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1.
Microb Drug Resist ; 29(1): 28-33, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36656990

RESUMO

Objectives: This study reported a fatal stent-associated respiratory tract infection (SARTI) caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Case: A bare-metal stent in the left main bronchus and a Y-shaped stent graft in the tracheal bronchus were placed successively in a 50-year-old woman due to shortness of breath after undergoing multiple chemotherapy treatments for lung cancer. Unfortunately, the followed SARTI and lung abscess in our patient caused by CR-hvKP eventually led to the death of the patient, despite our aggressive clearing of phlegm and potent antibiotics. The genomic analysis showed it was caused by a KPC-2-producing extensively drug-resistant K64-ST11 hypervirulent K. pneumoniae harboring several virulence and antimicrobial resistance genes. Conclusion: This study highlights the risk of SARTI caused by CR-hvKP in immunocompromised individuals.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Infecções Respiratórias , Feminino , Humanos , Pessoa de Meia-Idade , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Antibacterianos/farmacologia , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológico , Testes de Sensibilidade Microbiana , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecções Respiratórias/tratamento farmacológico , Stents/efeitos adversos
2.
Genome Med ; 15(1): 3, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658655

RESUMO

BACKGROUND: Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden  in other geographical regions. METHODS: Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. RESULTS: We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. CONCLUSIONS: Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.


Assuntos
Carbapenêmicos , Infecções por Klebsiella , Humanos , Carbapenêmicos/farmacologia , Klebsiella pneumoniae , Virulência/genética , Plasmídeos/genética , beta-Lactamases/genética , Genômica , Antibacterianos/farmacologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia
3.
Antimicrob Agents Chemother ; 67(1): e0135422, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36602346

RESUMO

The carbapenem-resistant Klebsiella pneumoniae (CRKP) strain GX34 was recovered from the respiratory tract of an elderly male with severe pneumonia, and only susceptible to amikacin, tigecycline, and colistin. Complete genome suggested that it belonged to K51-ST16 and harbored plasmid-encoded NDM-4 and OXA-181, located on IncFIB plasmid GX34p1_NDM-4 and ColKP3/IncX3 plasmid GX34p4_OXA-181, respectively. A series of transconjugants generated in the plasmid conjugation assays, including Escherichia coli J53-N1 (harboring a self-transmissible and blaNDM-1-producing plasmid Eco-N-1-p), J53-N2 (harboring a blaNDM-4-producing plasmid and a helper plasmid GX34p5), and J53-O (harboring a blaOXA-181-producing plasmid), could be stably inherited after 10 days of serial passage and no significant biological fitness costs were detected. Furthermore, we first reported the blaNDM-1 gene, derived from blaNDM-4 mutation (460C>A) under meropenem pressure, could be in vitro transferred into a self-conjugative, recombined plasmid Eco-N-1-p of J53-N1. Eco-N-1-p was mainly recombined by GX34p4_OXA-181 (40,449 bp, 75.16%) and GX34p1_NDM-4 (8,553 bp, 15.89%), in which IS26 and IS5-like probably played a major role. Eco-N-1-p could be transferred into the conjugation recipient K. pneumoniae KP54 and make the latter sacrifice fitness. The retention rates of blaNDM-1 remained high stability (>80% after 200 generations). The comparative genomic analysis of GX34 and those carrying blaNDM-4 or blaOXA-181 genes retrieved from the NCBI RefSeq database showed all blaNDM-4 (26/26, 100.00%) and blaOXA-181 (13/13, 100.00%) were surrounded by IS26. The immediate environment of blaNDM-4 and blaOXA-181 in GX34 and some retrieved strains shared identical features, hinting at their possible dissemination. Effective measures should be taken to monitor the spread of this clone.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Masculino , Idoso , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Elementos de DNA Transponíveis , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Escherichia coli/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética
4.
Pathog Dis ; 812023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36633541

RESUMO

Klebsiella pneumoniae is an opportunistic pathogen associated with biofilm-based infections, which are intrinsically antibiotic resistant. Extracellular DNA plays a crucial role in biofilm formation and self-defence, with nucleases being proposed as promising agents for biofilm disruption. This study evaluated the in vitro and in vivo efficacy of DNase I in improving the activity of cefotaxime, amikacin, and ciprofloxacin against K. pneumoniae biofilms. K. pneumoniae ATCC 700603 and a clinical isolate from catheter-related bloodstream infection were cultured for biofilm formation on microtiter plates, and the antibiofilm activity of the antibiotics (0.03-64 mg/L), with or without bovine pancreatic DNase I (1-32 mg/L) was determined by XTT dye reduction test and viable counting. The effect of ciprofloxacin (2 mg/L) and DNase I (16 mg/L) was further evaluated in vitro on 1-cm-long silicon catheter segments, and in a mouse model of subcutaneous catheter-associated infection. Combination with DNase I did not improve the biofilm-preventive capacity of the three antibiotics or the biofilm-eradicating capacity of cefotaxime and amikacin. The biofilm-eradicating capacity of ciprofloxacin was increased by 8-fold and 4-fold in K. pneumoniae ATCC 700603 and clinical isolate, respectively, with DNase I. The combination therapy caused 99% reduction in biofilm biomass in the mouse model.


Assuntos
Antibacterianos , Klebsiella pneumoniae , Camundongos , Animais , Bovinos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amicacina/farmacologia , Desoxirribonuclease I/farmacologia , Testes de Sensibilidade Microbiana , Ciprofloxacina/farmacologia , Biofilmes , Modelos Animais de Doenças , Cefotaxima/farmacologia
5.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688750

RESUMO

The present study revealed the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and the associated driving factors in an urban river system surrounding Cuttack city, Odisha. The high contamination factor and contamination degree indicate poor water quality. The CRKP isolates showed 100% resistance against piperacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftriaxone, ceftazidime, meropenem, and imipenem but less resistance to colistin (12.85%). Among the CRKP isolates, carbapenemase genes blaNDM, blaOXA-48-like, and blaKPC were detected in 94.28%, 35%, and 10% of isolates, respectively. The resistance genes (blaNDM, blaTEM, and blaCTX-M) were found to be significantly correlated with toxic metals (As, Cd, Co, Cu, Fe, Mn, Pb) (P < 0.05). Detection of virulence factors (yersiniabactin and aerobactin) and capsular serotypes (K1, K2, and K54 types) explain the pathogenicity of CRKP isolates. Enterobacterial repetitive intergenic consensus-PCR based molecular typing separated the CRKP strains into 13 clusters, of which VI and XI clusters showed similar resistance and virulence determinants, indicating the dissemination of clones from wastewater to the river system. Our results provide first-hand information on assessing risks to public health posed by the CRKP isolates and toxic metals in the Kathajodi River. Molecular surveillance of nearby hospitals for the prevalence of CRKP will help trace their transmission route.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Klebsiella pneumoniae , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Carbapenêmicos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Piperacilina , Rios , Índia
6.
Artigo em Inglês | MEDLINE | ID: mdl-36700602

RESUMO

BACKGROUND: The spread of carbapenemase- and extended-spectrum ß-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of ß-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. METHODS: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The ß-lactamase-encoding genes were investigated using polymerase chain reaction. RESULTS: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-ß-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. CONCLUSIONS: C/A and C/T were active against microorganisms with ß-lactam-resistant phenotypes, except when resistance was mediated by metallo-ß-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more ß-lactamase-encoding genes (62.5% and 77.4%, respectively).


Assuntos
Antibacterianos , Lactamas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil , Hospitais Gerais , Ceftazidima/farmacologia , Cefalosporinas/farmacologia , Tazobactam/farmacologia , Combinação de Medicamentos , Bactérias Gram-Negativas/genética , Pseudomonas aeruginosa , Klebsiella pneumoniae , Carbapenêmicos , beta-Lactamases/genética , Testes de Sensibilidade Microbiana
7.
Ann Clin Microbiol Antimicrob ; 22(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597098

RESUMO

BACKGROUND: Carbapenem resistance is endemic in the Indian sub-continent. In this study, carbapenem resistance rates and the prevalence of different carbapenemases were determined in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa during two periods; Pre-COVID (August to October 2019) and COVID (January to February 2021) in a north-Indian tertiary care hospital. METHODS: Details of patient demographics and clinical condition was collated from the Hospital Information System and detection of carbapenemases NDM, OXA-48, VIM, IMP and KPC was done by Polymerase chain reaction (PCR) in 152 and 138 non-consecutive carbapenem resistant isolates during the two study periods respectively. Conjugation assay and sequencing of NDM and OXA-48 gene was done on a few selected isolates. RESULTS: As compared to Pre-COVID period, co-morbidities and the mortality rates were higher in patients harbouring carbapenem resistant organisms during the COVID period. The overall carbapenem resistance rate for all the four organisms increased from 23 to 41% between the two periods of study; with Pseudomonas aeruginosa and Klebsiella pneumoniae showing significant increase (p < 0.05). OXA-48, NDM and co-expression of NDM and OXA-48 were the most common genotypes detected. NDM-5 and OXA-232 were most common variants of NDM and OXA-48 family respectively during both the study periods. CONCLUSION: Higher rate of carbapenem resistance in COVID times could be attributed to increase in number of patients with co-morbidities. However, genetic elements of carbapenem resistance largely remained the same in the two time periods.


Assuntos
Antibacterianos , COVID-19 , Humanos , Antibacterianos/farmacologia , Centros de Atenção Terciária , COVID-19/epidemiologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , beta-Lactamases/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética
8.
J Coll Physicians Surg Pak ; 33(1): 59-65, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36597237

RESUMO

OBJECTIVE: To determine the frequency of Klebsiella pneumoniae Carbapenemase (blaKPC) and New Delhi Metallo-Beta-Lactamase (blaNDM) resistant genes among clinical isolates of Enterobacterales in a set of Karachi population. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Microbiology, Dr. Ziauddin University Hospital, Karachi, Pakistan, from January 2019 to December 2020. METHODOLOGY: A total of 2100 clinical isolates of Enterobacterales were collected. All isolates of Carbapenem-Resistant Enterobacterales (CRE) (Escherichia coli, Enterobacter and Klebsiella species) on the basis of Meropenem screening test positivity were included in the study. DNA was extracted and PCR was performed for resistant genes detection. Frequencies and percentages were computed for categorical variables and mean values and standard deviation for quantitative variables. RESULTS: Among 2100 isolates of Enterobacterales, the majority were E. coli 1260 (60%), followed by Klebsiella species 462 (22%), and Enterobacter species 210 (10%). The sources of CRE isolates included 34 (25%) from respiratory (tracheal aspirate, pleural fluid, and gastric lavage); 33 (24.26%) urine, 32 (25.53%) pus, 15 (11.03%) blood, and 20 (14.7%) others (ascitic fluid, stents, and tissue). All isolates of CRE were sensitive (100%) to Colistin, Tigecycline and Fosfomycin. Biochemically confirmed CRE 136 (6.5%) isolates, (79 (58%) males and 57 (42%) females), were selected for detecting resistant genes. The PCR showed 32 (23.52%) positive for both NDM and KPC resistant genes, 28 (20.58%) for NDM and 19 (13.97%) for KPC alone. Out of 79 followed up patients, 58 (73.4%) expired while 21 (26.6%) were discharged. CONCLUSION: The frequency of blaNDM and blaKPC resistant genes in CRE isolates depicted increasing trend. Colistin, Fosfomycin, and Tigecycline showed high antimicrobial sensitivities in vitro. Further measures need to be applied for CRE with comprehensive resistant genes detection to curtail antimicrobial resistance. KEY WORDS:  Frequency, KPC, NDM, Klebsiella species, Carbapenemases, Enterobacterales E.coli.


Assuntos
Fosfomicina , Klebsiella pneumoniae , Masculino , Feminino , Humanos , Klebsiella pneumoniae/genética , Colistina , Escherichia coli/genética , Antibacterianos/farmacologia , Tigeciclina , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , Proteínas de Bactérias/genética , Carbapenêmicos
9.
Ann Clin Microbiol Antimicrob ; 22(1): 3, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627626

RESUMO

BACKGROUND: Knowledge about the prevalence, factors and mortality associated with subsequent carbapenem-resistant Enterobacterales (CRE) infection among hematological malignancies (HM) patients colonized with CRE is limited. METHODS: HM patients were screened for rectal CRE. A retrospective case-control study of subsequent CRE infection among HM patients colonized with CRE was conducted between January 1st, 2020 and January 31st, 2022. Cases were defined as CRE colonized patients with subsequent infection and controls were those without infection. Bacterial identification was performed using MALDI Biotyper and antimicrobial susceptibility testing of strains was carried out using the VITEK 2 system or standard broth microdilution method. Logistic analysis was used for analyzing associated factors and Kaplan-Meier method was used for survival estimates. RESULTS: A total of 953 HM patients were screened for rectal CRE and 98 (10.3%, 98/953) patients were colonized with CRE. Among the 98 colonized patients, 18 (18.4%, 18/98) patients developed subsequent infection. Most of the colonizing CRE isolates were Klebsiella pneumoniae (50.0%, 27/54), followed by Escherichia coli (27.8%, 15/54) and Enterobacter cloacae (9.3%, 5/54). As for the subsequent infecting CRE isolates, the dominated species was K. pneumoniae (55.6%, 10/18), followed by E. coli (33.3%, 6/18) and others (11.2%, 2/18). Receiving proton pump inhibitors and admission to ICU (P < 0.05) were the associated factors. Patients with subsequent CRE infection had significant higher mortality (33.3% vs 2.8%, P = 0.001) and shock was an associated factor (P = 0.008). CONCLUSIONS: Klebsiella pneumoniae was the dominate colonizing species and subsequent infecting species among HM patients with CRE colonization. Receiving proton pump inhibitors and admission to ICU increased the risk of subsequent CRE infection among CRE colonized HM patients. Implementing strict infection control measures targeting those high- risk patients may prevent subsequent CRE infection.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Humanos , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Estudos de Casos e Controles , Escherichia coli , Infecções por Enterobacteriaceae/microbiologia , Prevalência , Inibidores da Bomba de Prótons , Klebsiella pneumoniae
10.
Mikrobiyol Bul ; 57(1): 30-44, 2023 Jan.
Artigo em Turco | MEDLINE | ID: mdl-36636844

RESUMO

Klebsiella pneumoniae which is a causative agent of nosocomial infections, is protected from phagocytosis and the lethal effect of serum bactericidal proteins owing to its capsular polysaccharides (CPS). The important leading problem in treating infections caused by this bacterium that successfully develops antimicrobial resistance, especially via mobile genetic elements, is that it acquires beta-lactamase genes, which are responsible for the resistance against beta-lactam antibiotics. Due to the increase in studies targeting capsular polysaccharides in developing strategies for vaccination and treatment, we aimed to investigate the possible relationship of the capsular genotypes of K.pneumoniae isolates obtained from various clinical specimens with antibiotic susceptibility and beta-lactamase genes. In K.pneumoniae clinical isolates; K1, K2, K5, K20, K54 and K57, which are known as hypervirulent capsular types, were investigated by polymerase chain reaction (PCR) method. In isolates whose capsular genotypes were determined, antibiotic susceptibility was examined by Kirby-Bauer disc diffusion method. Colistin resistance was investigated by the broth microdilution method. Carbapenem resistance was confirmed with the carbapenem inactivation test. The beta-lactamase genes blaCTX-M1, blaCTX-M2, blaCTX-M9, blaCTX-M8/25, blaKPC, blaNDM-1, and blaOXA-48-like were investigated by using PCR. Of the 38 K.pneumoniae isolates whose capsular genotypes were determined, 15 (39.5%), 12 (31.6%), seven (18.4%), two (5.3%), one (2.6%) and one (2.6%) were K5-CPS, K2-CPS, K20-CPS, K1-CPS, K54-CPS and K57-CPS genotypes, respectively. blaOXA-48-like, blaNDM-1, and blaCTX-M1 were detected in 68.4, 10.5, and 7.9%, whereas coexistence of blaOXA-48-like with blaNDM-1, and blaOXA-48-like with blaCTX-M1 were determined in 7.9, and 5.3% of the isolates, respectively. The relationship of the blaCTX-M1 gene, detected only in three K20-CPS isolates, was found to be statistically significant with this genotype. In addition, of the blaNDM-1-positive four isolates, three were K5-CPS, and one was K2-CPS, while blaOXA-48-like was similarly detected mostly in K5-CPS and K2-CPS (10 and 9 isolates, respectively). Except for the two isolates that were resistant to colistin, one K1-CPS and the other K5-CPS, the highest resistance was detected against cefotaxime (36/38) and the lowest resistance was detected against gentamicin (23/38) as a result of antibiotic susceptibility tests. The resistance relationship of K5-CPS isolates with amoxicillin/clavulanate, piperacillin/tazobactam, cefoxitin and ertapenem and the susceptibility relationship of K20-CPs isolates with amoxicillin/clavulanate, piperacillin/tazobactam, imipenem, tetracycline and trimethoprim/sulfamethoxazole were found as statistically significant. Our study is the first to investigate the relationship between K.pneumoniae capsular genotypes and beta-lactamase genes in Turkey. As a result, it is believed that this research will contribute to the determination of vaccine and treatment options by providing data to wider and regional studies that will examine other capsule genotypes and antibiotic resistance genes to clarify the importance of the capsule in virulence.


Assuntos
Farmacorresistência Bacteriana , Klebsiella pneumoniae , beta-Lactamases , Amoxicilina/farmacologia , Antibacterianos/farmacologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Ácido Clavulânico/farmacologia , Colistina/farmacologia , Genótipo , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Piperacilina/farmacologia , Tazobactam/farmacologia , Farmacorresistência Bacteriana/genética
11.
Nat Commun ; 14(1): 78, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604442

RESUMO

Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Camundongos , Masculino , Klebsiella pneumoniae , Disbiose , Camundongos Endogâmicos C57BL , Pulmão , Ácidos Graxos Voláteis
12.
Euro Surveill ; 28(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695452

RESUMO

BackgroundSince the beginning of the war in Ukraine in February 2022, Ukrainians have been seeking shelter in other European countries.AimWe aimed to investigate the prevalence and the molecular epidemiology of multidrug-resistant Gram-negative (MDRGN) bacteria and meticillin-resistant Staphylococcus aureus (MRSA) in Ukrainian patients at admittance to the University Hospital Frankfurt, Germany.MethodsWe performed screening and observational analysis of all patients from March until June 2022. Genomes of MDRGN isolates were analysed for antimicrobial resistance, virulence genes and phylogenetic relatedness.ResultsWe included 103 patients (median age: 39 ±â€¯23.7 years), 57 of whom were female (55.3%; 95% confidence interval (CI): 45.2-5.1). Patients were most frequently admitted to the Department of Paediatrics (29/103; 28.2%; 95% CI: 19.7-37.9). We found 34 MDRGN isolates in 17 of 103 patients (16.5%; 95% CI: 9.9-25.1). Ten patients carried 21 carbapenem-resistant (CR) bacteria, five of them more than one CR isolate. Four of six patients with war-related injuries carried eight CR isolates. In six of 10 patients, CR isolates caused infections. Genomic characterisation revealed that the CR isolates harboured at least one carbapenemase gene, bla NDM-1 being the most frequent (n = 10). Core genome and plasmid analysis revealed no epidemiological connection between most of these isolates. Hypervirulence marker genes were found in five of six Klebsiella pneumoniae CR isolates. No MRSA was found.ConclusionHospitals should consider infection control strategies to cover the elevated prevalence of MDRGN bacteria in Ukrainian patients with war-related injuries and/or hospital pre-treatment and to prevent the spread of hypervirulent CR isolates.


Assuntos
Infecções por Klebsiella , Staphylococcus aureus Resistente à Meticilina , Lesões Relacionadas à Guerra , Humanos , Criança , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Filogenia , Lesões Relacionadas à Guerra/tratamento farmacológico , beta-Lactamases/genética , Bactérias , Hospitais Universitários , Alemanha/epidemiologia , Bactérias Gram-Negativas/genética , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológico
13.
Virulence ; 14(1): 233-245, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36529894

RESUMO

Emerging mobile colistin resistance (mcr) genes pose a significant threat to public health for colistin was used as the last resort to treat multidrug-resistant (MDR) pathogenic bacterial infections. Hypervirulent Klebsiella pneumoniae (hvKP) is a clinically significant pathogen resulting in highly invasive infections, often complicated by devastating dissemination. Worryingly, the untreatable and severe infections caused by mcr-harbouring hvKP leave the selection of antibiotics for clinical anti-infective treatment in a dilemma. Herein, we screened 3,461 isolates from a tertiary teaching hospital from November 2018 to March 2021, and an mcr-8.2-harbouring hvKP FAHZZU2591 with a conjugative plasmid was identified from paediatric sepsis. This is the first report of MCR-8-producing hvKP from paediatric sepsis to our best knowledge. The susceptibility, genetic features, and plasmid profiles of the isolate were investigated. Further, we assessed the virulence potential of FAHZZU2591 and verified its pathogenicity and invasive capacity using a mouse model. The phylogenetic analysis of mcr-8-bearing K. pneumoniae revealed that China is the predominant reservoir of the mcr-8 gene, and the clinic is the primary source. Our work highlights the risk for the spread of mcr-positive hvKP in clinical, especially in paediatric sepsis, and the persistent surveillance of colistin-resistance hvKP is urgent.


Assuntos
Infecções por Klebsiella , Sepse , Humanos , Colistina/farmacologia , Klebsiella pneumoniae , Filogenia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Plasmídeos/genética , Genômica , Infecções por Klebsiella/microbiologia
14.
Microb Drug Resist ; 29(1): 34-38, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36576900

RESUMO

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of the recipient microbiota did not mirror the donor stool taxa at either site, but an increase in the relative proportion of the genus Bacteroides as compared with Prevotella was noted in the stool post-transplant. FMTs may be a promising treatment option for recurrent multidrug-resistant infections.


Assuntos
Klebsiella pneumoniae , Infecções Urinárias , Humanos , Klebsiella pneumoniae/genética , Transplante de Microbiota Fecal/efeitos adversos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Infecções Urinárias/tratamento farmacológico , beta-Lactamases/genética , beta-Lactamases/uso terapêutico
15.
Comput Biol Chem ; 102: 107800, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36516617

RESUMO

Antimicrobial peptides (AMPs) are short peptides with a broad spectrum of antimicrobial activity. They play a key role in the host innate immunity of many organisms. The growing threat of microorganisms resistant to antimicrobial agents and the lack of new commercially available antibiotics have made in silico discovery of AMPs increasingly important. Machine learning (ML) has improved the speed and efficiency of AMP discovery while reducing the cost of experimental approaches. Despite various ML platforms developed, there is still a lack of integrative use of ML platforms for AMP discovery from publicly available protein databases. Therefore, our study aims to screen potential AMPs with antibiofilm properties from databases using ML platforms, followed by protein-peptide molecular docking analysis and molecular dynamics (MD) simulations. A total of 5850 peptides classified as non-AMP were screened from UniProtKB and analyzed using various online ML platforms (e.g., CAMPr3, DBAASP, dPABBs, Hemopred, and ToxinPred). Eight potential AMP peptides against Klebsiella pneumoniae with antibiofilm, non-toxic and non-hemolytic properties were then docked to MrkH, a transcriptional regulator of type 3 fimbriae involved in biofilm formation. Five of eight peptides bound more strongly than the native MrkH ligand when analyzed using HADDOCK and HPEPDOCK. Following the docking studies, our MD simulated that a Neuropeptide B (Peptide 3) bind strongly to the MrkH active sites. The discovery of putative AMPs that exceed the binding energies of the native ligand underscores the utility of the combined ML and molecular simulation strategies for discovering novel AMPs with antibiofilm properties.


Assuntos
Peptídeos Antimicrobianos , Klebsiella pneumoniae , Simulação de Acoplamento Molecular , Ligantes , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Peptídeos/metabolismo , Simulação de Dinâmica Molecular
16.
Microb Pathog ; 174: 105906, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36494020

RESUMO

The bacteriophage vB8388 can lyse multi-drug resistant Klebsiella oxytoca strain FK-8388 and maintain stability in a wide range of temperatures (from 4 °C to 80 °C) and pHs (3-11). Bioinformatics analysis showed that vB8388 is a linear double-stranded DNA virus that is 39,750 long with 50.65% G + C content and 44 putative open reading frames (ORFs). Phage vB8388 belongs to the family Autographviridae and possesses a non-contractile tail. The latency period of vB8388 was approximately 20 min. The combination of phage vB8388 and gentamicin, amikacin, or tobramycin could effectively inhibit the growth of K. oxytoca strain FK-8388, with a decrease of more than 4 log units within 12 h in vitro. Phage vB8388 showed a strong synergistic effect with gentamicin that could enhance the anti-biofilm effect of vB8388. The phage + gentamicin combination also showed synergy in vivo in the larval infection model of Galleria mellonella. In conclusion, the findings of this study suggest the potential of phage + antibiotic combination therapy to be used as an alternative therapeutic approach for treating infectious diseases caused by multidrug-resistant bacteria.


Assuntos
Aminoglicosídeos , Bacteriófagos , Animais , Aminoglicosídeos/farmacologia , Bacteriófagos/genética , Klebsiella oxytoca , Antibacterianos/farmacologia , Gentamicinas/farmacologia , Klebsiella pneumoniae
17.
Eur J Med Chem ; 247: 115026, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36577217

RESUMO

The ESKAPE (Escherichia coli/E. coli, Staphylococcus aureus/S. aureus, Klebsiella pneumonia/K. pneumoniae, Acinetobacter Baumannii/A. baumannii, Pseudomonas aeroginosa/P. aeroginosa and Enterobacter spp.) pathogens, which could escape or evade common therapies through diverse antimicrobial resistance mechanisms and biofilm formation, are deemed as highly virulent bacteria responsible for life-threatening diseases, calling for novel chemotherapeutics. Quinolones including 2-quinolones and 4-quinolones have occupied a propitious place in drug design and development due to their excellent pharmacological profiles. Quinolones especially fluoroquinolones could inhibit the synthesis of nucleic acid of ESKAPE pathogens, leading to the rupture of bacterial chromosome. However, the resistance of ESKAPE pathogens to quinolones develops rapidly and spreads widely. Accordingly, it has become increasingly urgent to enhance the potency of quinolones against both drug-susceptible and drug-resistant ESKAPE pathogens. Quinolone hybrids can bind with different drug targets simultaneously and have been considered as useful prototypes to circumvent drug resistance. The purpose of this review is to summarize the current scenario (2018-present) of quinolone hybrids with potential antibacterial activity against ESKAPE pathogens, together with the structure-activity relationships and mechanisms of action to facilitate further rational design of more effective candidates.


Assuntos
Quinolonas , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Quinolonas/farmacologia , Klebsiella pneumoniae , Enterobacter
18.
J Microbiol Methods ; 204: 106659, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36529157

RESUMO

The water is used in many textile manufacturing steps beyond cleaning. The quantity and the significant chemical load of the effluents generated constitute the primary challenge of the textile industry. In order to discover new sustainable methods to overcome this problem, the aim of this research was to study the potential for degradation of Reactive Blue 214, Reactive Red 195, and Reactive Yellow 145 using a dye degrading bacterium. Sequencing analysis reveals it to be Klebsiella pneumoniae MW815592. This strain completely decolorized artificial effluent (200 mg/L) after 42 h at pH 9 and 46 °C. The decolorization rate increased in the presence of glucose and yeast extract (2 g). In addition, our finding revealed that the decolorization is due to biodegradation rather than adsorption on the bacterial surface.


Assuntos
Corantes , Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Corantes/metabolismo , Naftalenossulfonatos , Compostos Azo/metabolismo , Têxteis , Biodegradação Ambiental
19.
Int J Antimicrob Agents ; 61(1): 106702, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36476965

RESUMO

BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis. METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU. RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination. CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.


Assuntos
Fosfomicina , Infecções por Klebsiella , Osteomielite , Humanos , Animais , Coelhos , Klebsiella pneumoniae , Colistina/uso terapêutico , Colistina/farmacologia , Fosfomicina/uso terapêutico , Fosfomicina/farmacologia , Klebsiella , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Ceftazidima/uso terapêutico , Ceftazidima/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , beta-Lactamases/farmacologia , Compostos Azabicíclicos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Combinação de Medicamentos , Inibidores de beta-Lactamases/uso terapêutico , Gentamicinas/uso terapêutico , Osteomielite/tratamento farmacológico , Testes de Sensibilidade Microbiana
20.
J Drugs Dermatol ; 21(12): 1311-1315, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468950

RESUMO

BACKGROUND: Antibiotic resistance has become one of the largest pitfalls of modern medicine, and this has fueled the search for a safe and effective alternative. Of these alternatives, bacteriophage (phage) therapy has emerged as a potential option since it is capable of destroying pathogenic bacteria, without disrupting commensal bacterial populations. Although numerous studies have shown its efficacy in various conditions such as dysentery, sepsis, and meningitis, very little research has focused on its prospective usage to treat dermatological conditions. This review discusses the emerging phage therapy studies surrounding infections caused by Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae). Phage therapy shows major potential for future usage in the field of dermatology, yet further research must be performed to assure safety and efficacy in humans. J Drugs Dermatol. 2022;21(12):1311-1315. doi:10.36849/JDD.6638.


Assuntos
Bacteriófagos , Humanos , Staphylococcus aureus , Estudos Prospectivos , Klebsiella pneumoniae , Pseudomonas aeruginosa , Resistência Microbiana a Medicamentos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
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