Annals of Clinical Microbiology and Antimicrobials最新文献

Background: Proteus mirabilis has emerged as an important multidrug-resistant opportunistic pathogen, with the production of metallo-β-lactamases (MBLs) being a major contributor to its broad-spectrum resistance. Although the aztreonam-avibactam (ATM-AVI) combination represents a key therapeutic option against MBL-producing Enterobacteriaceae, the mechanisms underlying ATM-AVI resistance in P. mirabilis has not yet been reported.

Methods: A total of 176 multidrug-resistant P. mirabilis isolates were collected from a tertiary hospital in China (2017-2024). Antimicrobial susceptibility testing identified ATM-AVI-resistant isolates (MIC ≥ 8/4 µg/mL). Whole-genome sequencing, gene cloning, RT-qPCR, and copy number analyses were used to determine resistance mechanisms. Growth rate assays evaluated fitness costs, and global phylogenetic analysis elucidated evolutionary and dissemination patterns.

Results: Twelve isolates (6.8%, 12/176) were resistant to ATM-AVI, all carrying the bla_PER-4 gene. Cloning experiments confirmed that bla_PER-4 conferred significantly higher ATM-AVI resistance than bla_PER-1. Increased resistance correlated with bla_PER-4 overexpression and gene copy number amplification. Whole-genome analysis showed that bla_PER-4 was embedded in ISCR1-associated class 1 integrons located on both plasmids and chromosomes, with a strain carrying eight tandem chromosomal copies. These structures likely mediated gene amplification via rolling-circle replication and homologous recombination. Phylogenetic analysis revealed that bla_PER-4-positive isolates were mainly associated with the ST135 lineage, suggesting transmission event within hospitals. Global data demonstrated that bla_PER-4-carrying P. mirabilis strains were predominantly found in China (80%, 12/15), while bla_PER-1 strains were more common in the United States.

Conclusions: The bla_PER-4-carrying P. mirabilis, particularly the ST135 clone, represents a high-risk lineage associated with high-level ATM-AVI resistance mediated by gene overexpression and copy number amplification. This finding highlights a novel mechanism of ATM-AVI resistance and underscores the need for continuous genomic surveillance and rational antimicrobial stewardship to prevent its further dissemination.

Background: Nocardiosis, traditionally an opportunistic infection, lacks comprehensive characterization in immunocompetent individuals. This study aimed to describe and analyze the demographics, clinical features, and outcomes of Nocardia infections in this population based on the literature.

Methods: A systematic analysis of 530 immunocompetent Nocardia cases (2020-2024) was conducted using reports from PubMed, CNKI, and MedNexus. Demographics, exposures, clinical characteristics, laboratory, treatment, and outcome were recorded and analyzed.

Results: Patients (median age: 59 years; 69.8% male) exhibited pulmonary (46.5%), cutaneous (20.0%), or cerebral (15.7%) involvements. Risk factors included soil/dust exposure (97/530, 18.3%), trauma (44/530, 8.3%), and comorbidities (255/530, 48.1%, e.g., diabetes, bronchiectasis). Cure/improvement (82.6%) group exhibited younger age (P = 0.01) and higher prevalence of local infections (P < 0.001), while more cases of disseminated infection (P < 0.001), N. farcinica (P = 0.01), and unclassified Nocardia spp. (P = 0.02) were in the deterioration/mortality group. Trimethoprim-sulfamethoxazole (71.9%) was the primary therapy. Species-specific patterns demonstrated: N. brasiliensis preferentially linked to cutaneous infections (P < 0.001), N. farcinica to cerebral disease (P < 0.001), and N. cyriacigeorgica to pulmonary involvement (P < 0.001).

Conclusion: Nocardiosis in immunocompetent hosts demonstrates distinct risk profiles, site-specific species associations, and prognostic factors. Early diagnosis, species identification, and antimicrobial therapy are critical for optimizing outcomes. This study underscores the need for heightened clinical suspicion and improved diagnostic protocols in non-immunocompromised populations.

Introduction: Helicobacter pylori is a slow-growing, gram-negative strictly pathogenic bacterium, which colonizes the stomachs of half the global population and is responsible for gastritis, peptic ulcer and even adenocarcinoma, Treatment of choice for eradication is a combination of PPIs and multiple antibiotic therapy. Recently, therapeutic failures began to be attributable to increased antibiotic resistance due to mutations in identified genes (rpoB, 16S rRNA coding gene, gyrA, 23S rRNA coding gene, pbp1A, frxA, rdxA).

Objectives: This study aimed to determine, using ultra-deep sequencing, the distribution of mutations in patient s hospitalized or undergoing screening for H. pylori.

Methods: Gastric biopsies were obtained from two different anatomical regions (antrum/fundus) in 18 patients' samples from 1998 to 2021, in four French hospitals. Following automated extraction, DNA of H. pylori was amplified using multiplexed PCR, before sequencing on the Illumina iSeq100 platform.

Results: Antral diversification of H. pylori populations is significantly greater than that at the fundic level for rpoB and rdxA. Fundic diversification of H. pylori populations is significantly greater than that at the antral level for the 23S rRNA coding, rdxA and rpoB genes (p < 0.05), with inter-individual variation.Conversely, the 16S rRNA, frxA, gyrA and pbp1A genes exhibited no significant variation (p > 0.05).

Discussion: This first study using in-house high-throughput sequencing of H. pylori on clinical biopsies from the same patients reinforces the hypothesis that the bacterial population within the same host is heterogeneous. The presence of minority variants justifies the need for at least two biopsies to ensure robust testing of the H. pylori antibiotic susceptibility profile.

Background: Severe community-acquired pneumonia (SCAP) remains a major cause of intensive care unit (ICU) admission and mortality. Prompt pathogen identification and timely administration of appropriate antimicrobial therapy are essential for improving patient outcomes. Although metagenomic next-generation sequencing (mNGS) enables rapid pathogen detection, the prognostic impact of the timing of mNGS-guided antibiotic adjustment remains unclear.

Methods: We conducted a multicenter retrospective study of ICU patients diagnosed with SCAP who underwent both bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs). Patients were categorized into early (≤ 72 h) and late (> 72 h) antibiotic adjustment groups based on the interval from ICU admission to the time of antibiotic adjustment guided by mNGS results. Subgroup analyses were performed according to immune status.

Results: In our study, mNGS significantly outperformed conventional microbiological tests (CMTs) in pathogen detection (92.70% vs. 57.18%, P < 0.001), with a particularly higher yield for mixed infections (51.63% vs. 19.14%, P < 0.001). Early mNGS-guided antibiotic adjustment was associated with a significantly reduced 28-day mortality compared to late adjustment (41.98% vs. 53.76%, P = 0.037). Furthermore, multivariate logistic regression analysis confirmed early adjustment as an independent protective factor for 28-day mortality (adjusted OR = 0.44, 95% CI: 0.23-0.83, P = 0.011). In the immunocompromised subgroup, early mNGS-guided adjustment was associated with significantly lower 28-day mortality than late adjustment (39.29% vs. 60.00%, P = 0.029), with a significant interaction observed between timing and immune status (P = 0.042).

Conclusion: Early mNGS-guided antibiotic adjustment is associated with improved survival among ICU patients with SCAP. This benefit is more pronounced in immunocompromised patients, underscoring the importance of early mNGS application to guide antimicrobial decision-making in this vulnerable population.

Background: The gut microbiota plays an important role in defending against infectious diseases. However, data on the clinical implications of the microbiome profiles in patients with candidemia remain limited. In this study, we investigated the association between the intestinal microbiome and mortality in patients with candidemia.

Methods: This prospective, observational, pilot cohort study enrolled adult patients with culture-confirmed candidemia. Fecal samples were collected within 5 days of diagnosis and analyzed using 16 S ribosomal RNA gene sequencing for microbiota profiling and gas chromatography-mass spectrometry for metabolomic analysis. Multivariate logistic regression was used to identify predictors of in-hospital mortality, defined as death during hospitalization.

Results: Fifty-nine patients with candidemia were analyzed, and the in-hospital mortality rate was 40.7%. The median Shannon diversity index of the gut microbiota was significantly lower in non-survivors than that in survivors (P = 0.009). Linear discriminant analysis revealed 11 bacterial species that differed significantly between the two groups. Among the 111 fecal metabolites, only 3-isopropoxy-hexamethyl-tetrasiloxane differed significantly between the survivors and non-survivors (P = 0.007). Septic shock (adjusted odds ratio: 10.59; 95% confidence interval, 1.70-65.97), underlying malignancy (7.79 [1.41-43.10]), and Shannon diversity index (0.40 [0.19-0.84]) were significant predictors of in-hospital mortality.

Conclusions: Low gut bacterial diversity is independently associated with mortality in patients with candidemia. These preliminary findings warrant confirmation through larger, well-powered studies.

Aspergillus fumigatus is a significant fungal pathogen responsible for allergic bronchopulmonary aspergillosis (ABPA), a global respiratory disease characterized by high morbidity and mortality. Accurate diagnosis of ABPA remains challenging due to the overlap of clinical and radiological features with other respiratory infections. This study aimed to identify A. fumigatus specific antigens and epitopes to advance immunodiagnostic and immunotherapeutic strategies for ABPA. Clinically confirmed ABPA patients were recruited, and their sera were tested for immunoreactivity against A. fumigatus crude and recombinant allergens. Proteomic analysis was done by employing two-dimensional electrophoresis (2DE) immunoblotting of A. fumigatus cytosolic fractions using sera from 10 individual patients. IgE-reactive spots identified via Q-TOF mass spectrometry revealed 18 allergenic proteins. Among these, two known allergens (Asp-f12 and Asp-f22) and three predicted allergens (sorbitol/xylulose-reductase, Hsp70-chaperone Hsp88, and Hsp70) exhibited cross-reactivity with allergens from other fungi. Notably, 13 allergenic proteins demonstrated significant immunoreactivity specific to ABPA patient sera. In silico epitope analysis identified 9 A. fumigatus specific B-cell and 4 T-cell epitopes with antigenic potential. Molecular docking studies confirmed the binding of representative B-cell and T-cell epitopes to their respective receptors (B-cell receptor and MHC-II complex), demonstrating receptor-specific interactions. These findings highlight pathogen-specific allergens and epitopes that could serve as valuable resources for developing targeted immunodiagnostic and immunotherapeutic tools. This approach may improve the clinical management of ABPA and help reduce its global disease burden.

Introduction: Peritonsillar abscess is the most frequent complication of acute tonsillitis. Although adult epidemiology and microbiology are well characterized, age-specific pediatric data remain limited. We investigated the incidence, microbiology, and suitability of penicillin monotherapy for pediatric peritonsillar abscess.

Methods: We conducted a retrospective cohort study of patients aged 0-17 years admitted with peritonsillar abscess to Aarhus University Hospital, Denmark (2012-2024). Age-stratified incidence rates were calculated using national population data. Bacterial findings and treatment outcomes were analysed across age groups.

Results: A total of 395 patients (mean age 13.9 ± 3.5 years) were included; 88% (349/395) had cultures performed, of which 81% (281/349) were positive. Fusobacterium necrophorum and Streptococcus pyogenes predominated, with marked age variation: Streptococcus pyogenes prevailed in children ≤ 11 years (61%), while Fusobacterium necrophorum dominated in adolescents aged 16-17 years (57%) (p < 0.001). Peritonsillar abscess incidence increased steadily with age, peaking at 78.4/100,000 in the oldest group. Most patients were treated with penicillin, either intravenously (158/395, 40%) or orally (130/395, 33%). Twelve patients (3%) received broader-spectrum antibiotics, and 95 (24%) patients underwent acute tonsillectomy without antibiotic treatment. Complications were rare (3/395, 1%), all of which involved postoperative pneumonia following tonsillectomy.

Conclusion: Peritonsillar abscess incidence increases with age, accompanied by a microbiological shift from Streptococcus pyogenes in younger children to Fusobacterium necrophorum among adolescents. Given the high susceptibility of both pathogens to penicillin and the low complication rate, penicillin monotherapy appears to be a safe and adequate empirical treatment across all pediatric age groups.

Key points: Peritonsillar abscess incidence in children increases with age, with Streptococcus pyogenes predominating in young children and Fusobacterium necrophorum in adolescents. Penicillin monotherapy yielded excellent outcomes, supporting stewardship-conscious empiric therapy tailored to pediatric patients.

Background: Group A Streptococcus (GAS) is a major bacterial pathogen associated with diverse clinical diseases. Despite its general susceptibility to β-lactam antibiotics, GAS outbreaks remain a significant global health and economic concern. In this study, we retrospectively analyzed the clinical features and antimicrobial resistance patterns of GAS infections in pediatric patients in Beijing over the past decade.

Methods: Data on all GAS infections from 2014 to 2023 were collected from the microbiology department of Beijing Children's Hospital. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.

Results: From 2014 to 2023, a total of 1,445 strains of GAS were isolated. School-age children (6-18 years) had the highest isolation rate (77.7%) among all age groups. Among the isolates, 53.6% were from outpatients (except pediatric gynecology). The top 3 wards with the highest GAS isolation rates were the rheumatology and immunology, pulmonology and dermatology wards. Most GAS infections were superficial (95.8%). Invasive infections were primarily due to bacteremia, which accounted for 40.0% of invasive cases. The isolation rate of GAS peaked in 2017 and remained at a lower level during the SARS-CoV-2 pandemic, specifically from 2019 to 2022. GAS infections also showed seasonal variation, with the highest prevalence in winter. No GAS strains were resistant to penicillin, cephalosporins, vancomycin, or linezolid. The resistance rates to erythromycin and clindamycin were generally above 90%.

Conclusion: In the post-SARS-CoV-2 period, the isolation rate of GAS has increased. GAS infections are more common in winter and summer, so children, especially school-age children, should be cautious. Given the high resistance of GAS to erythromycin and clindamycin, clinicians should limit the use of these two drugs to avoid treatment failure.