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2.
BMC Infect Dis ; 20(1): 916, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267829

RESUMO

BACKGROUND: Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors, validate the prediction efficiency of pediatric Sequential Organ Failure Assessment (SOFA) and establish better early predictors of mortality in pediatric patients with Kp-BSI. METHODS: All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019. Basic characteristics, symptoms and physical examinations, treatments, laboratory statistics, and SOFA at the onset of Kp-BSI were recorded. The Cox proportional hazard model and receiver operating characteristic curves were used to assess the association between the variables and the 90-day mortality and their predictive value. DeLong's test of receiver operating characteristic curves and integrated discrimination improvement index were used to determine the improvement in predictive capacity of the modified SOFA models. A predictive score was developed using multivariate logistic regression. RESULTS: Of the 146 children enrolled, 33 (22.6%) patients died within 90 days. Hospitalization in the last 6 months, intra-abdominal source of infection, presence of organ failure, and altered levels of blood biomarkers, including C-reactive protein, albumin, and lactate were significant risk factors for 90-day mortality. The area under the curve (AUC) of SOFA for predicting 90-day mortality was 0.80 (95% CI 0.71-0.89). Moreover, we found that a prediction model combining SOFA with two other parameters, namely hospitalization in the last 6 months and intra-abdominal source of infection, was better at predicting mortality (AUC = 0.89, 95% CI 0.82-0.96; sensitivity = 0.86; specificity = 0.84). According to this novel risk model, we defined three statistically different groups: low-risk, medium-risk and high-risk groups, with an observed 90-day mortality of 5.4, 35.7, and 72.0%, respectively. With reference to the low-risk patients, the medium-risk and high-risk groups had a higher mortality, with hazard ratios of 8.36 (95% CI 3.60-27.83) and 20.27 (95% CI 7.47-54.95), respectively. CONCLUSIONS: The modified SOFA may be better than the original score to predict 90-day mortality in pediatric patients with Kp-BSI. Future prospective studies are required to validate this novel scoring system in external cohorts.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/isolamento & purificação , Escores de Disfunção Orgânica , Área Sob a Curva , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Hospitalização , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/microbiologia , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco
3.
BMC Infect Dis ; 20(1): 810, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158426

RESUMO

PURPOSE: The purpose of this study was to explore the clinical features, risk factors, and outcomes of mixed Candida albicans/bacterial bloodstream infections (mixed-CA/B-BSIs) compared with monomicrobial Candida albicans bloodstream infection (mono-CA-BSI) in adult patients in China. METHODS: All hospitalized adults with Candida albicans bloodstream infection (CA-BSI) were recruited for this retrospective observational study from January 1, 2013, to December 31, 2018. RESULTS: Of the 117 patients with CA-BSI, 24 patients (20.5%) had mixed-CA/B-BSIs. The most common copathogens were coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (20.0%) and Staphylococcus aureus (16.0%). In the multivariable analysis, a prior ICU stay > 2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152-48.132) was an independent risk factor for mixed-CA/B-BSIs. Compared with patients with mono-CA-BSI, patients with mixed-CA/B-BSIs had a prolonged length of mechanical ventilation [17.5 (4.5, 34.8) vs. 3.0 (0.0, 24.5), p = 0.019] and prolonged length of ICU stay [22.0 (14.3, 42.2) vs. 8.0 (0.0, 31.5), p = 0.010]; however, mortality was not significantly different. CONCLUSIONS: There was a high rate of mixed-CA/B-BSIs cases among CA-BSI cases, and CNS was the predominant coexisting species. A prior ICU stay > 2 days was an independent risk factor for mixed -CA/B-BSIs. Although there was no difference in mortality, the outcomes of patients with mixed -CA/B-BSIs, including prolonged length of mechanical ventilation and prolonged length of ICU stay, were worse than those with mono-CA-BSI; this deserves further attention from clinicians.


Assuntos
Bacteriemia/complicações , Candida albicans/isolamento & purificação , Candidíase/complicações , Infecções por Klebsiella/complicações , Klebsiella pneumoniae/isolamento & purificação , Infecções Estafilocócicas/complicações , Staphylococcus aureus/isolamento & purificação , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Candidíase/microbiologia , Candidíase/mortalidade , China/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Masculino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade
4.
Proc Natl Acad Sci U S A ; 117(44): 27620-27626, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33087568

RESUMO

The extracellular polysaccharide capsule of Klebsiella pneumoniae resists penetration by antimicrobials and protects the bacteria from the innate immune system. Host antimicrobial peptides are inactivated by the capsule as it impedes their penetration to the bacterial membrane. While the capsule sequesters most peptides, a few antimicrobial peptides have been identified that retain activity against encapsulated K. pneumoniae, suggesting that this bacterial defense can be overcome. However, it is unclear what factors allow peptides to avoid capsule inhibition. To address this, we created a peptide analog with strong antimicrobial activity toward several K. pneumoniae strains from a previously inactive peptide. We characterized the effects of these two peptides on K. pneumoniae, along with their physical interactions with K. pneumoniae capsule. Both peptides disrupted bacterial cell membranes, but only the active peptide displayed this activity against capsulated K. pneumoniae Unexpectedly, the active peptide showed no decrease in capsule binding, but did lose secondary structure in a capsule-dependent fashion compared with the inactive parent peptide. We found that these characteristics are associated with capsule-peptide aggregation, leading to disruption of the K. pneumoniae capsule. Our findings reveal a potential mechanism for disrupting the protective barrier that K. pneumoniae uses to avoid the immune system and last-resort antibiotics.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Cápsulas Bacterianas/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Cápsulas Bacterianas/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Feminino , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/citologia , Camundongos , Testes de Sensibilidade Microbiana , Polissacarídeos Bacterianos/metabolismo
5.
Trop Anim Health Prod ; 52(6): 3923-3929, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33025455

RESUMO

In the present study, sudden mortalities were reported due to pneumonia in four neonatal camels (5 to 10 days old) of an organized dromedary camel farm. The clinical manifestations in affected camels were weakness, mild to high fever, not suckling, respiratory distress, and sudden death. On the basis of gross and histopathological lesions, the pneumonia was classified into bronchopneumonia (n = 2), bronchointerstitial pneumonia (n = 1), and interstitial pneumonia (n = 1). In bacterial culture, Klebsiella pneumoniae was isolated from lung of all the four cases. These bacteria were also confirmed by PCR from DNA isolated from culture as well as lung tissue. The sequencing of PCR products from four isolates of K. pneumoniae revealed homology with other pathogenic K. pneumoniae isolates from India and other countries. These findings confirmed the role of K. pneumoniae as an important etiological agent for causing pneumonia with sudden mortalities in suckling neonatal dromedary camels.


Assuntos
Camelus , Infecções por Klebsiella/veterinária , Klebsiella pneumoniae/isolamento & purificação , Pneumonia/veterinária , Animais , Animais Recém-Nascidos , Humanos , Índia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/genética , Pneumonia/microbiologia , Pneumonia/patologia
6.
Sci Rep ; 10(1): 16778, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033293

RESUMO

Carbapenemase-producing Klebsiella pneumoniae emerged as a nosocomial pathogen causing morbidity and mortality in patients. For infection prevention it is important to track the spread of K. pneumoniae and its plasmids between patients. Therefore, the major aim was to recapitulate the contents and diversity of the plasmids of genetically related K. pneumoniae strains harboring the beta-lactamase gene blaKPC-2 or blaKPC-3 to determine their dissemination in the Netherlands and the former Dutch Caribbean islands from 2014 to 2019. Next-generation sequencing was combined with long-read third-generation sequencing to reconstruct 22 plasmids. wgMLST revealed five genetic clusters comprised of K. pneumoniae blaKPC-2 isolates and four clusters consisted of blaKPC-3 isolates. KpnCluster-019 blaKPC-2 isolates were found both in the Netherlands and the Caribbean islands, while blaKPC-3 cluster isolates only in the Netherlands. Each K. pneumoniae blaKPC-2 or blaKPC-3 cluster was characterized by a distinct resistome and plasmidome. However, the large and medium plasmids contained a variety of antibiotic resistance genes, conjugation machinery, cation transport systems, transposons, toxin/antitoxins, insertion sequences and prophage-related elements. The small plasmids carried genes implicated in virulence. Thus, implementing long-read plasmid sequencing analysis for K. pneumoniae surveillance provided important insights in the transmission of a KpnCluster-019 blaKPC-2 strain between the Netherlands and the Caribbean.


Assuntos
DNA Bacteriano/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Klebsiella pneumoniae/isolamento & purificação , Países Baixos
7.
Appl Environ Microbiol ; 86(24)2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-32917755

RESUMO

Hospital wastewater is an increasingly recognized reservoir for resistant Gram-negative organisms. Factors involved in establishment and persistence of Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) in hospital wastewater plumbing are unclear. This study was conducted at a hospital with endemic KPCOs linked to wastewater reservoirs and robust patient perirectal screening for silent KPCO carriage. Over 5 months, both rooms occupied and rooms not occupied by KPCO-positive patients were sampled at three wastewater sites within each room (sink drain, sink P-trap, and toilet or hopper). Risk factors for KPCO positivity were assessed using logistic regression. Whole-genome sequencing (WGS) identified environmental seeding by KPCO-positive patients. A total of 219/475 (46%) room sampling events were KPCO positive in at least one wastewater site. KPCO-positive patient exposure was associated with increased risk of environmental positivity for the room and toilet/hopper. Previous positivity and intensive care unit room type were consistently associated with increased risk. Tube feeds were associated with increased risk for the drain, while exposure to patients with Clostridioides difficile was associated with decreased risk. Urinary catheter exposure was associated with increased risk of P-trap positivity. P-trap heaters reduced risk of P-trap and sink drain positivity. WGS identified genomically linked environmental seeding in 6 of 99 room occupations by 40 KPCO-positive patients. In conclusion, KPCO-positive patients seed the environment in at least 6% of opportunities; once positive for KPCOs, wastewater sites are at greater risk of being positive subsequently. Increased nutrient exposure, e.g., due to tube food disposal down sinks, may increase risk; frequent flushing may be protective.IMPORTANCE Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are bacteria that are resistant to most antibiotics and thus are challenging to treat when they cause infections in patients. These organisms can be acquired by patients who are hospitalized for other reasons, complicating their hospital stay and even leading to death. Hospital wastewater sites, such as sink drains and toilets, have played a role in many reported outbreaks over the past decade. The significance of our research is in identifying risk factors for environmental positivity for KPCOs, which will facilitate further work to prevent transmission of these organisms to patients from the hospital environment.


Assuntos
Proteínas de Bactérias/análise , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Águas Residuárias/microbiologia , beta-Lactamases/análise , Hospitais , Humanos , Infecções por Klebsiella/microbiologia , Virginia/epidemiologia , Águas Residuárias/análise
8.
Pan Afr Med J ; 36: 191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952835

RESUMO

Over the past 20 years there has been growing awareness of community-acquired primary liver abscess caused by strains of Klebsiella pneumoniae (K. pneumoniae) especially in patients of Asian descent, a minority of which are characterized by metastatic spread. A common and frequent destructive complication is endophthalmitis as well as the involvement of the central nervous system (CNS), causing suppurative meningitis or brain abscess. Here we report a case of invasive liver abscess caused by K. pneumoniae in an Asian patient who presented to our hospital in Tanzania with bilateral lower limb swelling for 6 weeks with acute onset of difficulty in breathing.


Assuntos
Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/isolamento & purificação , Abscesso Hepático/diagnóstico , Humanos , Infecções por Klebsiella/microbiologia , Abscesso Hepático/microbiologia , Masculino , Pessoa de Meia-Idade , Síndrome , Tanzânia
9.
Lett Appl Microbiol ; 71(6): 652-659, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32916001

RESUMO

The emergence of novel resistant markers hampers the efficacy of beta-lactam antibiotics to treat infections caused by micro-organisms carrying such resistances. This study investigated the antimicrobial susceptibility pattern, the carpapenem-associated determinants and the molecular epidemiology of Klebsiella pneumoniae showing a New Delhi (NDM) metallo-ß-lactamase phenotype, isolated from a patient admitted to intensive care unit of the main hospital for acute care of Molise region, central Italy. Antimicrobial susceptibility was assessed for nineteen antibiotics by disc diffusion and agar dilution methods. Carbapenem-associated resistance determinants were detected through gene-specific amplifications, targeting blaNDM-1 , blaSHV and blaTEM , blaCTX-M , blaKPC , blaVIM , blaIMP , blaGES and blaOXA-48-lixe . Molecular characterization was carried out through multilocus sequence typing. The strain showed a multidrug resistant profile, and PCR and sequencing confirmed the presence of blaNDM-1 gene. Among the multiple resistance-associated determinants tested, the isolate, which was assigned to the sequence type ST11, only harboured blaSHV and blaTEM genes. This is the first report of NDM-1 variant in the regional healthcare setting for acute patients, raising significant concerns about the increase in the antimicrobials resistance spread through a different mechanism from the endemic KPC carbapenemase, and underlining the circulation of a virulent clone never identified before in this area.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Hospitais/estatística & dados numéricos , Humanos , Itália/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , beta-Lactamases/genética
10.
Arch Virol ; 165(12): 2799-2806, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989574

RESUMO

The increasing population infected by carbapenem-resistant Klebsiella pneumoniae necessitates the development of alternative therapies. In this study, we isolated, characterized, and sequenced a bacteriophage, P509, which was able to specifically infect and lyse carbapenem-resistant K. pneumoniae of K locus type KL64. A one-step growth curve experiment showed that the latent time period of phage P509 was 5 min, and the burst size was about 85 phage particles/cell. Stability tests confirmed that P509 was stable over a wide range of temperatures (4 to 50 °C) and pH (3 to 11) conditions. Phage P509 was identified as a linear double-stranded DNA phage with a genome of 40,954 bp with 53.2% G + C content, encoding 50 predicted proteins. Genomic and morphological analysis suggested that P509 belonged to the genus Przondovirus, family Autographiviridae, order Caudovirales. Further analysis showed that no virulence-related genes or lysogen-formation gene clusters were detected in the genome, suggesting that P509 is a lytic phage, making it potentially suitable for clinical applications. In vitro, the number of viable cells in three phage-treated groups (MOI = 0.1, 0.01, 0.001) decreased by 3.75 log10 CFU/ml, 3.32 log10 CFU/ml and 3.21 log10 CFU/ml, respectively, after 80 min of incubation, in comparison to that in the untreated group. Based on these characteristics, phage P509 may be a promising candidate for future phage therapy applications.


Assuntos
Bacteriófagos/isolamento & purificação , Klebsiella pneumoniae/virologia , Bacteriófagos/genética , Composição de Bases , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Enterobacteriáceas Resistentes a Carbapenêmicos/virologia , Genoma Viral , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Fatores de Virulência/genética
11.
PLoS One ; 15(9): e0239147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960928

RESUMO

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.


Assuntos
Adjuvantes Farmacêuticos/farmacologia , Antibacterianos/farmacologia , Hexilresorcinol/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Sepse/tratamento farmacológico , Adjuvantes Farmacêuticos/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Escherichia coli/efeitos dos fármacos , Feminino , Hexilresorcinol/uso terapêutico , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Camundongos , Testes de Sensibilidade Microbiana , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Sepse/microbiologia , Staphylococcus aureus/efeitos dos fármacos
12.
Artigo em Inglês | MEDLINE | ID: mdl-32872324

RESUMO

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen that causes a variety of infectious diseases, including urinary tract infections, bacteremia, pneumonia, and liver abscesses. With the emergence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKP) strains, the rapid spread of these clinical strains in geography is particularly worrying. However, the detailed mechanisms of virulence and antibiotic resistance in K. pneumoniae are still not very clear. Therefore, studying and elucidating the pathogenic mechanisms and drug resistance mechanism of K. pneumoniae infection are important parts of current medical research. In this paper, we systematically summarized the virulence, biofilm, and antibiotic tolerance mechanisms of K. pneumoniae, and explored the application of whole genome sequencing and global proteomics, which will provide new clues for clinical treatment of K. pneumoniae.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Genes Bacterianos , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , Reação em Cadeia da Polimerase , Virulência/genética , Fatores de Virulência
13.
Proc Natl Acad Sci U S A ; 117(40): 25043-25054, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32968015

RESUMO

Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, bla OXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, bla VIM and bla NDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, bla KPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying bla KPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Linhagem da Célula/genética , Cromossomos Bacterianos/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Genoma Bacteriano/genética , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Plasmídeos/genética , Análise de Sequência de DNA/métodos
14.
Mikrobiyol Bul ; 54(3): 378-391, 2020 Jul.
Artigo em Turco | MEDLINE | ID: mdl-32755515

RESUMO

Klebsiella pneumoniae is the cause of complicated and difficult-to-treat nosocomial infections such as sepsis, urinary tract infection, catheter related infections, pneumonia and surgical site infections in intensive care units. The biggest problem in infections with K.pneumoniae is that treatment options are limited due to multiple antibiotic resistance and consequently the increased morbidity and mortality. The widespread and improper use of carbapenems can lead to epidemics that are difficult to control, especially in intensive care units because of the acquired resistance to this group of antibiotics. Outbreaks and sporadic cases caused by carbapenem resistant K.pneumoniae (CRKP) species have been reported all over the world in recent years with increased frequency. The aim of this study was to determine the risk factors related to carbepenem resistance and mortality caused by K.pneumoniae infections in a university hospital anesthesia intensive care unit. The study was conducted between January 1st, 2016, and December 31st, 2018. Retrospective data were obtained from the patient and laboratory-based surveillance records. Adult patients (≥ 18 years) with K.pneumoniae growth in the blood, urine, abscess and tracheal aspirate samples collected 48 hours after admission to the intensive care unit were considered as the relevant infection locus-related agent and treated with antibacterial therapy. Clinical samples collected from patients were inoculated onto 5% sheep blood and eosin-methylene-blue (EMB) agar except the blood samples. Blood samples were cultured in blood culture bottles and incubated in an automated system. Gram staining was performed for the samples showing growth signal within five days and then inoculated onto 5% sheep blood and EMB agar media and were incubated for 18-24 hours at 35.5-37°C. Identification of the isolates was performed using Bruker IVD MALDI Biotyper 2.3 (Bruker Daltonik GmbH, Bremen, Almanya) based on "matrix-assisted laser desorption/ionization time-of-mass spectrometry (MALDI-TOF MS)". K.pneumoniae isolates were identified by obtaining reliability scores of 2.0 and above in the study. Antibiotic susceptibility tests were performed with Phoenix 100 (BD, New Jersey, ABD) automated system. Interpretations were made according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Combination disk diffusion test and polymerase chain reaction based tests were used to show the presence of carbapenemase in CRKP isolates. A total of 88 patients with K.pneumoniae infection were included in the study. The mean age of the patients was 74 ± 15 (range= 21-93) years and 60.2% were female. CRKP was detected in 32 patients (36.4%) and carbapenem-sensitive K.pneumoniae (CSKP) was detected in 56 patients. The presence of OXA-48 was found to be 68.8% in the carbapenem screening test performed by combination disc method in patients with CRKP. Multivariate logistic regression analysis showed that previous use of colistin [Odds ratio (OR)= 19.108; 95% confidence interval (CI)= 2.027-180.133; p= 0.010] and aminoglycoside (OR= 12.189; 95% CI= 1.256-118.334; p= 0.031) was an independent risk factor in terms of CRCP among the patients with K.pneumoniae infection. The 28-day mortality rates were 71.9% in the CRKP group (23/32) and 37.5% in the CSKP group (21/56). Presence of CRKP in terms of 28-day mortality (OR= 5.146; 95% CI= 1.839-14.398; p= 0.002) was an independent risk factor. The data obtained in this study will guide for conducting effective and continuous surveillance studies and implementing rational antibiotic programs to prevent the increase in CRKP.


Assuntos
Carbapenêmicos , Farmacorresistência Bacteriana , Unidades de Terapia Intensiva , Infecções por Klebsiella , Klebsiella pneumoniae , Pneumonia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Ovinos
15.
Epidemiol Infect ; 148: e191, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32782064

RESUMO

Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.


Assuntos
Genótipo , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Lipopolissacarídeos/metabolismo , Polissacarídeos/metabolismo , China/epidemiologia , Regulação Bacteriana da Expressão Gênica , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Lipopolissacarídeos/genética , Polissacarídeos/genética
16.
PLoS One ; 15(8): e0237474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857767

RESUMO

The effective treatment of carbapenemase-producing Klebsiella pneumoniae infection has been limited and required novel potential agents. Due to the novel drug development crisis, using old antimicrobial agents and combination therapy have been highlighted. This study focused on fosfomycin which inhibits cell wall synthesis and has potential activity on Enterobacteriaceae. We evaluated fosfomycin activity against carbapenemase-producing K. pneumoniae and characterized fosfomycin resistance mechanisms. Fosfomycin revealed effective activity against only 31.8% of carbapenemase-producing K. pneumoniae isolates. The major resistance mechanism was FosA3 production. The co-occurrence of FosA3 overexpression with the mutation of glpT (or loss of glpT) and/or uhpT was mediated high-level resistance (MIC>256 mg/L) to fosfomycin. Moreover, fosA3 silenced in sixteen fosfomycin-susceptible isolates and the plasmid carrying fosA3 of these isolates increased 32- to 64-fold of fosfomycin MICs in Escherichia coli DH5α transformants. The in vitro activity of fosfomycin combination with amikacin by checkerboard assay showed synergism and no interaction in six (16.2%) and sixteen isolates (43.3%), respectively. No antagonism of fosfomycin and amikacin was observed. Notably, the silence of aac (6)'-Ib and aphA6 was observed in amikacin-susceptible isolates. Our study suggests that the combination of fosfomycin and amikacin may be insufficient for the treatment of carbapenemase-producing K. pneumoniae isolates.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Fosfomicina/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , beta-Lactamases/metabolismo , Amicacina/farmacologia , Substituição de Aminoácidos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Escherichia coli/metabolismo , Humanos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Plasmídeos/metabolismo , RNA Mensageiro/metabolismo , beta-Lactamases/genética
17.
Sci Rep ; 10(1): 12974, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737397

RESUMO

Extended early antibiotic exposure in the neonatal intensive care unit is associated with an increased risk for the development of late-onset sepsis (LOS). However, few studies have examined the mechanisms involved. We sought to determine how the neonatal microbiome and intestinal immune response is altered by transient early empiric antibiotic exposure at birth. Neonatal mice were transiently exposed to broad-spectrum antibiotics from birth for either 3- (SE) or 7-days (LE) and were examined at 14-days-old. We found that mice exposed to either SE or LE showed persistent expansion of Proteobacteria (2 log difference, P < 0.01). Further, LE mice demonstrated baseline translocation of E. coli into the liver and spleen and were more susceptible K. pneumoniae-induced sepsis. LE mice had a significant and persistent decrease in type 3 innate lymphoid cells (ILC3) in the lamina propria. Reconstitution of the microbiome with mature microbiota by gavage in LE mice following antibiotic exposure resulted in an increase in ILC3 and partial rescue from LOS. We conclude that prolonged exposure to broad spectrum antibiotics in the neonatal period is associated with persistent alteration of the microbiome and innate immune response resulting in increased susceptibility to infection that may be partially rescued by microbiome reconstitution.


Assuntos
Antibacterianos/efeitos adversos , Escherichia coli/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata/efeitos dos fármacos , Klebsiella pneumoniae/imunologia , Linfócitos/imunologia , Sepse , Animais , Animais Recém-Nascidos , Antibacterianos/farmacologia , Translocação Bacteriana/efeitos dos fármacos , Translocação Bacteriana/imunologia , Suscetibilidade a Doenças , Infecções por Escherichia coli/induzido quimicamente , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Klebsiella/induzido quimicamente , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Linfócitos/patologia , Masculino , Camundongos , Sepse/induzido quimicamente , Sepse/imunologia , Sepse/microbiologia , Sepse/patologia
18.
Euro Surveill ; 25(26)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32643598

RESUMO

BackgroundAlgorithms for predicting infection with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) on hospital admission or in patients with bacteraemia have been proposed, aiming to optimise empiric treatment decisions.AimWe sought to confirm external validity and transferability of two published prediction models as well as their integral components.MethodsWe performed a retrospective case-control study at University Hospital Basel, Switzerland. Consecutive patients with ESBL-producing Escherichia coli or Klebsiella pneumoniae isolated from blood samples between 1 January 2010 and 31 December 2016 were included. For each case, three non-ESBL-producing controls matching for date of detection and bacterial species were identified. The main outcome measure was the ability to accurately predict infection with ESBL-PE by measures of discrimination and calibration.ResultsOverall, 376 patients (94 patients, 282 controls) were analysed. Performance measures for prediction of ESBL-PE infection of both prediction models indicate adequate measures of calibration, but poor discrimination (area under receiver-operating curve: 0.627 and 0.651). History of ESBL-PE colonisation or infection was the single most predictive independent risk factor for ESBL-PE infection with high specificity (97%), low sensitivity (34%) and balanced positive and negative predictive values (80% and 82%).ConclusionsApplying published prediction models to institutions these were not derived from, may result in substantial misclassification of patients considered as being at risk, potentially leading to wrong allocation of antibiotic treatment, negatively affecting patient outcomes and overall resistance rates in the long term. Future prediction models need to address differences in local epidemiology by allowing for customisation according to different settings.


Assuntos
Bactérias/enzimologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , beta-Lactamases/biossíntese , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Estudos de Casos e Controles , Escherichia coli , Feminino , Humanos , Klebsiella pneumoniae , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Suíça , Resistência beta-Lactâmica
19.
Sci Rep ; 10(1): 11803, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678251

RESUMO

Extended spectrum ß lactamase-producing Klebsiella pneumoniae (ESBL-KP) is being reported with high morbidity and mortality rates and is considered as the highest priority for new antimicrobial strategies. To develop an alternative antimicrobial agent, phage KP1801 with broad lytic activity was isolated. The genome of phage KP1801 was double stranded DNA of 49,835 base pairs, with a GC content of 50.26%. There were 75 putative open reading frames. Phage KP1801 was classified as being in the order Caudovirales, belonging to the Siphoviridae family. About 323 proteins were detected by shotgun proteome analysis. The phage inhibited biofilm formation and reduced pre-formed biofilm in a dose dependent manner. Scanning electron microscopic studies demonstrated a membrane damage of bacterial cells treated with phage, resulting in cell death. Prophylactic and therapeutic efficacies of the phage were evaluated in Galleria mellonella. Administration of ESBL-KP infection with phage significantly improved the survival of G. mellonella. The number of intracellular bacteria in larvae showed a significant decrease compared with untreated control while the number of phage increased. These studies suggested that phage KP1801 has the potential for development as an alternative for antibiotics and biocontrol agents against ESBL-KP infection.


Assuntos
Bacteriófagos/fisiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/virologia , beta-Lactamases/genética , Animais , Bacteriólise , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Bacteriófagos/ultraestrutura , Biofilmes , Genoma Viral , Especificidade de Hospedeiro , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/terapia , Klebsiella pneumoniae/efeitos dos fármacos , Mariposas/microbiologia , Terapia por Fagos , Filogenia , Replicação Viral , Sequenciamento Completo do Genoma
20.
Sci Rep ; 10(1): 10876, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616840

RESUMO

The emergence of multidrug-resistant Klebsiella pneumoniae is a worldwide problem. K. pneumoniae possesses numerous resistant genes in its genome. We isolated mutants resistant to various antimicrobials in vitro and investigated the importance of intrinsic genes in acquired resistance. The isolation frequency of the mutants was 10-7-10-9. Of the multidrug-resistant mutants, hyper-multidrug-resistant mutants (EB256-1, EB256-2, Nov1-8, Nov2-2, and OX128) were identified, and accelerated efflux activity of ethidium from the inside to the outside of the cells was observed in these mutants. Therefore, we hypothesized that the multidrug efflux pump, especially RND-type efflux pump, would be related to changes of the phenotype. We cloned all RND-type multidrug efflux pumps from the K. pneumoniae genome and characterized them. KexEF and KexC were powerful multidrug efflux pumps, in addition to AcrAB, KexD, OqxAB, and EefABC, which were reported previously. It was revealed that the expression of eefA was increased in EB256-1 and EB256-2: the expression of oqxA was increased in OX128; the expression of kexF was increased in Nov2-2. It was found that a region of 1,485 bp upstream of kexF, was deleted in the genome of Nov2-2. K. pneumoniae possesses more potent RND-multidrug efflux systems than E. coli. However, we revealed that most of them did not contribute to the drug resistance of our strain at basic levels of expression. On the other hand, it was also noted that the overexpression of these pumps could lead to multidrug resistance based on exposure to antimicrobial chemicals. We conclude that these pumps may have a role to maintain the intrinsic resistance of K. pneumoniae when they are overexpressed. The antimicrobial chemicals selected many resistant mutants at the same minimum inhibitory concentration (MIC) or a concentration slightly higher than the MIC. These results support the importance of using antibiotics at appropriate concentrations at clinical sites.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/fisiologia , Proteínas de Bactérias/genética , Transporte Biológico , Humanos , Infecções por Klebsiella/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação
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