Acta microbiologica et immunologica Hungarica最新文献

Stenotrophomonas maltophilia is an opportunistic pathogen primarily associated with hospital-acquired infections, particularly in individuals who are immunocompromised. S. maltophilia infections pose a significant clinical challenge due to the bacterium's sophisticated intrinsic and acquired mechanisms, which render it naturally multidrug resistant. The management of such infections is thus difficult, as the availability of effective therapeutic agents is limited. Antibiotic therapy options include co-trimoxazole, minocycline, tigecycline, levofloxacin, cefiderocol, and ceftazidime-avibactam. Co-trimoxazole, which comprises a synergistic combination of trimethoprim and sulfamethoxazole, remains the recommended first-line therapy for S. maltophilia infections. In this review, we critically evaluate the current evidence on the efficacy of co-trimoxazole against S. maltophilia. The present global prevalence of co-trimoxazole resistance in S. maltophilia clinical isolates varies from <5% to approximately 44%, raising concerns about its long-term reliability. Resistance to co-trimoxazole arises through several mechanisms. Horizontal gene transfer can introduce sul genes, which encode sulfonamide-insensitive dihydropteroate synthase, or dfrA genes, which encode trimethoprim-insensitive dihydrofolate reductase. Both enzymes function within the folate biosynthesis pathway, and their expression directly confers co-trimoxazole resistance. S. maltophilia can also acquire co-trimoxazole resistance through genetic mutations. The overexpression of efflux systems such as SmeVWX and SmeDEF, contributes to high-level resistance to co-trimoxazole, often triggered by mutations in the transcriptional regulators. Resistant strains frequently emerge due to improper antimicrobial use, as environmental antibiotic residues can act as selection pressure, facilitating the emergence and persistence of resistant strains. Despite these challenges, co-trimoxazole continues to demonstrate substantial clinical utility. It remains effective in many settings, either as monotherapy or in combination with other antibiotics such as minocycline, tigecycline, cefiderocol, or levofloxacin, and often achieves favorable outcomes.

Lack of standardized criteria for discontinuing contact precautions (CP) in patients colonized or infected with multidrug-resistant bacteria (MDRB) can prolong isolation and strain healthcare resources. This retrospective cohort study aimed to assess the safety of a protocol-guided CP discontinuation strategy and identify risk factors for MDRB reacquisition. The study evaluated 88 adult patients under CP who met an institutional protocol for CP discontinuation between 2018 and 2023. The protocol required: no active infection; no antibiotic use in the preceding seven days; no drains or open wounds; no diarrhea; a negative culture from the initial site of MDRB identification; and a subsequent confirmatory negative screening (culture and/or PCR). Patients were followed for one year after CP discontinuation to assess MDRB reacquisition, defined as a new positive specimen for the same species. Potential risk factors for reacquisition were analyzed using multivariable Cox regression. At the one-year follow-up, MDRB reacquisition occurred in 17% (15/88) of patients. The reacquired pathogens included carbapenem-resistant Enterobacterales (9/50), methicillin-resistant Staphylococcus aureus (6/30), and vancomycin-resistant Enterococcus spp. (0/8). Independent risk factors for reacquisition were chronic obstructive pulmonary disease (HR 5.76, 95% CI 1.34-24.81), shorter duration of isolation (HR 0.98 per day, 95% CI 0.97-0.99), frequent hospitalizations (HR 1.75 per admission, 95% CI 1.07-2.88), and central venous catheterization (HR 13.04, 95% CI 2.63-64.69). Protocol-guided CP discontinuation was associated with a low rate of MDRB reacquisition and appears safe in appropriately selected patients. This approach may reduce unnecessary isolation in eligible patients, though high-risk individuals require closer monitoring.

The etiological diagnosis of peripheral pulmonary infectious lesions (PPILs) is challenging due to the limitations of conventional microbiological methods (CMMs). This study aimed to evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) performed on bronchoalveolar lavage fluid (BALF) obtained via radial endobronchial ultrasound (r-EBUS) for PPILs. This single-center, retrospective diagnostic accuracy study enrolled 110 patients with PPILs who underwent r-EBUS-guided BALF between January 2023 and December 2024. BALF samples were subjected to both mNGS and CMMs. The final diagnosis was established by two senior pulmonologists based on a comprehensive review of all clinical data. The diagnostic performance of mNGS and CMMs was compared against this final diagnosis. A definitive diagnosis was established in all 110 patients, with 68 cases identified as infectious lesions and 42 as non-infectious. The sensitivity of mNGS for detecting pathogens in infectious lesions was significantly higher than that of CMMs (89.7% vs. 47.1%, P < 0.001). The overall diagnostic accuracy of mNGS was also superior to CMMs (90.9% vs. 66.4%, P < 0.001). Among patients with positive mNGS results, clinical management was altered in 73.8% of cases based on the findings. mNGS uniquely identified pathogens in 31 cases that were missed by CMMs. For patients with PPILs, mNGS analysis of BALF samples obtained via r-EBUS demonstrates significantly greater diagnostic sensitivity and accuracy than conventional methods. This approach has a substantial impact on clinical decision-making, facilitating targeted antimicrobial therapy and representing a powerful tool in the diagnostic workflow for peripheral pulmonary infections.

This study reports on a multidrug-resistant (MDR) Acinetobacter baumannii isolate identified through microbiological surveillance of rectal swabs from a patient admitted to an intensive care unit (ICU) of a public hospital in Pernambuco, Brazil, in 2022. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK® automated system, and species confirmation was carried out by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The presence of antibiotic resistance genes, including blaKPC, blaIMP, blaVIM, blaNDM, blaSPM, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and mcr-1 to mcr-10, was investigated by polymerase chain reaction (PCR). The A. baumannii isolate exhibited resistance to all tested antimicrobials and demonstrated strong biofilm-forming capacity. Molecular analysis revealed the presence of blaNDM-1, blaOXA-23 and blaOXA-58 genes, representing a concerning genetic combination associated with carbapenem resistance. The A. baumannii isolate exhibited resistance to polymyxin B but lacked mcr-1 to mcr-10 genes. Asymptomatic colonization of MDR A. baumannii in a patient at ICU underscores the risk of possible infection that may become invasive. These findings highlight the importance of continuous microbiological surveillance to monitor the dissemination of MDR pathogens in hospital environments.

Diarrhea is one of the leading infectious diseases, causing the greatest health burden in most developing countries, with Clostridioides difficile-associated diarrhea being the primary cause of hospital-acquired diarrhea. Given the demonstrated mortality associated with diarrhea and its consequences and the significant association between C. difficile and diarrhea, this study aimed to investigate the ribotype distribution of C. difficile isolated from patients with diarrhea in Ahvaz, Iran. From May to November of 2025, 50 patients with diarrhea were admitted to the hospital. The tpi gene was amplified by the PCR method to detect C. difficile isolates. The other method was a real-time PCR to identify C. difficile isolates from stool samples. The two diagnostic methods applied in this study were comparable. PCR was used to investigate the presence of C. difficile toxin genes. Among the 12 positive isolates, the tcdA gene was detected in 6/12 (50%) of the isolates. Additionally, 6/12 (50%) of the isolates was detected the tcdB gene. 1/12 C. difficile isolate was resistant to vancomycin, but all isolates were susceptible to metronidazole and fidaxomicin. Ribotype 001 was the most dominant (n = 4, 33.3%), with ribotype 126 representing the second most common at 25% (n = 3). Ribotype 070 (n = 2, 16.7%), 084 (n = 2, 16.7%), and 078 (n = 1, 8.3%) were detected at lower frequencies. The detection of toxin-producing genes in some isolates is also an indication of the bacterium's significant virulence potential. The findings indicated the need for ongoing surveillance of C. difficile and the antibiotic resistance characteristics in hospital settings.

Antimicrobial resistance (AMR) poses a critical threat to pediatric health, particularly in resource-limited settings. This study aimed to evaluate the association between the maturity of antimicrobial stewardship programs (ASPs) and clinical outcomes in Peruvian hospitals. A multicenter, retrospective cohort study was conducted in three pediatric referral hospitals in Peru, including 1,250 patients hospitalized for bloodstream or urinary tract infections between 2020 and 2023. Multilevel logistic regression models and propensity score matching (PSM) analysis were used to assess risk factors for infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and the impact of ASP intervention. The prevalence of ESBL-producing Enterobacteriaceae infection was 32.9% in the three pediatric hospitals of this study. Prior antibiotic use (adjusted Odds Ratio, aOR 5.82) and the presence of a central venous catheter (aOR 2.10) were the main patient-level risk factors. Higher ASP maturity at the hospital level was associated with a lower likelihood of ESBL infection (aOR 0.85). PSM analysis revealed that direct ASP intervention was associated with a significant reduction in hospital length of stay (median of 3 days), 30-day mortality (4.2% difference), and time to appropriate therapy. In conclusion, pediatric AMR in Peru is a severe problem, but investment in and strengthening of ASPs constitute an evidence-based, highly effective strategy with a measurable impact on improving clinical outcomes and hospital efficiency.

To evaluate the effect of montelukast combined with inhaled corticosteroids (ICS) on the microbiome-metabolism-immunity axis in children with asthma and to quantify the mediating role of short-chain fatty acids, this single-center, randomized controlled trial enrolled 100 asthmatic children (aged 6-11) who received inhaled corticosteroids with or without montelukast for 12 weeks (n = 50 in the combination group and n = 50 in the ICS-alone group). Microbiome profiles from nasal and fecal samples were assessed via 16S sequencing, and short-chain fatty acids (SCFAs) were quantified by LC-MS/MS. Immune markers (Tregs, cytokines) were measured by flow cytometry and Bio-Plex. Efficacy analyses employed linear mixed-effects models, and SCFA mediation was tested using bootstrap analysis. The combination group demonstrated significantly greater improvements in clinical outcomes including fractional exhaled nitric oxide (FeNO) (β_int = -10.24 ppb, 95% CI -16.37 to -4.11, P = 0.001), Childhood Asthma Control Test (C-ACT) score (β_int = +1.83, P < 0.05) and FEV1% (β_int = +1.87, P < 0.05) compared to ICS alone. Microbiome analysis revealed enhanced α-diversity in both nasal and fecal samples (interaction P < 0.01) with significant community structure changes (PERMANOVA interaction P_perm < 0.01). Specific genus-level alterations included reduced nasal Moraxella and Haemophilus (logFC < 0, q < 0.10) and increased fecal SCFA-producing taxa including Faecalibacterium, Roseburia, Subdoligranulum, Agathobacter, and Eubacterium hallii group (logFC > 0, q < 0.10). The combination therapy also led to elevated fecal and serum SCFA levels (β_int > 0, P < 0.01), enhanced regulatory T cell (Treg) and IL-10 responses, and suppressed Th2 cytokines (IL-4/IL-5/IL-13). Mediation analysis confirmed SCFAs partially mediated FeNO improvement, with proportions of 30.0% for total SCFAs and 37.5% for butyrate (ACME and ADE both negative, P < 0.01). The combination of montelukast and inhaled corticosteroids was superior to inhaled corticosteroids alone, providing clinical benefits that were linked to favorable remodeling of the airway-gut microbiome and enhanced Treg/IL-10 immunity. This improvement was partially mediated by short-chain fatty acids, with a comparable safety profile.

The relationship between gut microbiota dysbiosis and bone mineral density (BMD) in hemodialysis patients, mediated through immune-metabolic pathways, remains to be fully elucidated. In this single-center prospective cross-sectional study, 165 maintenance hemodialysis patients were included to evaluate the independent association between gut microbiota composition and BMD, quantify the mediating roles of immune markers and gut-derived metabolites, and assess the effect modification by nursing-modifiable factors. Fecal samples underwent 16S rRNA sequencing and functional prediction. Inflammatory cytokines (IL-6, TNF-α), gut-derived metabolites (indoxyl sulfate, butyrate), and BMD via dual-energy X-ray absorptiometry (DXA) were measured. Gut microbiota community structure significantly differed across BMD tertiles (R2 = 0.033, P = 0.003). After full adjustment, principal coordinate 1 (PCoA-PC1, beta-diversity) was negatively associated with femoral neck BMD, while the Shannon diversity index showed a positive association (both P < 0.05). We identified 15 differentially abundant genera between high and low BMD groups. Functional prediction revealed short-chain fatty acid pathways were positively associated with BMD, while indole/p-cresol pathways showed negative associations. Mediation analysis demonstrated that immune markers and gut-derived metabolites collectively explained 45.71% of the microbiota-BMD relationship. Nursing factors significantly modified this association, with the negative relationship strengthened by low fiber intake, severe constipation, proton pump inhibitor use, and inadequate dialysis (Kt/V < 1.4). In conclusion, gut microbiota dysbiosis is independently associated with lower BMD in hemodialysis patients, partially mediated through immune-inflammatory pathways and gut-derived metabolites. Dietary fiber optimization, constipation management, prudent proton pump inhibitor prescribing, and dialysis adequacy represent actionable nursing targets to mitigate gut-mediated bone loss in this vulnerable population.

The incidence of fungaemia caused by rare yeasts, particularly Trichosporon species, is rising globally, posing diagnostic and therapeutic challenges-especially in immunocompromised patients. This systematic review aims to analyse the epidemiology, diagnostic approaches, antifungal susceptibility, and clinical outcomes of Trichosporon fungaemia (TF) in South-Eastern Europe, including Turkey. A comprehensive search was conducted in PubMed and Scopus in August 2025. A total of 59 cases from 12 studies were identified, with Trichosporon asahii being the most prevalent species (86.4%). Cases originated from Turkey (79.7%), Greece (18.6%), and Croatia (1.7%). Diagnostic techniques varied, with phenotypic methods still widely used. MALDI-TOF MS and DNA sequencing were mainly applied as confirmatory methods. Haematologic disorders were the most frequently reported underlying conditions among the patients. Sixteen breakthrough fungaemia cases-occurring despite empirical or prophylactic antifungal therapy-were identified. Although rare, TF represents a severe infection with significant mortality in South-Eastern Europe. Early and accurate species identification-facilitated by advanced diagnostic tools-is crucial for effective management. In addition to diagnostic difficulties, treatment is also challenging. Voriconazole appears to be the preferred antifungal agent, even in breakthrough fungaemia cases. Enhanced awareness, routine use of molecular diagnostics, and ongoing epidemiological monitoring are essential to improve patient outcomes.

The gut microbiota plays a crucial role in modulating mucosal immunity and allergic responses, yet its predictive value for sublingual immunotherapy (SLIT) outcomes remains underexplored in Artemisia pollen-induced allergic rhinitis (AR). In this single-center prospective cohort study, 204 adults with Artemisia pollen-induced AR underwent baseline stool collection before initiating standardized SLIT. Gut microbiota was analyzed using 16S rRNA sequencing of the V3-V4 region, with prespecified features including Shannon diversity index, composite abundance of butyrate-producing bacteria (Faecalibacterium, Roseburia, Eubacterium rectale group), and Prevotella-to-Bacteroides (P/B) ratio. Clinical response was defined as ≥30% reduction in combined symptom-medication score (CSMS) during the peak pollen season. We developed three prediction models: Model A (clinical variables only), Model B (clinical variables plus microbiota features), and Model C (parsimonious model via L1 regularization). The response rate was 54.41% (111/204). In multivariable analysis, all three microbiota features independently predicted treatment response: butyrate-producing bacteria (OR = 1.59, q = 0.006), P/B ratio (OR = 1.43, q = 0.020), and Shannon diversity (OR = 1.33, q = 0.046). Model B demonstrated superior discrimination compared to Model A (AUC 0.79 vs 0.71, ΔAUC = 0.08, P = 0.021), with improved calibration (intercept α = -0.03, slope β = 0.98) and significant net reclassification improvement (NRI = 0.36, P = 0.002). Decision curve analysis confirmed greater net benefit across clinically relevant threshold probabilities. The parsimonious Model C maintained good performance (optimism-corrected AUC = 0.78) with 77.48% sensitivity and 72.04% specificity. Baseline gut microbiota characteristics, particularly butyrate-producing bacterial abundance, microbial diversity, and Prevotella/Bacteroides community structure, significantly predict SLIT response in Artemisia pollen-induced AR and provide substantial incremental value over conventional clinical parameters. These findings support the integration of gut microbiota assessment into pretreatment stratification algorithms for allergen immunotherapy.