Infection and Drug Resistance最新文献

Objective: To evaluate the clinical utility of loop-mediated isothermal amplification (LAMP) for detecting carbapenemase genes in carbapenem-resistant Enterobacteriaceae (CRE).

Methods: From January 2023 to December 2024, 112 clinical CRE isolates were collected, including 104 carbapenem-resistant Klebsiella pneumoniae (CR-KP), 7 Escherichia coli (CR-EC), and 1 Klebsiella oxytoca (CR-KO). These isolates were obtained primarily from sputum (n=65), urine (n=29), and bronchoalveolar lavage fluid (n=9). The isolates were predominantly isolated from neurosurgery (38.39%), intensive care unit (21.42%), and respiratory critical care medicine (15.18%). Carbapenemase genes were detected in parallel using both sequencing (reference standard) and LAMP methods under blinded conditions. Statistical analysis included cross-tabulation and Cohen's kappa coefficient for agreement assessment.

Results: Among the 112 CRE isolates, 96.43% (108/112) carried carbapenemase resistance genes. KPC variants predominated (89/108, 82.4%), including blaKPC-2 (n=87) and blaKPC-33 (n=2). NDM variants were detected in 29 isolates (26.9%), comprising blaNDM-1 (n=14) and blaNDM-5 (n=15). OXA-48 was identified in 3 isolates (2.8%). Compared with sequencing, LAMP demonstrated perfect sensitivity (100%) for all three gene types, with specificities of 91.30% (KPC), 96.38% (NDM), and 100% (OXA-48). However, the performance data for OXA-48 should be considered preliminary due to the low number of positive isolates (n=3).The kappa values indicated excellent agreement: 0.943 (KPC), 0.932 (NDM), and 1.000 (OXA-48).

Conclusion: LAMP technology shows high diagnostic accuracy for detecting major carbapenemase genes particularly KPC and NDM in CRE isolates, offering a reliable tool for guiding appropriate antibiotic therapy. Its operational simplicity and cost-effectiveness make it particularly suitable for implementation in primary healthcare settings.

Staphylococcus aureus is a clinically prevalent, Gram-positive pathogen that can cause multiple severe infections. Macrophage polarization plays a central role in host defense and inflammatory regulation, with its M1/M2 dynamic equilibrium directly determining infection outcomes. The M1 phenotype eliminates pathogens through pro-inflammatory responses in the early phase, but excessive activation readily leads to tissue damage. In contrast, the M2 phenotype suppresses inflammation and promotes healing during the repair phase, although it may become a pathogen refuge in chronic infections. Recent studies have elucidated the roles of PAMPs, virulence factors, immunometabolism, and epigenetics in regulating polarization and have explored intervention strategies involving stem cells, exosomes, nanodelivery, novel formulations, and natural medicines, offering new avenues to overcome antibiotic limitations. However, existing evidence remains confined to animal studies, and challenges related to polarization heterogeneity and clinical translation require urgent resolution. This review summarizes the mechanisms of macrophage polarization and targeted therapeutic advances in the context of S. aureus infection, aiming to provide insights for immune interventions against drug-resistant infections.

Kodamaea ohmeri is an emerging opportunistic yeast pathogen frequently misidentified as Candida, posing significant diagnostic challenges. This report describes a case of K. ohmeri bloodstream infection in a 70-year-old female with poorly controlled diabetes following radical gastrectomy. Despite broad-spectrum antibacterial therapy for postoperative complications, she developed persistent fever. Blood cultures identified K. ohmeri, and antifungal susceptibility testing (AST) revealed a low voriconazole minimum inhibitory concentration (0.06 μg/mL), prompting targeted therapy that led to the clearance of fungemia and full clinical recovery. This case underscores the critical importance of rapid pathogen identification and AST-directed therapy in managing life-threatening K. ohmeri infections.

We report a case of an adult male with a history of recurrent cough and chest pain for five years. Mycobacterium arosiense was identified in his alveolar lavage fluid, and whole-exome sequencing revealed heterozygosity for CD209 in this patient. After 17 months of combined antibiotic therapy, the patient recovered completely.

Background: The emergence of multidrug-resistant (MDR) pathogens in intensive care units (ICUs) has become a pressing global health issue, contributing to mortality rates exceeding 40%. Among these, carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii are especially problematic. Seasonal fluctuations in resistance patterns have been observed, yet the genomic mechanisms underlying these trends remain insufficiently characterized.

Objective: This study investigated the seasonal variation in resistance gene prevalence among ICU-derived bacterial isolates and elucidates the genomic features contributing to antimicrobial resistance.

Methods: Environmental and clinical samples were collected from ICU settings over multiple seasons using a systematic, stratified approach. Whole-genome sequencing was conducted on isolates via Illumina and Nanopore platforms. Resistance genes were annotated using CARD, VFDB, and BiocideResistance databases. Statistical associations were assessed using logistic regression and generalized linear mixed models, while phylogenetic trees evaluated clonal relationships.

Results: The bla_CTX-M-3 gene was detected in 100% of autumn isolates (n=52), showing a statistically significant association with increased bed turnover and prolonged disinfection intervals (p=0.003). During winter, 75% of isolates (n=50) tested positive for qacEΔ1, correlating with elevated multidrug resistance indices (p=0.01) and patterns consistent with clonal expansion based on whole-genome SNP profiling. These winter strains also exhibited enhanced biofilm formation capacity (OD₅₉₅=0.67 ± 0.11) and upregulation of efflux pump transcripts (2.3-fold increase vs summer; p=0.02), supporting environmental adaptation under low-temperature stress. Notably, aac(6')-Ib7, an aminoglycoside-modifying enzyme gene, was the most frequently detected resistance determinant, present in 68% of isolates, highlighting substantial antibiotic selection pressure.

Conclusion: This study reveals distinct seasonal genomic patterns in ICU drug-resistant pathogens and emphasizes the necessity for adaptive infection control strategies. Targeted disinfection, antibiotic stewardship, and consideration of phage therapy as a complementary strategy particularly during winter may help mitigate the spread of high-risk resistant clones, though further in vitro and in vivo validation is required.

Backgroud: To investigate the molecular epidemiology of intestinal colonization by carbapenem-resistant Enterobacteriaceae (CRE) and identify risk factors for subsequent infection, providing evidence for early risk stratification and targeted prevention.

Methods: From August 2023 to August 2024, we retrospectively enrolled CRE-positive patients identified through active rectal swab screening at the First Affiliated Hospital of Kunming Medical University and monitored them for subsequent infections. Colonizing and infecting isolates were collected and tested for carbapenem-resistance genes, major virulence genes, capsular serotypes, and were subjected to multilocus sequence typing (MLST). Clinical data were integrated and multivariate logistic regression was performed to identify risk factors associated with secondary infections.

Results: Among 8,088 patients who underwent active intestinal CRE screening, the positivity rate was 0.53% (43/8,088). Among patients with colonization, the incidence of secondary infection was 37.2% (16/43). All patients with secondary infections were colonized and infected with Klebsiella pneumoniae, with the lower respiratory tract, bloodstream, and urinary tract being the primary infection sites. Multivariable analysis showed that having more than three comorbidities was an independent risk factor for hospital-acquired infection among colonized patients (odds ratio [OR]=0.118; 95% CI:0.017-0.812; P=0.030). The carriage rate of bla _KPC was 77.8% among colonizing strains and 100% among infecting strains. Among virulence genes, aerobactin, allS, and peg344 were significantly more prevalent in infecting strains (P<0.05). Homology analysis revealed that, except for one patient, the colonizing and infecting isolates in patients with secondary infections were highly homologous ST11-KL64, KPC-producing K. pneumoniae.

Conclusion: Although the intestinal colonization rate of CRE was relatively low, the risk of secondary infection remained substantial. Bacterial genetic traits and host conditions contribute to secondary infections. Establishing surveillance systems based on clinical and molecular epidemiology coupled with intensified screening in high-risk departments may help identify high-risk patients early and enable proactive interventions to reduce CRE-related secondary infections.

Purpose: With the advancement of metagenomic next-generation sequencing (mNGS), its role in diagnosing lower respiratory tract infections (LRTIs) has expanded rapidly. LRTIs remain a major global health burden, particularly in critically ill patients where diagnosis is challenging. Routine microbiological testing (RMT), including culture, microscopy, antigen detection, and PCR-are limited by low sensitivity, long turnaround times, and restricted pathogen coverage. This study assesses the diagnostic performance of mNGS in LRTIs, with emphasis on pathogen detection and resistance gene prediction, and compares it with traditional methods to clarify its clinical benefits and limitations.

Methods: This retrospective study included 367 hospitalized patients with suspected LRTIs. All patients underwent mNGS testing, which was compared with traditional diagnostic methods. We also used mNGS to explore the pathogen spectrum characteristics in critically ill patients with pneumonia and evaluated its applicability in predicting antimicrobial resistance genes and adjusting antibiotic treatment.

Results: For patients diagnosed with LRTIs, mNGS demonstrated superior microbial detection efficacy, particularly for bacteria and fungi, relative to culture (bacteria: 56.58% vs 17.37%, P < 0.0001; fungi: 49.65% vs 16.78%, P < 0.0001) and PCR (65.14% vs 45.14%, P < 0.05). In contrast to the non-severe pneumonia group, the detection rate of Enterococcus faecium was highest in the severe pneumonia group (P < 0.001), and the severe pneumonia group had more mixed infections (P < 0.001). In addition, mNGS showed high accuracy in predicting antibiotic resistance genes, with 90.57% agreement with antibiotic susceptibility testing (AST) results. Based on the mNGS results, 97.82% of patients underwent active adjustment to their antibiotic treatment regimen.

Conclusion: mNGS is an effective tool for diagnosing LRTIs, with significantly higher pathogen detection rates than traditional methods. mNGS also demonstrates high accuracy in predicting antimicrobial resistance, providing crucial support for clinical treatment decisions.

Background: Talaromycosis is increasingly recognized in immunocompromised individuals beyond those with HIV, including patients with primary immunodeficiencies such as Hyper-IgE syndrome (HIES). However, diagnosing disseminated infection remains challenging due to nonspecific clinical manifestations and limitations of conventional diagnostic methods.

Case presentation: We report a rare case of recurrent disseminated Talaromyces marneffei (T. marneffei) infection in a 25-year-old male with STAT3-mutated HIES. Initially presenting with abnormal liver function tests, the patient had a history of T. marneffei pulmonary infection successfully treated with itraconazole. During the current admission, he developed intermittent fever, jaundice, and splenomegaly. Initial evaluations led to a misdiagnosis of chronic drug-induced liver injury (DILI). Subsequent fever recurrence and worsening liver function prompted further investigation. Metagenomic next-generation sequencing (mNGS) and histopathology of liver revealed T. marneffei, confirming disseminated infection involving the liver. Histopathological examination of the liver showed granulomatous inflammation with IgG4-positive plasma cell infiltration, further complicating the differential diagnosis. The patient responded well to intravenous voriconazole, with significant improvement in liver function and radiological findings.

Conclusion: Disseminated talaromycosis should be considered in immunocompromised patients presenting with unexplained fever, hepatosplenomegaly, or organ dysfunction, even in the absence of classic symptoms. Integration of mNGS into diagnostic workflows enhances pathogen detection, and long-term antifungal prophylaxis may be necessary in patients with persistent immune deficiencies.

Background: Cardiovascular disease represents the leading cause of mortality among tuberculosis (TB) patients. Both patients with tuberculosis or coronary artery disease (CAD) commonly exhibit lipid metabolism disorders. This study aims to identify specific lipids to enable early diagnosis of tuberculosis-coronary artery disease comorbidity (TB-CAD).

Methods: Blood samples were collected from hospitalized patients with TB, TB-CAD, or CAD, as well as normal healthy controls (NC), at the affiliated Changsha Central Hospital of University of South China between April 2024 and February 2025. A broad-targeted lipidomics approach based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to identify differential lipids.

Results: The K-Means analysis showed sphingolipid, glycerolipid, and glycerophospholipid levels were decreased in patients with TB-CAD. A total of 49 differential lipids were identified to distinguish TB-CAD from the other groups. The results of receiver operating characteristic curve analysis revealed three lipids such as CE(20:0), PC(14:0_20:4) and CE(18:0) as potential biomarkers for early diagnosis of TB-CAD. The integrated diagnostic model comprising these three lipids demonstrated favorable performance, achieving AUC, sensitivity, and specificity values of 0.834, 0.900, and 0.622, respectively. KEGG analysis showed the metabolism of linoleic acid, alpha-linolenic acid, and arachidonic acid were considered pathways related to tuberculosis-coronary artery disease comorbidity.

Conclusion: This study not only identified potential biomarkers for TB-CAD diagnosis but also provided a foundation for in-depth exploration of the pathogenesis underlying tuberculosis-coronary artery disease comorbidity.

Background: Inappropriate antibiotic use drives antimicrobial resistance (AMR). Performing pathogen detection before initiating antimicrobial therapy is essential for antimicrobial stewardship (AMS), enabling targeted treatment. Robust evidence on multifaceted interventions' sustained impact on pre-therapy pathogen detection specimen submission rates, AMS metrics, and multidrug-resistant organisms (MDROs) is limited.

Methods: Interrupted time series analysis evaluated a comprehensive AMS intervention (April 2023) at a tertiary care hospital in China (April 2022-May 2025). Interventions included: team establishment, lab expansion, education, electronic restrictions for restricted/special use-levels antibiotics (mandating pre-therapy pathogen detection specimen submission rate), audit/feedback, and monitoring. Segmented regression assessed level (immediate) and slope (trend) changes in pre-therapy pathogen detection specimen submission rate, antimicrobial use, costs, and MDRO isolate rates.

Results: Post-intervention, overall pre-therapy pathogen detection specimen submission rate increased immediately (+9.82%, P=0.009) with sustained monthly growth (+1.21%, P<0.001); increases occurred across all antimicrobial classes (all P<0.05). Antimicrobial use intensity reversed significantly from a pre-intervention upward trend (β₁ = +1.22 DDDs/100PD, P=0.002) to a sustained downward trajectory (β₃ = -1.36, P=0.001), with non-restricted agents showing the steepest decline (net slope = -0.16). Concurrently, antimicrobial utilization rate, per capita costs, and cost proportion reversed to downward trends (all P<0.05), while testing costs remained stable Only carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibited sustained reduction (-0.87%/month, P=0.013); other MDROs showed no significant changes.

Conclusion: The intervention significantly improved pre-therapy pathogen detection specimen submission rate and optimized antimicrobial use (reduced intensity/costs), but demonstrated limited resistance impact beyond CRKP reduction. Sustainable AMR control requires integrating diagnostic stewardship with infection prevention programs.