Infection and Drug Resistance最新文献

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.

Objective: To examine the species distribution, clinical prevalence, antimicrobial profiles, and carbapenemase phenotypes of carbapenem-resistant Enterobacterales (CRE) isolated from a tertiary hospital over the past two years, thereby providing a reference for clinical anti-infection strategies and hospital infection control measures.

Methods: A retrospective analysis was performed to examine the distribution of CRE strains isolated from inpatients at a tertiary hospital between 2023 and 2024, their resistance profiles to commonly used antibiotics and carbapenemase phenotypes.

Results: A total of 239 distinct CRE strains were identified between 2023 and 2024, predominantly in sputum, urine, and blood samples. The primary species of CRE include Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis. These CRE strains were mainly isolated from departments such as geriatrics, intensive care units (ICU), and respiratory medicine. Among the 239 CRE isolates, there was a notably high resistance rate to cephalosporins, enzyme inhibitor combinations, aminoglycosides, and quinolones, exceeding 85%, with carbapenems exhibiting a resistance rate of over 90%. Conversely, the resistance rates to tigecycline, ceftazidime/avibactam, and polymyxin B were 1.26%, 24.24%, and 5.43%, respectively. The majority of strains (74.06%) produced class A serine carbapenemases, specifically the KPC type.

Conclusion: The CRE isolation and resistance rates in this hospital are similar to international trends, both showing an upward trend, and comparison with domestic data reveals significant regional differences. CRE infections are difficult to treat and have a high mortality rate. Therefore, to meet the needs of Infection Prevention and Control, it is necessary to strengthen the monitoring of CRE resistance in this institution, contributing to the prevention, control, and clinical management capabilities for infections.

Purpose: This study aimed to evaluate the clinical effectiveness and safety of high-dose versus standard-dose cefoperazone-sulbactam in patients with severe infections, particularly those caused by multidrug-resistant organisms (MDROs).

Patients and methods: A multicenter retrospective cohort study was conducted across four hospitals from January 2020 to October 2024. Adult patients who received cefoperazone-sulbactam for severe infections, defined as admission to the intensive care unit (ICU), requirement for mechanical ventilation, or an increase in Sequential Organ Failure Assessment (SOFA) score of more than 2, or MDROs were categorized into high-dose (2 g-2 g q8h) and standard-dose (2 g-2 g q12h) groups. The primary outcome was clinical cure at day 14. Secondary outcomes included microbiological eradication, in-hospital mortality, and adverse events (AEs). Multivariate logistic regression and subgroup analyses were performed to identify treatment-associated factors.

Results: A total of 383 patients were included: 141 in the high-dose group and 242 in the standard-dose group. The high-dose group demonstrated significantly higher clinical cure rates (49.7% vs 38.8%; adjusted odds ratio [aOR]: 1.61, 95% CI: 1.05-2.50) and microbiological eradication rates (46.1% vs 20.3%; aOR: 3.85, 95% CI: 2.37-6.26). There was no significant difference in in-hospital mortality (17.7% vs 21.1%, aOR: 0.71; 95% CI: 0.41-1.25). Subgroup analyses showed greater benefit of high-dose therapy in patients with pneumonia, acute respiratory failure, ICU admission, and Charlson Comorbidity Index >4. Changes in liver function tests, renal function (serum creatinine), and coagulation parameters over the course of therapy did not differ significantly between the high-dose and standard-dose groups.

Conclusion: High-dose cefoperazone-sulbactam showed superior clinical and microbiological efficacy compared to the standard dose without increased safety concerns. These findings support the use of high-dose regimens in critically ill patients or those with MDRO infections.

Background: This study aimed to compare the efficacy and safety of colistimethate sodium (CMS) and polymyxin B (PMB) in treating carbapenem-resistant Gram-negative bacteria (CR-GNB)-induced bloodstream infection (BSI) based on real-world data. While international studies on CMS and PMB have yielded conflicting results, there is a lack of direct comparative data from Chinese cohorts, where the pathogen distribution may influence outcomes.

Methods: A retrospective analysis was conducted on 373 Chinese patients with CR-GNB-induced BSI who received CMS-containing therapy (n=132) or PMB-containing therapy (n=241) between Dec 2021 and Dec 2023. Propensity score matching was used to balance the two groups at a ratio of 1:2. The primary outcome was clinical success. The secondary outcomes included inpatient days, in-hospital mortality, 28-day all-cause mortality, and incidence of adverse events. Statistical analysis was performed with Wilcoxon rank sum test, Student's t-test, chi-square test, and Fisher's exact test as appropriate.

Results: In this cohort, Acinetobacter baumannii was the predominant pathogen (53.4%). No significant differences were observed in efficacy outcomes between the two groups (p>0.05). For safety, the difference in hyperpigmentation incidences between the two groups was statistically significant (CMS vs PMB: 0.0% vs 6.36%, p=0.04). Incidences of hypersensitivity, neurotoxicity, and nephrotoxicity were similar between groups (p>0.05). A longer treatment course (>12 days), while associated with a higher incidence of hyperpigmentation, was linked to significantly improved clinical outcomes, including higher success rate, reduced in-hospital mortality, and lower 28-day all-cause mortality (p<0.05).

Conclusion: This study provides the first large, real-world comparative evidence from a Chinese cohort with CR-GNB BSIs. In this setting, CMS and PMB demonstrated comparable efficacy. The critical difference lay in the safety profile, with CMS associated with a markedly lower incidence of hyperpigmentation. This finding provides a tangible basis for antibiotic stewardship, positioning CMS as a valuable first-line polymyxin option.

Introduction: The objective of the current investigation was to develop a clinical predictive model for virological treatment failure in HIV patients with low level viremia.

Methods: The study included 786 patients with HIV-associated low-level viremia (LLV). Using Lasso and multivariable logistic regression, we developed a predictive model from clinical and laboratory variables to identify significant predictors. This predictive model was presented as a nomogram and subsequently transformed into a scoring system. Following model construction, internal validation was performed to evaluate the model's calibration capability and clinical utility.

Results: The final model incorporated five predictors (HLLV, NVP/3TC/AZT, WHO stage 1, ART delay, triglyceride) into a point-based scoring system. Using the Youden index, a threshold of 6 points was determined. The model demonstrated good performance, with training and internal validation AUCs of 0.762 and 0.759, respectively, and satisfactory calibration and diagnostic accuracy.

Conclusion: New scoring system predicts virological failure in low-level viremia, supporting early clinical intervention.

Background: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus traditionally associated with HIV-related immunosuppression. However, increasing reports have described infections in HIV-negative patients with hematologic malignancies, particularly those receiving novel immunosuppressive therapies.

Case presentation: We report a case of disseminated T. marneffei in an HIV-negative 55-year-old woman with T-prolymphocytic leukaemia (T-PLL) undergoing chemotherapy and targeted therapy with chidamide and golidocitinib. The patient presented with fever, pancytopenia, and signs of systemic infection. Blood cultures confirmed T. marneffei, with identification supported by dual-phase morphology and internal transcribed spacer (ITS) sequencing. Due to unavailability of amphotericin B, the patient was treated successfully with voriconazole, achieving rapid clinical improvement and negative follow-up cultures.

Discussion: This case adds to the growing evidence that T. marneffei can cause invasive infections in non-HIV immunocompromised hosts. Through a review of 10 published cases, we identify common features such as neutropenia, kinase inhibitor use, and diagnostic delays. We emphasize the importance of early fungal culture and phase-specific morphology for diagnosis, and highlight voriconazole as a viable alternative therapy when amphotericin B is inaccessible.

Conclusion: Clinicians should maintain high suspicion for talaromycosis in immunosuppressed hematologic patients in endemic regions, regardless of HIV status. Prompt recognition and appropriate antifungal therapy are essential to improve outcomes.