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Clinical Microbiology Reviews Jun 2023Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern... (Review)
Review
Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Linezolid; Bacteremia; Vancomycin-Resistant Enterococci; Anti-Infective Agents; Sepsis; Gram-Positive Bacterial Infections
PubMed: 37067406
DOI: 10.1128/cmr.00059-22 -
Nature Feb 2024Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics...
Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4 T cells and agonism of the pregnane X receptor. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.
Topics: Animals; Humans; Bifidobacterium; Bile Acids and Salts; CD4-Positive T-Lymphocytes; Clostridium; Cohort Studies; Crohn Disease; Enterococcus; Esters; Fatty Acids; Inflammatory Bowel Diseases; Metabolomics; Phenotype; Pregnane X Receptor; Reproducibility of Results; Tandem Mass Spectrometry; Amides
PubMed: 38052229
DOI: 10.1038/s41586-023-06906-8 -
Frontiers in Cellular and Infection... 2023The human-bacterial association is long-known and well-established in terms of both augmentations of human health and attenuation. However, the growing incidents of... (Review)
Review
The human-bacterial association is long-known and well-established in terms of both augmentations of human health and attenuation. However, the growing incidents of nosocomial infections caused by the ESKAPE pathogens (, , , , , and sp.) call for a much deeper understanding of these organisms. Adopting a holistic approach that includes the science of infection and the recent advancements in preventing and treating infections is imperative in designing novel intervention strategies against ESKAPE pathogens. In this regard, this review captures the ingenious strategies commissioned by these master players, which are teamed up against the defenses of the human team, that are equally, if not more, versatile and potent through an analogy. We have taken a basketball match as our analogy, dividing the human and bacterial species into two teams playing with the ball of health. Through this analogy, we make the concept of infectious biology more accessible.
Topics: Humans; Quorum Sensing; Anti-Bacterial Agents; Virulence; Staphylococcal Infections; Enterococcus faecium
PubMed: 37457962
DOI: 10.3389/fcimb.2023.1159798 -
The Journal of Hospital Infection Nov 2023Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however,... (Meta-Analysis)
Meta-Analysis Review
Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however, remains fragmented. We aimed to summarize recent studies on VRE epidemiology and outcomes in hospitals, long-term-care facilities (LTCFs) and nursing homes worldwide based on current epidemiological reports. We searched MEDLINE/PubMed, the Cochrane Library, and Web of Science for observational studies, which reported on VRE faecium and faecalis infections in in-patients published between January 2014 and December 2020. Outcomes were incidence, infection rate, mortality, length of stay (LOS), and healthcare costs. We conducted a meta-analysis on mortality (PROSPERO registration number: CRD42020146389). Of 681 identified publications, 57 studies were included in the analysis. Overall quality of evidence was moderate to low. VRE incidence was rarely and heterogeneously reported. VRE infection rate differed highly (1-55%). The meta-analysis showed a higher mortality for VRE faecium bloodstream infections (BSIs) compared with VSE faecium BSIs (risk ratio, RR 1.46; 95% confidence interval (CI) 1.17-1.82). No difference was observed when comparing VRE faecium vs VRE faecalis BSI (RR 1.00, 95% CI 0.52-1.93). LOS was higher in BSIs caused by E. faecium vs E. faecalis. Only three studies reported healthcare costs. In contrast to previous findings, our meta-analysis of included studies indicates that vancomycin resistance independent of VRE species may be associated with a higher mortality. We identified a lack of standardization in reporting outcomes, information regarding healthcare costs, and state-of-the-art microbiological species identification methodology, which may inform the set-up and reporting of future studies.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Vancomycin-Resistant Enterococci; Sepsis
PubMed: 37734679
DOI: 10.1016/j.jhin.2023.09.008 -
Frontiers in Cellular and Infection... 2023Antimicrobial-resistant ESKAPE (, , , , , and species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens... (Review)
Review
Antimicrobial-resistant ESKAPE (, , , , , and species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens in nosocomial infections, and a considerable number of their clinical isolates are not susceptible to conventional antimicrobial therapy. Therefore, innovative therapeutic strategies that can effectively deal with ESKAPE pathogens will bring huge social and economic benefits and ease the suffering of tens of thousands of patients. Among these strategies, CRISPR (clustered regularly interspaced short palindromic repeats) system has received extra attention due to its high specificity. Regrettably, there is currently no direct CRISPR-system-based anti-infective treatment. This paper reviews the applications of CRISPR-Cas system in the study of ESKAPE pathogens, aiming to provide directions for the research of ideal new drugs and provide a reference for solving a series of problems caused by multidrug-resistant bacteria (MDR) in the post-antibiotic era. However, most research is still far from clinical application.
Topics: Humans; CRISPR-Cas Systems; Acinetobacter baumannii; Anti-Bacterial Agents; Cross Infection; Enterococcus faecium
PubMed: 37662004
DOI: 10.3389/fcimb.2023.1223696 -
Scientific Reports Sep 2023Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor...
Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with gastrointestinal disorders. Nevertheless, it is still unclear how antibiotics can cause anxiety and depression. In this study, oral administration of cefaclor, a second-generation cephalosporin antibiotic, induced anxiety- and depression-like behaviors and colitis with gut microbiota alteration in mice. Cefaclor reduced serotonin levels and fluctuated 5-HT receptor mRNA expressions such as Htr1a, Htr1b, and Htr6 in the hippocampus. Vagotomy attenuated the cefaclor-induced anxiety- and depression-like symptoms, while the cefaclor-induced changes in gut bacteria alteration and colitis were not affected. Fluoxetine attenuated cefaclor-induced anxiety- and depression-like behaviors. Furthermore, fluoxetine decreased cefaclor-resistant Enterobacteriaceae and Enterococcaceae. Taken together, our findings suggest that the use of antibiotics, particularly, cefaclor may cause gut dysbiosis-dependent anxiety and depression through the microbiota-gut-blood-brain and microbiota-gut-vagus nerve-brain pathway. Targeting antibiotics-resistant pathogenic bacteria may be a promising therapeutic strategy for the treatment of anxiety and depression.
Topics: Animals; Mice; Cefaclor; Depression; Dysbiosis; Fluoxetine; Serotonin; Anti-Bacterial Agents; Vagus Nerve; Colitis
PubMed: 37726354
DOI: 10.1038/s41598-023-42690-1 -
PeerJ 2023Kawasaki disease (KD) is a multi-systemic vasculitis that primarily affects children and has an unknown cause. Although an increasing number of studies linking the gut...
BACKGROUND
Kawasaki disease (KD) is a multi-systemic vasculitis that primarily affects children and has an unknown cause. Although an increasing number of studies linking the gut microbiota with KD, the unchallengeable etiology of KD is not available.
METHODS
Here, we obtained fecal and oral samples from KD patients and healthy controls, and then we use high-throughput sequencing to examine the diversity and composition of microbiota.
RESULTS
Results showed that both in the gut and oral microbiota, the diversity of KD patients was significantly lower than that of the healthy controls. In the gut microbiota, a higher abundance of (40.12% less than 0.1%), (20.71% 3.06%), (17.56% 0.61%), (5.97% 0.11%) and (4.69% 0.1%) was observed in the KD patients, and enrichment of in the patients was observed. In terms of oral microbiota, the prevalence of (21.99% 0.1%), (3.02% 0.1%), and (0.68% 0.0%) were significantly higher in the KD patients, with the enrichment of and . Additionally, significant differences in microbial community function between KD patients and healthy controls in the fecal samples were also observed, which will affect the colonization and reproduction of gut microbiota.
CONCLUSIONS
These results suggested that the dysbiosis of gut and oral microbiota are both related to KD pathogenesis, of which, the prevalence of in the gut and higher abundance of and in the oral cavity will be a potential biomarker of the KD. Overall, this study not only confirms that the disturbance of gut microbiota is a causative trigger of KD but also provides new insight into the oral microbiota involved in KD pathogenesis.
Topics: Child; Humans; Gastrointestinal Microbiome; Mucocutaneous Lymph Node Syndrome; Enterococcus; Microbiota; Feces; Escherichia; Shigella
PubMed: 37456866
DOI: 10.7717/peerj.15662 -
International Journal of Molecular... Jul 2023species are known for their ability to form biofilms, which contributes to their survival in extreme environments and involvement in persistent bacterial infections,... (Review)
Review
species are known for their ability to form biofilms, which contributes to their survival in extreme environments and involvement in persistent bacterial infections, especially in the case of multi-drug-resistant strains. This review aims to provide a comprehensive understanding of the mechanisms underlying biofilm formation in clinically important species such as and the less studied but increasingly multi-drug-resistant , and explores potential strategies for their eradication. Biofilm formation in involves a complex interplay of genes and virulence factors, including gelatinase, cytolysin, Secreted antigen A, pili, microbial surface components that recognize adhesive matrix molecules (MSCRAMMs), and DNA release. Quorum sensing, a process of intercellular communication, mediated by peptide pheromones such as Cob, Ccf, and Cpd, plays a crucial role in coordinating biofilm development by targeting gene expression and regulation. Additionally, the regulation of extracellular DNA (eDNA) release has emerged as a fundamental component in biofilm formation. In , the autolysin N-acetylglucosaminidase and proteases such as gelatinase and serin protease are key players in this process, influencing biofilm development and virulence. Targeting eDNA may offer a promising avenue for intervention in biofilm-producing infections. Overall, gaining insights into the intricate mechanisms of biofilm formation in may provide directions for anti-biofilm therapeutic research, with the purpose of reducing the burden of -associated infections.
Topics: Enterococcus; Biofilms; Enterococcus faecalis; Quorum Sensing; Gelatinases; Bacterial Proteins
PubMed: 37511337
DOI: 10.3390/ijms241411577 -
Frontiers in Cellular and Infection... 2023This study aims to investigate the distribution and drug resistance of bacteria in clinical blood culture specimens from children in Jiangxi province in recent years and...
OBJECTIVE
This study aims to investigate the distribution and drug resistance of bacteria in clinical blood culture specimens from children in Jiangxi province in recent years and to provide a foundation for preventing and treating bloodstream infection diseases in children.
METHODS
The study involved a statistical analysis of the isolation and drug resistance of bacterial strains obtained from blood culture specimens of children in Jiangxi province between 2017 and 2021. The analysis was performed using the WHONET 5.6 software.
RESULTS
A total of 7,977 bacterial strains were isolated from the blood samples of children between 2017 and 2021. Of these, 2,334 strains (29.3%) were identified as Gram-negative bacteria, and 5,643 strains (70.7%) were identified as Gram-positive bacteria. The most commonly isolated pathogens were coagulase-negative , , and Among the Gram-negative bacteria, (840 strains, 36.0%), pneumoniae (385 strains), (283 strains), (137 strains), and (109 strains) were the most prevalent. Among the Gram-positive bacteria, coagulase-negative (3,424 strains, 60.7%), (679 strains), (432 strains), sp. (292 strains), and (192 strains) were the most common. Resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) was observed in 45.9% and 56.0% of and strains, respectively, while resistance to carbapenems was observed in 4.6% and 20.3% of these strains, respectively. Resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) was observed in 15.5% of strains, while resistance to imipenem was absent. Carbapenem resistance was observed in 17.1% (20/117) and 13% (14/108) of and strains, respectively. Methicillin-resistant (MRSA) was detected in 32.7% of the strains, while methicillin-resistant coagulase-negative was detected in 64.3% of the coagulase-negative strains. No bacteria resistant to vancomycin were detected. Four strains of vancomycin-resistant were detected over the 5-year period, and one strain of linezolid-resistant was detected.
CONCLUSION
Gram-positive cocci were the most commonly isolated clinical pathogens in blood specimens from children in Jiangxi province. The composition of the pathogen species showed a slight change over the years. The detection ratios of pathogens varied with age group and season. Although the isolation rate of common carbapenem-resistant Enterobacter bacteria has decreased, it remains high. It is necessary to monitor the antimicrobial resistance of pathogens causing bloodstream infections in children more closely, and antimicrobial agents should be used with caution.
Topics: Humans; Child; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Ceftriaxone; Vancomycin; Coagulase; Drug Resistance, Bacterial; Bacteria; Staphylococcus aureus; Cefotaxime; Gram-Positive Bacteria; Staphylococcal Infections; Gram-Negative Bacteria; Staphylococcus; Enterococcus; Carbapenems; Drug Resistance; Escherichia coli
PubMed: 37424793
DOI: 10.3389/fcimb.2023.1163312 -
Emerging Microbes & Infections Dec 2024The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens -... (Review)
Review
The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.
Topics: Humans; Anti-Bacterial Agents; Bacterial Infections; Klebsiella pneumoniae; Drug Resistance, Multiple, Bacterial; Enterococcus faecium
PubMed: 38356197
DOI: 10.1080/22221751.2024.2317915