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1.
J Microbiol Immunol Infect ; 57(2): 300-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38350840

RESUMO

PURPOSES: This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB). METHODS: We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays. RESULTS: Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL. CONCLUSION: Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Colistina/farmacologia , Colistina/uso terapêutico , Polimixina B/farmacologia , Sinergismo Farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla
2.
J Fam Psychol ; 38(3): 411-420, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38300533

RESUMO

Despite the well-established relationship between parenting and child aggression, the mechanisms by which children incur this risk and whether genetic sources contribute to the heterogeneity in their vulnerability are not entirely clear. This study utilized a longitudinal sample of adolescents (n = 1,047, 50.2% females, Mage = 13.32 ± 0.48 years at Time 1) to examine the effects of positive and negative parenting on aggression, as mediated by inhibitory control and moderated by the serotonin receptor 2A (5-HTR2A) haplotype. Mediation analysis revealed that inhibitory control indirectly mediated the link between both positive and negative parenting and overt aggression but not relational aggression. Further, the indirect effect of negative parenting on overt aggression via inhibitory control was moderated by the 5-HTR2A haplotype. Compared to adolescents carrying zero copies of Thymine-Thymine haplotype, those with one copy of Thymine-Thymine haplotype had better inhibitory control when experiencing less negative parenting, which buffers the risk for overt aggression. However, the mediating role of inhibitory control did not hold in the positive parenting model. These findings elucidate the manner by which adolescents with different genetic predispositions develop aggressive behaviors in the context of family and suggest different etiology of overt and relational aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Agressão , Poder Familiar , Criança , Feminino , Adolescente , Humanos , Masculino , Poder Familiar/psicologia , Agressão/psicologia , Haplótipos , Receptor 5-HT2A de Serotonina , Timina
3.
Ann Clin Microbiol Antimicrob ; 22(1): 107, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072972

RESUMO

OBJECTIVE: To evaluate effect of inoculum size of extended-spectrum ß-Lactamase (ESBL)-producing-, AmpC-producing-, and KPC-producing Escherichia coli and Klebsiella pneumoniae on the in vitro antibacterial effects of imipenem/relebactam (IMR) and ceftazidime/avibactam (CZA). METHODS: We compared the impact of inoculum size on IMR and CZA of sixteen clinical isolates and three standard isolates through antimicrobial susceptibility tests, time-kill assays and in vitro PK/PD studies. RESULTS: When inoculum size increased from 105 to 107 CFU/mL, an inoculum effect was observed for 26.3% (5/19) and 52.6% (10/19) of IMR and CZA, respectively; time-kill assays revealed that the concentration of CZA increased from ≥ 4 × MIC to 16 × MIC to reach 99.9% killing rate against K. pneumoniae ATCC-BAA 1705 (KPC-2-, OXA-9- and SHV-182-producing) and 60,700 (SHV-27- and DHA-1-producing). While for IMR, a concentration from 1 × MIC to 4 × MIC killed 99.9% of the four strains. When the inoculum size increased to 109 CFU/mL, neither IMR nor CZA showed a detectable antibacterial effect, even at a high concentration. An in vitro PK/PD study revealed a clear bactericidal effect when IMR administered as 1.25 g q6h when inoculum size increased. CONCLUSION: An inoculum effect on CZA was observed more frequent than that on IMR. Among the ß-lactamase-producing strains, the inoculum effect was most common for SHV-producing and KPC-producing strains.


Assuntos
Ceftazidima , Klebsiella pneumoniae , Humanos , Ceftazidima/farmacologia , Escherichia coli , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , beta-Lactamases/genética , Combinação de Medicamentos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana
4.
Clin Microbiol Infect ; 29(10): 1336.e1-1336.e8, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37423426

RESUMO

OBJECTIVES: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major clinical concern, and polymyxin B (PMB) is a 'last resort' antibiotic for its treatment. Understanding the effects of drug susceptibility transformation in CRKP-infected patients undergoing PMB treatment would be beneficial to optimize PMB treatment strategies. METHODS: We retrospectively collected data from patients infected with CRKP and treated with PMB from January 2018 to December 2020. CRKPs were collected before and after PMB therapy, and patients were classified into the 'transformation' group (TG) and 'non-transformation' group (NTG) by the shift of susceptibility to PMB. We compared clinical characteristics between these groups, and further analysed the phenotypic and genome variation of CRKP after PMB susceptibility transformation. RESULTS: A total of 160 patients (37 in the TG and 123 in the NTG) were included in this study. The duration of PMB treatment before PMB-resistant K. pneumoniae (PRKP) appearance in TG was even longer than the whole duration of PMB treatment in NTG (8 [8] vs. 7 [6] days; p 0.0496). Compared with isogenic PMB-susceptible K. pneumoniae (PSKP), most PRKP strains had missense mutations in mgrB (12 isolates), yciC (10 isolates) and pmrB (7 isolates). The competition index of 82.4% (28/34) of PRKP/PSKP pairs was <67.6% (23/34), and 73.5% (25/34) of PRKP strains showed a higher 7-day lethality in Galleria mellonella and a greater ability to resist complement-dependent killing than their corresponding PSKP, respectively. CONCLUSION: Low dose with longer PMB treatment durations may be associated with the emergence of polymyxin resistance. The evolution of PRKP is predominantly mediated by an accumulation of mutations, including those in mgrB, yciC, and pmrB. Lastly, PRKP exhibited reduced growth and increased virulence compared with parental PSKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Polimixina B/farmacologia , Polimixina B/uso terapêutico , Klebsiella pneumoniae , Estudos Retrospectivos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Testes de Sensibilidade Microbiana
5.
Int J Antimicrob Agents ; 62(2): 106877, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37271474

RESUMO

In order to investigate ceftazidime/avibactam (CZA) resistance characteristics and mechanisms of bacteraemic Enterobacterales strains that had not been treated previously with CZA, 9708 strains were collected from 43 hospitals in 18 provinces across China from January 2019 to June 2020. The minimum inhibitory concentration (MIC) values of CZA in 165 (1.70%) strains were ≥8/4 mg/L. Ten (6.06%) CZA-resistant strains without metallo-ß-lactamase production were obtained from the individuals without prior exposure to CZA, including six Escherichia coli isolates, three Klebsiella pneumoniae isolates and one Enterobacter cloacae isolate. Whole-genome sequencing revealed that ECB88611, ECB142593 and ECB144539 had encoded disrupted OmpF loss of function. OmpF of ECB126041 had a 2_9 MKRNILAV deletion; OmpK35 of three K. pneumoniae isolates harboured amino acid fragment deletions from positions 1 to 38; and ELB117287 had encoded disrupted OmpF. The G132D amino acid substitution of OmpC of ECB88611, ECB142593 and ECB144539, and the 134_135GD insertion of OmpK36 of three K. pneumoniae isolates were predicted to alter ceftazidime permeability. 333_334 YRIK or YRIN insertions occurred in PBP3 of six E. coli isolates. The relative expression of blaKPC-2 in KPB125108 was 4.527 ± 0.2166 times higher than the control strain, and the relative expression of acrF in six E. coli isolates was 2-3 times higher than the control strain. The addition of phenylalanine-arginine-ß-naphthylamine at 100 mg/L decreased the MIC values of CZA against nine strains significantly. In conclusion, the antimicrobial resistance mechanisms in 10 isolates included increased expression of blaKPC-2, non-functional OMPs, upregulation of efflux pump activity, and variants of PBP3. Most of these mechanisms affected the antimicrobial activity of CZA by impeding ceftazidime.


Assuntos
Ceftazidima , Proteínas de Escherichia coli , Humanos , Ceftazidima/farmacologia , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Impedância Elétrica , Compostos Azabicíclicos/farmacologia , Combinação de Medicamentos , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Proteínas de Membrana
6.
Front Aging Neurosci ; 15: 1108205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875700

RESUMO

Objective: To investigate the role of gut microbiota and metabolites in POCD in elderly orthopedic patients, and screen the preoperative diagnostic indicators of gut microbiota in elderly POCD. Method: 40 elderly patients undergoing orthopedic surgery were enrolled and divided into Control group and POCD group following neuropsychological assessments. Gut microbiota was determined by 16S rRNA MiSeq sequencing, and metabolomics of GC-MS and LC-MS was used to screen the differential metabolites. We then analyzed the pathways enriched by metabolites. Result: There was no difference in alpha or beta diversity between Control group and POCD group. There were significant differences in 39 ASV and 20 genera bacterium in the relative abundance. Significant diagnostic efficiency analyzed by the ROC curves were found in 6 genera bacterium. Differential metabolites in the two groups including acetic acid, arachidic acid, pyrophosphate etc. were screened out and enriched to certain metabolic pathways which impacted the cognition function profoundly. Conclusion: Gut microbiota disorders exist preoperatively in the elderly POCD patients, by which there could be a chance to predict the susceptible population. Clinical Trial Registration: [http://www.chictr.org.cn/edit.aspx?pid=133843&htm=4], identifier [ChiCTR2100051162].

7.
Microbiol Spectr ; 11(1): e0110722, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36622219

RESUMO

Carbapenem-resistant Enterobacteriaceae, especially carbapenemase-producing Klebsiella pneumoniae, is an urgent problem in health care facilities worldwide. K. pneumoniae isolates classified as sequence type 11 (ST11) are largely responsible for the spread of carbapenem-resistant K. pneumoniae (CRKP) in China. Our previous phylogenetic reconstruction suggested that CRKP ST11 capsular locus 64 (KL64) was derived from an ST11-KL47 ancestor through recombination. However, the molecular origin of KL64 remains largely unknown, and our understanding of the recombination is incomplete. Here, we screened a global sample of 22,600 K. pneumoniae genomes and searched for KL64-harboring STs, which were found to be ST1764, ST3685, ST1764-1LV, ST30, ST505, ST147, and ST11, wherein ST1764, ST3685, ST1764-1LV, and ST30 belonged to a clonal complex, CC1764. We compared the genetic structures of representative strains from ST11-KL47, ST11-KL64, CC1764-KL64, ST505-KL64, and ST147-KL64 and further performed phylogenetic analysis and single-nucleotide polymorphism analysis among 248 isolates from all these STs. The results suggested a recombination event has occurred in a homologous ~154-kb region covering KL and the lipopolysaccharide biosynthesis locus (OL) between a recipient ST11-KL47-OL101 and a donor CC1764 (except ST30), giving rise to ST11-KL64-O2v1 strains (recombination I). Furthermore, we also found an infrequent ST11-KL64-O2v1 subclone which was not produced by recombination I but was hybridized from ST11-KL47-OL101 and ST147-KL64-O2v1 strains through recombination of a homologous ~485-kb region covering KL and OL (recombination II). Our findings provide important insights into the role of recombination in the evolution of clinical strains and the diversity of capsule and lipopolysaccharide of widely distributed KPC-associated ST11 K. pneumoniae in China. IMPORTANCE Chromosomal recombination events are considered to contribute to the genetic diversification and ultimate success of many bacterial pathogens. A previous study unravelled the molecular evolution history of ST258 strains, which have been largely responsible for the spread of KPC in the United States. Here, we used comparative genomic analyses to discover two recombination events in ST11 CRKP strains, which is a predominant KPC-associated CRKP clone in China. Two new ST11-CRKP subclones with altered capsule and lipopolysaccharide, which are two primary determinants of antigenicity and antigenic diversity among K. pneumoniae, were produced through these two recombination events, respectively. Horizontal transfer of the KL and OL appears to be a crucial element driving the molecular evolution of K. pneumoniae strains. These findings not only extend our understanding of the molecular evolutionary history of ST11 but also are an important step toward the development of preventive, diagnostic, and therapeutic strategies for CRKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Klebsiella pneumoniae , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Filogenia , Lipopolissacarídeos , Carbapenêmicos/uso terapêutico , China/epidemiologia , Infecções por Klebsiella/microbiologia , Recombinação Genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/genética
8.
Intensive Care Med ; 48(11): 1573-1581, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36129475

RESUMO

PURPOSE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the leading causes of healthcare-associated infections (HAIs) and is particularly pervasive in intensive care units (ICUs). This study takes ICU layout as the research object, and integrates clinical data and bacterial genome analysis to clarify the role of separate, small wards within the ICU in controlling the transmission of CRKP. METHODS: This study prospectively observed the carriage and spread of CRKP from a long-term in-hospital patient (hereafter called the Patient) colonized with CRKP in the gut and located in a separate, small ward within the ICU. The study also retrospectively investigated CRKP-HAIs in the same ICU. The relationship and transmission between CRKP isolates from the Patient and HAI events in the ICU were explored with comparative genomics. RESULTS: In this study, 65 CRKP-HAI cases occurred during the investigation period. Seven CRKP-HAI outbreaks were also observed. A total of 95 nonrepetitive CRKP isolates were collected, including 32 strains from the Patient in the separate small ward. Phylogenetic analysis based on core genome single-nucleotide polymorphism (cgSNP) showed that there were five possible CRKP clonal transmission events and two clonal outbreaks (A1, A2) during the study. CRKP strains from the Patient did not cause CRKP between-patient transmission or outbreaks in the ICU during the 5-year study period. CONCLUSION: The presence of a long-term hospitalized patient carrying CRKP and positioned in a separate, small ward did not lead to CRKP transmission or infection outbreaks in the ICU. Combining a small-ward ICU layout with normative HAI control measures for multidrug-resistant pathogen infection was effective in reducing CRKP transmission.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecção Hospitalar , Infecções por Klebsiella , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia , Hospitais , Unidades de Terapia Intensiva , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae , Filogenia , Estudos Retrospectivos
9.
Infect Drug Resist ; 15: 5035-5042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36068833

RESUMO

Purpose: With the spread of multiple drug-resistant bacteria, bla NDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of bla NDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both bla NDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We isolated an E. hormaechei strain DY1901 carrying both bla NDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying bla NDM-1 was 45Kb in length and belonged to IncX3. Conclusion: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.

11.
WIREs Mech Dis ; 14(6): e1571, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35891616

RESUMO

Ceftazidime/avibactam (CAZ/AVI), a combination of ceftazidime and a novel ß-lactamase inhibitor (avibactam) that has been approved by the U.S. Food and Drug Administration, the European Union, and the National Regulatory Administration in China. CAZ/AVI is used mainly to treat complicated urinary tract infections and complicated intra-abdominal infections in adults, as well as to treat patients infected with Carbapenem-resistant Enterobacteriaceae (CRE) susceptible to CAZ/AVI. However, increased clinical application of CAZ/AVI has resulted in the development of resistant strains. Mechanisms of resistance in most of these strains have been attributed to blaKPC mutations, which lead to amino acid substitutions in ß-lactamase and changes in gene expression. Resistance to CAZ/AVI is also associated with reduced expression and loss of outer membrane proteins or overexpression of efflux pumps. In this review, the prevalence of CAZ/AVI-resistance bacteria, resistance mechanisms, and selection of detection methods of CAZ/AVI are demonstrated, aiming to provide scientific evidence for the clinical prevention and treatment of CAZ/AVI resistant strains, and provide guidance for the development of new drugs. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.


Assuntos
Antibacterianos , Ceftazidima , Adulto , Humanos , Ceftazidima/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , beta-Lactamases/genética
12.
Front Cell Infect Microbiol ; 12: 926209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811669

RESUMO

Aztreonam/avibactam (AZA), as one of the novel ß-lactamases and ß-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC , ompK35, and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Sepse , Antibacterianos/uso terapêutico , Compostos Azabicíclicos , Aztreonam/metabolismo , Aztreonam/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Genômica , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/metabolismo
13.
Infect Drug Resist ; 15: 2835-2841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677527

RESUMO

Purpose: Nosocomial infections caused by New Delhi metallo-ß-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene bla NDM-1 and also have antibiotic resistance genes such as ß-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship. Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded bla NDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.

14.
Front Microbiol ; 13: 782210, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308401

RESUMO

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a common cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, but its infection and colonization state are difficult to distinguish. If the judgment is wrong, it may aggravate the abuse of antibiotics and further accelerate the evolution of drug resistance. We sought to provide new clues for the diagnosis, pathogenesis and treatment of CRAB VAP based on lower respiratory tract (LRT) microbiota. Methods: A prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed. Results: Fifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81, P < 0.05). Abundances of 11 key genera differed between the groups. Acinetobacter was most abundant in CRAB-I (76.19%), moderately abundant in CRAB-C (59.14%), and least abundant in CRAB-N (11.25%), but its interactions with other genera increased in turn. Metagenomics and WGS analysis showed that virulence genes were more abundant in CRAB-I than in CRAB-C. Multi-locus sequence typing (MLST) of 46 CRAB isolates revealed that the main types were ST208 (30.43%) and ST938 (15.22%), with no difference between CRAB-I and CRAB-C. Conclusion: Lower respiratory tract microbiota dysbiosis including elevated relative abundance of Acinetobacter and reduced bacterial interactions, and virulence enrichment may lead to CRAB VAP.

15.
Emerg Microbes Infect ; 10(1): 2244-2255, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34756150

RESUMO

Clostridioides difficile is the most common pathogen causing antibiotic-associated diarrhea. Previous studies showed that diverse sources, aside from C. difficile infection (CDI) patients, played a major role in C. difficile hospital transmission. This study aimed to investigate relationships and transmission potential of C. difficile strains from different sources. A prospective study was conducted both in the intensive care unit (ICU) and six livestock farms in China in 2018-2019. Ninety-eight strains from CDI patients (10 isolates), asymptomatic hospitalized carriers (55), the ICU environment (12), animals (14), soil (4), and farmers (3) were collected. Sequence type (ST) 3/ribotype (RT) 001, ST35/RT046, and ST48/RT596 were dominant types, distributed widely in multiple sources. Core-genome single-nucleotide polymorphism (cgSNP) analysis showed that hospital and farm strains shared several common clonal groups (CGs, strains separated by ≤ 2 cgSNPs) (CG4/ST3/RT001, CG7/ST35/RT046, CG11/ST48/RT596). CDI patients, asymptomatic carriers, and the ICU environment strains also shared several common CGs. The number of virulence genes was not statistically different between strains from different sources. Multi-source strains in the same CG carried identical virulence gene sequences, including pathogenicity genes at the pathogenicity locus and adhesion-related genes at S-layer cassette. Resistance genes (ermB, tetM, etc.) were widespread in multiple sources, and multi-source strains in the same CG had similar resistance phenotypes and carried consistent transposons and plasmid types. The study indicated that interspecies and cross-regional transmission of C. difficile occurs between animals, the environment, and humans. Community-associated strains from both farms and asymptomatic hospitalized carriers were important reservoirs of CDI in hospitals.


Assuntos
Animais Domésticos/microbiologia , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecções por Clostridium/veterinária , Animais , China , Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Fezes/microbiologia , Genoma Bacteriano , Humanos , Filogenia , Estudos Prospectivos , Virulência
16.
Gut Pathog ; 13(1): 59, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645508

RESUMO

BACKGROUND: To investigate the antimicrobial profiles and genomic characteristics of MDR-Citrobacter spp. strains isolated from Fennec fox imported from Sudan to China. METHODS: Four Citrobacter spp. strains were isolated from stool samples. Individual fresh stool samples were collected and subsequently diluted in phosphate buffered saline as described previously. The diluted fecal samples were plated on MacConkey agar supplemented with 1 mg/l cefotaxime and incubated for 20 h at 37 °C. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used for identification. Antimicrobial susceptibility testing was performed using the broth microdilution method. Whole-genome sequencing was performed on an Illumina Novaseq-6000 platform. Acquired antimicrobial resistance genes and plasmid replicons were detected using ResFinder 4.1 and PlasmidFinder 1.3, respectively. Comparative genomic analysis of 277 Citrobacter genomes was also performed. RESULTS: Isolate FF141 was identified as Citrobacter cronae while isolate FF371, isolate FF414, and isolate FF423 were identified as Citrobacter braakii. Of these, three C. braakii isolates were further confirmed to be extended-spectrum ß-lactamases (ESBL)-producer. All isolates are all multidrug resistance (MDR) with resistance to multiple antimicrobials. Plasmid of pKPC-CAV1321 belong to incompatibility (Inc) group. Comparative genomics analysis of Citrobacter isolates generated a large core-genome. Genetic diversity was observed in our bacterial collection, which clustered into five main clades. Human, environmental and animal Citrobacter isolates were distributed into five clusters. CONCLUSIONS: To our knowledge, this is the first investigation of MDR-Citrobacter from Fennec Fox. Our phenotypic and genomic data further underscore the threat of increased ESBL prevalence in wildlife and emphasize that increased effort should be committed to monitoring the potentially rapid dissemination of ESBL-producers with one health perspective.

17.
Microbiol Res ; 253: 126881, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592562

RESUMO

This study was conducted to explore the prevalence and transmission of mcr-1 Escherichia coli among healthy rural residents in Shandong, China, and to provide theoretical basis for the prevention and control of spread and treatment of multi-drug resistant Escherichia coli. A total of 218 healthy residents from 3 villages in Guan County, Shandong Province, China were included in this study, and their fecal samples were collected. Colistin-resistant Escherichia coli were selected, and their drug sensitivity and plasmids' transferability were measured. After analysis, some conclusions can be drawn. The colistin-resistant Escherichia coli, most strains of which are MDROs, is common and highly transmissible in healthy residents in rural areas in China. Interventions should be implemented to prevent the spread of colistin-resistant Escherichia coli through health education and tighter regulation of antibiotics.


Assuntos
Colistina , Farmacorresistência Bacteriana , Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli , China/epidemiologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Prevalência
18.
Infect Drug Resist ; 14: 3011-3017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413655

RESUMO

BACKGROUND: The emergence of the plasmid-borne colistin-resistant gene (mcr-1) poses a great threat to human health. What is worse, the recent observations of the coexistence of mcr-1 with carbapenemase encoding genes in some bacteria caused even more concern. Yet, there is a lack of observations of such strains in the human gut. METHODS: The isolation of E. coli L889 was performed on selective medium plates. Antibiotic susceptibilities were determined by an agar dilution and a broth microdilution method. Multi-locus sequence typing (MLST) and acquired resistance genes were also characterized. Transferability of bla NDM-9/mcr-1-carrying plasmids was determined by conjugation, replicon typing and S1-Pulsed-field gel electrophoresis (S1-PFGE), and Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Novaseq and Nanopore platforms. RESULTS: E. coli L889 was identified as ST1101 concomitantly carrying bla NDM-9 and mcr-1 from a stool sample. Antimicrobial susceptibility tests showed that it was resistant to various antimicrobial agents and only susceptible to tigecycline. Notably, bla NDM-9 was located on a ~114-kb untypable plasmid, while mcr-1 was located on a ~63-kb IncI2 plasmid. CONCLUSION: Our research, to our knowledge, first reported an ST1101 E. coli strain with an untypeable bla NDM-9-harbouring plasmid and an IncI2 mcr-1-carrying plasmid. The colonized E. coli strains potentially contribute to the dissemination and transfer of bla NDM-9 and mcr-1 to clinical isolates, which is a considerable threat to public health and should be closely monitored.

19.
Infect Drug Resist ; 14: 185-192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500639

RESUMO

PURPOSE: To explore the epidemiological characteristics and risk factors of bloodstream infections (BSI) in patients who develop agranulocytosis fever after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study also provides a basis for the clinical treatment of BSI. METHODS: A retrospective analysis of 397 allo-HSCT patients in the Department of Hematology of our hospital was conducted from January 2013 to December 2017 to analyze the incidence of BSI, the distribution and types of pathogenic bacteria, and drug resistance rates. We also determined whether various parameters are risk factors to BSI, including the patient age, gender, disease type, transplantation method, stem cell source, pre-treatment with anti-thymocyte globulin (ATG), and agranulocytosis time. RESULTS: Among the 397 allo-HSCT patients, 294 had a fever during the period of agranulocytosis, and 52 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 17.7% (52/294). Among the 60 pathogens detected, 43 (71.67%), 10 (16.67%), and 7 (11.67%) were Gram negative strains, Gram positive strains, and fungi, respectively. The most common bacteria were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The detection rate of extended-spectrum ß-lactamase (ESBL) was 40.0%, and carbapenem-resistant Enterobacteriaceae (CRE) accounted for 17.9%. Single-factor and multi-factor analyses showed that pre-treatment with ATG, agranulocytosis time (≥21 days), and stem cell source were risk factors for BSI. CONCLUSION: We found that in our hospital, BSIs in allo-HSCT patients are mainly caused by Gram-negative bacteria, and the resistance rate to carbapenem drugs is high. Pre-treatment with ATG, agranulocytosis time (≥21 days), and stem cell source are risk factors for BSI.

20.
Semin Cardiothorac Vasc Anesth ; 25(1): 39-45, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33148132

RESUMO

Stanford type A acute aortic dissection (AAD) is a life-threatening illness that presents with chest pain and hemodynamic instability. AAD prompt and accurate evaluation and management are critical for survival as it is a cardiac surgical emergency. The initial treatment of AAD mandates strict blood pressure stabilization with intravenous antihypertensive medications. The progressive nature of the disease will increase the mortality as time elapses between diagnosis and surgical intervention. In addition, the patient's blood pressure control is challenged in the presence of renal failure requiring hemodialysis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or named 2019-nCoV) pneumonia was a newly underrecognized illness (COVID-19 [coronavirus disease 2019]). COVID-19 can cause severe acute respiratory distress syndrome, acute kidney injury, heart injury, and liver dysfunction, which would aggravate the progress of aortic dissection. In this article, we report the successful anesthesia management in a pneumonia patient with AAD complicated with renal failure during the COVID-19 epidemic period, who underwent emergency surgery and deep hypothermic circulatory arrest repair.


Assuntos
Anestesia/métodos , Dissecção Aórtica/cirurgia , COVID-19/complicações , Insuficiência Renal/etiologia , SARS-CoV-2 , Adulto , Dissecção Aórtica/complicações , Feminino , Humanos
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