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Scientific Reports Jun 2024This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative...
This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety.
Topics: beta-Lactamases; China; Bacterial Proteins; Humans; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Male; Female; Microbial Sensitivity Tests; Adult; Middle Aged; Carbapenems; Anti-Bacterial Agents; Aged; Drug Resistance, Multiple, Bacterial; Child; Adolescent; Child, Preschool; Young Adult; Klebsiella pneumoniae; Acinetobacter baumannii; Infant
PubMed: 38909136
DOI: 10.1038/s41598-024-65106-0 -
Journal of Infection and Public Health Jun 2024Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess...
Evaluation of antimicrobial selective pressure using the multicenter semiautomatic surveillance system Japan surveillance for infection prevention and healthcare epidemiology.
BACKGROUND
Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data.
METHODS
Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin-tazobactam [PIP/TAZ], ampicillin-sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated.
RESULTS
In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection.
CONCLUSION
CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.
PubMed: 38908067
DOI: 10.1016/j.jiph.2024.102474 -
Cell Communication and Signaling : CCS Jun 2024Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway....
BACKGROUND
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells.
METHODS
Human telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood.
RESULTS
EVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control.
CONCLUSIONS
This is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.
Topics: Humans; Pseudomonas aeruginosa; Extracellular Vesicles; Pseudomonas Infections; Neutrophils; Epithelial Cells; Cytokines; HL-60 Cells
PubMed: 38907250
DOI: 10.1186/s12964-024-01609-7 -
Science Advances Jun 2024The central nervous system coordinates peripheral cellular stress responses, including the unfolded protein response of the mitochondria (UPR); however, the contexts for...
The central nervous system coordinates peripheral cellular stress responses, including the unfolded protein response of the mitochondria (UPR); however, the contexts for which this regulatory capability evolved are unknown. UPR is up-regulated upon pathogenic infection and in metabolic flux, and the olfactory nervous system has been shown to regulate pathogen resistance and peripheral metabolic activity. Therefore, we asked whether the olfactory nervous system in controls the UPR cell nonautonomously. We found that silencing a single inhibitory olfactory neuron pair, AWC, led to robust induction of UPR and reduction of oxidative phosphorylation dependent on serotonin signaling and -mediated mitophagy. Further, AWC ablation confers resistance to the pathogenic bacteria partially dependent on the UPR transcription factor and fully dependent on mitophagy machinery. These data illustrate a role for the olfactory nervous system in regulating whole-organism mitochondrial dynamics, perhaps in preparation for postprandial metabolic stress or pathogenic infection.
Topics: Animals; Caenorhabditis elegans; Mitophagy; Mitochondria; Caenorhabditis elegans Proteins; Smell; Unfolded Protein Response; Pseudomonas aeruginosa; Ubiquitin-Protein Ligases; Oxidative Phosphorylation; Signal Transduction; Serotonin; Transcription Factors
PubMed: 38905346
DOI: 10.1126/sciadv.adn0014 -
Frontiers in Cellular and Infection... 2024Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A...
INTRODUCTION
Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A extended-spectrum β-lactamase, has been well documented . However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing clinical isolates that were ceftazidime and/or carbapenem non-susceptible.
METHODS
Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics.
RESULTS
Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried . One isolate carried but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the evolved isolate.
DISCUSSION
PER-3-producing ST309 is a successful multidrug-resistant clone with gene implicated in resistance to CZA and other β-lactams.
Topics: Ceftazidime; Pseudomonas aeruginosa; Azabicyclo Compounds; Microbial Sensitivity Tests; Humans; Drug Combinations; beta-Lactamases; Anti-Bacterial Agents; Pseudomonas Infections; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Chile; Whole Genome Sequencing; Mutation
PubMed: 38903939
DOI: 10.3389/fcimb.2024.1410834 -
PeerJ 2024Pathogenic bacteria are the cause of most skin diseases, but issues such as resistance and environmental degradation drive the need to research alternative treatments....
BACKGROUND
Pathogenic bacteria are the cause of most skin diseases, but issues such as resistance and environmental degradation drive the need to research alternative treatments. It is reported that silk cocoon extract possesses antioxidant properties. During silk processing, the degumming of silk cocoons creates a byproduct that contains natural active substances. These substances were found to have inhibitory effects on bacterial growth, DNA synthesis, the pathogenesis of hemolysis, and biofilm formation. Thus, silk cocoon extracts can be used in therapeutic applications for the prevention and treatment of skin pathogenic bacterial infections.
METHODS
The extract of silk cocoons with pupae (SCP) and silk cocoons without pupae (SCWP) were obtained by boiling with distilled water for 9 h and 12 h, and were compared to silkworm pupae (SP) extract that was boiled for 1 h. The active compounds in the extracts, including gallic acid and quercetin, were determined using high-performance liquid chromatography (HPLC). Furthermore, the total phenolic and flavonoid content in the extracts were investigated using the Folin-Ciocalteu method and the aluminum chloride colorimetric method, respectively. To assess antioxidant activity, the extracts were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Additionally, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of silk extracts and phytochemical compounds were determined against skin pathogenic bacteria. This study assessed the effects of the extracts and phytochemical compounds on growth inhibition, biofilm formation, hemolysis protection, and DNA synthesis of bacteria.
RESULTS
The HPLC characterization of the silk extracts showed gallic acid levels to be the highest, especially in SCP (8.638-31.605 mg/g extract) and SP (64.530 mg/g extract); whereas quercetin compound was only detected in SCWP (0.021-0.031 mg/g extract). The total phenolics and flavonoids in silk extracts exhibited antioxidant and antimicrobial activity. Additionally, SCP at 9 h and 12 h revealed the highest anti-bacterial activity, with the lowest MIC and MBC of 50-100 mg/mL against skin pathogenic bacteria including , methicillin-resistant (MRSA), and . Hence, SCP extract and non-sericin compounds containing gallic acid and quercetin exhibited the strongest inhibition of both growth and DNA synthesis on skin pathogenic bacteria. The suppression of bacterial pathogenesis, including preformed and matured biofilms, and hemolysis activity, were also revealed in SCP extract and non-sericin compounds. The results show that the byproduct of silk processing can serve as an alternative source of natural phenolic and flavonoid antioxidants that can be used in therapeutic applications for the prevention and treatment of pathogenic bacterial skin infections.
Topics: Animals; Bombyx; Antioxidants; Silk; Anti-Bacterial Agents; Biofilms; Pupa; Free Radicals; Microbial Sensitivity Tests; Hemolysis
PubMed: 38903886
DOI: 10.7717/peerj.17490 -
Frontiers in Microbiology 2024In patients admitted to intensive care units (ICUs), Gram-negative bacteria (GNB) infections pose significant challenges due to their contribution to morbidity,...
INTRODUCTION
In patients admitted to intensive care units (ICUs), Gram-negative bacteria (GNB) infections pose significant challenges due to their contribution to morbidity, mortality, and healthcare costs. During the SARS-CoV-2 pandemic, Italy witnessed a rise in healthcare-associated infections (HAIs), with GNBs involved in a substantial proportion of cases. Concerningly, carbapenem-resistant GNBs (CR-GNBs) have increased worldwide, posing therapeutic challenges.
METHODS
Retrospective multicentre study analysing data from over 299,000 patients admitted to Italian ICUs from 2013 to 2022.
RESULTS
The study revealed an average of 1.5 infections per patient, with HAIs peaking during the pandemic years. Ventilator associated pneumonia (VAP) emerged as the most common HAI, with spp. and predominating. Alarmingly, CR-GNBs accounted for a significant proportion of infections, particularly in VAP, bloodstream infections, and intra-abdominal infections.
DISCUSSION
Our findings underscore the pressing need for enhanced infection control measures, particularly in the ICU setting, to mitigate the rising prevalence of CR-GNBs and their impact on patient outcomes. The study provides valuable insights into the epidemiology of HAIs in Italian ICUs and highlights the challenges posed by CR-GNBs, especially in the context of the SARS-CoV-2 pandemic, which exacerbated the issue and may serve as a crucial example for the management of future viral pandemics.
PubMed: 38903794
DOI: 10.3389/fmicb.2024.1405390 -
Frontiers in Microbiology 2024has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction...
OBJECTIVE
has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of isolates and clinical samples by genotype is helpful for timely antibiotic treatment.
METHODS
In the study, whole genome sequencing (WGS) data of 494 isolates were used to screen key anti-microbial resistance (AMR)-associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of to four antibiotics by the AMR-associated features screened, we collected 74 positive sputum samples to sequence by metagenomics next-generation sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model.
RESULTS
We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in . The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of , in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance.
CONCLUSION
In summary, mNGS can predict the resistance of by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria.
PubMed: 38903781
DOI: 10.3389/fmicb.2024.1413434 -
Health Science Reports Jun 2024as an opportunistic pathogen produces several virulence factors. This study evaluated the relative frequency of exoenzymes () A, U and S genes and integron classes (I,...
BACKGROUND
as an opportunistic pathogen produces several virulence factors. This study evaluated the relative frequency of exoenzymes () A, U and S genes and integron classes (I, II, and III) among multi-drug-resistant clinical isolates from burn patients in Ahvaz, southwest of Iran.
METHODS
In this cross-sectional study isolates were recovered from 355 wound samples. The antimicrobial susceptibility test was done by disk agar diffusion method on Muller-Hinton agar according to the Clinical and Laboratory Standards Institute. MDR isolates were defined if they showed simultaneous resistance to 3 antibiotics. Extensively drug-resistant was defined as nonsusceptibility to at least one agent in all but two or fewer antimicrobial categories. The presence of class I, II, and III integrons and virulence genes was determined using a PCR assay on extracted DNA.
RESULTS
Overall, 145 clinical isolates were confirmed with biochemical and PCR tests. Overall, 35% (52/145) of the isolates were taken from males and 64% (93/145) from female hospitalized burn patients. The highest resistance rates of isolates to antibiotics were related to piperacillin 59% ( = 86/145) and piperacillin-tazobactam 57% ( = 83/145). A total of 100% of isolates were resistant to at least one antibiotic. MDR and XDR had a frequency of 60% and 29%, respectively. The prevalence of integron classes I, II, and III in was 60%, 7.58%, and 3.44%, respectively. was more common in MDR and XDR isolates. In addition, 70(48%) of isolates did not harbor integron genes. Besides, , and in had a frequency of 55%, 55%, and 56%, respectively.
CONCLUSION
It was found that as a potent pathogen with strong virulence factors and high antibiotic resistance in the health community can cause refractory diseases in burn patients.
PubMed: 38903659
DOI: 10.1002/hsr2.2164 -
Frontiers in Immunology 2024Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability,... (Review)
Review
Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by and ImpA secreted by , as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αβ on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
Topics: Extracellular Vesicles; Phagocytosis; Humans; Animals; Bacterial Proteins; Neoplasms; Integrin alphaVbeta3; Hyaluronan Receptors; Pseudomonas aeruginosa
PubMed: 38903499
DOI: 10.3389/fimmu.2024.1418061