Clinical characteristics of community-onset Clostridioides difficile infections at a tertiary hospital in mainland China: A fourteen-year (2010-2023) retrospective study.

BACKGROUND: Clostridioides difficile infection (CDI) is an increasingly common disease in healthcare facilities and community settings. However, there are limited reports of community-onset CDI (CO-CDI) in China. METHODS: We collected diarrheal stool samples from 3885 patients who went to outpatient department or emergency department in a tertiary hospital in China during 2010-2023, analyzed the correlation between patients' basic information and the detection rate of CDI. Besides, all stool samples from 3885 outpatients included were tested by culturing. Moreover, we randomly selected 89 patients' stools during the 14 years and isolated 126 C. difficile strains from them. The presence of toxin genes (tcdA, tcdB, cdtA, and cdtB) were confirmed by PCR. Toxigenic strains were typed using multilocus sequence typing (MLST). Susceptibility to 9 antimicrobials was evaluated using the E-test. RESULTS: 528 of 3885 patients (13.6 %) with diarrhea were finally diagnosed as CDI. The median age of patients included was 51 years (6 months-95 years), while the median of patients with CDI was older than patients with negative results [55.5 years (6 months-93 years) vs. 50 years (9 months -95 years), p < 0.001]. In winter, patients with diarrhea might be more likely to have CDI. The detection rate of CDI of patients in emergency department was much higher than those in other outpatients (20.7 % vs. 12.4 %, p < 0.001), and did differ from each outpatient departments (p < 0.05). There were 95 isolated strains detected as toxigenic C. difficile. Among these strains, 82 (86.3 %) had the tcdA and tcdB genes (A+B+) and 5 of these 82 strains were positive for the binary toxin genes (cdtA and cdtB) (A+B+CDT+). There were 15 different sequence types (STs) by multilocus sequence typing (MLST), while the most ST was ST-54 (23.2 %). ST types composition was relatively stable over the time span of this study. Some strains had high resistance to ciprofloxacin, clindamycin, and erythromycin. Twenty-three isolates (24.2 %) were multidrug-resistant. CONCLUSIONS: Outpatients with CDI were common among patients having diarrhea during this period in our hospital. Elderly patients and patients went to emergency department may be susceptible to CDI. Based on MLST, the result revealed that the C. difficile isolates had high genetic diversity and maintained stability in this period. All isolates were susceptible to metronidazole and vancomycin, and nearly one quarter of all isolates had multidrug resistance.

Deep learning enables contrast-robust super-resolution reconstruction in structured illumination microscopy.

Structured illumination microscopy (SIM) is a powerful technique for super-resolution (SR) image reconstruction. However, conventional SIM methods require high-contrast illumination patterns, which necessitate precision optics and highly stable light sources. To overcome these challenges, we propose a new method called contrast-robust structured illumination microscopy (CR-SIM). CR-SIM employs a deep residual neural network to enhance the quality of SIM imaging, particularly in scenarios involving low-contrast illumination stripes. The key contribution of this study is the achievement of reliable SR image reconstruction even in suboptimal illumination contrast conditions. The results of our study will benefit various scientific disciplines.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. METHODS: We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves. RESULTS: There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI-lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI-lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. CONCLUSION: 18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

Characteristics and Source Apportionment of Volatile Organic Compounds in a Coastal Industrial Area: A Case Study in the Yangtze River Delta of China.

In recent years, the coastal area in East China has experienced elevated volatile organic compounds (VOCs) levels during specific periods. VOCs have become one of the major atmospheric pollutants in these areas. In this study, 64 compounds including alkanes, alkenes, halohydrocarbons, aromatics, and oxygenated VOCs (OVOCs) were obtained by the TO-15 method through a 12-month campaign in industrial, urban and suburban areas in the Yangtze River Delta of China. The overall trends of total VOC (TVOC) concentrations at eight sampling sites were as follows: winter > autumn > spring > summer. The proportion of VOC categories was various at industrial sites, while OVOCs and halohydrocarbons had high proportions at urban sites and suburban sites, respectively. Coating, vehicle emission, petrochemical source, industrial source, and gasoline volatilization were identified as the major VOC emission sources by the positive matrix factorization model. Petrochemical and coating sources were the prime VOC sources at industrial sites. Aromatics contributed the most ozone formation potential at industrial sites, while OVOCs provided the main contributions at both urban and suburban sites during four seasons. According to the health risk assessment, a high probability of non-carcinogenic risk existed at three industrial sites. Special attention should be given to certain VOCs, such as acrolein and 1,2-dibromoethane in industrial areas.

Delayed Displacement of Enterprise Stent in Treating Symptomatic Intracranial Atherosclerotic Stenosis: A Case Report.

A 53-year-old patient was admitted to the stroke unit with sudden onset of weakness on the left side and dysarthria. This patient had been diagnosed with symptomatic intracerebral artery stenosis two months previously and had been administered dual oral antiplatelet agents and an aggressive dose of atorvastatin. The patient underwent percutaneous transluminal angioplasty and stenting two weeks after admission. Interventional treatment was technically successful when a self-expandable Enterprise stent was used. She was followed up for 2 years after discharge, without any cerebrovascular incidents. Repeat CTA revealed delayed displacement of the Enterprise stent and a discussion was had.

Bilateral Bow Hunter Syndrome Associated with Loss of Cervical Physiological Curvature.

BACKGROUND Bow hunter syndrome is a rare disease that is often overlooked. It presents with complex and variable clinical symptoms and causes, making diagnosis and treatment challenging. This case report focuses on a young patient with bilateral bow hunter syndrome, possibly caused by the loss of cervical physiological curvature. The aim is to enhance understanding and awareness of the disease. It is important to consider the possibility of bow hunter syndrome in young patients with long-term poor neck posture and symptoms such as dizziness, nausea, vomiting, and neck rotation-related symptoms. In such cases, thorough examination of posterior circulation hemodynamics and vascular morphology is recommended. CASE REPORT A 25-year-old woman was admitted to the hospital mainly because of "dizziness for 10 hours." The dizziness was aggravated when the right side of the neck was turned and the body position changed. This was accompanied by visual rotation, nausea, and vomiting. Bow hunter syndrome was diagnosed based on the clinical symptoms and hemodynamic examination of the posterior circulation. The patient was given a cervical collar to limit excessive twisting of the neck and instructed to avoid large-angle deflection of the neck after discharge. During the 3-month follow-up, no characteristic symptoms (such as dizziness) reappeared. CONCLUSIONS Bow hunter syndrome is a rare clinical posterior circulation compression syndrome with complex etiology. This case suggests that the simple disappearance of cervical curvature may be related to the occurrence of bow hunter syndrome. The dynamic monitoring of blood flow by color Doppler ultrasound and transcranial Doppler in different head positions provides clear clues to suspected bow hunter syndrome. With the help of computed tomography angiography, the diagnosis of bow hunter syndrome may be obtained by noninvasive examination.

In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA.

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole's MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians.

Rapid discrimination between clinical Clostridioides difficile infection and colonization by quantitative detection of TcdB toxin using a real-time cell analysis system.

Objectives: It is important to accurately discriminate between clinical Clostridioides difficile infection (CDI) and colonization (CDC) for effective antimicrobial treatment. Methods: In this study, 37 stool samples were collected from 17 CDC and 20 CDI cases, and each sample were tested in parallel through the real-time cell analysis (RTCA) system, real-time PCR assay (PCR), and enzyme-linked immunosorbent assay (ELISA). Results: RTCA-measured functional and toxical C. difficile toxin B (TcdB) concentrations in the CDI group (302.58 ± 119.15 ng/mL) were significantly higher than those in the CDC group (18.15 ± 11.81 ng/mL) (p = 0.0008). Conversely, ELISA results revealed no significant disparities in TcdB concentrations between the CDC (26.21 ± 3.57 ng/mL) and the CDI group (17.07 ± 3.10 ng/mL) (p = 0.064). PCR results indicated no significant differences in tcdB gene copies between the CDC (774.54 ± 357.89 copies/µL) and the CDI group (4,667.69 ± 3,069.87 copies/µL) (p = 0.407). Additionally, the functional and toxical TcdB concentrations secreted from C. difficile isolates were measured by the RTCA. The results from the CDC (490.00 ± 133.29 ng/mL) and the CDI group (439.82 ± 114.66 ng/mL) showed no significant difference (p = 0.448). Notably, RTCA-measured functional and toxical TcdB concentration was significantly decreased when mixed with pooled CDC samples supernatant (p = 0.030). Conclusion: This study explored the novel application of the RTCA assay in effectively discerning clinical CDI from CDC cases.

ESKAPE in China: epidemiology and characteristics of antibiotic resistance.

The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative ß-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.

Efficacy of ceftazidime-avibactam in the treatment of carbapenem-resistant Klebsiella pneumoniae infections: Focus on solid organ transplantation recipients.

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.

Clinical and economic evaluation of blood culture whole process optimisation in critically ill adult patients with positive blood cultures.

OBJECTIVES: Optimising blood culture processing is important to ensure that bloodstream infections are accurately diagnosed while minimising adverse events caused by antibiotic abuse. This study aimed to evaluate the impact of optimised blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures. METHODS: From March 2020 to October 2021, this microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimisation of bottle reception, graded reports and an upgraded laboratory information system. A total of 122 ICU patients were included in the pre-optimisation group from March 2019 to February 2020, while 179 ICU patients were included in the post-optimisation group from November 2021 to October 2022. RESULTS: Compared with the pre-optimisation group, the average reporting time of identification and antimicrobial sensitivity was reduced by 16.72 hours in the optimised group. The time from admission to targeted antibiotic therapy within 24 hours after receiving both the Gram stain report and the final report were both significantly less in the post-optimisation group compared with the pre-optimisation group. The average hospitalisation time was reduced by 6.49 days, the average antimicrobial drug cost lowered by $1720.85 and the average hospitalisation cost by $9514.17 in the post-optimisation group. CONCLUSIONS: Optimising blood culture processing was associated with a significantly increased positive detection rate, a remarkable reduction in the length of hospital stay and in hospital costs for ICU patients with bloodstream infections.

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae.

ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the "mcsw" morphotype. Two distinct morphotypes ("ntrd" and "msdw") were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (wza, wzc, and wbaP), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.

The complete mitochondrial genome of the Baishanzu horned toad Boulenophrys baishanzuensis (Anura: Megophryidae).

The mitochondrial genome (mitogenome) of Boulenophrys baishanzuensis (Anura: Megophryidae) was sequenced by the Illumina platform. The assembled circular mitogenome of B. baishanzuensis had a total length of 17,040 bp, with a GC content of 41.25%. It consisted of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and a D-loop region. The majority of the PCGs were encoded by the H-strand, while one PCG (nad6) and eight tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser2, tRNA-Glu, and tRNA-Pro) were encoded in the L-strand. Phylogenetic analysis revealed that the newly sequenced species formed a clade with other Boulenophrys species, while the genus Boulenophrys itself formed a sister group with the genus Atympanophrys.

Taohong Siwu decoction alleviates cognitive impairment by suppressing endoplasmic reticulum stress and apoptosis signaling pathway in vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear. AIM OF STUDY: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway. MATERIALS AND METHODS: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression. RESULTS: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins. CONCLUSION: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway.

Characterization and dynamics of intestinal microbiota in patients with Clostridioides difficile colonization and infection.

Gut microbiota dysbiosis increases the susceptibility to Clostridioides difficile infection (CDI). In this study, we monitored C. difficile colonization (CDC) patients from no CDC status (CDN) to CDC status (CDCp) and CDI patients from asymptomatic status before CDI (PRECDI), CDI status (ONCDI), to asymptomatic status after CDI (POSTCDI). Based on metagenomic sequencing, we aimed to investigate the interaction pattern between gut microbiota and C. difficile. There was no significant difference of microbiota diversity between CDN and CDCp. In CDCp, Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria increased, with a positive correlation between SCFA-producing bacteria and C. difficile colonization. Compared with PRECDI, ONCDI and POSTCDI showed a significant decrease in microbiota diversity, particularly in Bacteroidetes and SCFA-producing bacteria, with a positive correlation between opportunistic pathogen and C. difficile. Fatty acid metabolism, and amino acid biosynthesis were enriched in CDN, CDCp, and PRECDI, while bile secretion was enriched in ONCDI and POSTCDI. Microbiota and metabolic pathways interaction networks in CDN and CDCp were more complex, particularly pathways in fatty acid and bile acid metabolism. Increasing of Bacteroidetes and SCFA-producing bacteria, affecting amino acid and fatty acid metabolism, is associated with colonization resistance to C. difficile and inhibiting the development of CDI.