Infection and Drug Resistance最新文献

Purpose: Pneumocystis jirovecii pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on P. jirovecii drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii in non-HIV patients in China, providing a reference for drug usage.

Methods: We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including P. jirovecii infection (n = 14) and P. jirovecii colonization (n = 31). This analysis also considered clinical characteristics, P. jirovecii burden, treatment response, and prognosis.

Results: Compared to the P. jirovecii colonization, P. jirovecii infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, P<0.05) with higher P. jirovecii burden (P<0.05) and worse prognosis (P<0.05). Additionally, patients with P. jirovecii infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.

Conclusion: Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.

Background: Amphotericin B deoxycholate (AmB-D) have potential toxic effects in the treatment of talaromycosis, and high-quality, non-generic liposomal AmB (L-AMB) is still inaccessible in many regions of China. As such, the efficacy and safety of alternative drugs warrant further investigation for the management of talaromycosis. This study aimed to compare the efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) and AmB-D for the treatment of talaromycosis in a retrospective cohort of HIV-infected patients.

Methods: This was a retrospective study and the data of HIV-infected patients with talaromycosis who received ABCD or AmB-D from January 2018 to December 2022, were retrospectively collected and analyzed. We compared the efficacy and safety of the two antifungal drugs.

Results: Overall, 38 patients receiving ABCD and 33 patients receiving AmB-D were included. The conversion rates to fungal negativity at one week post-treatment were 86.84% (33/38) in the ABCD group and 90.09% (30/33) in the AmB-D group, which reached 100.00% in both groups at two weeks post-treatment. A higher symptom remission rate was observed at two weeks in the ABCD group compared with the AmB-D group (94.74% vs 75.76%; p=0.003). Additionally, the serum creatinine level significantly increased from baseline in the AmB-D group, whereas it did not increase significantly in the ABCD group. Furthermore, significantly fewer patients discontinued antifungal treatment due to drug intolerance in the ABCD group, and the incidences of leukopenia and elevated creatinine levels were lower in the ABCD group compared with the AmB-D group.

Conclusion: ABCD has a clinical efficacy comparable to AmB-D, with higher symptom remission rate, lower nephrotoxicity, and lower bone marrow suppression, indicating that ABCD may be an appropriate alternative option for the clinical management of talaromycosis.

[This retracts the article DOI: 10.2147/IDR.S485049.].

Streptococcus pneumoniae is the main pathogen that plays a dual role, on the one hand as an asymptomatic carrier in the nasopharyngeal mucosa and on the other hand directly responsible for triggering invasive pneumococcal infections with various important localizations, especially in the pediatric population. Thus, invasive pneumococcal infections represent one of the main causes of mortality and morbidity in children under 5 years of age. Immunization is a key preventive measure against these infections. The evolution of these infections caused by S. pneumoniae is influenced both directly and indirectly by several factors: the immunization status of the patient, the regional and seasonal distribution of pneumococcal serotypes, susceptibility to anti-biotics, the existence of viral or bacterial co-infections and the socio-economic conditions specific to each region. This review gathers the current open-access PubMed evidence on the incidence of invasive pneumococcal infections and their susceptibility to antibiotics in the 0-5 age group during and after the COVID-19 pandemic. We have chosen this association with the SARS-COV- 2 virus because this pandemic has caused major changes on all personal, social, professional, and medical levels worldwide. Both pneumococcal disease and COVID-19 have similar risk factors, and S. pneumoniae was one of the most common co-infecting agents during the COVID-19 pandemic. The attention was focused on 8 clinical trials published in the pre- and post COVID-19 period that had as main subject acute otitis media caused by Streptococcus pneumoniae in children aged 0-5 years. The studies were collected from different geographical regions, both from socio-economically developed and developing countries such as Niger, Malawi, China and Papua New Guinea, Japan, Australia, Italy, in order to have a global overview. In conclusion, the COVID-19 pandemic had a major impact on the quality of life of pediatric patients diagnosed with pneumococcal acute otitis media both in terms of non-vaccine serotypes and antimicrobial resistance.

Background: Bone and joint infections (BJIs) are challenging to diagnose. This study evaluated the utility of 16S rRNA gene sequencing in diagnosing BJIs, comparing it with conventional bacterial culture to explore microbial diversity in orthopedic infections.

Methods: Thirty patients with BJIs were enrolled from January 2019 to September 2020 at a single orthopedic center. Diagnoses were based on the Musculoskeletal Infection Society standards. DNA extraction, 16S rRNA sequencing, and microbial composition analysis were performed. Conventional bacterial culture results were compared with metagenomics detection, and associations with blood routine and biochemical test factors were analyzed.

Results: The study enrolled 30 patients with BJIs. Traditional bacterial culture successfully identified pathogens in 60% (18/30) of cases, predominantly Staphylococcus aureus. In contrast, 16S rRNA metagenomics sequencing revealed distinct microorganisms in all cases, it unveiled a diverse microbial landscape. The correlation between bacterial culture and metagenomics detection showcased both concordance and discrepancies. Consistency of detection between the two methods showed that metagenomics detection detected the same genus or species in 14 (87.5%) of the 16 samples identified as species by bacterial culture. In nearly half of the patients with negative cultures, pathogenic microorganisms were detected, highlighting the capability of 16S rRNA sequencing to identify microorganisms, even in samples with negative or unidentified culture results. Moreover, no significant correlation was observed between bacterial culture, metagenomics detection and the factors of blood routine and biochemical test.

Conclusion: This study deepens our understanding of the microbial complexity in BJIs. While traditional culture methods are cost-effective and practical, 16S rRNA gene sequencing proves valuable for complementary microbial analysis, particularly when traditional methods fail or rapid identification is critical. This emerging diagnostic approach can enhance the accuracy and speed of pathogen identification, enabling more effective interventions in the management of BJIs.

Purpose: Psittacosis is an often-neglected cause of community acquired pneumonia (CAP). The limited diagnostic methods for psittacosis pneumonia invariably result in an unfavourable prognosis. Consequently, the early detection of psittacosis pneumonia is crucial. This study aimed to analyse the characteristics, clinical features and treatments of the patients to improve early diagnosis and outcomes.

Patients and methods: We retrospectively analyzed the clinical features and outcomes of 52 cases of psittacosis pneumonia diagnosed with next-generation sequencing (NGS) from January 2022 to August 2024 in a local tertiary hospital in China.

Results: Of the 52 patients, 18 had a clear exposure to poultry or birds. The main clinical manifestations included fever (100%, 52/52), cough (75.0%, 39/52), fatigue (57.7%, 30/352), and dyspnea (36.5%, 19/52). Significant elevations in neutrophil counts (NEUT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), D-dimer, lactate dehydrogenase (LDH), creatine kinase (CK), interleukin-6 (IL-6) and interferon-γ (IFN-γ), as well as reductions in lymphocyte (LY) and albumin (ALB) were observed. The main chest computed tomography (CT) features were consolidated. Eight patients diagnosed with severe CAP (SCAP) exhibited higher NEUT, CRP, procalcitonin (PCT), blood urea nitrogen (BUN), creatinine, D-Dimer and IL-6 levels, as well as lower oxygen index. The interval between the onset of symptoms and diagnosis was 6-34 days. C. psittaci infection was identified by metagenomic NGS (mNGS) or targeted NGS (tNGS) in all cases, and the average length of hospital stay for these patients was 9.4 days. Following the identification of the aetiology, all patients were promptly initiated on tetracycline- or fluoroquinolone-based therapy, with complete recovery observed in all cases.

Conclusion: Patients exposed to poultry should be alert to Chlamydia psittaci pneumonia. The application of NGS has improved the diagnostic accuracy of C. psittaci pneumonia, reduced unnecessary use of antibiotics, and shortened the course of disease. Patients who received tetracycline-based therapy showed a good prognosis.

Background: Recent advancements in artificial intelligence have led to increased adoption of machine learning in disease identification, particularly for challenging diagnoses like necrotizing fasciitis and Vibrio vulnificus infections. This shift is driven by the technology's efficiency, objectivity, and accuracy, offering potential solutions to longstanding diagnostic hurdles in clinical practice.

Methods: This investigation incorporated 180 inpatients suffering from soft tissue infections. The participants were categorized into groups: cellulitis, non-Vibrio necrotizing fasciitis (NF), or V. Vulnificus NF. To predict the three relevant outcomes, we employed Light Gradient Boosting Machine (LightGBM) and 5-fold cross-validation methodologies for the development of a multi-class categorization model. Moreover, we applied the SHapley Additive exPlanations (SHAP) methodology to decipher the model's predictions.

Results: The multi-classification model possesses substantial predictive capacity, with a weighted-average AUC of 0.86, sensitivity of 87.2%, specificity of 74.5%, NPV of 81.6%, and PPV of 85.4%. The model's calibration was assessed using the Brier score, yielding a weighted mean of 0.084. This low value demonstrates a strong correlation between predicted probabilities and actual outcomes, indicating high predictive accuracy and reliability in the model's forecasts.

Conclusions: We effectively developed a multiclassification model aimed at forecasting the occurrence of cellulitis, non-Vibrio NF, or V. Vulnificus NF in patients suffering from soft tissue infection, and we further described the model's predictions using the SHAP algorithm.

Background: Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effectiveness of standard-dose compared with low-dose steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS).

Methods: This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022. Demographics, clinical characteristics, and outcomes were compared between patients receiving standard-dose and those receiving low-dose steroids. Survival times were assessed using Kaplan-Meier curves and compared with the Log rank test. Cox proportional hazards regression analysis was conducted to identify independent risk factors for 28-day and 60-day mortality.

Results: A total of 105 non-HIV PCP with ARDS were included, with 48 patients in the standard-dose steroid group (66.7% male, 50.5±12.6 years) and 57 in the low-dose steroid group (61.4% male, 55.5±14.2 years). The 60-day mortality was lower in the standard-dose group than in the low-dose group (63.2% vs 48.3%, p=0.04), while 28-day mortality showed no significant difference (50.8% vs 35.4%, p=0.11). After adjusting for confounders, standard-dose steroids reduced 28-day mortality (aHR: 0.339, 95% CI: 0.147-0.780) and 60-day mortality (aHR: 0.328, 95% CI: 0.152-0.709), particularly in patients aged <65 years, non-smokers, those requiring mechanical ventilation, with albumin<30 g/L, or a PaO₂/FiO₂ ratio <150 mmHg. No differences in co-infections or gastrointestinal bleeding were observed.

Conclusion: The standard-dose steroid therapy significantly reduced 28-day and 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS. These findings highlight the potential survival benefit of standard-dose corticosteroid regimen in this population.

Background: Streptococcus intermedius is a commensal microflora commonly found in various mucosal sites in the respiratory, gastrointestinal, and genitourinary tracts. It causes invasive suppurative infections including liver and brain abscesses along with thoracic empyema. However, it rarely causes meningitis without abscess formation.

Case presentation: A 56-year-old immunocompetent man who presented with fever and headache. Bacterial meningitis was confirmed using cerebrospinal fluid analysis. Magnetic resonance imaging of the brain revealed leptomeningitis and ventriculitis. However, conventional methods, such as microbiological culture failed to identify the causative pathogens. Metagenomic next-generation sequencing of cerebrospinal fluid revealed the presence of S. intermedius. It allowed us the optimal treatment for him. The patient underwent antibiotic treatment with 6-week duration of ceftriaxone administration accompanied by surgical intervention, resulting in a favorable prognosis.

Conclusion: Herein, we report a rare case of meningitis and ventriculitis caused by S. intermedius using metagenomic next-generation sequencing. The patient recovered well after antibiotic treatment and surgery. We present this rare case and summarize previous studies to remind clinicians that timely identification of the pathogen and optimal treatment are crucial for management of S. intermedius-induced infections.

Background: Clostridioides difficile sequence type (ST) 81, mainly associated with ribotype (RT) 369, is a TcdA-negative and TcdB-positive genotype and a common ST found in China. Furthermore, ST81 strains are reported with highest resistance rates to many antimicrobial agents. However, given the potential for C. difficile ST81 transmission, research into the epidemiological characteristics of this type of ST remain limited.

Methods: We conducted a genomic epidemiology study addressing the genetic characteristics of C. difficile ST81 in five tertiary hospitals covering different regions in China between January 2010 and January 2021. Clinical toxigenic C. difficile strains were identified, typed by multi-locus sequence typing (MLST), and phylogenetic analysis, antimicrobial resistant gene (AMR) identification were performed after all these strains were conducted by whole genome sequencing (WGS).

Results: In total, 108 clinical C. difficile strains of ST81 were isolated and successfully analyzed by WGS, which showed that the percentage of isolates with AMRs was common in this type of ST. Furthermore, two types of transposons, Tn916 and Tn6189, were also detected. We found that all C. difficile ST81 genomes were closely related as pairwise core-genomic SNP (cgSNP) distance between the strains was on average 13 cgSNPs (range, 0-425 cgSNPs). Notably, these isolates were split into two sub-lineages (SL I and SL II) by Bayesian analysis, which suggested that both sub-lineages emerged independently. It is noted that some AMRs (such as clbA, dfrF, and cfrB) and Tn916 were only detected in SL I.

Conclusion: C. difficile ST81 is among the common STs in this study. Two independent sub-lineages of C. difficile ST81 strains are found. Furthermore, the presence of a high number of AMR genes and multiple mobile elements indicate a potential risk for transmission of C. difficile ST81. Based on these results, a robust surveillance system is crucial for identifying outbreaks, tracking infection trends, and implementing timely interventions.