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Journal of Korean Medical Science Jul 2024A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with...
A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant (CRKP) harboring carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of variants.
Topics: Humans; Ceftazidime; Klebsiella pneumoniae; Male; Azabicyclo Compounds; Drug Combinations; Adult; Anti-Bacterial Agents; beta-Lactamases; Klebsiella Infections; Bacteremia; Microbial Sensitivity Tests; Carbapenems; Whole Genome Sequencing; Bacterial Proteins; Meropenem; Drug Resistance, Multiple, Bacterial
PubMed: 38952349
DOI: 10.3346/jkms.2024.39.e208 -
ACS Nano Jul 2024Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection,...
Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.
Topics: Photochemotherapy; Microwaves; Animals; Mice; Reactive Oxygen Species; Wireless Technology; Photosensitizing Agents; Light; Staphylococcus aureus; Staphylococcal Infections; Mice, Inbred BALB C; Anti-Bacterial Agents
PubMed: 38952327
DOI: 10.1021/acsnano.4c03654 -
Clinical and Translational Science Jul 2024The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination... (Randomized Controlled Trial)
Randomized Controlled Trial
The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.
Topics: Humans; Acinetobacter baumannii; Meropenem; Middle Aged; Microbial Sensitivity Tests; Female; Male; Anti-Bacterial Agents; Colistin; Adult; Aged; Animals; Treatment Outcome; Mice; Acinetobacter Infections; Translational Research, Biomedical; Drug Therapy, Combination; Models, Biological
PubMed: 38952168
DOI: 10.1111/cts.13870 -
Journal of Nanobiotechnology Jul 2024Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial...
BACKGROUND
Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers.
RESULTS
The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds.
CONCLUSIONS
The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection.
Topics: Wound Healing; Nanofibers; Photothermal Therapy; Animals; Bandages; Anti-Bacterial Agents; Mice; Biofilms; Chitosan; Male; Diabetes Mellitus, Experimental; Temperature; Rats; Infrared Rays; Cell Proliferation; Rats, Sprague-Dawley; Humans; Wound Infection
PubMed: 38951903
DOI: 10.1186/s12951-024-02621-2 -
Journal of Nanobiotechnology Jul 2024Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have... (Review)
Review
Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.
Topics: Metal-Organic Frameworks; Wound Healing; Humans; Animals; Anti-Infective Agents; Anti-Bacterial Agents; Porosity; Wound Infection
PubMed: 38951841
DOI: 10.1186/s12951-024-02637-8 -
BMC Medical Genomics Jul 2024This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus...
BACKGROUND
This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms.
METHODS
A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS).
RESULTS
Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage.
CONCLUSION
Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
Topics: Linezolid; Humans; China; Microbial Sensitivity Tests; Enterococcus faecium; Gram-Positive Bacterial Infections; Male; Middle Aged; Enterococcus faecalis; Female; Vancomycin; Anti-Bacterial Agents; Molecular Epidemiology; Adult; Vancomycin Resistance; Aged; Retrospective Studies; Vancomycin-Resistant Enterococci; Young Adult; Enterococcus
PubMed: 38951840
DOI: 10.1186/s12920-024-01948-x -
BMC Pediatrics Jun 2024The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the...
BACKGROUND
The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET).
METHODS
IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively.
RESULTS
76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached.
CONCLUSION
The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.
Topics: Humans; Helicobacter Infections; Child; Male; Female; Adolescent; Prospective Studies; Helicobacter pylori; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Severity of Illness Index; Inflammatory Bowel Diseases; Gastroscopy; Follow-Up Studies; Anti-Bacterial Agents
PubMed: 38951792
DOI: 10.1186/s12887-024-04902-z -
BMC Microbiology Jun 2024Inflammatory Bowel Diseases (IBD) are a major public health issue with unclear aetiology. Changes in the composition and functionality of the intestinal microbiota are...
BACKGROUND
Inflammatory Bowel Diseases (IBD) are a major public health issue with unclear aetiology. Changes in the composition and functionality of the intestinal microbiota are associated with these pathologies, including the depletion of strict anaerobes such as Feacalibacterium prausnitzii. Less evidence is observed for depletion in other anaerobes, among which bifidobacteria. This study characterized the taxonomic and functional diversity of bifidobacteria isolated from the human intestinal microbiota in active and non-active IBD patients by a culturomics approach and evaluated if these bifidobacteria might be used as probiotics for gut health.
RESULTS
A total of 341 bifidobacteria were isolated from the intestinal microbiota of IBD patients (52 Crohn's disease and 26 ulcerative colitis patients), with a high proportion of Bifidobacterium dentium strains (28% of isolated bifidobacteria). In ulcerative colitis, the major species identified was B. dentium (39% of isolated bifidobacteria), in active and non-active ulcerative colitis. In Crohn's disease, B. adolescentis was the major species isolated from non-active patients (40%), while similar amounts of B. dentium and B. adolescentis were found in active Crohn's disease patients. The relative abundance of B. dentium was increased with age, both in Crohn's disease and ulcerative colitis and active and non-active IBD patients. Antibacterial capacities of bifidobacteria isolated from non-active ulcerative colitis against Escherichia coli LF82 and Salmonella enterica ATCC 14028 were observed more often compared to strains isolated from active ulcerative colitis. Finally, B. longum were retained as strains with the highest probiotic potential as they were the major strains presenting exopolysaccharide synthesis, antibacterial activity, and anti-inflammatory capacities. Antimicrobial activity and EPS synthesis were further correlated to the presence of antimicrobial and EPS gene clusters by in silico analysis.
CONCLUSIONS
Different bifidobacterial taxonomic profiles were identified in the microbiota of IBD patients. The most abundant species were B. dentium, mainly associated to the microbiota of ulcerative colitis patients and B. adolescentis, in the intestinal microbiota of Crohn's disease patients. Additionally, the relative abundance of B. dentium significantly increased with age. Furthermore, this study evidenced that bifidobacteria with probiotic potential (antipathogenic activity, exopolysaccharide production and anti-inflammatory activity), especially B. longum strains, can be isolated from the intestinal microbiota of both active and non-active Crohn's disease and ulcerative colitis patients.
Topics: Humans; Probiotics; Bifidobacterium; Adult; Female; Male; Middle Aged; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Young Adult; Aged; Colitis, Ulcerative; Crohn Disease; Phylogeny; Feces; RNA, Ribosomal, 16S; Phenotype; Adolescent; Anti-Bacterial Agents
PubMed: 38951788
DOI: 10.1186/s12866-024-03368-4 -
Mikrochimica Acta Jul 2024A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection...
A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 10-5 × 10 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.
Topics: Staphylococcus aureus; Colorimetry; Gold; Platinum; Limit of Detection; Porosity; Benzidines; Hydrogen Peroxide; Aptamers, Nucleotide; Metal Nanoparticles; Vancomycin; Biosensing Techniques; Catalysis; Humans
PubMed: 38951285
DOI: 10.1007/s00604-024-06460-8 -
Communications Biology Jul 2024Colistin remains an important antibiotic for the therapeutic management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colistin resistance in...
Colistin remains an important antibiotic for the therapeutic management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colistin resistance in clinical strains, it remains unclear exactly when and how different mutational events arise resulting in reduced colistin susceptibility. Using a bioreactor model of infection, we modelled the emergence of colistin resistance in a susceptible isolate of K. pneumoniae. Genotypic, phenotypic and mathematical analyses of the antibiotic-challenged and un-challenged population indicates that after an initial decline, the population recovers within 24 h due to a small number of "founder cells" which have single point mutations mainly in the regulatory genes encoding crrB and pmrB that when mutated results in up to 100-fold reduction in colistin susceptibility. Our work underlines the rapid development of colistin resistance during treatment or exposure of susceptible K. pneumoniae infections having implications for the use of cationic antimicrobial peptides as a monotherapy.
Topics: Klebsiella pneumoniae; Colistin; Anti-Bacterial Agents; Bioreactors; Drug Resistance, Bacterial; Klebsiella Infections; Microbial Sensitivity Tests; Humans
PubMed: 38951173
DOI: 10.1038/s42003-024-06378-0