Drug Resistance Rate Research Articles

Prevalence, Serotypes and Antimicrobial Resistance of Salmonella Isolated from Children in Guangzhou, China, 2018-2023.

Acute gastroenteritis caused by Salmonella spp. among children post a great threat for global public health. The increasing rate of drug-resistant Salmonella spp. has also become a challenging problem worldwide. In this study, the prevalence, serotypes, and antimicrobial characteristics of Salmonella isolated from children in Guangzhou, China, were investigated to provide supporting information for clinical treatment and prevention. Clinical data of children featured with gastroenteritis symptoms from 2018 to 2023 in Guangdong Women and Children Hospital were collected. The difference and fluctuation of antimicrobial resistance between serotypes and years were retrospectively analyzed. A total of 1304 Salmonella isolates were cultural-confirmed. The overall positive rate of Salmonella isolated from stool samples was 22.0% (1304/5924). Salmonella infections occur mainly from June to September and the majority of infected children aged under 4 years. Serogroup B was the most common serogroup among Salmonella isolates (74.6%, 973/1304). The predominant serotypes of Salmonella isolates were Typhimurium (63.1%, 823/1304). Higher drug resistance rate of Salmonella spp. to ceftriaxone was observed in 2023. The drug resistance rates of Salmonella isolates to sulfamethoxazole/trimethoprim and ampicillin are at high level during the past 6 years. Notably, higher multi-drug resistance (MDR) rate was demonstrated in Salmonella Typhimurium compared with other serotypes. Salmonella Typhimurium was the most common serotype isolated from children in Guangzhou, China, and it may mainly account for the high drug resistance rate in Salmonella spp. to most of the antimicrobial profiles. For controlling the high drug resistance rate of Salmonella spp. continuous surveillance of drug resistance and appropriate use of antibiotics based on clinical and laboratory results are of great significance.

Effect of the COVID-19 epidemic on drug resistance of Staphylococcus aureus infection

Introduction: Staphylococcus aureus was associated with more than 1 million deaths in 2019. The coronavirus disease 2019 (COVID-19) pandemic has lasted three years. In China, measures to control COVID-19 cases were adjusted in December 2022. In this study, we investigated the effects of the COVID-19 pandemic on the drug resistance of S. aureus infection. Methodology: A retrospective analysis was performed, focusing on the clinical distribution and drug resistance of distributions of S. aureus isolated from the Fifth Affiliated Hospital of Sun Yat-sen University during the COVID-19 pandemic from January 2020 to March 2023. The effects of COVID-19 control measures on the drug resistance of S. aureus infection were further investigated. Results: A total of 1437 strains of S. aureus were isolated, with a methicillin-resistant S. aureus (MRSA) detection rate of 19.2%. The department with the highest detection rate was the oncology department (17.0%, 244/1437), followed by the intensive care unit (11.1%, 159/1437), the dermatology department (10.7%, 154/1437), and the wound repair and burn department (9.7%, 139/1437). The most frequent specimens were secretions (42.0%, 603/1437), followed by sputum (23.3%, 335/1437), blood (10.7%, 154/1437), and pus (5.4%, 78/1437). The population distribution was primarily male (62.3%, 895/1437). S. aureus infections were most common among those aged 50–65 (32.8%, 472/1437), followed by those aged 18–49 (30.7%, 441/1437). S. aureus was most resistant to penicillin G (86.3%), followed by erythromycin (37.9%) and clindamycin (37.3%). The antibiotics with no resistance were linezolid, teicoplanin, tigecycline, and vancomycin. There was no significant difference in the drug-resistance rate between COVID-19–positive and COVID-19–negative patients. Conclusions: The outbreak of COVID-19 in 2020 and the adjustment of control measures had no significant impact on the drug resistance of S. aureus infection.

Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Clinical Characteristics, Species Distribution, and Drug Resistance of Non-Tuberculous Mycobacteria Lung Disease in Qingdao, China.

To analyze the clinical characteristics, species distribution and drug resistance of patients with non-tuberculous mycobacteria (NTM) lung disease in Qingdao, China. Clinical data of patients with NTM lung disease and pulmonary tuberculosis (TB) treated at Qingdao Chest Hospital from July 2021 to July 2023 were retrospectively analyzed. The prevalence of NTM lung disease was 8.03%, with a high rate of drug resistance during the study period. Patients with NTM lung disease had higher rates of older age, bronchiectasis, malignancy, HIV infection and bronchial dilatation shadow and lower rates of hollow shadow compared to patients with pulmonary TB. Comprehensive understanding of NTM lung disease, improved laboratory testing techniques and appropriate treatment regimens are essential for the management of NTM lung disease.

Comparison of molecular and microbiological detection rates of Mycobacterium tuberculosis and prevalence of SARS-CoV-2 variants in Monterrey, Mexico

BackgroundTuberculosis (TB) is a severe global health problem, with high drug resistance rates. The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused worldwide setback progress in TB control. Our aim was to compare detection rates of Mycobacterium tuberculosis at different COVID-19 pandemic waves. MethodsPatients (n = 1800) were evaluated using microbiological and molecular assays for mycobacterial detection in a hospital from Monterrey, Mexico. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by real-time PCR. Data from existing reports of circulating SARS-CoV-2 variants was compared to data of TB prevalence. ResultsThe prevalence of TB was 30.4%. Compared to pre-pandemic, the detection rate of mycobacteria was higher during the first wave. The co-infection of Mycobacterium tuberculosis complex (MTC) and SARS-CoV-2 occurred in seven patients. MTC cases showed several waves which might depend on the prevalence of specific SARS-CoV-2 variants. ConclusionThe COVID-19 pandemic impacted on TB detection on our population, although it is still uncertain if it was mostly due to the influence of specific SARS-CoV-2 variants or to restrictions measures in the region. Public health measures should include the combination of TB and COVID-19 diagnostic screening in TB-endemic settings, such as ours, to restore TB control attempts.

Prevalence of antibiotic resistance in Clostridium difficile: A meta-analysis

In recent years, the resistance of Clostridium difficile to various common mainstream antibiotics cannot be ignored, the incidence of CDI in many areas is also increasing year by year, posing a great threat to public safety. Literature collection was carried out on 6 open databases, and high-quality literature data conforming to classification criteria were screened and extracted. The WPR and WPF of each antibacterial drug were calculated using the random effects model. Subgroup analysis was used to investigate the influence of regional and experimental methods. Results: A total of 40 studies were included. The WPR of vancomycin was 0.0372, 95%CI: [0.0148; 0.0671], I: 93.7%, WPF was 0.2195, I: 94.0%. The WPR of fidaxomicin was 0.0051, 95%CI: [0.0000; 0.0205], I: 82.7%, WPF was 0.1757, I: 93.6%. The WPR of metronidazole was 0.0318, 95%CI: [0.0056; 0.0727], I: 91.6%. Among the three antibiotics, the highest resistance of C. difficile to metronidazole were mainly distributed in the Middle East and Africa. The conclusion seems to indicate that C. difficile is most sensitive to Fidaxomicin, and the clinical cure rate is better than vancomycin. However, the clinical cure failure rate increased significantly from 2007 to 2019, while the drug resistance rate did not change significantly, suggesting that other factors besides drug resistance may affect the therapeutic effect of fidaxomicin on CDI. There was no significant difference in the results of AGAR dilution and e test, the main methods for drug susceptibility testing.

Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate

Epithelial-mesenchymal transition (EMT) is a common process during tumor progression and is always related to residual tumor, drug resistance and immune suppression. However, considering the heterogeneity in EMT process, there is still a need to establish robust EMT classification system with reasonable molecular, biological and clinical implications to investigate whether these unfavorable survival factors are common or unique in different individuals. In our work, we classify tumors with four EMT status, that is, EMTlow, EMTmid, EMThigh-NOS (Not Otherwise Specified), and EMThigh-AKT (AKT pathway overactivation) subtypes. We find that EMThigh-NOS subtype is driven by intrinsic somatic alterations. While, EMThigh-AKT subtype is maintained by extrinsic cellular interplay between tumor cells and macrophages in an AKT-dependent manner. EMThigh-AKT subtype is both unresectable and drug resistant while EMThigh-NOS subtype can be treated with cell cycle related drugs. Importantly, AKT activation in EMThigh-AKT not only enhances EMT process, but also contributes to the immunosuppressive microenvironment. By remodeling tumor immune-microenvironment by AKT inhibition, EMThigh-AKT can be treated by immune checkpoint blockade therapies. Meanwhile, we develop TumorMT website (http://tumormt.neuroscience.org.cn/) to apply this EMT classification and provide reasonable therapeutic guidance.

Prevalence and drug susceptibility of clinical Candida species in nasopharyngeal cancer patients in Vietnam

In the nature, Candida species are normal inhabitants and can be observed in a wide variety of vertebrates. In humans, especially for cancer patients who fall prey to opportunistic pathogens, this group of susceptible multi-drug resistant and biofilm-forming yeasts, are among the commonest ones. In this study, Candida species in 76 oral lesion samples from Vietnamese nasopharyngeal-cancer patients were isolated, morphologically identified using CHROMagar™, germ tube formation, and chlamydospore formation tests, and molecularly confirmed by PCR-RFLP. The drug susceptibility of these isolates was then tested, and the gene ERG11 was DNA sequenced to investigate the mechanism of resistance.The results showed that Candida albicans remained the most prevalent species (63.16% of the cases), followed by Candida glabrata, Candida tropicalis, and Candida krusei. The rates of resistance of non-albicans Candida for tested drugs were 85.71%, 53.57%, and 57.14% to fluconazole, clotrimazole, and miconazole, respectively. Although the drug-resistance rate of Candida albicans was lower than that of non-albicans Candida, it was higher than expected, suggesting an emerging drug-resistance phenomenon. Furthermore, ERG11 DNA sequencing revealed different mutations (especially K128T), implying the presence of multiple resistance mechanisms. Altogether, the results indicate an alarming drug-resistance situation in Candida species in Vietnamese cancer patients and emphasize the importance of species identification and their drug susceptibility prior to treatment.

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolates among children in Suzhou, China.

Streptococcus pneumoniae (SP) is responsible for pneumococcal diseases with severe morbidity and mortality. High rates of drug resistance constitute serious public health concerns. Vaccination has proven to be an effective means of reducing disease burden. Epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. This study reported the serotype distribution and antibiotic resistance pattern of SP in hospitalized children in Suzhou during the years 2017-2018. The aim is to reduce pneumococcal resistance and guide vaccination. The clinical data of hospitalized children with SP were collected and analyzed. A total of 2,446 strains of SP were isolated from these patients. Serotypes were determined using the Quellung reaction. Antibiotic resistance was tested using the E-test diffusion method. The non-susceptible rates of the isolates to penicillin, amoxicillin, and cefotaxime were 9.5%, 27.7%, and 27.2%, respectively. And 97.6% of SP isolates showed multidrug-resistant (MDR). The most common resistance pattern of non-invasive isolates was macrolides + sulfamethoxazole + clindamycin + tetracycline. The major serotypes of this resistance pattern were 6A, 23F, 6B, 19F, 15B. The most extensive resistance pattern of invasive isolates was macrolides + β-lactams + sulfamethoxazole + clindamycin + tetracycline. The most common serotypes of the pattern were 19F, 19A, 6B, 23F, 6A. The most common serotypes were 19F (28.6%), 6B (11.9), 23F (11.2%), 6A (10.6%), and 19A (9.1%). In the isolates with MDR, the first five most common serotypes were 19F, non-vaccine serotype (NVT), 6B, 6A and 23F. Strains belonging to different serotypes exhibited distinct antimicrobial resistance patterns and were found to be associated with different diseases. The coverage rates of pneumococcal conjugate vaccine (PCV)7 and PCV13 in all isolates reached 60.4% (310/513) and 80.9% (415/513), respectively. The main serotypes of SP in Suzhou were 19F, 6B, 23F, 6A, and 19A. The use of PCV13 is beneficial to children in Suzhou.

Bedaquiline, Delamanid, Linezolid, Clofazimine, and Capreomycin MIC Distributions for Drug Resistance Mycobacterium tuberculosis in Shanghai, China.

New antituberculosis drugs have recently been approved for the treatment of multidrug-resistant tuberculosis TB (MDR-TB). We aimed to describe the distributions of bedaquiline, delamanid, linezolid, clofazimine, and capreomycin MIC values for M. tuberculosis. M. tuberculosis clinical isolates were originally isolated from 2020 to 2021 from 1452 different pulmonary tuberculosis patients of the Shanghai Pulmonary Hospital in China. The drug susceptibility testing was performed using the Sensititre custom plates (SHTBMY) (TREK Diagnostic Systems, Thermo Fisher Scientific In., USA) consisting of a 96-well microtitre plate containing 4 (bedaquiline, delamanid, clofazimine, capreomycin) antimicrobial agents. MICs were determined for linezolid using a microdilution method. Based on the latest definitions, 156 (10.74%) were MDR-TB, 93 (6.40%) were pre-XDR-TB, and 27 (1.86%) were XDR-TB. The rate of BDQ resistance in cases of MDR-TB was 7.69%, while it was observed to be 10.75% in cases of pre-XDR-TB, and significantly higher at 37.04% in cases of XDR-TB. The lowest rate of drug resistance against M. tuberculosis was DLM (0.14%). For LZD, 11 (0.76%) clinical isolates were resistant, based on the CLSI breakpoint of 1μg/mL. The five strains with a MIC value of >32 for LZD resistance were XDR-TB isolates. Among all MDR, pre-XDR, and XDR isolates tested, LZD' MIC50 increased from 0.25 and 0.5 to 1μg/mL. The MIC90 value of LZD against XDR-TB isolates was 32μg/mL. For CFZ, six isolates with elevated MICs of ≥2μg/mL. CFZ's MIC50 and MIC90 values in all isolates were 0.12μg/mL and 0.25μg/mL, respectively. The study findings indicate that BDQ, DLM, CFZ, and LZD may exhibited excellent in vitro activity against MDR-TB isolates. Detection of resistance to BDQ and LZD was alarming for XDR-TB isolates. It is necessary to perform universal drug sensitivity testing for M. tuberculosis, especially MDR-TB and XDR-TB patients.

HIV Type-1 Genotyping in the Context of the COVID-19 Pandemic: A Critical Tool for Identifying Antiretroviral Drug Resistance and Optimizing Treatment Strategies

Abstract Introduction/Objective The COVID-19 pandemic strained the healthcare system and the WHO recently reported increased rates of antibiotic resistance. Meanwhile, antiretroviral resistance can also lead to treatment failure and disease progression, especially in HIV patients. Here, we investigated the rates of HIV drug resistance (HIVDR) in our HIV population between pre and post-COVID-19 eras. Methods/Case Report The post-COVID-19 era began on 03/11/2020. Patients positive for HIV-1 between 01/2019- 08/2021 were included (total: 94 patients, 46 pre-COVID-19; 48 post-COVID-19). Patients’ charts were reviewed for demographics, laboratory results (including HIV-1 sequencing/genotyping (e.g., Genosure)), clinical presentation and management. Student t-test and Fisher exact test were calculated. Results (if a Case Study enter NA) Most patients were male (70%) and had a mean age of 49 years. 70% of patients had sufficient viral loads in samples reflexed to HIV genotyping. Post-COVID-19 patients harbored lower viral loads (1.8x105 vs. 3.4x105 copies/mL, p=0.05), CD4 counts (174 vs. 196 cells/mcL, p=0.7), CD8 counts (555 vs. 800 cells/mcL, p=0.04), and higher CD4/CD8 ratio (0.312 vs. 0.266, p=0.57). Overall, 20% of patients had HIVDR. Following COVID-19 pandemic, there was a 9% increase in HIVDR, predominantly seen in non-nucleotide reverse transcriptase inhibitors (NNRTI), although insignificant. Specifically, high resistance was documented for drugs Efavirenz (16%), Nevirapine (16%), and Rilpivirine (13%). We observed an increased prevalence of G190A, K101, K103, and E138 mutations conferring resistance to NNRTIs. Changes to therapy were observed in 47.8% (42/88) of total cases, with an increase of 12.5% in patients from post-COVID-19 era. Additionally, changes to therapy were observed more in patients with infectious diseases consultation (16% increase). Conclusion Increasing HIVDR was seen in our patient population post-COVID-19. Continued surveillance is critical to managing HIVDR and improving patient outcomes. The clinical utility of sequencing tests can outweigh the cost if results are appropriately acted upon which may involve the participation of other clinical teams and the antimicrobial stewardship committee.

Epidemiological Characteristics and Drug-Resistance Genotype of CRE in Patients with Hematological Diseases in a Single Center of China

Patients with blood diseases have a significantly higher risk of infections and mortality rates compared with other type of patients. Referring to the 2019 CDC criteria for CRE, we examined the carbapenemase producing genotype and resistance characteristics of CRE strains (760 strains) in patients with hematological diseases. Among these, carbapenemase producing CRE (CP-CRE) accounts for 60.39% (459/760), non-carbapenemase producing CRE (non-CP-CRE) accounts for 39.61% (301/760). The data indicated that the most common bacteria in patients with hematologic disorders were Escherichia coli, Klebsiella pneumoniae and Enterbater cloacae, which primarily produced NDM-type metallo-β-lactamases. The rates of drug resistance in CP-CRE strains with MIC≥16 to Meropenem and Imipenem were 92.51% (420/454) and 86.12% (391/454), respectively. The drug resistance rates of non-CP-CRE strain with MIC≥16 to Meropenem and Imipenem were only 22.22% and 15.34%, respectively. Furthermore, we discovered that 36.88% (111/301) of non-CP-CRE strains were resistant to Ertapenem alone but still susceptible to Meropenem and Imipenem. The therapy of such CRE may differ significantly from that of other CRE strains, ETP-CRE may not be a typical CRE. In conclusion, Our data determined that the CRE colonized or infected in patients with hematological diseases was dominated by Escherichia coli and metallo-carbapease-producing types, among which the NDM genotypes was predominant. This is quite different from the domestic statistics, indicating that the CRE types infected by hematological disease patients are special and not consistent with other patients. We discovered that some patients with hematological diseases carried or were infected with ETP-CRE, which was sensitive to Meropenem and Imipenem. In terms of therapy, ETP-CRE strains may differ from other CRE in patients with hematological diseases，it may not be a typical CRE.

ANTIBIOTIC SENSITIVITY OF BACTERIAL BLOODSTREAM INFECTIONS IN THE INTENSIVE CARE UNIT PATIENTS OF UNIVERSITY HOSPITALS IN SANA'A CITY, YEMEN

Aim: High rates of morbidity and mortality are associated to bacterial bloodstream infections (B-BSI) in many hospitals, especially in the intensive care unit. This study investigated the prevalence of antibiotic- and multidrug-resistant bacteria isolated from blood samples of patients in intensive care units of university hospitals in the city of Sana'a, Yemen. Subjects and methods: A cross-sectional study was conducted on sepsis patients admitted to intensive care units in four hospitals in Sana'a, Yemen, between January 1 and April 30, 2022. The blood cultures of patients suspected of suffering from sepsis were performed. The potential bacterial pathogens were isolated and identified using standard laboratory methods, and microbial susceptibility testing was performed using the disk diffusion technique. Results: For all identified bacteria, the average resistance rate to a broad spectrum of antibiotics tested ranged from 22.5% to 98.1%, with cefazoline (98.1%) having the greatest resistance rates, followed by amoxicillin (87.2%) and cefixime (83%). Vancomycin had a resistance rate of 4.8% whereas erythromycin had a resistance rate of 75% for Gram-positive bacteria. For Gram-negative bacteria, the resistance rates to narrow spectrum antibiotics ranged from 2.3% for colistin sulphate to 84.8% for aztreonam. Our isolates' MDR rates for resistance to at least three classes of antibiotics were 52.2% and 8.7%, respectively, for resistance to 10 different classes of broad-spectrum antibiotics and their subclasses. Conclusion: Gram positive bacteria are highly resistant to erythromycin and penicillin, while gram negative organisms are highly resistant to amoxcillin+clavulanic acid, ciprofloxacin, and all generations of cephalosporins. This study highlights the significance of prompt clinical and bacteriological monitoring among patients in critical care conditions, such as ICU patients, and also illustrates the establishment and rates of Multi Drug Resistance (MDR) pathogens. Peer Review History: Received: 27 August 2023; Revised: 13 September; Accepted: 29 October, Available online: 15 November 2023 Academic Editor: Dr. Asia Selman Abdullah, Pharmacy institute, University of Basrah, Iraq, asia_abdullah65@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Dr. Tamer Elhabibi, Suez Canal University, Egypt, tamer_hassan@pharm.suez.edu.eg Dr. Wadhah Hassan Ali Edrees, Hajja University, Yemen, edress2020@gmail.com

Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

BIOM-29. FIBRONECTIN TYPE III DOMAIN CONTAINING 3B AS PROGNOSTIC BIOMARKER AND REGULATORY TARGET FOR MALIGNANT BRAIN TUMOR

Abstract Malignant brain tumor (MBT) is an aggressive tumor with high drug-resistance and recurrence rates. Using ‘Oncopression’ big data analysis, we found that a fibronectin-related protein, fibronectin type III domain containing 3B (FNDC3B), was specifically overexpressed in brain tumor patients and conducted a pilot and mechanism study on the role of FNDC3B in MBT. We evaluated the functional significance of FNDC3B in MBT using FNDC3B specific siRNA and performing cell viability assay, real-time qPCR, Western blot, 3D-invasion assay, and wound healing assay. Furthermore, using proteome profiler human phospho-kinase arrays, we investigated the correlated signaling which activated while FNDC3B-mediated MBT cell progression. We found that down-regulation of FNDC3B decreased tumor cell proliferation, migratory and invasiveness properties as well as stemness phenotype which are hallmarks of cancer progression. Furthermore, we demonstrate that PI3K/AKT signaling pathways were involved mainly in FNDC3B-related tumor growth and mesenchymal phenotypes. Although follow-up studies are necessary, the results of this study suggest that FNDC3B is worth investigating as a novel alternative diagnostic and therapeutic target candidate for MBT.

A stochastic co-infection model for HIV-1 and HIV-2 epidemic incorporating drug resistance and dual saturated incidence rates

This study investigates a mathematical model encompassing both HIV-1 and HIV-2 epidemics, with a focus on drug resistance and dual saturated incidence rates. We begin by analyzing the local stability of equilibrium points in the deterministic system using Routh-Hurwitz and Jacobian matrix approaches. Furthermore, we establish the existence of a global positive solution for our model. We identify specific parameter conditions that lead to disease extinction. Additionally, we explore the persistence of HIV-1 and HIV-2 infections by examining their mean values. To assess the practical implications of our theoretical analysis, we conduct graphical evaluations under various noise disturbances, employing Milstein's Higher Order Method. This research contributes to a deeper understanding of the dynamics of HIV-1 and HIV-2 co-infection, with potential implications for treatment strategies and disease management.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/β-catenin oncogenic signaling

BackgroundMetastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PurposeThe study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. MethodsPurified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. ResultsPurified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 μM, and of A375 cells at 100 and 200 μM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/β-catenin axis to exert its antitumor effect. ConclusionThese findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

Incidence and related factors of antiviral drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4+T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.