Antibiotic-Resistance Profiles and Genetic Diversity of Shigella Isolates in China: Implications for Control Strategies.

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.

The dynamic change of serotype distribution and antimicrobial resistance of pneumococcal isolates since PCV13 administration and COVID-19 control in Urumqi, China.

Objective: This study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector's immunization program and COVID-19 control was administrated in the last 2 years. Methods: Serotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014-2015, 2018-2019, and 2020-2021. Results: A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 (χ 2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014-2015 to 1.4% in 2018-2019 and 0% in 2020-2021 (Fisher = 24.463, P < 0.01). Conclusion: The common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage.

Hydroxyapatite/silver electrospun fibers for anti-infection and osteoinduction.

Bone implant materials cause the most common complication of bone infections in orthopedic surgery, resulting in implant failure. Antibiotic treatment of bone infections leads to problems such as bacterial resistance and reduced osteogenic capacity. In this study, dopamine (DA) was self-polymerized on the surface of Polylactic acid (PLLA)/Hydroxyapatite (HA) nanowire composite fibers to form an adhesive polydopamine (PDA) membrane, and a stable silver-nanoparticles (Ag-NPs) coating layer was constructed on it by electrochemically driven Ag+ coordination and chelation through Polypyrrole (PPy) mediation, achieving steady and slow release of Ag-NPs. With optimized DA soaking time of 24 h and soaking concentration of 0.5 g·L-1, nanoparticles were uniformly distributed on PLLA/HA/PDA/PPy/Ag composite fibers and the hydrophilicity of the composite fibers was well-behaved. Besides, the composite fibers possessed good physiological stability and 100% antibacterial rate against Escherichia coli (E. coli) as well as Staphylococcus aureus (S. aureus). In addition, the composite fibers had promoted apatite nucleation and growth on surface and good cytocompatibility with osteoblasts, indicating ability of inducing osteogenic differentiation. In summary, a multi-functional PLLA/HA/PDA/PPy/Ag composite fiber with long-term antibacterial property, bioactivity and osteoinductivity was successfully constructed by electrospinning and electrochemical deposition.

Osteogenic and antiseptic nanocoating by in situ chitosan regulated electrochemical deposition for promoting osseointegration.

Ti and titanium alloy have been extensively utilized in the areas of orthopedics and other related fields, however, limited abilities in antibiosis, ossification and vascularization restrict the application of these materials in clinical. In this research, pulse electrochemical deposition was used as a method to make chitosan regulate Ag+ and Ca2+ in situ, achieving ions' dual regulations and coprecipitation of HA nanoparticles (HA-NPs) and Ag nanoparticles (Ag-NPs) on the surface of Ti. The spherical nanoparticles with even distribution were fabricated by optimizing deposition potential and the concentration of Ag+. The physical stabilities of coatings were significantly improved by the chelation among CS, Ag+ and Ca2+ reducing the release rate of Ag+, Ca2+. The coatings also exhibited noticeable abilities in anti-bacteria. Bone marrow mesenchymal stem cells (BMSCs) displayed adhesion, proliferation and differentiation abilities on the surface of coatings, at the same time the composite coatings revealed promising capability in inducing BMSCs differentiation to osteoblast, which is proved by the results of fluorescent dye. Similar results also can be found in investigations about vascular endothelial cells, desirable adhesion between cells and materials and proliferation are able to prove that this kind of materials has outstanding biocompatibility with VECs cells. The animal experiments indicated that the composite coatings were biocompatible with smooth muscle, myocardium and lung with slightly negative impacts on liver and kidney. According to the results of alizarin red staining, the calcified nodules were dyed red, which reveal that this material can promote bone formation. Electrochemical method was utilized in this research to successfully construct multifunctional composite coatings, such as antibiosis, osteogenesis and angiogenesis, on the surface of Ti.

A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection.

The main limitation of tissue engineering lies in the inability to stimulate osteogenesis, angiogenesis of stem cells and broad-spectrum antimicrobial activity. However, the development of multifunctional bioactive materials with these capabilities remains a great challenge. In this study, we prepared mesoporous silica nanoparticles encapsulated with silver nanocrystals (AG-MSN) with uniform sphere size and mesopores. Platelet-derived growth factor BB (PDGF-BB) was effectively loaded in the AG-MSN mesopores (P-AG-MSN). The silicon ions (Si) released by P-AG-MSN stimulate osteogenic differentiation of bone marrow stromal cells (BMSC) by activating the alkaline phosphatase (ALP) activity of bone-related genes and increasing protein (OCN, RUNX2 and OPN) expression. Ag+ ions could be slowly released from the interior of the shell, highlighting their durable antibacterial activity. The sustained release of PDGF-BB from P-AG-MSN stimulated the angiogenic differentiation of BMSC, as indicated by the enhanced secretion of vascular endothelial growth factor (VEGF), HIF-1α, HGF and ANG-1 and protein expression. Our results show that P-AG-MSN can clearly promote BMSC osteostimulation and vascularization. This research serves as a preliminary study of the utilization of this multifunctional mixture to fabricate a new active biological scaffold that integrates BMSC osteostimulation, vascularization and bactericidal effects by 3D printing technology.