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 meta...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 hospit...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...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 progra...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 sin...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 cro...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...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 aller...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.
Tuberculosis (TB) control remains severely challenged in Pakistan, with urban slum populations bearing a disproportionate burden due to pronounced socioeconomic disparities. The emergence of multidrug-resistant TB (MDR-T...Tuberculosis (TB) control remains severely challenged in Pakistan, with urban slum populations bearing a disproportionate burden due to pronounced socioeconomic disparities. The emergence of multidrug-resistant TB (MDR-TB) poses a critical public health threat; however, community-level data from these high-transmission settings remain limited, obscuring the true scale of the epidemic. A cross-sectional study involving 3,317 individuals was conducted across the urban slum of six districts in Punjab, Pakistan between June 2024 and May 2025. Sputum samples were analyzed using smear microscopy, GeneXpert MTB/RIF, and comprehensive drug susceptibility testing (DST). Sociodemographic and clinical data were collected to assess potential risk factors. The prevalence of Mycobacterium tuberculosis (MTB) infection confirmed by GeneXpert was 17.0% (564/3,317), significantly higher than the 12.8% detected by smear microscopy. Initial molecular testing identified rifampicin resistance in 40.2% (227/564) of MTB-positive cases, with 39.0% (220/564) fulfilling the criteria for MDR-TB. The MDR-TB burden was markedly higher among retreatment cases (68.1%) compared with new cases (29.8%) and exhibited significant geographic clustering, with prevalence exceeding 53% in Lahore and Kasur. Smoking emerged as the most significant risk factor, observed in 73.8% of MTB-positive individuals (P < 0.001). Among rifampicin-resistant isolates subjected to extended DST, resistance rates were 96.9% for isoniazid, 100% for rifampicin, 46.3% for ofloxacin, 4.4% for amikacin, 22.9% for kanamycin, and 8.4% for capreomycin. The prevalence of MDR-TB in the urban slums of Punjab was alarmingly higher than national and global estimates. These findings necessitate an urgent need for expanded molecular diagnostics, active case-finding, and targeted public health interventions in these marginalized communities. Without immediate and coordinated action, urban slums risk becoming focal points for the accelerated emergence of untreatable TB.
The identification of mutations associated with drug resistance is of paramount importance for the rapid detection of drug-resistant Mycobacterium tuberculosis strains. The objective of this study was to identify the mut...The identification of mutations associated with drug resistance is of paramount importance for the rapid detection of drug-resistant Mycobacterium tuberculosis strains. The objective of this study was to identify the mutations responsible for conferring resistance to rifampicin (RIF) and isoniazid (INH) in M. tuberculosis. A total of 84 drug-resistant M. tuberculosis strains including 41 multidrug-resistant (MDR) strains, 37 INH-resistant, RIF-susceptible strains, and 6 RIF-resistant, INH-susceptible strains were analyzed. The 86 M. tuberculosis strains were isolated from clinical samples, between 2022 and 2023 in Ankara, Turkey. PCR amplification and sequencing of rpoB, katG and inhA genes were performed to detect mutations. In the 47 RIF-resistant strains, the predominant mutation in rpoB was S450L observed in 40 of 47 strains (85%), followed by H445Y detected in two strains (4.3%). The Q432K/P, M434I, D435Y, T444I, H445G, S450W, and S450F mutations were identified in one strain each. The S315T mutation in the katG gene was identified in 60 of the 78 INH-resistant strains (76.9%). The rate of mutation -15C>T in inhA was 29.5% (23/78). Both S315Y and -15C>T mutations were detected in six strains (7.7%). This study provided comprehensive information regarding the genetic background of drug-resistant tuberculosis in terms of prevalent mutations responsible for RIF and INH resistance. These findings contribute to develop more sensitive qPCR tests that target mutations for the rapid detection of drug-resistant TB.
Accurate and rapid identification of carbapenemase-producing Gram-negative bacteria is essential for appropriate antimicrobial therapy and infection control. This study compared the diagnostic performance of two multiple...Accurate and rapid identification of carbapenemase-producing Gram-negative bacteria is essential for appropriate antimicrobial therapy and infection control. This study compared the diagnostic performance of two multiplex lateral flow immunoassays, the NG-Test CARBA 5 (NG) and a Colloidal Gold Immunoassay (CGI), for the detection of major carbapenemases in clinical isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa. A total of 100 non-duplicate carbapenem-resistant isolates collected in 2024 were included. An in-house polymerase chain reaction assay targeting blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like genes served as the reference standard.Overall, the NG assay demonstrated higher sensitivity than the CGI assay, while both tests showed excellent specificity. For OXA-48-like enzymes, both assays exhibited 100% specificity and 89.6% sensitivity. Detection of NDM was more sensitive with NG (96.9%) than with CGI (87.7%), whereas both maintained 100% specificity. For KPC detection, NG achieved 100% sensitivity, while CGI showed a markedly lower sensitivity (73.7%). Diagnostic performance was generally superior in K. pneumoniae compared with P. aeruginosa, and both assays showed reduced sensitivity in isolates co-harboring multiple carbapenemase genes.These findings indicate that although both lateral flow assays are rapid and practical tools for routine laboratory use, their performance may vary depending on the carbapenemase type and local epidemiology. Molecular confirmation remains essential, particularly in settings with a high prevalence of multiple carbapenemase-producing isolates.
The present study aimed to investigate the resistome of four trimethoprim-sulfamethoxazole (SXT)-resistant Stenotrophomonas maltophilia complex (Smc) isolates from Bulgarian hematopoietic stem cell transplantation (HSCT)...The present study aimed to investigate the resistome of four trimethoprim-sulfamethoxazole (SXT)-resistant Stenotrophomonas maltophilia complex (Smc) isolates from Bulgarian hematopoietic stem cell transplantation (HSCT) recipients and to subject them to phylogenomic analysis involving all sul1-positive strains of the identified species with available genomes worldwide. Preliminary identification by MALDI-TOF mass spectrometry determined all four isolates as S. maltophilia. The sources of isolation were stools (SM175, SM176, and SM179) and urine (SM178). SM176 and SM178 also showed high-level levofloxacin resistance. All isolates demonstrated in vitro susceptibility to minocycline and cefiderocol. Whole-genome sequencing (WGS) assigned SM175, SM176, and SM178 as Stenotrophomonas forensis. Two types of class 1 integrons were detected in the four isolates, namely SM175 and SM179 carried empty integrons, whereas SM176 and SM178 carried a gene cassette (3,748 bp in length) consisting of aac6'-Ib-cmlB-blaOXA-9. Alignment against public databases revealed that this cassette has not been found in Stenotrophomonas species so far, but it was present in Pseudomonas aeruginosa and Enterobacterales. Phylogenomic analysis of our assembled sequences, together with all 26 sul1-positive S. maltophilia and S. forensis genomes, indicated that S. maltophilia SM179 was not part of any S. maltophilia cluster. SM175, SM176, and SM178 were closely related (differences of 35-101 SNPs). To the best of our knowledge, this is the first report of SXT-resistant Smc isolates from post-HSCT patients with hematological malignancies in Bulgaria, which presents WGS-based resistome and phylogenomic analyses. We also report on the first sul1-containing S. forensis clinical isolates. Our findings reveal high global heterogeneity of sul1-positive S. maltophilia.
Understanding the long-term determinants of antibody levels against SARS-CoV-2 is crucial for evaluating population immunity and guiding public health strategies. While short- and mid-term immune responses after COVID-19...Understanding the long-term determinants of antibody levels against SARS-CoV-2 is crucial for evaluating population immunity and guiding public health strategies. While short- and mid-term immune responses after COVID-19 vaccination have been extensively studied, data on long-term humoral immunity remain limited.This observational study was conducted at G. Gennimatas General Hospital of Thessaloniki, Greece. A total of 104 healthcare workers with varying vaccination and infection histories were included to identify the key factors influencing antibody levels. Participants had received three or more doses of the Pfizer-BioNTech mRNA COVID-19 vaccine (BNT162b2, Comirnaty), except for 11 individuals who had received only two doses. Serum samples were collected three years after the third vaccine dose between October 2024 and November 2024.Antibody levels increased after the second and third vaccine doses and subsequently declined over time. In a multivariable regression analysis adjusting for age, sex, number of vaccine doses, and number of infections, we showed that the most important determinant of antibody levels was the individual-specific time (in days) elapsed since the last immunological event, either vaccination or infection. Other factors, including demographic characteristics and cumulative exposure to the virus or vaccines, had no significant independent effect when accounting for time.These findings suggest that waning immunity is the primary driver of antibody levels, emphasizing the need for periodic booster vaccinations to maintain protection in healthcare workers.
The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge globally. This study reports on a ceftazidime-avibactam resistant KPC-35 producing K. pneumoniae strain from a patient with...The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge globally. This study reports on a ceftazidime-avibactam resistant KPC-35 producing K. pneumoniae strain from a patient with cerebral hemorrhage undergoing ceftazidime-avibactam (CZA) treatment. In this study, three K. pneumoniae strains were isolated from blood samples of a patient after intracerebral hemorrhage. Broth microdilution, checkerboard assays, and time-kill assays were employed to evaluate antimicrobial susceptibility and combination regimens. Whole-genome sequencing (WGS) was used to investigate the genetic characteristics of the three K. pneumoniae strains. The results showed that, K. pneumoniae KP29870 strain belonged to ST15, it was KPC-35 positive and exhibited a 16-fold higher minimum inhibitory concentration (MIC) of CZA (32 vs 1-2 mg L-1) but significantly lower MICs of imipenem (2 vs ≥ 16 mg L-1) and meropenem (1 vs ≥ 16 mg L-1), compared to the other two K. pneumoniae strains, that harboured KPC-2. CZA resistant K. pneumoniae remained highly susceptible to aztreonam-avibactam (MIC 0.03/4 mg L-1). The single base mutation (T503C) resulted in the substitution of leucine with proline at Ambler amino acid position 169 (L169P), corresponding to an evolution from blaKPC-2 to blaKPC-35. Checkerboard and time-kill assays demonstrated synergistic antibacterial effects for CZA combined with imipenem, meropenem, or with aztreonam against KPC-35 positive K. pneumoniae. This is the first report in China of a K. pneumoniae ST15 strain harboring blaKPC-35 emerging from a blaKPC-2-positive ancestor during CZA treatment. The new β-lactamase inhibitor combination such as aztreonam-avibactam monotherapy or CZA combined with carbapenems or with aztreonam represents promising treatment strategies against such KPC mutants. We recommend prompt susceptibility testing and KPC genotyping if resistance emergence is suspected during CZA therapy.
In recent years, the presence of microbiota in tumors has been discovered through extensive research, overturning the longstanding belief that "tumors are sterile." Advanced techniques such as 16S rRNA gene sequencing, f...In recent years, the presence of microbiota in tumors has been discovered through extensive research, overturning the longstanding belief that "tumors are sterile." Advanced techniques such as 16S rRNA gene sequencing, fecal microbiota transplantation, and the construction of mouse models specific to different tumor types have been utilized to validate the existence of microbiota within various tumors. The intratumoral microbiota significantly influences tumor development by modulating immune responses, mediating inflammatory reactions, and interfering with or enhancing immunotherapy or chemotherapy. For instance, Aspergillus sydowii in lung adenocarcinoma promotes immunosuppression via the Dectin-1/CARD9 pathway, while colibactin-producing Escherichia coli in colorectal cancer facilitates tumor progression through lipid metabolism dysregulation. Moreover, intratumoral microbiota can predict patient prognosis and guide personalized cancer treatment strategies, highlighting their potential as therapeutic targets. This review synthesizes current evidence on the roles of intratumoral microbiota across multiple cancer types and discusses their clinical implications.
The emergence of mupirocin-resistant Staphylococcus aureus strains poses a significant challenge to public health due to limited treatment options and the risk of multidrug resistance. This study aims to investigate the...The emergence of mupirocin-resistant Staphylococcus aureus strains poses a significant challenge to public health due to limited treatment options and the risk of multidrug resistance. This study aims to investigate the antibiotic susceptibility and molecular characteristics of mupirocin resistant S. aureus isolates. A total of 65 mupirocin-resistant isolates were included in the study. The isolates were characterized using antimicrobial susceptibility testing, biofilm formation assay, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and polymerase chain reaction analysis to detect resistance (mecA, mecC, mupA, erm(A), erm(B), erm(C), tet(M), ant (4')-Ia, aac (6')-Ie/aph (2″), and aph (3')-IIIa) and toxin genes (eta, etb, pvl, and tst). Resistance to mupirocin was observed in 12.5% of the S. aureus isolates collected during the study period. Among the 65 mupirocin-resistant MRSA isolates, 75.4% were classified as HLMUPR and 24.6% as LMUPR. cMLSB and iMLSB phenotypes were identified in 41.5 and 36.9% of the isolates. Our results showed that 49.2, 30.8, and 15.4% of isolates were classified as strong, intermediate, and weak biofilm-forming strains, respectively. Our result revealed that about three-quarters of isolates harbored mecA (100%), tet(M) (76.9%), mupA (75.4%) resistance genes. MLST revealed that the 65 isolates belonged to seven clonal complexes, including CC8 (41.5%), followed by CC22 (20%), CC5 (10.8%), CC30 (10.8%), CC15 (7.7%), CC1 (4.6%) and CC80 (4.6%). The vast majority of S. aureus isolates belonged to CC8/ST239-MRSA (21.5%). Among the 32 strong biofilm producers, the majority (28.1%) belonged to CC8/ST8 MRSA clone. Our result revealed that 39.1% of PVL-positive strains belonged to CC/ST22. The fusidic acid resistance isolates belonged to CC/ST8-MRSA (7.7%), CC8/ST239-MRSA (12.3%), CC/ST22-MRSA (7.7%), and CC30/ST80-MRSA (1.5%) lineages. In conclusion, this study provides valuable insights into the characteristics of mupirocin-resistant S. aureus isolates from Tehran, Iran. The results highlight a high prevalence of HLMUPR in this research. Additionally, the study reveals a diverse genetic landscape, with isolates belonging to various clonal complexes, particularly CC8, CC22, and CC5. The high frequency of biofilm formation and resistance to other antibiotics underscores the need for ongoing surveillance and the development of more effective treatment strategies to combat these multidrug-resistant strains.
Bronchoalveolar lavage (BAL) is a basic diagnostic method for the detection of fungal infections in lung transplant recipients. Aspergillus species are frequently identified, typically by the presence of septate hyphae;...Bronchoalveolar lavage (BAL) is a basic diagnostic method for the detection of fungal infections in lung transplant recipients. Aspergillus species are frequently identified, typically by the presence of septate hyphae; however, the visualization of conidia in cytologic preparations is rare. Aspergillosis caused by Aspergillus niger is an uncommon but recognized infectious complication in this patient population.We report on the case of a 60-year-old lung transplant recipient who underwent routine surveillance bronchoscopy eight weeks post-transplantation in August 2025. A substantial amount of adherent secretion was noted at the medial part of the right bronchial anastomosis. Surveillance BAL was performed from the right S8 segment, and cytospin preparations revealed intracellular Aspergillus conidia within alveolar macrophages. Galactomannan antigen assay was negative; however, fungal culture confirmed A. niger after five days.This case highlights the diagnostic value of identifying fungal conidia in BAL cytology, which may facilitate early recognition of invasive fungal infection or fungal colonization potentially leading to invasive disease or facilitate chronic lung allograft dysfunction (CLAD) development.
The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specif...The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specific bacterial taxa may influence both efficacy and immune-related adverse events (irAEs). However, the magnitude and consistency of these associations remain unclear. A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted through March 2025. Eligible studies evaluated baseline gut microbiota composition, fecal microbiota transplantation (FMT), probiotic/prebiotic interventions, or antibiotic exposure in cancer patients treated with ICIs. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for response rates and irAEs, were estimated using random-effects models. Across 38 studies involving 5,642 patients were included. Pooled analysis demonstrated that enrichment of Akkermansia muciniphila, Bifidobacterium longum and Faecalibacterium prausnitzii was significantly associated with improved OS (HR 0.62, 95% CI 0.51-0.76) and PFS (HR 0.69, 95% CI 0.55-0.83). Conversely, antibiotic exposure before or during ICI treatment was associated with worse OS (HR 1.84, 95% CI 1.45-2.34). Patients undergoing FMT from responders exhibited higher objective response rates (OR 2.91, 95% CI 1.48-5.73). Microbiota diversity indices were consistently higher in responders than in non-responders. Collectively, gut microbiota composition and its modulation significantly impact the therapeutic efficacy and toxicity profile of ICIs. These findings highlight the translational potential of microbiome-based biomarkers and interventions in optimizing immunotherapy.
The 16S rRNA sequencing technology was used to investigate changes in the abundance of intestinal microbiota, metabolites of blood and fecal samples were analyzed and their relationships with neurotransmitters were evalu...The 16S rRNA sequencing technology was used to investigate changes in the abundance of intestinal microbiota, metabolites of blood and fecal samples were analyzed and their relationships with neurotransmitters were evaluated in patients with liver cirrhosis after hepatitis B infection. The liver function phenotypes correlated with Phylum Proteobacteria, Class Clostridia and Gamma Proteobacteria, Family Enterobacteriaceae, Ruminococcaceae, Streptococcaceae, Lachnospiraceae and Lactobacillaceae, Genus Faecalibacterium, Streptococcus, species Escherichia coli, etc. Genus Streptococcus has a good diagnostic value for patients with liver cirrhosis in the COM (Compensated liver disease) group, with an AUC of 0.81 (95% CI: 0.70-0.92), while Genus Streptococcus, Veillonella, Faecalibacterium, Blautia, and Bacteroides have a better diagnostic value for patients with liver cirrhosis in the DECOM (Decompensated liver disease) group (including DECOM1 and DECOM2), with the combined AUC reaching 0.93 (95% CI: 0.88-0.98). The level of ammonia in the DECOM2 group was significantly higher than that of the COM group (P < 0.01). Patients with post-hepatitis B cirrhosis have intestinal flora disorder, which leads to abnormal amino acid metabolism and further leads to neurotransmitter disorder in patients with cirrhosis and accelerates the disease progression. Probiotics can reduce the serum ammonia level in patients with cirrhosis and may prevent the occurrence of hepatic encephalopathy.
This study evaluated the reliability of different laboratory methods for detecting resistance to glycopeptide antibiotics-vancomycin and teicoplanin-in clinical Staphylococcus aureus and coagulase-negative staphylococci...This study evaluated the reliability of different laboratory methods for detecting resistance to glycopeptide antibiotics-vancomycin and teicoplanin-in clinical Staphylococcus aureus and coagulase-negative staphylococci (CoNS) isolates. While automated systems are widely used in clinical microbiology laboratories due to their efficiency and ease of use, they may yield inaccurate results when assessing glycopeptide susceptibility. A total of 87 previously collected clinical isolates (22 S. aureus and 65 CoNS), initially identified as resistant to at least one of the vancomycin or teicoplanin by an automated system, were retrospectively analyzed. All isolates were stored at -80 °C and retested using three methods: the same automated system (following the manufacturer's protocol), the gradient diffusion method, and the reference broth microdilution (BMD) method. Interpretations were made according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Upon re-evaluation, all isolates were found to be susceptible to vancomycin and teicoplanin using the BMD method. The automated system yielded 100% concordance with BMD for vancomycin and 77% for teicoplanin, while the gradient method produced similar findings. Notably, five S. aureus isolates (23%) remained resistant to teicoplanin according to both the automated system and the gradient method but were susceptible by BMD. These results emphasize that automated systems, although practical, may lead to overestimation of glycopeptide resistance. Therefore, when resistance is suspected, especially to teicoplanin, confirmatory testing with the BMD reference method is essential to ensure accurate interpretation and avoid misclassification.