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Drug Resistance Updates : Reviews and... Jun 2024Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are...
Surface chemistry engineered selenium nanoparticles as bactericidal and immuno-modulating dual-functional agents for combating methicillin-resistant Staphylococcus aureus Infection.
Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, in vivo studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8 and CD4 T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.
PubMed: 38936006
DOI: 10.1016/j.drup.2024.101102 -
JAMA Network Open Jun 2024Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily...
IMPORTANCE
Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.
OBJECTIVE
To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission.
EXPOSURES
Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use.
MAIN OUTCOMES AND MEASURES
Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics.
RESULTS
Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.
Topics: Humans; Anti-Bacterial Agents; Cross-Sectional Studies; Sepsis; Male; Female; Middle Aged; Community-Acquired Infections; United States; Aged; Methicillin-Resistant Staphylococcus aureus; Adult; Hospitals
PubMed: 38935374
DOI: 10.1001/jamanetworkopen.2024.18923 -
Journal of Clinical Microbiology Jun 2024In this study, we investigated the genomic changes in a major methicillin-resistant (MRSA) clone following a significant outbreak at a hospital. Whole-genome sequencing...
In this study, we investigated the genomic changes in a major methicillin-resistant (MRSA) clone following a significant outbreak at a hospital. Whole-genome sequencing of MRSA isolates was utilized to explore the genomic evolution of post-outbreak MRSA strains. The epidemicity of the clone declined over time, coinciding with the introduction of multimodal infection control measures. A genome-wide association study (GWAS) identified multiple genes significantly associated with either high or low epidemic success, indicating alterations in mobilome, virulence, and defense mechanisms. Random Forest models pinpointed a gene related to fibrinogen binding as the most influential predictor of epidemicity. The decline of the MRSA clone may be attributed to various factors, including the implementation of new infection control measures, single nucleotide polymorphisms accumulation, and the genetic drift of a given clone. This research underscores the complex dynamics of MRSA clones, emphasizing the multifactorial nature of their evolution. The decline in epidemicity seems linked to alterations in the clone's genetic profile, with a probable shift towards decreased virulence and adaptation to long-term carriage. Understanding the genomic basis for the decline of epidemic clones is crucial to develop effective strategies for their surveillance and management, as well as to gain insights into the evolutionary dynamics of pathogen genomes.
PubMed: 38934681
DOI: 10.1128/jcm.00203-24 -
Infection and Drug Resistance 2024To analyze the antibiotic resistance profile, virulence genes, and molecular typing of () strains isolated in skin and soft tissue infections at the First Affiliated...
OBJECTIVE
To analyze the antibiotic resistance profile, virulence genes, and molecular typing of () strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of .
METHODS
In 2023, 65 strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing.
RESULTS
In this study, of the 65 strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. was the most prevalent virulence gene (100%) in strains isolated in skin and soft tissue infections, followed by (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant isolates to various antibiotics were significantly higher than those of methicillin-susceptible isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST.
CONCLUSION
In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene and of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.
PubMed: 38933775
DOI: 10.2147/IDR.S465951 -
Pharmaceuticals (Basel, Switzerland) Jun 2024A tremendous increase in the green synthesis of metallic nanoparticles has been noticed in the last decades, which is due to their unique properties at the nano...
Exploring the Potential of Halotolerant Actinomycetes from Rann of Kutch, India: A Study on the Synthesis, Characterization, and Biomedical Applications of Silver Nanoparticles.
A tremendous increase in the green synthesis of metallic nanoparticles has been noticed in the last decades, which is due to their unique properties at the nano dimension. The present research work deals with synthesis mediated by the actinomycete of silver nanoparticles (AgNPs), isolated from Little and Greater Rann of Kutch, India. The confirmation of the formation of AgNPs by the actinomycetes was carried out by using a UV-Vis spectrophotometer where an absorbance peak was obtained at 420 nm. The X-ray diffraction pattern demonstrated five characteristic diffraction peaks indexed at the lattice plane (111), (200), (231), (222), and (220). Fourier transform infrared showed typical bands at 531 to 1635, 2111, and 3328 cm. Scanning electron microscopy shows that the spherical-shaped AgNPs particles have diameters in the range of 40 to 90 nm. The particle size analysis displayed the mean particle size of AgNPs in aqueous medium, which was about 55 nm (±27 nm), bearing a negative charge on their surfaces. The potential of the -mediated synthesized AgNPs was evaluated for their antimicrobial, anti-methicillin-resistant (MRSA), anti-biofilm, and anti-oxidant activity. The maximum inhibitory effect was observed against at (8 µg/mL), followed by and at (32 µg/mL), and against (64 µg/mL), whereas (128 µg/mL) and (256 µg/mL) were much less sensitive to AgNPs. The biosynthesized AgNPs displayed activity against MRSA, and the free radical scavenging activity was observed with an increase in the dosage of AgNPs from 25 to 200 µg/mL. AgNPs in combination with ampicillin displayed inhibition of the development of biofilm in and at 98% and 83%, respectively. AgNPs were also successfully coated on the surface of cotton to prepare antimicrobial surgical cotton, which demonstrated inhibitory action against (15 mm) and (12 mm). The present research integrates microbiology, nanotechnology, and biomedical science to formulate environmentally friendly antimicrobial materials using halotolerant actinomycetes, evolving green nanotechnology in the biomedical field. Moreover, this study broadens the understanding of halotolerant actinomycetes and their potential and opens possibilities for formulating new antimicrobial products and therapies.
PubMed: 38931410
DOI: 10.3390/ph17060743 -
Molecules (Basel, Switzerland) Jun 2024The aim of this study was to obtain new halolactones with a gem-dimethyl group in the cyclohexane ring (at the C-3 or C-5 carbon) and a methyl group in the lactone ring...
The aim of this study was to obtain new halolactones with a gem-dimethyl group in the cyclohexane ring (at the C-3 or C-5 carbon) and a methyl group in the lactone ring and then subject them to biotransformations using filamentous fungi. Halolactones in the form of mixtures of two diasteroisomers were subjected to screening biotransformations, which showed that only compounds with a gem-dimethyl group located at the C-5 carbon were transformed. Strains from the genus carried out hydrolytic dehalogenation, while strains from the genus carried out hydroxylation of the C-7 carbon. Both substrates and biotransformation products were then tested for antimicrobial activity against multidrug-resistant strains of both bacteria and yeast-like fungi. The highest antifungal activity against and strains was obtained for compound , while antimicrobial activity against MRSA was obtained for compound .
Topics: Lactones; Anti-Bacterial Agents; Biotransformation; Microbial Sensitivity Tests; Fusarium; Antifungal Agents; Absidia; Molecular Structure; Candida albicans; Methicillin-Resistant Staphylococcus aureus
PubMed: 38930886
DOI: 10.3390/molecules29122820 -
Molecules (Basel, Switzerland) Jun 2024Synthetic efforts toward complex natural product (NP) scaffolds are useful ones, particularly those aimed at expanding their bioactive chemical space. Here, we utilised...
Synthetic efforts toward complex natural product (NP) scaffolds are useful ones, particularly those aimed at expanding their bioactive chemical space. Here, we utilised an orthogonal cheminformatics-based approach to predict the potential biological activities for a series of synthetic bis-indole alkaloids inspired by elusive sponge-derived NPs, echinosulfone A () and echinosulfonic acids A-D (-). Our work includes the first synthesis of desulfato-echinosulfonic acid C, an α-hydroxy bis(3'-indolyl) alkaloid (), and its full NMR characterisation. This synthesis provides corroborating evidence for the structure revision of echinosulfonic acids A-C. Additionally, we demonstrate a robust synthetic strategy toward a diverse range of α-methine bis(3'-indolyl) acids and acetates (-) without the need for silica-based purification in either one or two steps. By integrating our synthetic library of bis-indoles with bioactivity data for 2048 marine indole alkaloids (reported up to the end of 2021), we analyzed their overlap with marine natural product chemical diversity. Notably, the C-6 dibrominated α-hydroxy bis(3'-indolyl) and α-methine bis(3'-indolyl) analogues (, , and ) were found to contain significant overlap with antibacterial C-6 dibrominated marine bis-indoles, guiding our biological evaluation. Validating the results of our cheminformatics analyses, the dibrominated α-methine bis(3'-indolyl) alkaloids (, , , and ) were found to exhibit antibacterial activities against methicillin-sensitive and -resistant . Further, while investigating other synthetic approaches toward bis-indole alkaloids, 16 incorrectly assigned synthetic α-hydroxy bis(3'-indolyl) alkaloids were identified. After careful analysis of their reported NMR data, and comparison with those obtained for the synthetic bis-indoles reported herein, all of the structures have been revised to α-methine bis(3'-indolyl) alkaloids.
Topics: Anti-Bacterial Agents; Indole Alkaloids; Cheminformatics; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Biological Products
PubMed: 38930871
DOI: 10.3390/molecules29122806 -
Molecules (Basel, Switzerland) Jun 2024The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-]thiazole-4,9-dione () using different amines, including benzylamine (), morpholine (), thiomorpholine (),...
The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-]thiazole-4,9-dione () using different amines, including benzylamine (), morpholine (), thiomorpholine (), piperidine (), and 4-methylpiperazine (), produced corresponding new tricyclic naphtho[2,3-]thiazole-4,9-dione compounds (-) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (-) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-]thiazole-4,9-dione skeleton and substituent effect, - showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-]thiazole-4,9-dione led to large bathochromic shifts in solution, and - exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. () is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of - against , MRSA, and . Compounds with thiomorpholine group and with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future.
Topics: Microbial Sensitivity Tests; Thiazoles; Anti-Bacterial Agents; Staphylococcus; Molecular Structure; Structure-Activity Relationship; Anti-Infective Agents; Fluorescent Dyes
PubMed: 38930841
DOI: 10.3390/molecules29122777 -
Microorganisms Jun 2024We determined antibiotic susceptibility and employed Oxford Nanopore whole-genome sequencing to explore strain diversity, resistance, and virulence gene carriage among...
We determined antibiotic susceptibility and employed Oxford Nanopore whole-genome sequencing to explore strain diversity, resistance, and virulence gene carriage among methicillin-resistant (MRSA) strains from different infection sites and timepoints in a tertiary Kenyan hospital. Ninety-six nonduplicate clinical isolates recovered between 2010 and 2023, identified and tested for antibiotic susceptibility on the VITEK ID/AST platform, were sequenced. Molecular typing, antibiotic resistance, and virulence determinant screening were performed using the relevant bioinformatics tools. The strains, alongside those from previous studies, were stratified into two periods covering 2010-2017 and 2018-2023 and comparisons were made. Mirroring phenotypic profiles, '″ [aminoglycosides]; (S84L) and (S80Y) [fluoroquinolones]; [anti-folates]; and [tetracycline] resistance determinants dominated the collection. While the proportion of ST239/241-t037-SCCmec III among MRSA reduced from 37.7% to 0% over the investigated period, ST4803-t1476-SCCmec IV and ST152-t355-SCCmec IV were pre-eminent. The prevalence of Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) genes was 38% (33/87) and 6.8% (6/87), respectively. We observed the displacement of HA-MRSA ST239/241-t037-SCCmec III with the emergence of ST152-t355-SCCmec IV and a greater clonal heterogeneity. The occurrence of PVL+/ACME+ CA-MRSA in recent years warrants further investigations into their role in the CA-MRSA virulence landscape, in a setting of high PVL prevalence.
PubMed: 38930553
DOI: 10.3390/microorganisms12061171 -
Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics....
Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [RW] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [RW] against () and methicillin-resistant (MRSA) by a checkered board assay. [RW] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [RW] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [RW] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [RW] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [RW] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [RW] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [RW] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [RW] and a change in antibacterial effectiveness MIC [RW] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [RW] warrants further consideration as a potential AMP.
PubMed: 38927221
DOI: 10.3390/antibiotics13060555