Infection and Drug Resistance最新文献

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy and a high mortality rate if untreated. While TTP can be primary or secondary to factors like drugs, reports linking it to anti-tuberculosis (anti-TB) therapy are scarce. This case highlights the diagnostic challenges and need for vigilance in TB patients receiving standard regimens.

Case presentation: A 76-year-old male on anti-TB therapy (isoniazid, rifampicin, pyrazinamide, ethambutol) presented with acute neurological symptoms, thrombocytopenia (platelets 9×10^9/L), microangiopathic hemolysis (schistocytes), and severely reduced ADAMTS13 activity (<5%). Imaging revealed multiple cerebral infarctions. Despite plasma exchange and steroids, the patient deteriorated and died after family-requested care withdrawal.

Conclusion: This case highlights TTP as a rare but serious complication of anti-TB therapy. Clinical vigilance is essential, including platelet monitoring during initial treatment and a low threshold for ADAMTS13 testing in cases of unexplained thrombocytopenia. Future multicenter studies are needed to investigate immune mechanisms and assess therapies such as rituximab, with the aim of optimizing management strategies for rare adverse drug events and improving patient outcomes.

Background and aim: Antimicrobial resistance (AMR) is a major global health threat, primarily driven by inappropriate antibiotic use. This cross-sectional study assessed the knowledge, attitudes, and practices of healthcare professionals in Saudi Arabia regarding antimicrobial use, resistance, and stewardship to identify gaps contributing to misuse.

Methodology: An observational cross-sectional study was conducted using a validated self-administered questionnaire among physicians, nurses, and pharmacists. Data were analyzed using univariate and multivariate methods.

Results: Among 236 respondents (45.3% physicians, 31.8% nurses, 22.9% pharmacists), most were aged 26-35 (33.9%), with nearly equal gender distribution (53.0% women). While 85.2% were aware of AMR, 64.1% reported limited access to infection control policies. Most (94.9%) acknowledged that unnecessary antibiotic use contributes to resistance, and 96.2% understood its transmissibility. Daily antibiotic prescribed, dispensed, or administered was reported by 57.6%. Key barriers to appropriate prescribing included time constraints (84.7%) and diagnostic uncertainty (75.8%). Only 20.3% used clinical guidelines, whereas 35.2% relied on pharmaceutical industry materials. In the multivariate regression, knowledge scores increased with age (+0.31 per decade, p = 0.024), profession was the strongest predictor (β = 6.4, p < 0.001), and antimicrobial stewardship (ASP) training improved scores by 1.6 points.

Conclusion: Significant gaps exist in access to guidelines and adherence to evidence-based practices. Targeted ASP interventions focusing on professional education, improved resource availability, and institutional support are essential to enhance stewardship and combat AMR in Saudi Arabia.

Objective: To analyze the risk factors for 30-day prognosis in patients with hemorrhagic fever with renal syndrome (HFRS) in the Dali region of China, and to provide a theoretical basis for the diagnosis and treatment of HFRS.

Methods: A retrospective analysis was conducted on the data of patients diagnosed with HFRS at the First Affiliated Hospital of Dali University and People's Hospital of Dali Bai Autonomous Prefecture from January 1, 2015, to January 31, 2025. Based on the 30-day prognosis, patients were categorized into the survival group (n = 341) and the deceased group (n = 32). Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to screen for influential factors affecting the 30-day prognosis of HFRS, followed by binary logistic regression analysis to identify risk factors for short-term prognosis of HFRS. Finally, a nomogram model was constructed based on the identified prognostic risk factors.

Results: A total of 373 patients with HFRS from the Dali region of China were included, with a 30-day mortality rate of 8.579%. LASSO-logistic regression analysis revealed that low levels of prothrombin time (PT), white blood cell (WBC), lactate dehydrogenase-to-albumin ratio (LAR), and free triiodothyronine (FT3) were risk factors for the 30-day prognosis of HFRS patients (P < 0.05). Based on these risk factors, a 30-day prognostic risk nomogram model for HFRS patients was constructed. The results indicated that the observed values in the nomogram model were largely consistent with the predicted values (χ² = 2.834, P = 0.944), and the C-index was 0.946 (95% CI: 0.914-0.978), demonstrating clinical validity. Monitoring these indicators is conducive to the early identification of HFRS patients with poor prognosis, providing a scientific basis for the implementation of individualized treatment and management in clinical practice.

Conclusion: PT, FT3, WBC levels, and LAR values are risk factors for 30-day mortality in patients with HFRS. Moreover, we have, for the first time, identified a close association between FT3 and LAR and the prognosis of HFRS. The developed nomogram demonstrates favorable predictive performance and can serve as an intuitive quantitative tool for the early identification of high-risk patients, thereby guiding clinical intervention strategies.

Purpose: This study leveraged CSF metagenomic next-generation sequencing (mNGS) to bridge this knowledge gap and elucidate the microbiota spectrum of CNS infections.

Patients and methods: We retrospectively analyzed CSF mNGS reports and clinical data from 264 patients with suspected CNS infections, who were enrolled from September 2019 to November 2023.

Results: According to diagnostic criteria, 145 patients were diagnosed with CNS infections, including bacterial (27 cases, 18.6%), Mycobacterium tuberculosis (30, 20.7%), fungal (23, 15.9%), and viral (65, 44.8%) infections. The mNGS positive detection rate was 46.2% (67/145), with significant differences among groups (p < 0.001). A total of 22 pathogens were identified, most commonly Cryptococcus neoformans (16, 23.9%), Mycobacterium tuberculosis (10, 14.9%), and Epstein-Barr virus (9, 13.4%). The most frequent background microorganisms detected by mNGS were Cutibacterium acnes (58.6%), Moraxella osloensis (29.0%), and Malassezia restricta (26.2%).

Conclusion: High-throughput sequencing using mNGS revealed the microbial compositions in CSF samples from patients with CNS infections. This approach may enhance our understanding of pathogens and assist clinicians in making effective therapeutic decisions.

Infectious diseases, especially sepsis from bacterial infections, significantly threaten global health, with antimicrobial resistance (AMR) complicating treatment and increasing clinical burdens. Antibiotic overuse contributes to AMR by creating selective pressure, reducing the efficacy of traditional therapies, and necessitating new approaches. Endogenous hydrogen sulfide (H₂S), a gaseous signaling molecule produced by most bacteria through cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), plays a crucial role in bacterial resistance. This review explores the biological functions of bacterial endogenous H₂S and its impact on AMR. H₂S enhances resistance by neutralizing antibiotic-induced reactive oxygen species (ROS), reducing oxidative stress and DNA damage, and promoting biofilm formation, which obstructs antibiotic penetration and facilitates resistance gene exchange. Furthermore, enhancing H₂S-based assays could significantly improve the diagnosis of AMR. Additionally, strategies such as targeting H₂S metabolism-through the use of H₂S synthase inhibitors or disrupting biofilms via H₂S clearance-or the combination of H₂S synthase inhibitors with antibiotics, may reverse resistance. A deeper understanding of the mechanisms by which H₂S mediates resistance is essential for the development of advanced diagnostic tools and innovative therapies to combat AMR. Its clinical translation may reverse AMR passivity, guide antibiotic sensitizer development, and optimize therapies, holding significant clinical and translational value.

Background: Infective endocarditis (IE) is a severe infectious disease affecting the endocardium and cardiac valves, caused by various pathogens. Among numerous pathogenic microorganisms, Staphylococcus aureus is the most common, followed by other streptococci such as Streptococcus viridans and enterococci. Bartonella, a Gram-negative, fastidious parasitic bacillus, is a rare causative agent of IE Streptococcus constellatus, belonging to the Streptococcus milleri group, commonly colonizes oral cavity, upper respiratory tract, and gastrointestinal tract, which can cause infections when host immunity is impaired. This study demonstrates a surviving case of infective endocarditis caused by Streptococcus constellatus, initially illustrating cardiac arrest and Bartonella infection.

Case presentation: A 59-year-old male with a history of Bartonella infection post-cat scratch presented progressive vision loss and dyspnea. Admitted to the emergency department, he suffered sudden cardiac arrest, necessitating CPR and intubation before transferring to the ICU. Multidisciplinary evaluation confirmed infective endocarditis (IE), and he was implemented a successful valve replacement surgery. Pathogen identification via high-throughput sequencing of valve tissue revealed Streptococcus constellatus. The patient received targeted anti-infective therapy, mechanical ventilation, and cardiopulmonary support, laying solid foundations for successful extubation and transfer for further specialized care.

Conclusion: Bartonella and Streptococcus are rare etiologies of infective endocarditis. This case underscores the vital role of intensive care in managing infective endocarditis resulted from cardiac arrest, as well as the challenges and significance of a multidisciplinary approach to such complex conditions. Furthermore, it highlights the critical utility of high-throughput sequencing in pathogen identification and guiding antimicrobial therapy optimization.

Background: Diagnosing tuberculosis (TB) infection remains a challenge for clinicians. According to recommendations from the World Health Organization (WHO), lipoarabinomannan (LAM) testing can be used to diagnose TB infection in individuals. A new generation of urinary LAM testing is now available. However, studies on its accuracy are limited and warrant further exploration.

Objective: This study aims to evaluate the accuracy of a new urinary LAM testing using LAM for diagnosing TB infection.

Methods: A cross-sectional study was conducted at the Fourth People's Hospital of Nanning, China. Participants were enrolled from December 2023 to May 2024. Fresh urine samples were collected from the participants and tested using LAM. The diagnostic accuracy of the LAM was compared with other tests for Mycobacterium tuberculosis (sputum culture, sputum smear or molecular biology testing). We compared the positive rates of different TB detection methods to evaluate the effectiveness of LAM. In the comparative analysis, the 95% confidence interval was calculated using the Wilson score method. The kappa value was computed, and the corresponding P-value was reported.

Results: The positive agreement rate of LAM was 64.37%, the negative agreement rate was 94.29%, and the overall agreement rate was 80.73%. The Kappa value was 0.6013, indicating good consistency between the test reagent and the reference method.

Conclusion: LAM can be used for the diagnosis of TB. It provides diagnostic information quickly, easily, and cost-effectively, particularly showing good performance in diagnosing TB.

Purpose: Despite red blood cell distribution width (RDW) is a routinely available hematological data and has been found to be associated with mortality in different diseases, the specific association of RDW on Klebsiella pneumoniae bloodstream infection (KP-BSI) outcome remains underexplored.

Methods: This retrospective cohort study investigates the association between RDW levels and in-hospital mortality in 267 adult patients with KP-BSI admitted to a tertiary hospital between 2019 and 2024. RDW was analyzed both as a continuous variable and categorized into tertiles. The primary outcome was in-hospital mortality. Multivariable logistic regression, subgroup analyses, and sensitivity analyses were systematically employed to investigate the association between RDW levels and mortality risk. Receiver operator characteristic (ROC) curve analysis was performed to evaluate the prognostic value of RDW for in-hospital mortality in KP-BSI.

Results: During hospitalization, 122 mortality events were recorded, constituting 45.7% of the study population (n=267). When RDW was examined as a continuous factor, a significant positive relationship was observed between RDW and mortality in the full adjusted model, the odds ratio (OR) was 1.05 (95% confidence interval [CI] (1.02~1.08), P=0.003). As RDW tertiles elevated, the incidence of mortality increased, with the OR for T3 (>50.8fL) group being higher than that for T1 (<43.2fL) group (OR: 7.63, 95% CI: 2.96-19.69; p<0.001) in Model 3. Subgroup and sensitivity analyses remain consistent. ROC analysis showed that RDW predicted in-hospital mortality with an AUC of 0.705.

Conclusion: High RDW values were independently associated with an increased risk of in-hospital mortality in patients with KP-BSI, indicating their potential utility as for prognostic assessment.

Background: Precore/Basal core promotor (PC/BCP) mutations are critical mechanisms by which hepatitis B virus (HBV) evades host immunity and antiviral therapy. These mutations are prevalent in HBeAg-positive chronic hepatitis B (CHB) patients, potentially leading to suboptimal responses to nucleos(t)ide analogues (NAs) and high relapse risk after treatment discontinuation.

Objective: This study aimed to investigate the impact of PC/BCP mutations on seroconversion and relapse rates and analyze their association with drug resistance mechanisms. The study also evaluated the significance of mutation count (one, two, or three mutations) and specific types of mutations (A1762T, G1764A, G1896A) in relation to the seroconversion and relapse processes.

Methods: From 2016 to 2019, 48 HBeAg-positive CHB patients were collected and divided into mutation (n=37) and non-mutation (n=11) groups based on PC/BCP status. Seroconversion rates after 144 weeks of NA therapy and relapse rates after 48 weeks of treatment discontinuation were analyzed. Baseline viral load (HBV DNA), liver function (ALT), and Precore/ Basal Core Promoter (PC/BCP) mutation status were analyzed for their correlation with clinical outcomes.

Results: Among the 37 patients in the mutation group, 9 exhibited G1896A mutation, 15 exhibited A1762T/G1764A double mutations, 13 exhibited A1762T/G1764A/G1896A triple mutations. The mutation group showed significantly lower seroconversion rates than the non-mutation group (37.8% vs 81.8%, P=0.016). The seroconversion rate was inversely correlated with the number of mutations, with triple mutations (A1762T, G1764A, G1896A) associated with the lowest seroconversion rate. The mutation group exhibited a 100% relapse rate (14/14 cases) with HBeAg reactivation, while no relapses occurred in the non-mutation group (0/9 cases, P=0.0001). PC/BCP mutations (eg, A1762T/G1764A) likely reduce NA sensitivity by enhancing viral replication (upregulating pgRNA transcription) and immune evasion (HBeAg epitope variation), leading to delayed treatment response and viral rebound after discontinuation of therapy.

Conclusion: PC/BCP mutations are independent risk factors for poor NA response and high relapse rates in HBeAg-positive CHB patients. Patients with these mutations should be managed as "occult HBeAg-negative CHB" to avoid premature treatment discontinuation. Routine PC/BCP mutation testing is recommended to guide individualized treatment duration in HBeAg-positive CHB patients.

Background: Pulmonary mucormycosis is a life-threatening fungal infection that primarily affects immunocompromised individuals. Underlying malignancy is a recognized risk factor for pulmonary mucormycosis, yet its independent effect on patient outcomes remains uncertain. This study aimed to evaluate the impact of underlying malignancy on the clinical characteristics and 30-day mortality of pulmonary mucormycosis.

Methods: We conducted a retrospective cohort study of 163 adults with proven or probable pulmonary mucormycosis at a single center in Taiwan (2021-2024). Clinical and laboratory variables were compared between groups. Predictors of 30-day all-cause mortality were assessed using Cox proportional hazards regression with purposeful variable selection, and proportional-hazards assumptions were verified using Schoenfeld residuals.

Results: The overall 30-day mortality rate was 18.4% (30 of 163 patients). Kaplan-Meier analysis confirmed lower 30-day survival in malignancy patients (log-rank χ² = 27.08, df = 1, p < 0.0001). In multivariable analysis, malignancy (aHR 3.65, 95% CI 1.40-9.53), neutrophil-to-lymphocyte ratio per 5 units (aHR 1.10, 95% CI 1.05-1.22), and alkaline phosphatase per 50 U/L (aHR 1.16, 95% CI 1.00-1.64) were independent predictors of early death. Clinically, patients with malignancy predominantly exhibited a cytopenic-immunosuppressed phenotype, whereas those without malignancy more frequently exhibited a metabolic-inflammatory profile characterized by chronic kidney disease or recent COVID-19.

Conclusion: Underlying malignancy independently triples 30‑day mortality in pulmonary mucormycosis. Easily available laboratory markers-neutrophil‑to‑lymphocyte ratio and alkaline phosphatase-also stratify early risk, underscoring the need for phenotype-tailored and timely antifungal management strategies.