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Microbiology Spectrum Jun 2024New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant . Carbapenemase gene acquisition...
UNLABELLED
New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant . Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant β-lactam resistance mechanisms of CZA-resistant (CZA) isolates. A total of 120 . isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). Among non-β-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZA strains subjected to whole-genome sequencing ( = 18), resistance was mainly due to the expression of metallo-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among clinical isolates in Southern Italy remained low. CZA isolates were mostly metallo-β-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of high-risk clones.
IMPORTANCE
Multidrug-resistant infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.
PubMed: 38934607
DOI: 10.1128/spectrum.04266-23 -
MSphere Jun 2024Phage therapy is increasing in relevance as an alternative treatment to combat antibiotic resistant bacteria. Phage cocktails are the state-of-the-art method of...
Phage therapy is increasing in relevance as an alternative treatment to combat antibiotic resistant bacteria. Phage cocktails are the state-of-the-art method of administering phages in clinical settings, preferred over monophage treatment because of their ability to eliminate multiple bacterial strains and reduce resistance formation. In our study, we compare monophage applications and phage cocktails to our chosen method of phage sequential treatments. To do so, we isolated four novel bacteriophages capable of infecting T3, a close relative of , and characterized them using sequencing and transmission electron microscopy. While investigating monophage treatments, we observed that different phage concentrations had a strong impact on the timing and amount of resistance formation. When using phage cocktails, we observed that were capable of forming resistance in the same timespan it took them to become resistant to single phages. We isolated mutants resistant to each single phage as well as mutants exposed to phage cocktails, resulting in bacteria resistant to all four phages at once. Sequencing these mutants showed that different treatments yielded unique single nucleotide polymorphism mutation patterns. In order to combat resistance formation, we added phages one by one in intervals of 24 h, thus managing to delay resistance development and keeping bacterial growth significantly lower compared to phage cocktails.IMPORTANCEWHO declared antimicrobial resistance a top threat to global health; while antibiotics have stood at the forefront in the fight against bacterial infection, the increasing number of multidrug-resistant bacteria highlights a need to branch out in order to address the threat of antimicrobial resistance. Bacteriophages, viruses solely infecting bacteria, could present a solution due to their abundance, versatility, and adaptability. For this study, we isolated new phages infecting a fast-mutating strain capable of forming resistance within 30 h. By using a sequential treatment approach of adding one phage after another, we were able to curb bacterial growth significantly more compared to state-of-the-art phage cocktails.
PubMed: 38934592
DOI: 10.1128/msphere.00707-23 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Defective bismuth telluride (BiTe) nanosheets, an artificial nanozyme mimicking haloperoxidase activity (hPOD), show promise as eco-friendly, bactericidal, and...
Defective bismuth telluride (BiTe) nanosheets, an artificial nanozyme mimicking haloperoxidase activity (hPOD), show promise as eco-friendly, bactericidal, and antimicrofouling materials by enhancing cytotoxic hypohalous acid production from halides and HO. Microscopic and spectroscopic characterization reveals that controlled NaOH (upto X = 250 µL) etching of the nearly inactive non-transition metal chalcogenide BiTe nanosheets creates controlled defects (d), such as Bispecies, in d-BiTe-X that induces enhanced hPOD activity. d-BiTe-250 exhibits approximately eight-fold improved hPOD than the as-grown BiTe nanosheets. The antibacterial activity of d-BiTe-250 nanozymes, studied by bacterial viability, show 1, and 45% viability for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, prevalent in marine environments. The hPOD mechanism is confirmed using scavengers, implicating HOBr and singlet oxygen for the effect. The antimicrofouling property of the d-BiTe-250 nanozyme has been studied on Pseudomonas aeruginosa biofilm in a lab setting by multiple assays, and also on titanium (Ti) plates coated with the nanozyme mixed commercial paint, exposed to seawater in a real setting. All studies, including direct microscopic evidence, exhibit inhibition of microfouling, up to ≈73%, in the presence of nanozymes. This approach showcases that defect engineering can induce antibacterial, and antimicrofouling activity in non-transition metal chalcogenides, offering an inexpensive alternative to noble metals.
PubMed: 38934508
DOI: 10.1002/smll.202401929 -
ChemMedChem Jun 2024Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate...
Design, Synthesis and Bioactivity Evaluation of Ag(I)-, Au(I)- and Au(III)-Quinoxaline-Wingtip N-Heterocyclic Carbene Complexes Against Antibiotic Resistant Bacterial Pathogens.
Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate (1.HPF6), and [Ag(1)2][PF6], (2); [Au(1)2][PF6], (3); and [Au(1)Cl3], (4) NHC complexes were synthesized. All the synthesized compounds were characterized by elemental analysis, NMR, and UV-Vis spectroscopy. Finally, single crystal X-ray structures revealed a linear geometry for complex 2 whereas a square planar geometry for complex 4. The formation of complex 3 was confirmed and supported by its MS spectra. The antibacterial activities of all the synthesized complexes were investigated against gram-positive bacteria and gram-negative bacteria. The Au(III)-NHC complex, 4 showed the highest antibacterial activity with extremely low MIC values against both the bacterial strains (0.24 µg.mL-1). Monitoring of zeta potential supports the higher activity of complex 4 compared to 2 and 3. ROS production by complex 4 has also been measured in vitro in the CT26 cancer cell lines, which is directly responsible for targetting and killing the bacterial pathogens. Cell cytotoxicity assay using 293T cell lines has been performed to investigate the biocompatibility nature of complex 4. Also, an excellent hemocompatibility was assigned to it from its hemolytic studies, which provide valuable insights into the design of novel antibacterial agents.
PubMed: 38934210
DOI: 10.1002/cmdc.202400236 -
Heliyon Jun 2024Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic...
Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic fibrosis (CF) lung environment. Recent adaptations of the Microbial Identification after Passive CLARITY Technique (MiPACT) in CF research have allowed for the direct imaging of PA biofilm spatial organization and structure in expectorated sputum. Here, we performed a comparative analysis of and within patient () measures of PA biofilms using sputa from new onset infected children with CF. MiPACT-fluorescent hybridization (FISH) and fluorescent anti-Psl monoclonal antibody (mAb) staining was performed to directly visualize PA and Psl (exopolysaccharide in PA biofilm matrix) in 11 CF sputum specimens. Corresponding PA isolates, recovered from the same sputum samples, were grown as biofilms in a glass slide chamber model, then visualized by fluorescent live-cell and anti-Psl mAb staining. We observed that PA biovolume, aggregation and Psl antibody binding (normalized per PA biovolume) in CF sputum did not correlate with the model, although a trend towards significance in the biovolume relationship was observed with the addition of sputum supernatant to the model.
PubMed: 38933957
DOI: 10.1016/j.heliyon.2024.e32424 -
Open Forum Infectious Diseases Jun 2024
PubMed: 38933740
DOI: 10.1093/ofid/ofae258 -
Materials Today. Bio Jun 2024Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a...
Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a life-threatening risk. Near-infrared (NIR)-assisted photothermal antibacterial combined with antioxidant hydrogel has shown significant potential in the healing of infected wounds. However, existing photothermal agents are typically metal-based, complicated to synthesize, or pose biosafety hazards. In this study, we utilized plant-derived blackcurrant extract (B) as a natural source for both photothermal and antioxidant properties. By incorporating B into a G-O hydrogel crosslinked through Schiff base reaction between gelatin (G) and oxidized pullulan (O), the resulting G--B hydrogel exhibited good injectability and biocompatibility along with robust photothermal and antioxidant activities. Upon NIR irradiation, the controlled temperature (around 45-50 °C) generated by the G--B hydrogel resulted in rapid (10 min) and efficient killing of (99 %), (98 %), and (82 %). Furthermore, the G--B hydrogel containing 0.5 % blackcurrant extract promoted collagen deposition, angiogenesis, and accelerated burn wound closure conclusively, demonstrating that this well-designed and extract-contained hydrogel dressing holds immense potential for enhancing the healing process of bacterial-infected burn wounds.
PubMed: 38933414
DOI: 10.1016/j.mtbio.2024.101113 -
Viruses May 2024Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the...
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, , another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate biofilm alone or in combination with phages PB10 and PA19 was investigated. The cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP-phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group ( < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene . While the ZnO-NPs repressed the gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells.
Topics: Zinc Oxide; Pseudomonas aeruginosa; Biofilms; Metal Nanoparticles; Green Chemistry Technology; Bacteriophages; Anti-Bacterial Agents; Nanoparticles
PubMed: 38932188
DOI: 10.3390/v16060897 -
Pharmaceutics May 2024The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. (DB) and (AT) are well...
The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. (DB) and (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25-38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against () and (). Along with that, the DB-AT NFs showed effective growth inhibition for both and compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.
PubMed: 38931828
DOI: 10.3390/pharmaceutics16060704 -
Pharmaceutics May 2024Skin lesions are an important health concern, exposing the body to infection risks. Utilizing natural products containing chamomile ( L.) holds promise for curative...
Skin lesions are an important health concern, exposing the body to infection risks. Utilizing natural products containing chamomile ( L.) holds promise for curative purposes. Additionally, hyaluronic acid (HA), an active ingredient known for its tissue regeneration capacity, can expedite healing. In this study, we prepared and characterized an extract of and integrated it into a nanoemulsion system stabilized with HA, aiming at harnessing its healing potential. We assessed the impact of alcoholic strength on flavonoid extraction and chemically characterized the extract using UHPLC/MS while quantifying its antioxidant and antimicrobial capacity. We developed a nanoemulsion loaded with extract and evaluated the effect of HA stabilization on pH, droplet size, polydispersity index (PDI), zeta potential, and viscosity. Results indicated that 70% hydroalcoholic extraction yielded a higher flavonoid content. The extract exhibited antioxidant capacity in vitro, a desirable trait for skin regeneration, and demonstrated efficacy against key microbial strains (, , , and ) associated with skin colonization and infections. Flavonoids spireoside and apiin emerged as the most abundant bioactives. The addition of HA led to increased viscosity while maintaining a suitable pH for topical application. Zeta potential, droplet size, and PDI met acceptable criteria. Moreover, incorporating extract into the nanoemulsion enhanced its antimicrobial effect. Hence, the nanoemulsion system loaded with and HA stabilization exhibits favorable characteristics for topical application, showing promise in aiding the healing processes.
PubMed: 38931825
DOI: 10.3390/pharmaceutics16060701