Infectious Medicine最新文献

Background

Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin (H^r-R^s TB) remain a neglected demographic, despite a high disease burden and poor outcomes of these patients. The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for H^r-R^s patients.

Methods

Mycobacterium tuberculosis isolates (n = 4922) obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify H^r-R^s strains. The minimal inhibitory concentrations (MICs) were established for the H^r-R^s strains to determine the isoniazid resistance levels. We also identified drug-resistance-associated mutations for five drugs (fluoroquinolones, ethambutol, pyrazinamide, streptomycin, and amikacin) in the H^r-R^s strains.

Results

Of the 4922 strains, 384 (7.8 %) were H^r-R^s. The subculture of seven strains failed, so 377 (98.2 %) strains underwent phenotypic MIC testing. Among the 384 genotypic H^r-R^s strains, 242 (63.0 %) contained the katG Ser315Thr substitution; 115 (29.9 %) contained the -15C>T in the promoter region of the fabG1 gene; and 16 (4.2 %) contained Ser315Asn in the katG gene. Of the 239 strains with the Ser315Thr substitution, 229 (95.8 %) had MIC ≥ 2 µg/mL, and of the 114 strains with the -15C>T mutation, 103 (90.4 %) had 0.25 µg/mL ≤ MIC ≤ 1 µg/mL. The genotypic resistance rates were 0.8 % (3/384) for pyrazinamide, 2.3 % (9/384) for ethambutol and fluoroquinolones; 39.6 % (152/384) of the strains were resistant to streptomycin, but only 0.5 % (2/384) of the strains were resistant to amikacin.

Conclusion

Ser315Thr in katG was the predominant mutation conferring the H^r-R^s phenotype, followed by the fabG1 -15C>T mutation. The combination of rifampicin, pyrazinamide, ethambutol, and levofloxacin should be effective in the treatment of patients with H^r-R^s tuberculosis because the resistance rates for these drugs in China are low.

Ocular tuberculosis (OTB) is a chronic eye infection caused by Mycobacterium tuberculosis. Some cases of myelitis are associated with Epstein-Barr virus (EBV), with 1-5% of EBV infections leading to neurologic complications. We describe a 34-year-old Iranian woman with OTB and EBV coinfection. Despite initial success with anti-TB agents, the disease progressed, necessitating enucleation. Mycobacterium tuberculosis was detected by a tuberculin coagulation test, and EBV was confirmed via polymerase chain reaction. MRI showed plaques in the spinal cord and brain. The patient was treated with anti-TB and antiretroviral agents. Recognizing TB in the differential diagnosis of EBV myelitis is crucial.

Background

Ventilator-associated pneumonia (VAP) is a significant and common health concern. The epidemiological landscape of VAP is poorly understood in neurosurgery patients. This study aimed to explore the epidemiology of VAP in this population and devise targeted surveillance, treatment, and control efforts.

Methods

A 10-year retrospective study spanning 2011 to 2020 was performed in a large Chinese tertiary hospital. Surveillance data was collected from neurosurgical patients and analyzed to map the demographic and clinical characteristics of VAP and describe the distribution and antimicrobial resistance profile of leading pathogens. Risk factors associated with the presence of VAP were explored using boosted regression tree (BRT) models.

Results

Three hundred ten VAP patients were identified. The 10-year incidence of VAP was 16.21 per 1000 ventilation days. All-cause mortality was 6.1%. The prevalence of gram-negative bacteria, fungi, and gram-positive bacteria among the 357 organisms isolated from VAP patients was 86.0%, 7.6%, and 6.4%, respectively; most were multidrug-resistant organisms. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common pathogens. The prevalence of carbapenem-resistant A. baumannii, P. aeruginosa, and K. pneumoniae was high and increased over time in the study period. The BRT models revealed that VAP was associated with number of days of ventilator use (relative contribution, 47.84 ± 7.25), Glasgow Coma Scale score (relative contribution, 24.72 ± 5.67), and tracheotomy (relative contribution, 21.50 ± 2.69).

Conclusions

Our findings provide a better understanding of the epidemiology of VAP and its risk factors in neurosurgery patients.

Hand, foot, and mouth disease (HFMD) is a prevalent infectious affliction primarily affecting children, with a small portion of cases progressing to neurological complications. Notably, in a subset of severe HFMD cases, neurological manifestations may result in significant sequelae and pose a risk of mortality. We systematically conducted literature retrieval from the databases PubMed (1957–2023), Embase (1957–2023), and Web of Science (1957–2023), in addition to consulting authoritative guidelines. Subsequently, we rigorously selected the most relevant articles within the scope of this review for comprehensive analysis. It is widely recognized that the severity of HFMD is attributed to a multifaceted array of pathophysiological mechanisms. The implication of multi-system dysfunction appears to be perturbances of the human defense system; therefore, it contributes to the severity of HFMD. In this review, we provide an overview and analysis of recent insights into the molecular mechanisms contributing to the severity of HFMD, with a particular focus on cytokine release syndrome, the involvement of the renin-angiotensin system, regional immunity, endothelial dysfunction, catecholamine storm, viral invasion, and the molecular mechanisms of neurological damage. We speculate that the domino effect of diverse physiological systems, initiated by damage to the central nervous system, serve as the primary mechanisms governing the severity of HFMD. Simultaneously, we emphasize the knowledge gaps and research urgently required to delineate a quick roadmap for ongoing and essential studies on HFMD.

Lactococcus garvieae is a known fish pathogen associated with numerous aquacultural outbreaks. In humans, L. garvieae primarily causes infective endocarditis, but infections involving other organs have also been reported. We report the first case of ruptured infectious intracranial aneurysm associated with L. garvieae bacteraemia without concomitant infective endocarditis. The diagnosis of a left distal posterior cerebral artery mycotic aneurysm was based on a computed tomography angiogram, catheter angiogram and histopathological examination of the resected aneurysm. Here, we review the literature on human L. garvieae infections and describe the clinical characteristics, risk factors, management and outcomes of the cases identified to date.

Background

People with cystic fibrosis (CF) may develop clinically significant chronic respiratory infections with Pseudomonas aeruginosa (PA) and non-tuberculous mycobacteria (NTM). Open water has been suggested to be an important source for continuous or intermittent exposure to these pathogens. To date, there has been a paucity of studies examining the relationship between chronic PA and NTM infection in CF patients and surfaces waters, including blue spaces. The aim of this study was therefore to examine the relationship between chronic pulmonary infection with PA and NTMs in children and adults with CF in European countries and area of surface waters, including blue spaces.

Methods

European CF registry data detailing incidence of chronic PA and NTM infection in adults and children with CF in Europe (n=41,486 in 24 European countries) was correlated with surface water area data from the same countries (approx. 678,278 km²) employing Spearman coefficients.

Results

Correlation of chronic PA infection in children and adults and surface water area were not significant (p=0.0680 and p=0.8448, respectively), as was NTM infection (p=0.7371 and p=0.0712, respectively).

Conclusions

Acquistion of PA and its avoidance in people with CF is a complicated dynamic, not solely driven by close association with surface water, but through the integration of several other factors, including mitigations by people with CF to avoid high risk scenarios with surface water. This study was unable to demonstrate a correlation between PA and NTM infection in people with cystic fibrosis and surface water area at a national level. CF patients should continue to be vigilant about potential infection risks posed by water and take evidence-based decisions regarding their behaviour around water to protect them for acquiring these organisms from these sources.

Health care-associated infections (HCAIs) pose a substantial threat to immunocompromised individuals and represent a frequent adverse event in health care delivery. The aim of this study was to evaluate the global research landscape of HCAIs among immunocompromised populations before and during the COVID-19 pandemic. A systematic search of articles published between 2013 and 2022 in the Web of Science Core Collection database was conducted, and content analytics and integrated science mapping were used for data analysis and interpretation. The review identified 1,473 articles. Only 633 articles authored by 4,151 individuals and published in 366 journals were included. The average citation rate was 14.27 per document, and research production grew annually by 9.07% peaking in 2021 during the COVID-19 pandemic but declining in 2022. The United States emerged as the most productive country, with 743 publication appearances and 2,485 citations. Keywords such as “epidemiology,” “infection,” “mortality,” and “risk factors” were frequently encountered in the analyzed literature. The main research themes, including “mortality,” “sepsis,” “immunosuppression,” “expression,” and “pneumonia,” underscored the focal points of importance within this domain. This study highlighted the growing interest regarding HCAIs in immunocompromised populations, especially during the COVID-19 pandemic. The study findings underscore the need to advance research efforts to understand different immunocompromised states, develop tailored infection prevention measures, and address health care disparities to mitigate the burden of HCAIs among immunocompromised individuals.

Background

The Alere PBP2a SA Culture Colony Test is an FDA-cleared in vitro immunochromatographic assay for rapid detection of penicillin-binding protein2a (PBP2a) in Staphylococcus aureus.

Methods

We investigated the performance of the PBP2a SA Culture Colony Test with 78 coagulase-negative Staphylococcus (CoNS) isolates from different body sites, with the Vitek 2 Antimicrobial Susceptibility Test (AST) as a reference standard.

Results

The CoNS species were 62 S. epidermidis; 6 S. lugdenensis; 3 S. hominis; 2 S. capitis; 2 S. haemolyticus; and 1 each of S. simulans, S. auricularis, and S. warneri. Of the 78 CoNS isolates, 68 showed concordance in the PBP2a IC assay and Vitek 2 AST. Discordance was seen for 10 S. epidermidis isolates, which showed negative in the PBP2a assay, despite oxacillin-resistance detection using the Vitek 2 AST (66.7% sensitivity and 100% specificity). All non-S. epidermidis CoNS were identified with 100% concordance using the PBP2a IC assay and Vitek 2 AST.

Conclusion

We demonstrated that, while the PBP2a IC assay has low sensitivity in determining the susceptibility of S. epidermidis to oxacillin, it highly accurately predicted the susceptibility of non-S. epidermidis CoNS to oxacillin. The diagnostic accuracy for non-S. epidermidis CoNS needs further assessment with more isolates to confirm our findings.

Background

Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide. JEV exhibits significant neuroinvasiveness and neurotoxicity, resulting in considerable damage to the nervous system. Japanese encephalitis is associated with high morbidity and mortality rate, seriously harming both human health and livestock production. The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent.

Methods

Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology. The antiviral effects of clomipramine HCl were evaluated through plaque assay, real-time quantitative PCR, immunofluorescence assay and western blotting assay. Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment. Finally, the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques.

Results

In this study, we screened nine compounds with significant anti-JEV activity, of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity. Mechanistically, clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response, thus inhibiting the assembly stage of JEV infection.

Conclusion

This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection, which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.

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