Infection and Drug Resistance最新文献

From being a curiosity in the 1990s, CTX-M-producing Escherichia coli invaded most parts of the globe during the 2000s and 2010s, with multidrug-resistant (MDR) clone ST131 and CTX-M-15 leading the charge. The most widely distributed CTX-M types, with the highest global frequencies (up to 70% in certain lower- and middle-income countries), are CTX-M-15, CTX-M-14 and CTX-M-27. E. coli isolates with bla _CTX-M-27 are currently emerging globally. The worldwide ascendancy of E. coli with bla _CTX-M genes occurred via the spread of IncF plasmids between isolates and the existence of certain successful clones (eg, ST131) that acted as repositories for these genes. This is an impressive "gene survival strategy" that aided with the endurance of bla _CTX-M in different environments, including the community and hospitals. The detection of extended-spectrum β-lactamase (ESBL)-producing E. coli (including CTX-M isolates) in clinical laboratories is reasonably straightforward. However, different methodologies (eg, immunogenic and genomic) have recently become available to specifically identify CTX-Ms in bacterial isolates as well as human specimens. The role of such tests is currently unclear. E. coli with CTX-M β-lactamases have indirectly been driving the carbapenemase pandemic and are forces to be reckoned with.

Background: In the small non-malignant specimens acquired through respiratory endoscopy, the conventional pathological examination approaches such as acid-fast staining have certain restrictions in the sensitivity of tuberculosis diagnosis.

Objective: To investigate the sensitizing effect and clinical value of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) based on fluorescent probe nucleic acid detection technology in improving the diagnostic positive rate of non-malignant small specimens obtained by respiratory endoscopy.

Methods: A retrospective analysis was conducted on 729 patients with suspected TB who underwent respiratory endoscopy. All patients provided small non-malignant specimens for TB-PCR, acid-fast staining, and mycobacterial culture. A clinical composite diagnosis served as the gold standard. Diagnostic performance was assessed by accuracy, sensitivity, specificity, and area under the ROC curve (AUC). A subgroup of 113 patients underwent additional testing (T-SPOT. TB, TB-Ab, BALF-G-Xpert, BALF-TB) for extended comparison.

Results: The AUC, accuracy, sensitivity, specificity, PPV and NPV of TB-PCR in the diagnosis of TB were 0.88 (95% CI: 0.86-0.90), 0.88 (95% CI: 0.85-0.90), 0.99 (95% CI: 0.98-1.00), 0.78 (0.74-0.82), 0.79 (95% CI: 0.75-0.83), 0.99 (95% CI: 0.97-1.00), respectively. Among 729 patients (391 TB+, 338 TB-), TB-PCR showed significantly higher overall diagnostic efficacy (AUC: 0.88) than acid-fast staining (AUC: 0.77, P<0.05) and was comparable to culture (AUC: 0.87). TB-PCR also demonstrated superior accuracy (0.89 vs 0.61-0.85, P<0.05) compared to immunologic and BALF-based tests in the subgroup analysis, achieving nearly perfect sensitivity (0.99-1.00) and high NPV (0.99-1.00).

Conclusion: The application of TB-PCR for the detection of lung samples obtained through respiratory endoscopy holds significant clinical application value in the diagnosis of TB. Clinicians should fully recognize the merits and potential of TB-PCR technology, proactively apply it in clinical practice, and choose appropriate detection methods based on the specific conditions of patients.

Purpose: This study aimed to evaluate the antimicrobial susceptibility and identify genetic determinants of resistance in Vibrio cholerae strains maintained in the culture collection of the Masgut Aikimbayev National Scientific Center for Especially Dangerous Infections (NSCEDI, Republic of Kazakhstan). The analyzed isolates were previously obtained from various environmental and laboratory sources as part of microbiological and epidemiological surveillance conducted between 1970 and 2024.

Methods: Twenty-six V. cholerae isolates representing different serogroups were analyzed using phenotypic and molecular methods. Antimicrobial susceptibility was determined by the Kirby-Bauer disk diffusion test and E-test against 59 antibacterial agents from major pharmacological classes. The presence of resistance genes to β-lactams and glycopeptides was examined using the BacResista GLA Real-Time PCR Detection Kit (DNA-Technology LLC, Moscow, Russia).

Results: All V. cholerae isolates demonstrated high susceptibility to key antibiotics, including doxycycline, ciprofloxacin, tetracycline, cefotaxime, and kanamycin. Sporadic intermediate resistance was observed to nalidixic acid, trimethoprim, and streptomycin. Real-time PCR screening did not detect any β-lactamase or glycopeptide resistance genes among the isolates.

Conclusion: The Vibrio cholerae strains preserved in the NSCEDI collection and isolated during 1970-2024 remain highly susceptible to first-line antibiotics and lack molecular markers of resistance. These findings confirm the continued effectiveness of current antimicrobial regimens for cholera treatment and underscore the importance of ongoing national surveillance of antimicrobial resistance to ensure preparedness and biosafety in potential outbreak situations.

Objective: This study aimed to analyze drug resistance patterns, mutation profiles in Mycobacterium tuberculosis isolates and clinical characteristics of tuberculosis patients in Shaoxing, Zhejiang, China.

Methods: Clinical specimens and data from tuberculosis patients admitted in 2024 were collected. Cultures were established using the MGIT liquid culture system, and drug susceptibility to twelve anti-tuberculosis agents (four first-line and eight second-line) was assessed by the microbroth dilution method. Mutations in the rpoB gene, katG gene, and inhA promoter were identified using a DNA microarray chip assay.

Results: Among 268 Mycobacterium tuberculosis isolates, 62 (23.1%) exhibited resistance to at least one anti-tuberculosis drug. These comprised 21 (7.8%) mono-resistant, 25 (9.3%) poly-resistant, and 16 (6.0%) multidrug-resistant strains, including 3 (1.1%) classified as pre-extensively drug-resistant and 1 (0.4%) as extensively drug-resistant. Among rifampicin-resistant isolates, mutations at codons 531 (47.4%) and 526 (21.1%) of the rpoB gene were most frequent, while the katG Ser315Thr substitution was detected in 44.8% of isoniazid-resistant strains. Compared with primary cases, re-treated patients were more frequently over 50 years of age, exhibited a higher prevalence of pulmonary cavities, and showed significantly elevated rates of drug resistance (P < 0.05).

Conclusion: Our findings indicate that although the overall prevalence of drug-resistant tuberculosis in Shaoxing remains low, the resistance patterns are heterogeneous. These results underscore the need for comprehensive drug susceptibility and genetic testing to guide effective treatment strategies.

Introduction: Sepsis is a common and life-threatening condition in clinical practice, leading to mortality among intensive care unit (ICU) patients. Due to its unclear pathogenesis, underscoring the urgent need for effective therapeutic strategies. Ferroptosis plays a pivotal role in sepsis progression, and ferroptosis-related genes represent promising intervention targets.

Methods:  This study performed bioinformatics to identify ferroptosis-related hub genes in sepsis. We used septic mice and lipopolysaccharide (LPS)-treated IECs to detected the role of TP53-mediated ferroptosis in sepsis. Furthermore, in vitro and in vivo experiments were conducted to validate the effect of hydroxysafflor yellow A (HSYA) on TP53-mediated ferroptosis and sepsis.

Results: TP53 has been identified as a ferroptosis-related hub gene in sepsis. Inhibition of TP53 with the specific TP53 inhibitor Pifithrin-α markedly reduced ferroptosis both in vitro and in vivo. Meanwhile, inhibition of TP53 significantly reduced inflammation and improved sepsis-induced intestinal barrier dysfunction. Furthermore, this study found that HSAY, a core component of XueBiJing, could stably bind to TP53, reduced the expression of TP53 and TP53-mediated ferroptosis in sepsis and improved animal survival.

Conclusion: This study clarified the role of TP53-mediated ferroptosis in sepsis-induced intestinal barrier dysfunction and discovered that HSYA could improve sepsis as an inhibitor of TP53, offering new strategies for the treatment of sepsis.

Background: Serogroup Y (MenY) invasive meningococcal disease (IMD) is uncommon in China, and MenY IMD cases combined with respiratory infections caused by several viruses are rare worldwide.

Case presentation: A 12‑year‑old boy was admitted by ambulance to a secondary hospital in Yunnan on January 9, 2025, due to sore throat for three days, fever, headache, and vomiting for six hours. Neisseria meningitidis (Nm) was cultured from the cerebrospinal fluid, whereas influenza A virus, adenovirus, and rhinovirus were detected in throat swab by PCR. After treatment with ceftriaxone and oseltamivir, the patient's condition improved and was discharged. Whole-genome sequence analysis of the Nm isolate (Nm534) showed a molecular type of Y: P1.5-1,10-1: F4-1: ST-1655(CC23) without antimicrobial resistance-associated mutations. Phylogenetic analysis indicated that Nm534 was assigned to Clade II and was closely related to isolates from Guangdong and Guangxi, which have the potential to be the infection source of this IMD case.

Conclusion: A rare case of MenY meningococcal meningitis combined with respiratory infection caused by three species of viruses was reported in China. It is recommended that school-aged children and adolescents be immunized with meningococcal polysaccharide conjugate vaccine ACYW.

Purpose: There was an increasing incidence of spinal infections. This study aimed to compare and contrast the clinical characteristics and treatment regimens for diverse types of spondylitis and to provide guidance for clinicians to make timely diagnosis and treatment.

Patients and methods: One hundred and twenty-five patients with spinal infections admitted to the First Affiliated Hospital of Anhui Medical University from October 2019 to December 2024 were recruited. The patients were classified as having tuberculous spondylitis (TBS), brucellosis spondylitis (BS), or pyogenic spondylitis (PS). The patient's treatment regimen and course were dynamically followed up during hospitalization and after discharge. Comparisons of clinical characteristics and treatment among the three groups were performed by SPSS 26.0 and GraphPad Prism 10 statistical software.

Results: The proportion of male patients was greater than female patients (65.00% vs 35.00%). Fever accompanied by pain was more prevalent in the BS and PS groups than in the TBS group (P=0.003). Compared with the TBS and BS groups, the PS group had the shortest duration from symptom onset to hospitalization (P<0.001). Sepsis, invasive manipulation, elevated inflammatory markers, psoas abscesses, and the involvement of three or more vertebrae were significantly associated with the PS. In this study, the median duration of treatment was 77 weeks for TBS, 19 weeks for BS, and 13 weeks for PS. Adverse drug reactions (ADRs) should be monitored during treatment. Our results indicated that omadacycline and contezolid exhibited remarkable efficacy in the treatment of spinal infections.

Conclusion: Patients of spinal infections with diverse etiologies presented varied clinical features and risk factors, the treatment should be individualized. Due to the long course of treatment, ADRs need to be monitored during treatment, and newer drugs such as omadacycline and contezolid are efficacious and have favorable safety profiles.

Fungal infections represent a growing global public health problem, particularly in immunocompromised individuals. The availability of effective treatments is limited, and the emergence of strains resistant to conventional antifungal agents further complicates disease management. Therefore, it is essential to explore novel therapeutic alternatives. This review analyzes compounds derived from natural sources with potential antifungal activity and highlights their structural and functional diversities. These include plant primary metabolites, fatty acids, antimicrobial peptides, secondary metabolites, crude extracts, terpenoids, essential oils, flavonoids, and saponins, as well as fungal metabolites and compounds extracted from marine algae. These natural products have demonstrated activity against various fungal species through multiple mechanisms of action, making them promising candidates for the development of new antifungal therapies. Compared with synthetic molecules or novel antifungal drugs under development, natural compounds often display lower toxicity, higher availability, and greater chemical diversity, which can be strategically exploited to overcome resistance. The compilation and analysis of this information underscores the value of natural sources as valuable resources in the search for therapeutic alternatives against human mycoses, particularly in the current context of increasing antifungal resistance.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major global health threat, and the emergence of ceftazidime-avibactam (CZA)-resistant KPC variants presents an increasing clinical challenge. This study aimed to investigate the in vivo evolution and phenotypic difference of a KPC-2 variant, KPC-71, during CZA therapy.

Methods: Seven CRKP isolates were sequentially collected from a single hospitalized patient over a 147-day period. Whole-genome sequencing, phylogenetic analysis, plasmid profiling, antimicrobial susceptibility testing, and virulence assays (including Galleria mellonella infection, siderophore production, and serum resistance) were performed to characterize the evolutionary dynamics and biological consequences of KPC-71.

Results: KPC-71 emerged repeatedly during CZA treatment, replacing KPC-2 and conferring high-level CZA resistance while reducing carbapenem MICs. Withdrawal of CZA resulted in reversion to KPC-2, restoring carbapenem resistance and CZA susceptibility, indicating a reversible resistance trade-off. Phylogenetic analysis revealed clonal expansion of the KPC-71-producing sublineage. Plasmid analysis identified bla _KPC genes located on a conserved IncFII/IncR-type plasmid containing an intact ISKpn27-bla _KPC-ISKpn6 transposon, while progressive remodeling of an IncFII(pCRY) plasmid in CRKP103 led to chromosomal integration of multiple resistance genes. Notably, the final isolate, CRKP103, exhibited markedly reduced capsule production, siderophore activity, serum survival, and attenuated virulence in G. mellonella, which associated with the loss of the iucABCD/iutA locus on an IncHI1B-type virulence plasmid. Functional validation confirmed that KPC-71 expression alone conferred high-level CZA resistance while modulating susceptibility to other β-lactams.

Conclusion: This study provides the first clinical evidence of the reversible in vivo evolution of an insertional KPC-71 variant under antibiotic pressure. The findings reveal a dynamic balance between resistance and virulence mediated by bla _KPC mutations and plasmid remodeling, highlighting the risk of resistance cycling during CZA treatment and the need for genomic surveillance in managing CRKP infections.