Infection and Drug Resistance最新文献

Background: Asymptomatic Clostridioides difficile colonization (CdC) serves as a reservoir for pathogen transmission and may precede clinical infection. While risk factors for CdC have been well described in hospitalized populations, community-based data-particularly regarding lifestyle-associated factors and gut microbiota alterations-remain limited in Taiwan. This study aimed to determine the prevalence and risk factors of community-acquired CdC and to explore associated gut microbiota differences.

Materials and methods: We conducted a cross-sectional study analyzing 250 residual stool samples from adults aged ≥40 years who participated in community health screenings in Tainan City between 2006 and 2009. CdC was detected by polymerase chain reaction targeting the triosephosphate isomerase (tpi) gene. Demographic characteristics, lifestyle factors, and laboratory parameters were collected and analyzed. Exploratory 16S rRNA gene sequencing was performed on selected samples to compare gut microbiota composition between CdC and non-CdC groups.

Results: The prevalence of CdC was 11.6% (29/250). Cigarette smoking was identified as the sole independent factor associated with CdC (adjusted OR 2.35, 95% CI 1.05-5.28; P = 0.038). Exploratory microbiota analysis revealed differences in community composition between CdC and non-CdC samples, including increased relative abundance of Proteobacteria in CdC.

Conclusion: Cigarette smoking was associated with an increased likelihood of community-acquired CdC in southern Taiwan. Distinct gut microbiota profiles were observed in individuals with CdC, supporting a potential link between smoking-related microbiota alterations and susceptibility to asymptomatic colonization. These findings underscore the relevance of modifiable lifestyle factors in the epidemiology of community CdC and warrant further investigation.

Talaromyces marneffei is an important opportunistic fungal pathogen closely related to acquired immunodeficiency syndrome (AIDS), and its infection is relatively rare in human immunodeficiency virus (HIV)-negative populations. Although HIV-related immunosuppression remains the main risk factor, the history of treated tuberculosis and subsequent structural lung damage may constitute an underrecognized predisposing condition in non-epidemic areas, especially in elderly patients. This report described a 69-year-old HIV-negative male pulmonary infection case from a non-endemic area of T. marneffei, with a history of treated pulmonary tuberculosis and residual fibrotic lesions on imaging. The patient complained of chest tightness and cough for one month and fever (temperature 38.0-38.5°C) for a week upon admission. The chest computed tomography (CT) scan observed patchy consolidation and multiple cavities in the upper lobes of both lungs, accompanied by pulmonary texture disorder and pleural adhesions and thickening. The imaging findings were difficult to distinguish from active pulmonary tuberculosis. The diagnosis of T. marneffei infection was confirmed through sputum culture, bronchoscopy sampling culture, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and metagenomics next-generation sequencing (mNGS). After diagnosis, the patient was given oral voriconazole 200 mg every 12 hours, resulting in gastrointestinal intolerance. Subsequently, the dosage was adjusted to 100 mg every 12 hours, and the gastrointestinal symptoms improved significantly. The patient was eventually discharged but subsequently lost to follow-up. The case emphasizes that among HIV-negative individuals in non-epidemic areas of T. marneffei, for patients with unexplained pneumonia, especially those who have a history of tuberculosis and other potential immunological impairments, the differential diagnosis approach should be broadened and modern diagnostic techniques should be actively applied. It also highlights the importance of addressing drug tolerance issues and implementing long-term follow-up management in clinical treatment.

Objective: This study aims to analyze the performance differences between targeted nanopore sequencing, Sanger sequencing, and metagenomic sequencing in comparatively identifying non-tuberculous mycobacteria (NTM) species. Additionally, it explores the clinical application potential of targeted nanopore sequencing for identifying NTM clinical isolates in the Shenzhen region.

Methods: This retrospective study collected a total of 50 suspected NTM isolates from drug-resistant tuberculosis surveillance across 10 districts in Shenzhen, China, between December 2024 and June 2025. The species of the NTM isolates were initially identified using fluorescence PCR probe melting curve analysis. Genomic DNA was extracted from all 50 isolates, and species identification was performed using targeted nanopore sequencing (tNS), metagenomic sequencing (mNGS), and Sanger sequencing. The Jaccard similarity index, Kappa coefficient for classification consistency, and F1 score for model performance were calculated to evaluate the concordance among the three sequencing methods and assess the detection performance of targeted nanopore sequencing in NTM species identification.

Results: The most frequently detected NTM species by tNS, mNGS, and Sanger sequencing were M.abscessus and M.fortuitum, while M. tuberculosis was predominantly identified through mNGS results. Among the 50 suspected NTM samples, 18 (36%) showed complete concordance between tNS, mNGS, and Sanger sequencing, with the highest agreement observed between mNGS and tNS (28 samples, 56%). The final species identification reference results for the 50 samples were confirmed through a comprehensive evaluation using the Jaccard similarity coefficient, precision, and recall. Based on reference results, the F1 scores for tNS, mNGS, and Sanger sequencing were 0.927, 0.896, and 0.543, respectively. The tNS exhibited the highest concordance with the reference results, outperforming the other two methods.

Conclusion: tNS represents a preferred auxiliary methodology for clinical identification of NTM isolates in Shenzhen, China, with identification results optimally validated through integration with mNGS findings. This study provides strong support for the application of tNS technology for NTM species identification.

Objective: This study aimed to report the genome of carbapenem-resistant ST58 Escherichia coli strain EC6622, isolated from the urine sample of a patient with lower limb fracture, and to explore the genomic characteristics of the bla _NDM-5-harboring IncHI2/IncHI2A plasmid and the multi-resistance IncF plasmid carried by strain EC6622.

Methods: The genome of E. coli strain EC6622 was fully sequenced using the Illumina and PacBio platforms, followed by hybrid assembly of the genome sequences. The identification of antibiotic resistance genes (ARGs) and the genetic context of ARGs were accomplished using bioinformatics tools. Comparative genomic analyses of the resistance plasmids carried by E. coli strain EC6622 were performed.

Results: E. coli strain EC6622, belonging to ST58 (Achman scheme) or ST87 (Pasteur scheme), harbored bla _NDM-5 on IncHI2/IncHI2A plasmid pEC6622-1. bla _NDM-5 was embedded in ΔISKox3-IS3000-ΔISAba125-IS5-bla _NDM-5-ble _MBL-trpF-dsbC-ΔcutA-IS26-ΔISVsa5-IS3000-IS1A. In addition, two class 1 integrons were also found in the IncHI2/IncHI2A plasmid pEC6622-1. IncFIB_AP001918/IncFII plasmid pEC6622-2 carried one 23-kb multidrug-resistant (MDR) region, including tet(A)-tetR(A), class 1 integron, and a Tn3-like region containing mer operon and bla _TEM-1B gene, which were nearly identical to those of seven IncF plasmids distributed in E. coli strains.

Conclusion: In the carbapenem-resistant E. coli strain EC6622 isolated from the urine sample of a 70-year-old patient with a lower limb fracture, the carbapenemase gene bla _NDM-5 was carried by the IncHI2/IncHI2A plasmid (pEC6622-1), while a coexisting IncFIB_AP001918/IncFII hybrid multidrug-resistance plasmid (pEC6622-2) was also identified. These findings provide detailed genetic information that enhances our understanding of the resistance mechanisms and potential dissemination routes of bla _NDM-harboring E. coli.

Background: Kidney transplant recipients are at high risk for tuberculosis (TB), particularly drug-resistant forms, due to prolonged immunosuppressive therapy. The diagnosis and treatment of TB in this population pose unique challenges, including infection control, graft protection, and drug interactions.

Case presentation: We report the case of a 28-year-old male kidney transplant recipient was diagnosed with pulmonary TB four months post-transplantation. The patient self-discontinued initial anti-TB therapy after one month, leading to relapse nine months later, with confirmed rifampicin resistant. Following three months of treatment with a second-line regimen including linezolid, he developed disseminated skeletal TB, with drug susceptibility testing indicating linezolid resistance. The treatment was adjusted to an all-oral regimen including isoniazid, moxifloxacin, clofazimine, cycloserine, and bedaquiline, resulting in significant clinical and radiological improvement.

Discussion: In the present case, the patient's non-adherence to the medication regimen resulted in initial treatment failure. Against the backdrop of immunosuppression, rifampicin resistance emerged rapidly. Although the subsequent linezolid-containing regimen was administered for a short duration, it likely triggered ribosomal target mutations-leading to linezolid resistance and hematogenous dissemination to the bone-driven by both drug selection pressure and the history of irregular treatment. Confronted with dual resistance and disseminated disease, the therapeutic strategy pivoted to a bedaquiline-based regimen. This shift highlights the clinical management art of finely balancing treatment efficacy with the risk of rejection through the optimized adjustment of immunosuppressants guided by therapeutic drug monitoring.

Conclusion: The management of drug-resistant tuberculosis in kidney transplant recipients necessitates a flexible and comprehensive strategy. This encompasses early clinical suspicion, the prompt performance of molecular and phenotypic drug susceptibility testing to guide therapeutic decisions, rigorous management of treatment adherence, and the real-time adjustment of therapeutic regimens based on evolving resistance profiles and clinical responses. Multidisciplinary collaboration is essential for balancing anti-tuberculosis efficacy with graft survival. Although novel agents such as bedaquiline offer promising options for salvage therapy, their administration in transplant recipients requires intensified monitoring for drug-drug interactions and adverse events.

Purpose: Carbapenem-resistant Acinetobacter baumannii (CRAB) and Klebsiella pneumoniae (CRKP) pose a serious public health threat, underscoring the urgent need for novel therapeutic options. This study compared the in vitro antimicrobial activity and associated clinical outcomes of three tetracycline-class antibiotics-eravacycline (ERV), tigecycline (TGC), and omadacycline (OMC)-against regional carbapenem-resistant isolates.

Patients and methods: A total of 106 CRKP and 117 CRAB non-duplicate clinical isolates were collected from Xuanwu Hospital (Beijing) between December 2024 and June 2025. Minimum inhibitory concentrations (MICs) were determined using broth microdilution (CLSI M07 guidelines). Time-kill assays (0-48 h) were used to evaluate bactericidal activity, and clinical outcomes were analyzed in patients treated with TGC or ERV.

Results: ERV demonstrated superior in vitro activity: its MIC₉₀ against CRKP (0.5 μg/mL) was 4-fold lower than TGC (2 μg/mL) and 8-fold lower than OMC (4 μg/mL). For CRAB, ERV's MIC₉₀ (0.25 μg/mL) was 4-fold lower than TGC (1 μg/mL). ERV maintained sustained bactericidal activity (≥3-log_{1 0} CFU/mL reduction) for 24-36 h against CRAB-2.3-fold longer than TGC and 3.1-fold longer than OMC. ERV-treated patients (n = 20) showed a 5% mortality rate (6.7% for CRAB and 0% for CRKP), compared with 18.9% (CRAB) and 16.7% (CRKP) in TGC-treated patients.

Conclusion: Current evidence indicates that ERV exhibits strong in vitro bactericidal activity and demonstrates more favorable clinical efficacy comparable to that of TGC against CRKP and CRAB infections, as observed in our retrospective clinical cohort.

Purpose: To characterize the genomic features of Pseudomonas aeruginosa isolates causing community-acquired pneumonia (CAP) and compare them with hospital-acquired pneumonia (HAP) genomes to identify setting-associated genetic determinants.

Patients and methods: Three CAP isolates collected in China underwent antimicrobial susceptibility testing and whole-genome sequencing. Comparative genomic analyses were performed against 84 complete HAP-associated genomes retrieved from NCBI RefSeq (accessed in December 2023), including core genome SNP phylogeny, profiling of antimicrobial resistance (AMR) determinants, virulence genes, and pangenome analysis to identify CAP-specific genes.

Results: The three CAP cases presented with severe pneumonia (including septic shock), with one fatality; however, all CAP isolates remained susceptible to the most commonly used antipseudomonal agents. CAP genomes were 6.5-7.1 Mb (GC 65.76-66.41%) and contained 5908-6633 predicted coding sequences. Core-SNP phylogeny showed clustering of the three CAP isolates. Compared with HAP genomes, CAP isolates harbored fewer acquired AMR genes and fewer resistance-associated mutations. Virulence profiling identified a subset of virulence genes absent from all CAP genomes (n = 40), largely annotated as immune modulation and including loci consistent with highly variable surface polysaccharide regions, together with several genes annotated to biofilm-related functions and effector delivery systems. Major type III secretion system effector profiles differed across CAP isolates (exoU in one isolate; exoS in two). Pangenome analysis identified 10,225 gene families, and 157 genes were specific to the CAP isolates, most encoding hypothetical proteins, with a subset related to lipid transport and metabolism, including fatty acid uptake and functions associated with β-oxidation. Given the limited number of CAP isolates, comparisons between groups are descriptive.

Conclusion: CAP-associated P. aeruginosa showed a distinct comparative genomic profile with reduced AMR determinant burden and a distinct virulence gene repertoire despite severe clinical presentation. CAP-specific genes, including those linked to lipid metabolism, may contribute to niche adaptation and warrant functional validation.

Purpose: To analyse the clinical features of Mycoplasma pneumoniae pneumonia (MPP) and the independent risk factors of severe MPP (SMPP) and to provide a theoretical basis for the early diagnosis of SMPP and timely judgment of changes in the disease's progress.

Patients and methods: The clinical data of children with MPP who were treated in our hospital from January 2021 to December 2022 were collected and retrospectively analysed. 83 cases were assigned to the severe group (SMPP group) and 152 cases were assigned to the general group (MPP group). The epidemiology, clinical characteristics and related influencing factors of SMPP were analysed.

Results: Compared with the MPP group, the SMPP group were older, had a longer fever time, had more imaging manifestations of large patchy consolidation and experienced a longer hospital stay. The peripheral blood white blood cell (WBC) count, C-reactive protein (CRP), serum IgA, serum IgG, serum IgM, lactate dehydrogenase (LDH) and ferritin (SF) in the SMPP group were significantly higher than those in the MPP group (P < 0.05). Logistic regression analysis showed that fever days (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.03-1.65, P = 0.021), CRP (OR = 1.16, 95% CI = 1.02-1.10, P = 0.006), LDH (OR = 1.021, 95% CI = 1.01-1.02, P = 0.002) and large patchy consolidation (OR = 10.38, 95% CI = 4.31-31.02, P = 0.001) were independent factors of SMPP.

Conclusion: All patients with MMP had a fever and a cough, and patients with SMPP had a high fever. Chest imaging examination of patients with SMPP showed extensive consolidation shadows in the lungs, and laboratory examinations showed significant increases in WBCs, CRP, LDH and SF. The fever time, CRP, LDH and imaging showed large patchy consolidation shadows are related to the severity of the disease.

Introduction: Cancer patients, particularly those with lung cancer, are highly susceptible to pulmonary infections due to both the disease itself and the immunosuppressive effects of treatments such as chemotherapy and immunotherapy. The objective of this study was to analyze pathogenic distribution characteristics of pulmonary infections in cancer patients and evaluated the guidance of metagenomic next-generation sequencing (mNGS) on clinical administration.

Methods: This retrospective study included 66 samples from cancer patients. Pathogens in patient specimens, encompassing peripheral blood, bronchoalveolar lavage fluid (BALF), sputum, and other samples, were identified using both mNGS and culture methods.

Results: Compared to culture methods, mNGS demonstrated a sensitivity of 95.5% across all samples. In terms of overall detections, Human gammaherpesvirus 4 was identified as the most frequently detected pathogen in cancer patients, while Escherichia coli and Candida albicans were ranked as the most common bacterial and fungal pathogens, respectively. During the perioperative period, non-surgical short-term treatment, non-surgical long-term treatment, and long-term treatment groups, Escherichia coli and Achromobacter xylosoxidans were all identified. Moreover, the treatment strategies for patients were timely adjusted based on the mNGS results, resulting in a significant improvement in clinical symptoms for 59.3% (16 out of 27) of the cancer patients.

Conclusion: mNGS is an advanced approach for pathogen detection in cancer patients, with commendable diagnostic performance demonstrated. The results of mNGS contribute to the rapid modification of clinical medication, which may improve the survival rate of cancer patients.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an advanced life support therapy, but evidence regarding its impact on the pharmacokinetic (PK) characteristics of ceftazidime-avibactam (CAZ-AVI) is still limited. This study reports a 47-year-old man who developed severe renal impairment during VA-ECMO support following cardiac arrest and was treated with CAZ-AVI for pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Therapeutic drug monitoring (TDM) was performed before and after VA-ECMO weaning. PK analysis showed that, compared to the period with VA-ECMO support, the clearances (CLs) of CAZ and AVI increased after VA-ECMO weaning, resulting in 31.1% and 34.5% decreases in systemic exposure to CAZ and AVI, respectively. Despite these reductions, trough concentrations remained above the PK/PD targets of 100% fT > 20.0 mg/L for CAZ and 100% fT > 4.0 mg/L for AVI, respectively. Unfortunately, the patient's renal function progressively worsened, complicated by hyperkalemia, and he experienced a second cardiac arrest on day 5 after ECMO weaning, resulting in death. These findings suggest that in patients undergoing prolonged VA-ECMO support, the exposure of CAZ-AVI may decline after ECMO weaning, underscoring the need for reassessment of dosing strategies.