Infection and Drug Resistance最新文献

Introduction: Sepsis is a common and life-threatening condition in clinical practice, leading to mortality among intensive care unit (ICU) patients. Due to its unclear pathogenesis, underscoring the urgent need for effective therapeutic strategies. Ferroptosis plays a pivotal role in sepsis progression, and ferroptosis-related genes represent promising intervention targets.

Methods:  This study performed bioinformatics to identify ferroptosis-related hub genes in sepsis. We used septic mice and lipopolysaccharide (LPS)-treated IECs to detected the role of TP53-mediated ferroptosis in sepsis. Furthermore, in vitro and in vivo experiments were conducted to validate the effect of hydroxysafflor yellow A (HSYA) on TP53-mediated ferroptosis and sepsis.

Results: TP53 has been identified as a ferroptosis-related hub gene in sepsis. Inhibition of TP53 with the specific TP53 inhibitor Pifithrin-α markedly reduced ferroptosis both in vitro and in vivo. Meanwhile, inhibition of TP53 significantly reduced inflammation and improved sepsis-induced intestinal barrier dysfunction. Furthermore, this study found that HSAY, a core component of XueBiJing, could stably bind to TP53, reduced the expression of TP53 and TP53-mediated ferroptosis in sepsis and improved animal survival.

Conclusion: This study clarified the role of TP53-mediated ferroptosis in sepsis-induced intestinal barrier dysfunction and discovered that HSYA could improve sepsis as an inhibitor of TP53, offering new strategies for the treatment of sepsis.

Background: Serogroup Y (MenY) invasive meningococcal disease (IMD) is uncommon in China, and MenY IMD cases combined with respiratory infections caused by several viruses are rare worldwide.

Case presentation: A 12‑year‑old boy was admitted by ambulance to a secondary hospital in Yunnan on January 9, 2025, due to sore throat for three days, fever, headache, and vomiting for six hours. Neisseria meningitidis (Nm) was cultured from the cerebrospinal fluid, whereas influenza A virus, adenovirus, and rhinovirus were detected in throat swab by PCR. After treatment with ceftriaxone and oseltamivir, the patient's condition improved and was discharged. Whole-genome sequence analysis of the Nm isolate (Nm534) showed a molecular type of Y: P1.5-1,10-1: F4-1: ST-1655(CC23) without antimicrobial resistance-associated mutations. Phylogenetic analysis indicated that Nm534 was assigned to Clade II and was closely related to isolates from Guangdong and Guangxi, which have the potential to be the infection source of this IMD case.

Conclusion: A rare case of MenY meningococcal meningitis combined with respiratory infection caused by three species of viruses was reported in China. It is recommended that school-aged children and adolescents be immunized with meningococcal polysaccharide conjugate vaccine ACYW.

Purpose: There was an increasing incidence of spinal infections. This study aimed to compare and contrast the clinical characteristics and treatment regimens for diverse types of spondylitis and to provide guidance for clinicians to make timely diagnosis and treatment.

Patients and methods: One hundred and twenty-five patients with spinal infections admitted to the First Affiliated Hospital of Anhui Medical University from October 2019 to December 2024 were recruited. The patients were classified as having tuberculous spondylitis (TBS), brucellosis spondylitis (BS), or pyogenic spondylitis (PS). The patient's treatment regimen and course were dynamically followed up during hospitalization and after discharge. Comparisons of clinical characteristics and treatment among the three groups were performed by SPSS 26.0 and GraphPad Prism 10 statistical software.

Results: The proportion of male patients was greater than female patients (65.00% vs 35.00%). Fever accompanied by pain was more prevalent in the BS and PS groups than in the TBS group (P=0.003). Compared with the TBS and BS groups, the PS group had the shortest duration from symptom onset to hospitalization (P<0.001). Sepsis, invasive manipulation, elevated inflammatory markers, psoas abscesses, and the involvement of three or more vertebrae were significantly associated with the PS. In this study, the median duration of treatment was 77 weeks for TBS, 19 weeks for BS, and 13 weeks for PS. Adverse drug reactions (ADRs) should be monitored during treatment. Our results indicated that omadacycline and contezolid exhibited remarkable efficacy in the treatment of spinal infections.

Conclusion: Patients of spinal infections with diverse etiologies presented varied clinical features and risk factors, the treatment should be individualized. Due to the long course of treatment, ADRs need to be monitored during treatment, and newer drugs such as omadacycline and contezolid are efficacious and have favorable safety profiles.

Fungal infections represent a growing global public health problem, particularly in immunocompromised individuals. The availability of effective treatments is limited, and the emergence of strains resistant to conventional antifungal agents further complicates disease management. Therefore, it is essential to explore novel therapeutic alternatives. This review analyzes compounds derived from natural sources with potential antifungal activity and highlights their structural and functional diversities. These include plant primary metabolites, fatty acids, antimicrobial peptides, secondary metabolites, crude extracts, terpenoids, essential oils, flavonoids, and saponins, as well as fungal metabolites and compounds extracted from marine algae. These natural products have demonstrated activity against various fungal species through multiple mechanisms of action, making them promising candidates for the development of new antifungal therapies. Compared with synthetic molecules or novel antifungal drugs under development, natural compounds often display lower toxicity, higher availability, and greater chemical diversity, which can be strategically exploited to overcome resistance. The compilation and analysis of this information underscores the value of natural sources as valuable resources in the search for therapeutic alternatives against human mycoses, particularly in the current context of increasing antifungal resistance.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major global health threat, and the emergence of ceftazidime-avibactam (CZA)-resistant KPC variants presents an increasing clinical challenge. This study aimed to investigate the in vivo evolution and phenotypic difference of a KPC-2 variant, KPC-71, during CZA therapy.

Methods: Seven CRKP isolates were sequentially collected from a single hospitalized patient over a 147-day period. Whole-genome sequencing, phylogenetic analysis, plasmid profiling, antimicrobial susceptibility testing, and virulence assays (including Galleria mellonella infection, siderophore production, and serum resistance) were performed to characterize the evolutionary dynamics and biological consequences of KPC-71.

Results: KPC-71 emerged repeatedly during CZA treatment, replacing KPC-2 and conferring high-level CZA resistance while reducing carbapenem MICs. Withdrawal of CZA resulted in reversion to KPC-2, restoring carbapenem resistance and CZA susceptibility, indicating a reversible resistance trade-off. Phylogenetic analysis revealed clonal expansion of the KPC-71-producing sublineage. Plasmid analysis identified bla _KPC genes located on a conserved IncFII/IncR-type plasmid containing an intact ISKpn27-bla _KPC-ISKpn6 transposon, while progressive remodeling of an IncFII(pCRY) plasmid in CRKP103 led to chromosomal integration of multiple resistance genes. Notably, the final isolate, CRKP103, exhibited markedly reduced capsule production, siderophore activity, serum survival, and attenuated virulence in G. mellonella, which associated with the loss of the iucABCD/iutA locus on an IncHI1B-type virulence plasmid. Functional validation confirmed that KPC-71 expression alone conferred high-level CZA resistance while modulating susceptibility to other β-lactams.

Conclusion: This study provides the first clinical evidence of the reversible in vivo evolution of an insertional KPC-71 variant under antibiotic pressure. The findings reveal a dynamic balance between resistance and virulence mediated by bla _KPC mutations and plasmid remodeling, highlighting the risk of resistance cycling during CZA treatment and the need for genomic surveillance in managing CRKP infections.

Background: T-cell responses are crucial in SARS-CoV-2 immune-control; however, limited data exist from African populations. We assessed interferon-gamma (IFN-γ) release by T cells among Tanzanian adults (18-70 years) previously infected with or without SARS-CoV-2 vaccination, using the ELISpot assay. We also characterized background plasma IFN-γ levels in this population.

Methods: Peripheral blood mononuclear cells (PBMCs) from 143 individuals, sampled 1-12 months post SARS-CoV-2 exposure, were stimulated with overlapping peptides spanning the Spike and Nucleocapsid proteins. T-cell responses were measured by ELISpot assay, and plasma IFN-γ concentrations by ELISA. Associations with participant characteristics were analyzed using gamma linear and modified Poisson regression models (p < 0.05 considered significant).

Results: We found high background T-cell IFN-γ release in 73.4% (105/143) of participants, leaving 38 (26.6%) with detectable responses above background; (38/38;100%) to Spike and (36/38;94.7%) to Nucleocapsid peptides. T-cell response magnitude did not differ by symptomatic/asymptomatic infection or vaccination status. However, each one-year increase in age was associated with a 1% decline in mean T-cell response (p = 0.029). Moreover, among participants with high background responses, 43/105;41% had elevated plasma IFN-γ, and 5/105; 4.8% showed cytokine storm-level concentrations. Alcohol consumption was significantly associated with elevated plasma IFN-γ (p = 0.041).

Conclusion: Strong and possibly cross-reactive T-cell responses to SARS-CoV-2 were detected in Tanzanian individuals following infection with/without vaccination. Moreover, high plasma IFN-γ levels were detected, especially among participants who consumed alcohol. We recommend for modifications of the ELISpot T-cell assays to optimize the evaluation of pathogen-specific T-cell responses among African residents given the high background IFN-γ release.

Antimicrobial resistance (AMR) poses one of the greatest global health challenges, particularly in healthcare-associated infections caused by multidrug-resistant Gram-negative bacilli. Rapid and reliable identification of these pathogens is critical to guide therapy, improve patient outcomes, and support infection control measures. This review explores the application of 16S ribosomal RNA (rRNA) gene sequencing for the identification of pathogenic Gram-negative bacilli included in the World Health Organization (WHO) antimicrobial resistance priority list. The 16S rRNA gene, with its conserved and hypervariable regions, provides a robust molecular marker widely used in bacterial taxonomy and clinical diagnostics. The analysis covers conventional Sanger sequencing, next-generation sequencing (NGS), and third-generation approaches, outlining their advantages, limitations, and clinical applicability. Results indicate that while 16S rRNA sequencing is a valuable tool for genus-level identification, comparative analysis reveals its resolution is often insufficient for distinguishing closely related species such as Escherichia coli and Shigella spp. or for taxa with low interspecies variability. In these cases, complementary strategies - such as multilocus sequence analysis, whole genome sequencing, or advanced mass spectrometry-based methods - are required to achieve accurate identification. Furthermore, the reliability of 16S-based identification depends heavily on the quality of reference databases, as demonstrated by in silico analysis of type strains, and adherence to interpretative guidelines. In conclusion, 16S rRNA sequencing remains a cornerstone of molecular diagnostics and epidemiological surveillance of multidrug-resistant Gram-negative pathogens, but its integration with additional molecular and proteomic tools is essential to overcome its limitations and strengthen infection management strategies.

Background: Agrobacterium radiobacter (A. radiobacter) is a gram-negative environmental bacterium primarily found in soil and plants. While it exhibits low virulence, it can act as an opportunistic pathogen in immunocompromised hosts. Its variable antibiotic resistance patterns pose challenges in clinical management. In this context, we reported a case of catheter-related bloodstream infection (CRBSI) caused by A. radiobacter and reviewed its clinical features, diagnostic challenges, and treatment strategies.

Case presentation: A 70-year-old male with stage IIIA gastric adenocarcinoma and a chemotherapy-associated central venous catheter (CVC) presented with fever and elevated procalcitonin (3.02 ng/mL). Blood cultures from CVC and periphery grew A. radiobacter. Empirical piperacillin/tazobactam transiently improved symptoms, but recurrent fever prompted CVC removal on day 10 of hospitalization, leading to rapid resolution of fever, normalization of procalcitonin, and negative follow-up blood cultures.

Conclusion: This case highlights the critical role of catheter removal and susceptibility-guided antibiotic therapy for A. radiobacter infections in immunocompromised patients, addressing biofilm challenges and informing antimicrobial stewardship. Collaborative research integrating microbiology, genomics, and clinical data is essential to refine treatment algorithms and improve outcomes in immunocompromised hosts.

Herbal creams are becoming increasingly popular in dermatology due to their potential to treat a variety of skin conditions, offering a natural, sustainable alternative to synthetic products. Derived from traditional medicine, these formulations contain plant-based bioactive compounds that provide anti-inflammatory, antimicrobial, antioxidant, and wound-healing properties. Common ingredients such as Aloe vera, tea tree oil, calendula, turmeric, chamomile, and liquorice are known to address skin issues including acne, eczema, psoriasis, and aging. Despite these advantages, safety concerns remain, as the natural origin of these products does not guarantee safety; some may cause allergic reactions or skin irritation, while impurities and contaminants pose additional risks. This underlines the importance of comprehensive safety evaluations. Furthermore, regulatory and quality control challenges make the market difficult to navigate, reinforcing the need for standardized production and rigorous testing to ensure consistency and safety. Although clinical trials and marketed formulations demonstrate the efficacy of herbal creams, variability in ingredient concentrations and a lack of regulation can affect outcomes. Future perspectives call for the integration of traditional herbal knowledge with modern scientific advancements to enhance the safety and effectiveness of these products. This review explores the antimicrobial and anti-infective efficacy of herbal creams, their skin penetration mechanisms, safety considerations, and regulatory challenges, emphasizing clinical trials and marketed formulations. By integrating traditional herbal knowledge with modern scientific advancements, herbal creams offer a promising approach to managing skin infections while minimizing antibiotic resistance, provided robust regulatory frameworks ensure product safety and consistency.

Antimicrobial resistance poses a serious threat to human health. Polymyxins, as cyclic polypeptide antibiotics, include polymyxin B (PMB) and polymyxin E. Although they have different metabolic pathways, their antibacterial activities are similar. Polymyxins exert their effects through mechanisms such as disrupting bacterial cell membranes, neutralizing endotoxins, and impairing the respiratory chain. In clinical practice, polymyxins are often used in combination with other drugs to treat infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). No difference in efficacy has been demonstrated between PMB and polymyxin E. An increasing amount of evidence suggests that combination therapy is not superior to monotherapy. The combination of intravenous administration and nebulization can help improve microbial clearance. Compared with other antibiotics, polymyxins have not shown obvious survival benefit. Polymyxins are associated with nephrotoxicity and neurotoxicity, and it is essential to closely monitor for related adverse events during the course of treatment.