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Pulmonary cryptococcosis in routine care: the clinical–radiologic spectrum and transparent evidence-tier reporting (confirmed versus presumed) among patients with no recorded immunocompromising conditions
DOI: 10.1099/jmm.0.002159
Authors: Xiao-yao Zhang
Abstract
Introduction: Pulmonary cryptococcosis is increasingly identified in routine care, including among patients with no recorded immunocompromising conditions.
Hypothesis/Gap Statement: Real-world descriptions of pulmonary cryptococcosis are difficult to interpret because diagnostic intensity and case definitions vary across studies, and many cohorts reflect pathway-based rather than population-based case capture.
Aim: This study aimed to describe the clinical presentation, including asymptomatic/incidental cases, and chest computed tomography (CT) patterns of pulmonary cryptococcosis by two-level immune status, and to report prespecified diagnostic evidence tiers (confirmed vs presumed).
Methodology: We conducted a single-centre, retrospective, observational study at a tertiary hospital in China (January 2016 to December 2020). The analytic cohort comprised adjudicated pulmonary cryptococcosis cases identified along a routine-care diagnostic pathway among patients with pulmonary imaging abnormalities who underwent serum cryptococcal antigen testing as part of clinical evaluation. Cases were classified using a prespecified two-tier evidence scheme (confirmed vs presumed).
Results: Among 62 cases, 23/62 (37.1%) were immunocompromised, and 39/62 (62.9%) had no recorded immunocompromising conditions. Evidence tiers comprised 32/62 (51.6%) confirmed and 30/62 (48.4%) presumed cases. Cryptococcal meningitis was documented in 11/62 (17.7%). Asymptomatic/incidental presentation was recorded in 16/62 (25.8%), including 4/23 (17.4%) immunocompromised cases and 12/39 (30.8%) cases with no recorded immunocompromising conditions. On chest CT, nodules/masses were the most frequently recorded pattern in both groups, observed in 17/23 (73.9%) and 31/39 (79.5%) cases, respectively. Opacities/consolidation, cavitation and loculated pleural effusion were recorded less often.
Conclusion: In this routine-care diagnostic-pathway cohort, nodules/masses were the most frequently recorded CT pattern, and asymptomatic/incidental presentation was documented in a substantial proportion of cases, including among patients with no recorded immunocompromising conditions. Separate reporting of confirmed and presumed cases may improve interpretation of cohorts assembled under non-uniform diagnostic work-up.”
Other specific DSP article suggested by Editorial Board
A comparison of routine blood culture methods and multiplex quantitative PCR for detecting pathogens in simulated polymicrobial blood cultures
DOI: 10.1099/jmm.0.002155
Authors: Mariam Doualeh
Abstract
Introduction: Polymicrobial bacteraemia, the simultaneous presence of multiple bacterial species in the bloodstream, complicates diagnosis and treatment and is linked to poorer patient outcomes. Accurate detection is essential for effective clinical management.
Gap Statement. Despite being the diagnostic gold standard, conventional blood culture may fail to detect all pathogens in polymicrobial infections, particularly when species differ in growth rate or abundance. The relative performance of culture versus molecular methods under these conditions remains poorly characterized.
Aim: To compare the performance of conventional blood culture and quantitative PCR (qPCR) for detecting pathogens in simulated polymicrobial blood cultures containing fast- and slow-growing bacteria at varying ratios and concentrations.
Methodology. Four clinically relevant polymicrobial mixtures were prepared using seven bacterial species. Human blood was spiked with bacterial suspensions at varying ratios and inoculated into BACTEC blood culture bottles. After incubation, samples were analysed using standard culture techniques and an in-house multiplex qPCR assay.
Results: Routine culture detected both organisms in only 42% of samples, while qPCR identified both pathogens in 83%. Differences in bacterial growth rates significantly influenced culture outcomes, with slower-growing or less abundant species frequently missed. Notably, Staphylococcus aureus was not detected when co-cultured with Escherichia coli at ratios of 1:1 to 25:1, and only visible on Gram stain when S. aureus was initially 50 times more abundant.
Conclusion. These findings highlight a key limitation of conventional methods in detecting polymicrobial infections and underscore the need for more sensitive diagnostics. qPCR offers improved detection, particularly when organism abundance and growth rates vary. Incorporating molecular tools alongside routine culture may enhance diagnostic accuracy and provide a more complete understanding of polymicrobial bacteraemia.”
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Dehydroeffusol from Juncus effusus L. exhibits antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo
Authors: Shengying Lou
Abstract
Background: Dehydroeffusol (DHE) is a natural phenanthrene compound derived from Juncus effusus L., traditionally used for its antimicrobial properties. Despite its historical use, its antibacterial efficacy and underlying mechanisms have not been fully explored.
Objectives: To evaluate the antibacterial activity, safety profile, and mechanism of action of DHE against Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), and to assess its potential as a therapeutic agent.
Methods: DHE was isolated and its antibacterial effects were assessed using broth microdilution, time-kill assays, and biofilm inhibition assays. The cytotoxicity and hemolytic activity of DHE were evaluated in vitro using several cell lines and red blood cells. Mechanistic studies included scanning electron microscopy, membrane potential and permeability assays, network pharmacology analysis, molecular docking, and untargeted metabolomic profiling.
Results:DHE exhibited appreciable bactericidal activity against S. aureus and MRSA with minimal cytotoxicity. It inhibited biofilm formation, disrupted bacterial membranes, and maintained bactericidal activity without rapid resistance, while synergizing with ciprofloxacin, streptomycin, and azithromycin. Network pharmacology and docking identified 56 infection-related targets (hub proteins EGFR, BCL2, HSP90AA1/B1, ESR1, SRC) enriched in PI3K–Akt/ErbB/EGFR pathways, supporting additional modulation of host infection-related signaling. In MRSA, untargeted metabolomics showed broad disturbances in amino acid, energy, and nucleotide metabolism, indicating disruption of essential biosynthetic and energy pathways. In vivo, DHE significantly reduced bacterial load and alleviated tissue damage in a murine MRSA infection model, demonstrating measurable protective effects.
Conclusions: DHE is a promising natural antimicrobial agent with notable activity against S. aureus and MRSA. Its mechanism of action involves membrane disruption and biofilm inhibition, along with preliminary safety in vitro, supporting its potential for further development as an effective antimicrobial agent.”
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Clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in the etiological diagnosis of community-acquired pneumonia in children
Authors: Rongjie Chen
Abstract
CAP is a major cause of pediatric hospitalization on a global scale, particularly in developing countries where the morbidity and mortality rates remain high. The etiological diagnosis of CAP in children is challenging, particularly for children with severe and high-risk conditions, such as immunodeficiency. This is primarily due to the nonspecific distribution of the causative agent and the limitations of traditional detection methods. As an emerging molecular diagnostic technology, BALF mNGS has been shown to detect the nucleic acid sequences of bacterial, viral, fungal, and atypical pathogens directly from clinical samples. This is attributed to the technology’s unbiased, high throughput, and high sensitivity, which significantly improves the detection rate of pathogens. Furthermore, BALF mNGS also improves the detection of mixed infections. This capacity for precise analysis is of significant value, as it facilitates the identification of drug-resistant genes and rare pathogens. Consequently, this enhanced diagnostic capability provides a reliable foundation for the precise treatment of childhood CAP. Nevertheless, its clinical application continues to encounter challenges, including high cost, invasive sampling methods, complex data analysis processes, and insufficient standardization of pre-analytical sample processing. The technical principles, clinical value and optimization strategies of BALF mNGS are systematically reviewed in this paper, with the aim of providing a reference for improving the pathogenetic diagnosis of CAP in children.
Other specific DSP article suggested by Editorial Board
Antimicrobial Stewardship Program in an acute care hospital in New Orleans: impact on antibiotic utilization.
Authors: Blyth MD, et al
Abstract
Objectives: To evaluate antibiotic utilization in relation to antimicrobial stewardship activities in a 170-bed Touro Infirmary hospital in New Orleans.
Methods: Antibiotic utilization for antipseudomonal beta-lactams, methicillin-resistant Staphylococcus aureus antibiotics (anti-MRSA), fluoroquinolones, and ceftriaxone were evaluated in relation to antimicrobial stewardship activities that were implemented at the hospital and monitored between August 1, 2018, and August 31, 2025. Days of antibiotic therapy and days of intravenous antibiotic administration for 19-months baseline were recorded, during 10 months of COVID-19-dictated antibiotic utilization, and during 14 months of MRSA PCR testing at Touro (Antimicrobial Stewardship Intervention [ASI] 1), 20 months of blood culture identification (BCID) at Touro (ASI 2, time 1), followed by 22 months of BCID and other cultures sent out to University Medical Center (ASI 2, time 2). Results: During the observation period, days of therapy for antipseudomonal beta-lactams, anti-MRSA, and fluoroquinolones consistently and significantly decreased from baseline to ASI 2, time 2 (P < .0001 for each decrease). Days of therapy for ceftriaxone significantly increased from ASI 1 to ASI 2, time 2 (P < .0001). Days of therapy for all antibiotics consistently decreased from baseline to ASI 2, time 1 (P < .0001) but not through time 2 (P = .571). Days of intravenous administration of antibiotics significantly decreased from baseline to the COVID-19 period (P = .002) and decreased again significantly from ASI 1 to ASI 2, time 1 (P = .003).
Conclusions: Clinical microbiology laboratories integrated into Antimicrobial Stewardship Program are associated with reductions in days of antibiotic therapy and days of intravenous antibiotic administration at Touro Infirmary.”
Other specific DSP article suggested by Editorial Board
The WHO priority list of antibiotic-resistant bacteria: challenges and opportunities for next-generation antimicrobial development.
Authors: Abdalllah EM, et al
Abstract
Antimicrobial resistance (AMR) remains one of the most serious global threats to public health, driven by the rapid emergence and dissemination of multidrug-resistant bacterial pathogens that compromise existing antibiotic therapies. In response, the World Health Organization (WHO) has defined priority lists of antibiotic-resistant bacteria to guide research, innovation, and drug development efforts. This narrative review synthesizes current knowledge on the molecular mechanisms underlying resistance in WHO-priority pathogens, including reduced membrane permeability, efflux pump overexpression, enzymatic drug inactivation, target modification, biofilm formation, and horizontal gene transfer. Beyond mechanistic insights, we critically evaluate the therapeutic limitations of conventional antibiotics, the failure of traditional discovery pipelines, and the growing clinical and economic burden of resistant infections. Emerging strategies, including artificial intelligence-assisted drug discovery, phage therapy, antimicrobial peptides, CRISPR-based systems, resistance-modifying combinations, and natural product-derived compounds and plant compounds, are assessed with emphasis on pharmacological feasibility, translational challenges, and clinical relevance. Particular attention is given to issues of delivery, toxicity, dosing optimization, resistance emergence, regulatory barriers, and real-world implementation. Finally, we highlight the central role of antimicrobial stewardship, surveillance, and a One Health framework integrating human, animal, and environmental sectors in mitigating resistance and sustaining therapeutic effectiveness. Collectively, this review underscores that addressing WHO-priority pathogens will require integrated, multidisciplinary strategies that bridge molecular biology, pharmacology, clinical translation, and public health.
Other specific DSP article suggested by Editorial Board
Differential modulation of gentamicin antibacterial activity by vitamin B12 and vitamin D3 against Gram-positive and Gram-negative bacteria: an in vitro-in silico study.
Authors: M’hamedi I, et al
Abstract
Introduction: Antimicrobial resistance and gentamicin-associated toxicity necessitate the development of non-antibiotic adjuvants that enhance aminoglycoside efficacy while reducing required doses. Vitamins B12 and D3 possess physicochemical and biological properties that may influence bacterial resistance pathways. This study aimed to evaluate the modulatory effects of these vitamins on gentamicin against representative bacterial strains using an integrated in vitro-in silico approach. Materials and methods: Eight ATCC Gram-negative and Gram-positive reference strains were evaluated. Antibacterial activity was assessed using agar disk diffusion and broth microdilution assays to determine inhibition zones, minimum inhibitory concentrations (MICs), and MIC fold reduction (MFR). In silico analyses targeted the 30S ribosomal subunit, a cobalamin riboswitch, and a proton motive force (PMF)-related protein to explore mechanistic interactions underlying observed phenotypes. Results: Vitamin B12 significantly enhanced gentamicin efficacy, reducing MICs by up to 8-fold and demonstrating synergistic activity (MFR ≥ 4) against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis. Conversely, vitamin D3 displayed antagonistic effects (MFR ≤ 0.5) in several Gram-positive strains, increasing gentamicin MICs by up to 16-fold. Computational results indicated cooperative stabilization of gentamicin at the ribosomal target and increased affinity for the cobalamin riboswitch in the presence of vitamin B12, whereas vitamin D3 showed strong binding to a PMF-related protein, consistent with impaired aminoglycoside uptake. Conclusion: Vitamin B12 represents a promising dose-sparing adjuvant for gentamicin, while vitamin D3 may compromise aminoglycoside efficacy under the tested conditions. These findings warrant further validation using clinical isolates and biofilm models before considering vitamin-based strategies in aminoglycoside stewardship.
Other specific DSP article suggested by Editorial Board
Detection to Disruption: A Comprehensive Review of Bacterial Biofilms and Therapeutic Advances.
Authors: Maroju PA, et al
Abstract
Bacterial biofilms are structured microbial communities enclosed within a self-produced extracellular polymeric substance matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This matrix promotes adhesion, structural stability, and the development of heterogeneous microenvironments that restrict antimicrobial penetration and shield bacteria from host immune responses. As a result, biofilms are major contributors to chronic, recurrent, device-related, and difficult-to-treat infections, posing a major challenge for clinical management and antimicrobial stewardship. This review summarizes current understandings of biofilm biology, its clinical relevance, including the stages of biofilm development, the composition and protective roles of the matrix, and the physiological heterogeneity that arises during maturation. It also examines key mechanisms underlying biofilm tolerance and resistance, such as limited antibiotic diffusion, and sequestration, enzymatic inactivation, efflux pump upregulation, persister cell formation, and horizontal gene transfer. In addition, it highlights important clinical settings in which biofilms are implicated, including cystic fibrosis, chronic wounds, osteomyelitis, implant- or device-associated infections, and breast implant illness, in which persistent implant-associated biofilms and the resulting chronic inflammatory milieu have been hypothesized to contribute to local and systemic manifestations in a subset of patients. The review further discusses conventional and emerging approaches for biofilm detection alongwith real-time monitoring. Biofilm-associated infections remain difficult to eradicate because persistence is driven by multiple interconnected protective mechanisms. Effective management therefore requires integrated strategies that combine accurate detection with multifaceted therapies, including antibiotics alongside matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophages, metabolic reactivators, and nanotechnology-based delivery systems. Advances in multi-omics and system-level modeling will be essential for developing next-generation strategies to prevent, monitor, and treat biofilm-associated disease.
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Genomic Epidemiology of ESBL and Non-ESBL-Producing Escherichia coli Across One Health Interfaces in Oman.
Authors: Al-Habsi HS, et al
Abstract
Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and non-ESBL Escherichia coli across One Health interfaces in Oman.
Methods: This prospective cross-sectional study analyzed 295 non-duplicate Escherichia coli isolates derived from 104 clinical, 173 animal [diseased (123) and healthy (50)], 14 sewage and four water sources. Antimicrobial susceptibility testing was performed phenotypically, and a representative subset of 50 ESBL and non-ESBL Escherichia coli from the three interfaces underwent whole genome sequencing to determine MLST, phylogroups, resistance genes, virulence determinants and plasmid replicons.
Results: ESBL prevalence was highest in human isolates (73%), followed by sewage (28.6%) and animals (16.3% diseased; 8% healthy). blaCTX-M-15 predominated in humans, whereas blaCTX-M-55 dominated in animals and sewage, suggesting ecological partitioning with partial overlap. Quinolone resistance was lowest in the animal interface. Sewage isolates harbored the most complex resistome, including rmtB and plasmid-mediated quinolone resistance genes. MLST analysis revealed high diversity in human isolates, including globally recognized ExPEC lineages (ST10, ST38, ST73, ST127, ST131), while ST224 dominated in animals with evidence of possible spillover to humans. ST167 was confined to sewage, consistent with environmental maintenance of high-risk clones. Phylogroup structuring showed predominance of A, B2 and D among human isolates and A, B1, and E among animal and sewage isolates. Virulence profiling demonstrated broader virulome diversity in humans, but shared core determinants (fimH, sitA, traT) across all domains. IncFIB(AP001918) was the dominant plasmid replicon, particularly among ESBL isolates, underscoring its role in horizontal gene dissemination. Alarmingly, mutation in pmrB (V161G) was identified in a healthy animal isolate, pointing to a need for greater colistin restriction in animal husbandry.
Conclusions: This study highlights plasmid-mediated resistance and shared virulence determinants linking reservoirs; although AMR profile was quite distinct across the three interfaces, human isolates demonstrated greater resistance than animal isolates, suggesting healthcare-driven AMR in Oman. Continued integrated genomic surveillance is essential to monitor gene flow and inform coordinated antimicrobial stewardship strategies.