval, CI = 0.52-45.8 %) in 2022 to 63.6 % (95 % CI = 31.6-87.6 %) in 2023. Species-specific identification revealed that Enterobacter hormaechei was the predominant CRECC species isolated in this study (53.4 %, 95 % CI = 44.0-62.6 %). The antimicrobial susceptibility profiles indicated that all 118 CRECC strains conferred high-level resistance to ß-lactam antibiotics, ceftacillin/avibactam, and polymyxin. Furthermore, all CRECC strains exhibited resistance to ß-lactams, quinolones, and fosfomycin, with a higher colistin resistance rate observed in the hospital sewage samples (67.2 %, 95 % CI = 54.2-78.1 %). Several antibiotic resistance genes were identified in CRECC strains, including Class A carbapenemases (blaKPC-2) and Class B carbapenemases (blaNDM-1/blaIMP), but not Class D carbapenemases. The WGS analysis showed that the majority of the CRECC strains carried carbapenemase-encoding genes, with blaNDM-1 being the most prevalent (86.9 %, 95 % CI = 77.4-92.9 %). Furthermore, sequence typing revealed that the isolated CRECC strains belonged to diverse sequence types (STs), among which ST418 was the most prevalent blaNDM-positive strain. The high risk of carbapenemase-producing ST418 E. hormaechei and the blaNDM-harboring IncFIB-type plasmid (81.4 %, 95 % CI = 72.9-87.7 %) were detected and emphasized in this study. This study provides valuable insights into the prevalence, antimicrobial resistance, genomic characteristics, and plasmid analysis of CRECC strains in diverse populations and environments. The clonal relatedness analysis showed sporadic clonal transmission of ST418 E. hormaechei strains, supporting inter-hospital transmission.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Enterobacter cloacae , Enterobacter cloacae/genética , Carbapenêmicos/farmacologia , Esgotos , Proteínas de Bactérias/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Plasmídeos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , China/epidemiologia , Testes de Sensibilidade Microbiana
16.
J Med Chem ; 67(5): 3795-3812, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38373290

RESUMO

Antimicrobial resistance is a global public health threat. Metallo-ß-lactamases (MBLs) inactivate ß-lactam antibiotics, including carbapenems, are disseminating among Gram-negative bacteria, and lack clinically useful inhibitors. The evolving bisthiazolidine (BTZ) scaffold inhibits all three MBL subclasses (B1-B3). We report design, synthesis, and evaluation of BTZ analogues. Structure-activity relationships identified the BTZ thiol as essential, while carboxylate is replaceable, with its removal enhancing potency by facilitating hydrophobic interactions within the MBL active site. While the introduction of a flexible aromatic ring is neutral or detrimental for inhibition, a rigid (fused) ring generated nM benzobisheterocycle (BBH) inhibitors that potentiated carbapenems against MBL-producing strains. Crystallography of BBH:MBL complexes identified hydrophobic interactions as the basis of potency toward B1 MBLs. These data underscore BTZs as versatile, potent broad-spectrum MBL inhibitors (with activity extending to enzymes refractory to other inhibitors) and provide a rational approach to further improve the tricyclic BBH scaffold.


Assuntos
Antibacterianos , Inibidores de beta-Lactamases , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , Antibacterianos/farmacologia , Antibacterianos/química , beta-Lactamases/química , Carbapenêmicos , Bactérias Gram-Negativas
17.
Infect Dis (Lond) ; 56(4): 320-329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38317598

RESUMO

BACKGROUND: Nosocomial infections (NIs) are the most frequent adverse events among patients and cause a heavy burden on both health and economics. To investigate epidemiology of NIs and identify risk factors for NIs by integrating continuous long-term surveillance data. METHODS: We performed an observational study among inpatients at the Chinese People's Liberation Army General Hospital between January 1, 2010, and December 31, 2019. Infection rates, mortality rates and percentage of NIs were calculated. Trends of yearly infection rates by pathogens were assessed using Mann-Kendall trend test. Controls were matched to cases (2:1) by age (±2 years), sex, admission date (±1 year) and admission diagnosis, and conditional logistic regression was used to estimate odds ratios. RESULTS: A total of 1,534,713 inpatients were included among which 33,468 NIs cases occurred with an infection rate of 2.18%. The most common infections were respiratory system infection (52.22%), bloodstream infection (17.60%), and genitourinary system infection (15.62%). Acinetobacter. baumannii (9.6%), Klebsiella. pneumoniae (9.0%), Pseudomonas. aeruginosa (8.6%), Escherichia. coli (8.6%) and Enterococcus. faecium (5.0%) were the top five isolated pathogens. Infection rates of K. pneumoniae and carbapenems-resistant K. pneumoniae significantly increased. Prior ICU stay, surgery, any device placement (including central venous catheter, mechanical ventilation, urinary catheter, and tracheotomy), prior use of triple or more antibiotics combinations, carbapenem, and ß-Lactamase inhibitors were significantly associated with NIs. CONCLUSION: K. pneumoniae has the potential to cause a clinical crisis with increasing infection rates and carbapenem resistance. Clinical management of invasive operations and antibiotics use should be further strengthened.


Assuntos
Infecção Hospitalar , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana , Escherichia coli , Klebsiella pneumoniae , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária
18.
BMC Infect Dis ; 24(1): 235, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383425

RESUMO

BACKGROUND: With the global increase in the older population, the proportion of those receiving care in long-term care facilities (LTCFs) has also been increasing. We assessed the epidemiology, antibiotic susceptibility, and colonization status of drug-resistant organisms in patients transferred from LTCFs. METHODS: We retrospectively reviewed the medical records of patients transferred from LTCFs between 2017 and 2022. The reasons for admission, antimicrobial susceptibility, and colonization rates of carbapenem-resistant Enterobacterales (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Acinetobacter baumannii (CRAB) were recorded. We analyzed the susceptibility and colonization rates by year to identify trends. RESULTS: Of the 936 patients transferred from LTCFs, 54.3% were admitted to the intensive care unit and 12.5% died. The most common reason for admission was infection (n = 573, 61.2%), followed by gastrointestinal bleeding (n = 67, 7.2%) and cerebrovascular disorder (n = 65, 6.9%). A total of 452 Enterobacterales strains were isolated, and their susceptibility rates to ciprofloxacin and cefotaxime were 33.3% and 35.6%, respectively. A total of 54.9% were extended-spectrum beta-lactamase-producing strains, and 4.9% of them were carbapenem-resistant, both of which showed an increasing trend (P = 0.024 and P < 0.001, respectively). The prevalence rates of CRE, CRAB, and MRSA colonization were 9.2%, 7.1%, and 23.1%, respectively. CRE colonization showed a significant increase (P < 0.001), with carbapenemase-producing Enterobacterales accounting for 75.9% of cases. CONCLUSIONS: Patients transferred from LTCFs are primarily affected by infections and exhibit high resistance rates. The increasing trend in CRE colonization rates each year highlights the need for the implementation of rigorous infection control measures for effective management.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Humanos , Estudos Transversais , Estudos Retrospectivos , Assistência de Longa Duração , Farmacorresistência Bacteriana Múltipla , Carbapenêmicos/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
19.
Ann Clin Microbiol Antimicrob ; 23(1): 19, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402160

RESUMO

OBJECTIVE: In our study, K. pneumoniae strains (non-susceptible to carbapenem) (n = 60) were obtained from various clinical samples from Rize State Hospital between 2015 and 2017 and it is aimed to identify antibiotic resistance genes and replicon typing. METHODS: Antibiotic susceptibility tests of the strains were performed with Kirby-Bauer disk diffusion test and the Vitek-2 automated system (BioMerieux, France). Antibiotic resistance genes and replicon typing was characterized by PCR method. RESULTS: It was determined that K. pneumaniae isolates were mostly isolated from the samples of the intensive care unit. All of the K. pneumoniae strains examined in this study were found to be ampicillin/sulbactam and ertapenem resistant but colistin susceptible. Amoxacillin/clavulonic acid resistance was detected at 98.14% of strains. The blaOXA-48 gene was mostly detected in isolates. The most common type of plasmid was I1 and 3 different plasmid types were found in five different strains together. CONCLUSION: This study also shows that the distribution of NDM-1 and OXA-48 carbapenemases has increased since the first co-display in Türkiye and that IncHI1 is the first record in our country. This study provides an overview of the major plasmid families occurring in multiple antibiotic-resistant strains of K. pneumoniae. To our knowledge, this study represents the first report of IncHI1 record in Türkiye.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Replicon
20.
BMC Microbiol ; 24(1): 65, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402189

RESUMO

BACKGROUND: Camels harbouring multidrug-resistant Gram-negative bacteria are capable of transmitting various microorganisms to humans. This study aimed to determine the distribution of anti-microbial resistance among Escherichia coli (E. coli) isolated from the feces of apparently healthy camels in Egyptian abattoirs. Additionally, we sought to characterize Shiga toxin-producing E. coli (STEC) strains, assess their virulence potential, and investigate the possibility of camels spreading carbapenem- and colistin-resistant E. coli. METHODS: 121 fecal swaps were collected from camels in different abattoirs in Egypt. Isolation and identification of E. coli were performed using conventional culture techniques and biochemical identification. All isolates obtained from the examined samples underwent genotyping through polymerase chain reaction (PCR) of the Shiga toxin-encoding genes (Stx1 and Stx2), the carbapenemase-encoding genes (blaKPC, blaOXA-48, blaNDM, and blaVIM), and the mcr genes for mcr-1 to mcr-5. RESULT: Bacteriological examination revealed 75 E. coli isolates. PCR results revealed that one strain (1.3%) tested positive for Stx1, and five (6.6%) were positive for Stx2. Among the total 75 strains of E. coli, the overall prevalence of carbapenemase-producing E. coli was 27, with 7 carrying blaOXA48, 14 carrying blaNDM, and 6 carrying blaVIM. Notably, no strains were positive for blaKPC but a high prevalence rate of mcr genes were detected. mcr-1, mcr-2, mcr-3, and mcr-4 genes were detected among 3, 2, 21, and 3 strains, respectively. CONCLUSION: The results indicate that camels in Egypt may be a primary source of anti-microbial resistance (AMR) E. coli, which could potentially be transmitted directly to humans or through the food chain.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli Shiga Toxigênica , Humanos , Animais , Colistina/farmacologia , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Camelus , beta-Lactamases/genética , Infecções por Escherichia coli/microbiologia , Escherichia coli Shiga Toxigênica/genética , Toxinas Shiga/genética , Proteínas de Escherichia coli/genética , Testes de Sensibilidade Microbiana , Plasmídeos
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