Infection and Drug Resistance最新文献

Introduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.

Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.

Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.

Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.

Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.

Objective: The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections.

Methods: Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed.

Results: Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2-4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients.

Conclusion: CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.

Clinical relevance statement: Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.

The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.

Peptoniphilus asaccharolyticus is a gram-positive anaerobic coccus that can cause infections in immunocompromised individuals. P. asaccharolyticus causing empyema has not been reported earlier. Here, we present a novel case of empyema caused by P. asaccharolyticus. A 72-year-old male had a constant fever with difficulty breathing. A chest computed tomography scan revealed infiltration in the right lower lobe and pleural effusion. Following hospital admission, pleural fluid drainage was conducted, and the culture isolated P. asaccharolyticus. Initially treated with piperacillin/tazobactam, the patient experienced excessive thick sputum production, prompting a tracheostomy. Subsequent sputum cultures identified Acinetobacter baumannii. After transitioning to cefoperazone/sulbactam for antibiotic treatment and continued pleural effusion drainage, recovery was achieved. Empyema can be caused by P. asaccharolyticus and further complicated by a secondary infection with A. baumannii. Management should include appropriate antibiotic therapy, pleural drainage, vigilant monitoring, and supportive care. We aim to raise clinicians' awareness of the potential for P. asaccharolyticus to cause empyema in immunocompromised patients and to provide early treatments, thereby improving morbidity and mortality.

Listeria monocytogenes is a prevalent gram-positive intracellular zoonotic pathogen that is frequently associated with foodborne illnesses and opportunistic infections. This bacterium is responsible for causing various clinical manifestations, including bacteremia, meningitis, and encephalitis, and is primarily transmitted through contaminated food consumption. This study presents two cases of severe endocarditis in patients with heart valve disease caused by L. monocytogenes. Infection was confirmed by blood culture and pathogen culture of the valve pus. Early detection, clinical suspicion, and appropriate treatment are crucial for improving the prognosis of patients with listeriosis. The combination of ampicillin and aminoglycosides remains the most effective treatment for listeriosis.

Objective: During conditions accompanied by the disruption of normal mucosal barriers, anaerobic bacteria, which a part of normal human mucosal microflora, may cause various infections. In this study, clinical features of anaerobic bloodstream infections (BSI) in a general hospital in China were investigated.

Methods: Patients with anaerobic BSI were retrospectively enrolled between 2012 and 2022. Demographic data, clinical manifestations, antibiotic treatments, and disease outcomes were analyzed.

Results: In total, 391 anaerobic bacterial strains were isolated from 381 patients aged older than 11 years of age. Given that medical records of 47 patients were missing, 334 patients were included in the clinical investigation. Patients with anaerobic BSI included in the study were predominantly older than 50 years of age. Intra-abdominal infections were the most common source of anaerobic BSI (59%), followed by those of the female genital tract (10.2%) and lower respiratory tract (7.2%). Among the isolates, Bacteroides and Clostridium spp. were the most frequently isolated anaerobes. Most of the patients received antibiotic therapy. The crude mortality was 4.5%.

Conclusion: The detection rate of anaerobic BSI in Ningxia, China, remained relatively stable from 2012 to 2022. These results provide a reference for the diagnosis and empirical treatment of anaerobic BSI in this region of China. Continuous mul-ticenter studies should be conducted to monitor the incidence of anaerobic BSI and drug resistance of anaerobic isolates to improve the treatment outcomes of patients.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Objective: To assess the diagnostic performance of the blood-based Cepheid 3-gene Host Response test (MTB-HR), urine-based Lipoarabinomannan (LAM), and a combination of MTB-HR and LAM (MTB-HR & LAM) for detecting active tuberculosis (ATB).

Methods: All participants were recruited from the First Affiliated Hospital, Zhejiang University School of Medicine, between June 8, 2023 and September 13, 2023. Subsequently, the participants were classified into the ATB group or non-active tuberculosis (non-ATB) group based on microbiological evidence. MTB-HR and LAM tests were performed using fingerstick blood and urine samples from each participant, respectively. The diagnostic performance of the tests was evaluated based on the sensitivity, specificity, Youden index, and Kappa value. Pairwise comparisons of the areas under the receiver operating characteristic curves (AUROCs) between different tests were conducted using nonparametric methods.

Results: A total of 297 participants were included. The MTB-HR test demonstrated diagnostic efficacy with a sensitivity of 77.37% (95% CI: 70.37-84.38) and a specificity of 85.63% (95% CI: 80.19-91.06). The LAM test demonstrated a high specificity of 97.50% (95% CI: 95.08-99.92), albeit with a lower sensitivity of 54.74% (95% CI: 46.41-63.082). The sensitivity and specificity of the MTB-HR & LAM were 83.21% (95% CI: 76.95-89.47) and 83.13% (95% CI: 77.32-88.93), respectively. Only MTB-HR & LAM exhibited higher values of area under the receiver operating characteristic curve than the LAM test (MTB-HR & LAM vs LAM: 0.83 vs 0.76, P=0.0031).

Conclusion: In this study, although both non-sputum-based triage MTB-HR and LAM do not meet the WHO diagnostic target currently, they show possible values for triage and diagnosis in ATB. Compared to single MTB-HR or LAM test, the combined MTB-HR & LAM does not demonstrate advantages.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally. Prominent factors include chronic hepatitis B (CHB) and chronic hepatitis C (CHC) virus infections, exposure to aflatoxin, alcohol abuse, diabetes, and obesity. The prevalence of hepatitis B (HBV) is substantial, and the significant proportion of asymptomatic carriers heightens the challenge in diagnosing and treating hepatocellular carcinoma (HCC), necessitating further and more comprehensive research. Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC) family members are single-stranded DNA cytidine deaminases that can restrict viral replication. The APOBEC-related mutation pattern constitutes a primary characteristic of somatic mutations in various cancer types such as lung, breast, bladder, head and neck, cervix, and ovary. Symptoms in the early stages of HCC are often subtle and nonspecific, posing challenges in treatment and monitoring. Furthermore, this article primarily focuses on the established specific mechanism of action of the APOBEC3B (A3B) gene in the onset and progression of HBV-related HCC (HBV-HCC) through stimulating mutations in HBV, activating Interleukin-6 (IL-6) and promoting reactive oxygen species(ROS) production, while also exploring the potential for A3B to serve as a therapeutic target and prognostic indicator in HBV-HCC.

Background: Timely detection and treatment of latent TB infection (LTBI) is part of WHO's strategy against tuberculosis (TB). Helminth infections can modulate immune responses, potentially impacting the performance of interferon-gamma release assays (IGRAs) such as the QuantiFERON-TB Gold Plus (QFT-Plus). This study evaluated the association between helminth infections and QFT-Plus results among participants from a TB-endemic region.

Methods: A cross-sectional study was conducted from October 2022 to March 2023 in Bahir Dar, Ethiopia. Stool samples of 314 potential participants were examined for helminths using wet mount and Kato-Katz techniques. LTBI was assessed by QFT-Plus from a total of 100 gender-matched helminth-positive and -negative participants. The association between helminth infection status, egg count, and QFT-Plus positivity was analyzed, and p values <0.05 were considered significant.

Results: Overall, 53 of 314 screened participants were infected with helminths (16.9%), with A. lumbricoides (47.2%) and hookworm (30.2%) as most prevalent species. The overall QFT-Plus positivity rate was 30.0%, with similar rates observed between helminth-positive and helminth-negative participants. Although QFT-Plus positivity was slightly lower in hookworm carriers (25%) compared to those with A. lumbricoides (32%), a higher-than-median hookworm egg burden was significantly associated with reduced QFT-Plus positivity (P = 0.029). QFT-Plus positivity was significantly higher among male participants than females (P = 0.032).

Conclusion: While overall helminth infection status did not significantly affect QFT-Plus positivity, higher hookworm burden was associated with reduced QFT-Plus reactivity. These findings suggest that the type of helminth and infection intensity, rather than its mere presence, may influence IGRA performance. Further studies with larger sample sizes are warranted to understand the species-specific effect of helminth infection on immune modulation of the host.