搜索结果：Diagnostic microbiology and infectious disease

Tuberculosis (TB) remains a major global health challenge, with an estimated 10.8 million new cases and 1.25 million deaths in 2023. Despite advances in molecular detection of Mycobacterium TB (MTB), significant diagnostic gaps remain: in 2023, only 48% of newly diagnosed TB cases received rapid diagnostic testing, far below the 100% target. These challenges are intensified in high-burden settings, where sputum collection and distinguishing TB from other illnesses are difficult. The Xpert MTB Host Response (Xpert-HR) assay measures host immune gene expression from blood, shows promise but variable accuracy across studies. Hence, this study will perform an Individual Patient Data Meta-Analysis (IPDMA) to evaluate the diagnostic accuracy, subgroup performance, predictive values and clinical benefit of Xpert-HR compared with conventional sputum-based testing. This systematic review and IPDMA will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Diagnostic Test Accuracy guidelines. Prospective studies including adolescents (>12 years) or adults with presumed TB tested using the Xpert MTB Host-Response assay will be identified through PubMed, Embase and Web of Science. Study quality will be assessed using an adapted diagnostic accuracy tool. Diagnostic accuracy will be pooled using random-effects models, with subgroup analyses where applicable. Decision curve analysis will evaluate clinical utility. Predictive values will be estimated across TB prevalences of 1-10%. Both one-stage and two-stage IPDMA approaches will be explored, and the proportion of unevaluable samples will be reported. The review will be based on deidentified individual patient data to be obtained upon request from the corresponding authors of studies fulfilling all the data sharing agreement. Ethical approval has been obtained from the Ethical Committee of the Medical Faculty of Heidelberg University (Approval No. S-043/2026). The results will be disseminated through publication in a peer-reviewed journal, and through presentations at academic conferences. CRD420251071857.

Pediatric patients are particularly susceptible to respiratory tract infections (RTIs) due to ongoing maturation of pulmonary and immune function, highlighting the need for rapid and accurate pathogen identification. Although targeted next-generation sequencing (tNGS) is increasingly applied in infectious disease diagnostics, its real-world clinical utility in pediatric RTIs remains underexplored. We conducted a retrospective study of 940 hospitalized children with RTIs in northern China between April and December 2023. All patients underwent tNGS alongside conventional microbiological tests (CMTs), including PCR, culture, and serology. Diagnostic performance metrics-including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)-were calculated. The clinical impact of tNGS was assessed by examining treatment adjustments, turnaround time (TAT), and patient outcomes. tNGS demonstrated superior diagnostic performance compared with CMTs: sensitivity 91.38% versus 29.68%, specificity 91.03% versus 90.17%, PPV 97.68% versus 77.78%, and NPV 73.39% versus 54.60%. tNGS identified a broader spectrum of pathogens, including RNA viruses and low-abundance organisms frequently missed by CMTs, and detected polymicrobial infections in 17.77% of cases versus 1.17% by CMTs. Based on tNGS, treatment was escalated in 35.32% and de-escalated in 29.04% of patients, with over 90% of adjustments made within 48 h, facilitated by a mean TAT of 28.5 h. Clinical improvement was observed in most adjusted cases. Pathogen distribution showed age- and season-specific patterns, underscoring the need for context-informed diagnostics and therapy. tNGS enhances pathogen detection accuracy in pediatric RTIs, enables timely and appropriate treatment modifications, and supports antimicrobial stewardship. Its high sensitivity, rapid TAT, and capacity to identify co-infections reinforce its clinical utility in guiding optimized management of pediatric respiratory infections.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is a highly effective biomedical intervention for the prevention of HIV acquisition. There is a strong interest among communities and policymakers for LAI-PrEP scale-up, accelerating the demand for clear guidance on testing approaches that balance accuracy with scalability. Unlike oral pre-exposure prophylaxis, LAI-PrEP may overcome adherence challenges, such as difficulty with frequent clinic visits. However, LAI-PrEP results in prolonged subtherapeutic drug levels after discontinuation, which can increase the risk of drug resistance among those who have an undetected HIV infection. This systematic review evaluates how different HIV testing strategies, including rapid diagnostic tests (RDTs), laboratory-based immunoassays and nucleic acid testing (NAT), affect clinical utility and programme delivery of LAI-PrEP. We searched databases and retrieved studies up to April 8, 2025, and supplemented findings with data collected through a World Health Organization (WHO) survey among ongoing and completed LAI-PrEP implementation studies. We included publications reporting original or primary data on clinical, diagnostic and resource-use outcomes of HIV testing for LAI-PrEP. Meta-analyses were conducted using random-effects models. Chi-square tests were used to examine differences between related outcomes. Certainty of evidence was determined using the GRADE methodology (Prospero: CRD42024605562). Risk Of Bias In Non-randomised Studies of Interventions, Version 2 (ROBINS-I V2) assessment tool was used to assess bias for non-randomised comparative studies. Of 7,698 records identified, 38 reports representing 22 studies (cabotegravir: 20, lenacapavir: 2) across 15 countries were included. The overall certainty of evidence was low. Most were observational cohorts (n = 13) or non-randomised comparator studies (n = 7). Among 8,171 LAI-PrEP users in four randomised controlled trials, HIV detection rates were similar across strategies (9/8171 (RDT) versus 14/8171 (NAT) (Odds ratio (OR) 0.66 (95% confidence interval: 0.29-1.50; P = 0.87)), with no difference in adverse events. Compared with laboratory-based tests, RDTs enabled faster turnaround (same-day versus up to 7 days), more rapid treatment initiation (1 day versus 6-9 days), and lower test costs (US$4 versus US$22). All tests had similar negative predictive value (~100%) at LAI-PrEP initiation and comparable positive predictive value (~55%) at continuation. There was little difference in delayed HIV detection (11/8171 (RDT) versus 0/8171 (NAT)). In the HPTN 083 trial, NAT use was occasionally associated with false-positive results, leading to unnecessary PrEP holds or discontinuation (7/2483). NAT might have detected HIV before resistance emerged, though no prospective or modelling evidence showed clinical benefit at a population level. There was limited evidence of HIV self-testing for LAI-PrEP delivery. We noted that our assessment of performance accuracy in different testing strategies may introduce selection bias. RDT-based testing strategies have comparable accuracy to laboratory-based strategies and are more accessible and scalable, which can ensure that testing does not become a barrier to accessing or continuing LAI-PrEP. As countries expand access to LAI-PrEP amid increasingly constrained resources, adoption of new WHO guidance supporting the use of RDTs can enable simpler, more affordable, and user-centred HIV testing approaches.

Mucormycosis ranks third among invasive mycoses after Candidiasis and Aspergillosis and is associated with high mortality. Its incidence has increased with the rising number of immunosuppressed patients. In developing countries, the most common predisposing factor is uncontrolled diabetes mellitus (DM), whereas in developed countries it is immunosuppressive conditions. To examine local epidemiological data, predisposing factors, diagnostic and therapeutic options and survival in our center eighty-six adult mucormycosis patients between 2000 and 2020 were retrospectively analyzed. Thirty-nine (45.35%) were male, 47 (54.65%) were female, and the median age was 52 years (IQR, 42.5-62). The most frequent clinical presentation was sinus involvement, observed in 77 cases (89.53%). Of these, 38 (44.18%) were sinonasal, 5 (5.81%) sinoorbital, 9 (10.47%) rhinocerebral, and 25 (29.07%) rhino-orbito-cerebral mucormycosis. The remaining 9 cases (10.47%) had pulmonary mucormycosis. Predisposing factors included hematologic diseases in 51 patients (59.30%), DM in 33 (38.37%), solid organ transplantation (SOT) in 7 (8.14%), and solid organ malignancy in 7 (8.14%). The most common symptoms were fever (70.93%), swelling around the eyes and face (51.16%), pain (40.7%), erythema (34.88%), nasal discharge (30.23%), and headache (25.58%). Most frequent physical examination findings were necrotic lesions in the oral cavity and sinuses (87.21%), ophthalmoplegia (29.07%), ptosis (26.74%), vision loss (25.58%), and proptosis (22.09%). In all cases, amphotericin B formulations were preferred as initial therapy. Patients who received combination therapy (n = 14), 13 used posaconazole (POS) + liposomal amphotericin B (L-AmB) and one patient used itraconazole (ITC) + L-AmB. POS was administered to 14 patients receiving sequential oral therapy. The median duration of amphotericin B therapy was 46.5 days (IQR, 14.7-84.5), and the median total duration of antifungal therapy was 46.5 days (IQR, 14.7-90.3). The most common adverse effect of amphotericin B formulations was hypokalemia [L-AmB 68.75%, amphotericin B deoxycholate (AmB-D) 54.84%, amphotericin B lipid complex (ABLC) 50%]. At least one surgical intervention was performed in 74.42% of cases. The 12-week mortality rate was 48.84%, overall mortality rate was 61.63%. In analysis advanced age [12-week: OR: 1.04 (95% CI: 1.01-1.07), p = 0.011; overall: OR: 1.04 (95% CI: 1.01-1.07), p = 0.026 respectively], coexistence of both hematologic disease and DM [12-week OR: 5.73 (95% CI: 1.16-28.33), p = 0.032] associated with mortality. No significant difference was observed in 12-week mortality between surgical and non-surgical patients (p = 0.107). In contrast, overall mortality was significantly higher in the non-surgical group (81.8% vs. 54.7%, p = 0.024). In univariable logistic regression analysis, surgical intervention was associated with a 73.2% reduction in the odds of overall mortality (OR: 0.268, 95% CI: 0.082-0.882, p = 0.030). In the multivariable logistic regression analysis, age was the only variable significantly associated with 12-week and overall mortality (respectively, p = 0.004 and p = 0.026). Each one-year increase in age was associated with an OR of 1.05 (95% CI: 1.02-1.09) for 12-week mortality and 1.04 (95% CI: 1.01-1.07) for overall mortality. In conclusion; our study showed that despite advanced diagnostic methods and antifungals, mortality remained high, sinus involvement was the most frequent involvement, surgical debridement increased survival, but increasing age was associated with poor prognosis.

Mosquito-borne arboviruses pose a growing public health concern in Canada, particularly in the context of climate change and increased global travel. This study aimed to quantify the burden of endemic and non-endemic mosquito-transmitted arboviral diseases in Canada by examining hospitalization trends from 2002 to 2023. Using administrative hospital data from the Canadian Institute for Health Information (CIHI) and national West Nile virus (WNV) surveillance data, we analyzed patient demographics, temporal and spatial patterns, and disease classification. Hospitalizations were classified as endemic (e.g., WNV) or non-endemic (e.g., dengue, chikungunya, Zika, yellow fever) based on historical presence and vector establishment in Canada. A total of 2,470 unique hospitalizations were identified, with 56.4% attributed to endemic diseases and 39.7% to non-endemic diseases. WNV accounted for over 99% of endemic-related hospitalizations, with peaks in 2003, 2007, and 2012 aligning with national surveillance data. Hospitalizations were highest among males aged 75-79 years, particularly in the southern regions of Saskatchewan, Manitoba, and Ontario. Non-endemic disease hospitalizations, primarily due to dengue and chikungunya, increased after 2010 and were more evenly distributed throughout the year, reflecting travel patterns. Younger adults (20-49 years) were most affected. The study highlights limitations in diagnostic coding and surveillance coverage, particularly the exclusion of Quebec data and underreporting of emerging arboviruses. These findings underscore the utility of hospital administrative data in complementing traditional surveillance systems and identifying populations at risk for severe outcomes. As climate change and travel continue to influence arboviral disease dynamics, integrated data sources are essential for guiding public health planning and response.

Clostridioides difficile (CD) is the leading cause of antimicrobial-associated diarrhea (AAD) and causes a spectrum of disease with high recurrence, morbidity, and mortality. CD pathogenicity is primarily driven by toxins A and B, and, in some strains, by the binary toxin. This study evaluated antimicrobial susceptibility profiles and resistance and virulence genes profiles of isolates from patients with antimicrobial‑associated diarrhea in hospitals across southern Brazil. Stool samples from 371 patients were analyzed by toxigenic cultures. Antimicrobial susceptibility to vancomycin, metronidazole, and ciprofloxacin was determined by gradient strip testing. Toxin production was confirmed by enzyme immunoassay and Polymerase Chain Reaction targeting toxin genes. Genomic DNA from selected isolates was sequenced on an Illumina MiSeq and analyzed using bioinformatics tools. Seventy-two CD isolates were recovered, of which 54 were toxigenic. All isolates were susceptible to metronidazole and vancomycin; all were resistant to ciprofloxacin. Multilocus sequence typing (MLST) identified 13 different sequence types (STs), with ST42 (23.5%), ST5 (20.6%), and ST2 (17.6%) most prevalent. Toxin genes and virulence factors related to adhesion and sporulation were detected. Although genes associated with vancomycin resistance were identified genotypically, no phenotypic resistance was observed. Clinical CD isolates from southern Brazil display substantial genomic diversity, with variable STs and distinct resistance and virulence gene profiles. An understanding of CD genomic diversity and toxin profiles is essential for guiding the development of new diagnostic tools, therapeutic strategies, and public-health interventions.

Despite increasing clinical reports of its emergence and multidrug resistance, particularly in cystic fibrosis (CF) patients, comprehensive genomic insights and effective therapeutic strategies targeting P. sputorum remain scarce. This study aimed to elucidate the evolutionary relationships and genomic characteristics of P. sputorum and to identify potential therapeutic targets and repurposable drugs via integrated computational approaches. Phylogenetic relationships were reconstructed via 16S rRNA gene sequences retrieved from the NCBI GenBank database, followed by comprehensive whole-genome-based comparative genomic analyses. Functional pathway and resistance gene profiling were conducted to characterize virulence and antimicrobial resistance traits. A subtractive genomics pipeline integrating Orthofinder, the Database of Essential Genes, BLASTp against the human proteome, and KEGG pathway analysis was applied to identify essential, non-host homologous drug targets. Structural modeling, binding pocket characterization, molecular docking, and protein-ligand interaction analyses were employed to screen and evaluate repurposable drug candidates. The results demonstrated that P. sputorum is closely related to Burkholderia species and shares a conserved genomic backbone while exhibiting notable genomic diversification. Functional profiling revealed shared antimicrobial resistance mechanisms, including efflux pumps and β-lactamases. Subtractive genomics prioritized three conserved cytoplasmic targets, LpxC, MurA, and DnaE. Structure-based molecular docking identified ten FDA-approved drugs with strong and stable binding affinities toward these targets. Notably, lumacaftor is a drug currently used in cystic fibrosis therapy. This study provides a comprehensive genome-guided framework for understanding P. sputorum and identifying therapeutic opportunities. The identified drug targets and repurposed candidates offer promising avenues for combating multidrug-resistant P. sputorum infections, particularly in CF and immunocompromised patients.

Improved diagnostic tools for tuberculosis that are suitable for use in peripheral health centers are essential for reducing the persistent gap between estimated and notified cases. The diagnostic accuracy and usability of the MiniDock MTB test for detecting pulmonary tuberculosis is unknown. We conducted a prospective, cross-sectional study at outpatient centers in India, Nigeria, the Philippines, South Africa, Uganda, Vietnam, and Zambia. Patients 12 years of age or older with presumptive pulmonary tuberculosis were enrolled between September 12, 2024, and March 31, 2025. Assessment with MiniDock MTB was performed with sputum swabs and tongue swabs. Diagnostic accuracy was evaluated against a sputum-culture-based reference and as compared with sputum-smear microscopy and Xpert MTB/RIF Ultra assay. Usability was assessed with a system usability scale and direct observation. A total of 1380 participants were enrolled; 255 (18.5%) had human immunodeficiency virus infection and 226 (16.4%) had culture-confirmed tuberculosis. MiniDock MTB sensitivity was 85.7% (95% confidence interval [CI], 80.4 to 90.0) with sputum and 79.6% (95% CI, 73.8 to 84.7) with tongue swabs; specificity was greater than 97.5% for both. Results of sputum tests with MiniDock MTB closely matched those with Xpert MTB/RIF Ultra for sensitivity (difference, -2.8 percentage points; 95% CI, -6.0 to 0.5). MiniDock MTB had greater sensitivity than smear microscopy for tests of sputum (difference, 24.3 percentage points; 95% CI, 17.9 to 30.7) and tongue swabs (difference, 18.3 percentage points; 95% CI, 12.0 to 24.7). The test showed diagnostic accuracy that was consistent with World Health Organization (WHO) accuracy targets for near-point-of-care tuberculosis diagnostics (≥85% sensitivity for sputum and ≥75% for nonsputum and ≥98% specificity for both). The median score on the system usability scale (range, 0 to 100, with higher scores indicating better perceived usability) was 75 (interquartile range, 65 to 80), which indicated good usability. No adverse events related to the index test were reported. MiniDock MTB met WHO targets for diagnostic accuracy and usability for tuberculosis detection across diverse clinical settings. (Funded by the National Institutes of Health and others; Rapid Research in Diagnostics Development for TB Network and Assessing Diagnostics at Point-of-Care for Tuberculosis ClinicalTrials.gov numbers, NCT04923958 and NCT05941052.).

Cryptococcus neoformans is an encapsulated opportunistic yeast widely distributed in the environment and classified as critical-priority fungal pathogen by the World Health Organisation due to its high mortality and limited access to timely diagnosis and effective treatment. Infection is typically acquired via inhalation, with the primary pulmonary focus often remaining asymptomatic. Particularly in individuals with impaired cell-mediated immunity, it may disseminate hematogenously to central nervous system (CNS), skin and other organs. Cutaneous cryptococcosis is a rare clinical manifestation and in most cases, represents secondary involvement of disseminated disease. Its clinical presentation is highly variable and may mimic cellulitis, abscesses, ulcers or necrotizing soft-tissue infections, posing significant diagnostic challenges. Ruxolitinib is a Janus-kinase inhibitor used to treat myelofibrosis and polycythemia vera. By suppressing interferon-γ and interleukin-12-mediated immune responses, it impairs macrophage activation, reduces T-helper-1 cell responses, suppresses natural-killer cell function, and regulates hematopoietic activity. However, these immunomodulatory effects predispose patients to invasive opportunistic infections, particularly fungal infections. In the literature, cryptococcal infections associated with ruxolitinib have been reported in a limited number of case reports, most commonly involving the pulmonary and/or central nervous system. Cutaneous involvement is exceedingly rare, and to date, no cases from Türkiye have been reported. In this case report, a 67-year-old woman with myelofibrosis who had been receiving ruxolitinib therapy for three-years and developed cutaneous cryptococcosis infection mimicking necrotizing fasciitis, accompanied by asymptomatic pulmonary involvement was presented. Despite broad-spectrum antibacterials, a small papule on the medial thigh rapidly progressed over 25 days, with severe disproportionate pain raising suspicion of necrotizing fasciitis. On admission, physical examination revealed an 8×8 cm ulcerative tissue defect on the left thigh, with surrounding erythema, ecchymosis, desquamation and hemopurulent discharge. Magnetic resonance imaging demonstrated findings suggestive of necrotising soft-tissue infection, prompting urgent surgical intervention. Intraoperatively, diffuse inflammation and patchy necrotic areas were observed and surgical debridement followed by vacuum-assisted wound closure was performed. Microbiological cultures of deep-tissue specimens yielded C.neoformans and the pathogen was confirmed by matrix-assisted laser desorption/ ionisation-time-of-flight-mass spectrometry (MALDI-TOF-MS). Antifungal susceptibility testing showed minimum inhibitory concentrations of 0.5 µg/mL for amphotericin B and 4 µg/mL for fluconazole. Histopathological examination demonstrated yeast cells within a background of suppurative inflammation and focal necrosis. Although the patient had no respiratory symptoms, chest computed tomography revealed a cavitary pulmonary nodule consistent with fungal infection. Bronchoalveolar lavage cultures showed no microbial growth. Evaluation for central nervous system involvement resulted negative for India-ink staining and cerebrospinal fluid multiplex polymerase chain reaction (PCR) test. These findings were considered consistent with systemic cryptococcosis involving the skin and lungs. Antibacterials were discontinued and intravenous liposomal amphotericin-B plus fluconazole was initiated. After central netvous system involvement was excluded, sequential therapy with fluconazole was planned. Ruxolitinib dose was adjusted by haematology. Significant clinical improvement was observed in the early phase of treatment and pain however, the patient died due to acute pulmonary embolism. This case highlights a rare cutaneous presentation of ruxolitinib-associated cryptococcosis and emphasizes the importance of clinical awareness for opportunistic fungal infections in immunosuppressed patients.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp., predominantly affecting individuals in Latin America. While extensive epidemiological and molecular studies have been conducted in Brazil, Colombia, and Venezuela, where PCM is a recognized public health concern, Paraguay remains largely overlooked. The scarcity of epidemiological and molecular data hinders accurate disease surveillance, early diagnosis, and effective treatment strategies. This study provides the first comprehensive epidemiological and molecular characterization of PCM in Paraguay. We report the patient demographics, clinical presentations of PCM patients, and estimates of genetic diversity among isolates. A retrospective analysis of 66 confirmed PCM cases from the Mycology Section at the Center for Dermatological Specialties in San Lorenzo (2014-2024) was conducted. Diagnoses were confirmed through direct microscopy or fungal culture, and clinical isolates were genotyped using whole-genome sequencing. Findings indicate that PCM is more common among male patients, as 69% were agricultural workers representing high occupational risk. The chronic form was the most prevalent, commonly affecting the lungs and mucosa in males 40-60 years of age. Less frequent manifestations included the kidneys, central nervous system, gastrointestinal tract, and adrenal glands. Most PCM cases were treated with itraconazole; severe cases received amphotericin B. Molecular analysis demonstrated that Paraguayan isolates belong to both S1b and S1a clades; however, they are distinct from Argentina and Mato Grosso do Sul, Brazil. These findings highlight the complexity of P. brasiliensis population structure in South America, emphasizing the need for enhanced diagnostic and treatment strategies in endemic regions. This study offers the first comprehensive epidemiological, clinical, and molecular overview of paracoccidioidomycosis in Paraguay, revealing the country’s endemic profile and underscoring the need for improved surveillance and disease management strategies.

Diagnostic testing of foot-and-mouth disease virus (FMDV) currently utilizes reverse transcription quantitative PCR (RT-qPCR) to detect the presence of viral RNA and double antibody sandwich ELISAs (DAS-ELISAs) to determine viral serotype. Serotype identification is critical to support informed vaccine selection to combat outbreaks. While DAS-ELISAs are capable of serotype identification, the test suffers from low sensitivity and requires a viral isolate for successful detection. In this study, we developed FMDV-ONTAPS: an Oxford Nanopore Technologies Amplicon P1 Sequencing protocol involving reverse transcription-PCR to amplify P1 of the FMDV genome, and Nanopore sequencing of the amplicons to provide genetic data for serotype and subtype/topotype identification. FMDV isolates representing all seven serotypes were successfully sequenced with this method. Additionally, the protocol successfully provided serotype identification from a variety of specimen matrices obtained from experimentally infected animals that included milk, serum, oral and nasal swabs, tissue suspensions, vesicular fluid, and oral fluid. The limit of detection for FMDV cell culture isolates was comparable for both sequencing and RT-qPCR detection. RT-qPCR Cq values for clinical samples evaluated ranged from 8 to 28.21. Sequencing was successful for all samples except for a single tissue suspension sample (Cq of 28.21). Identification of FMDV serotype in clinical samples is critical for effective outbreak response, and Nanopore sequencing offers a timelier and more sensitive alternative to DAS-ELISAs.

In individuals with compromised immune systems, strongyloidiasis disease can lead to disseminated infections that can be fatal if diagnosis and treatment are delayed. The human gut is composed of numerous bacteria that play essential roles in the development of acquired immunity, and protection against pathogenic factors. This case-control study was conducted on individuals who were referred to the Diagnostic Laboratory of Strongyloidiasis in the School of Public Health, Tehran University of Medical Sciences. After DNA extraction from fecal samples, the 16SrRNA gene was examined using Real-time PCR. The levels of Lactobacillus acidophilus and Bifidobacterium bifidum were calculated in both groups (one group consisted of individuals suspected of strongyloidiasis, compared with the other group with no underlying disease). Finally, the collected data were analyzed. Out of 28 participants in this study, 16 (57%) were men and 12 (43%) were women, with ages ranging from 43 to 76 years. A statistically significant relationship was observed between underlying diseases, vegetable washing practices, and clinical symptoms of strongyloidiasis. DNA extraction from the fecal samples was performed using a DNA Extraction kit. The average level of L. acidophilus and B. bifidum were (4.07250±3.132533) 1012× and, (6.12857±3.519169) 1012× in the case group, respectively, which were lower compared to the control group. However, no significant association was found between the bacterial levels in the case and control groups and the incidence of strongyloidiasis (p>0.05), the control group had (7.04733± 6.542372) 1012× and (8.36643± 4.754185) 1012×, respectively. The odds ratio for L. acidophilus and B. bifidum were 1.13 and 1.14, respectively. It was observed that for each increase of 1012 in the microliter of L.acidophilus and B. bifidum in the individual's intestines in areas endemic for strongyloidiasis, the chances of contracting this disease decreased by 13% and 14%, respectively. Future studies with a larger sample size, considering age, gender and other physiological factors related to strongyloidiasis, are suggested.

This study aimed to evaluate the diagnostic performance of serum galactomannan for invasive fungal infections in children with hematologic malignancies and to assess the impact of mold-active antifungal prophylaxis on test sensitivity and specificity. We retrospectively evaluated 280 pediatric patients with acute leukemia or mixed-phenotypic leukemia treated between February 2019 and December 2023 at a tertiary referral center. Demographic characteristics, antifungal prophylaxis, serum and BAL GM levels, clinical and radiologic findings, and outcomes were recorded. IFIs were classified according to the 2020 EORTC/MSGERC criteria. Diagnostic performance metrics (sensitivity, specificity, PPV, NPV, LR&#x207a;, LR&#x207b;) were calculated, and multivariate logistic regression was used to identify independent predictors of IFI. Among 280 pediatric patients with hematologic malignancies, 89 (31.8%) met IFI criteria, including 73 possible, 10 probable, and 6 proven cases. In the primary analysis restricted to proven/probable IFI, 16 patients (5.7%) were classified as having IFI and 264 (94.3%) as not having IFI. Baseline demographic and clinical characteristics were comparable between groups. Serum GM positivity was significantly associated with proven/probable IFI (62.5% vs. 2.3%, p < 0.001) and remained the only independent predictor in multivariable analysis (OR 73.040, 95% CI 11.979-445.344; p < 0.001). Serum GM showed moderate sensitivity (66.7%) and high specificity (97.3%), with PPV and NPV of 62.5% and 97.7%, respectively. GM positivity remained significant irrespective of antifungal prophylaxis, while mold-active prophylaxis did not significantly affect GM positivity or IFI rates. Serum galactomannan was a highly specific but moderately sensitive marker for proven/probable IFI in pediatric patients with hematologic malignancies. While a positive result supported the diagnosis, a negative result was insufficient to exclude IFI. GM should therefore be interpreted together with clinical, radiologic, and other mycological findings rather than used alone.

Dalbavancin is an alternative to prolonged intravenous therapy for complicated Staphylococcus aureus bacteremia, yet its pharmacokinetics (PK) in patients with this condition are uncertain. To characterize dalbavancin PK and evaluate associations of total and unbound exposures of dalbavancin with clinical success in patients with complicated S aureus bacteremia. This study was an exploratory prespecified secondary analysis of PK and exposure response within Dalbavancin as an Option for Treatment of S aureus Bacteremia (DOTS), a multicenter, randomized, open-label, assessor-blinded clinical trial conducted from April 2021 to December 2023. Data analysis was conducted from January 2024 to December 2025. Adults with complicated S aureus bacteremia who achieved bloodstream clearance were randomized to dalbavancin or standard therapy; PK analyses included dalbavancin recipients with at least 1 postdose concentration measurement. Dalbavancin 1500 mg intravenously on days 1 and 8 (1125 mg for patients with severe kidney impairment not receiving dialysis). Individual exposure metrics, including day 22 concentration and area under the concentration-time curve (AUC) from days 0 to 22, were derived using nonlinear mixed-effects population PK modeling. Exposure metrics were then assessed for association with clinical success at day 70 (exposure-response analysis). A total of 97 patients (mean [SD] age, 54.5 [15.8] years; 69 male [71.1%]) contributing 640 PK samples were included. Clearance was estimated at 0.066 L/h (95% CI, 0.062 to 0.069 L/h), and the central volume of distribution was estimated at 5.67 L (95% CI, 5.37 to 5.99 L). Interindividual variability was 22.6% (95% CI, 18.9% to 25.6%) for clearance and 19.7% (95% CI, 13.8% to 25.0%) for the central volume of distribution. Clearance increased with creatinine clearance according to a power function (exponent, 0.21; 95% CI, 0.16 to 0.30). Distribution volumes increased with body weight following power relationships, including the central volume (exponent, 0.57; 95% CI, 0.37 to 0.86), second peripheral volume (0.82; 95% CI, 0.37 to 1.46), and third peripheral volume (0.56; 95% CI, 0.30 to 0.82). Albumin was inversely associated with the second peripheral volume (exponent, -0.81; 95% CI, -1.79 to -0.32) and unbound-fraction scaling factor (exponent, -0.78; 95% CI, -0.98 to -0.54), and age was positively associated with the third peripheral volume via a power relationship (exponent, 0.63; 95% CI, 0.44 to 0.83). Among 93 evaluable patients, 72 individuals (77.4%) achieved clinical success at day 70. Patients with a day 22 concentration greater than 32 &#x3bc;g/mL (30 patients [32.3% of evaluable patients receiving dalbavancin]) had higher clinical success compared with 63 patients with a day 22 concentration of 32 &#x3bc;g/mL or less (29 patients [96.7%] vs 43 patients [68.3%]; adjusted difference, 25.3 percentage points; 95% CI, 3.5-47.0 percentage points) and experienced similar rates of serious adverse events (8 patients [26.7%] vs 27 patients [42.9%]; unadjusted difference, -16.2 percentage points, 95% CI -36.2 to 3.8 percentage points). In this study, dalbavancin pharmacokinetics were predictably influenced by kidney function, body weight, albumin levels, and age, and higher total day 22 concentrations were associated with greater clinical success without increased serious adverse events. These findings are exploratory and support further evaluation of exposure-guided dosing strategies. Clinical Trials.gov Identifier: NCT04775953.

Aeromonas species are Gram-negative bacilli capable of causing bloodstream infections in both immunocompromised and otherwise healthy individuals. However, data on their epidemiology and antimicrobial resistance remain limited in Europe. We conducted a multicentre, retrospective, observational study that included all Aeromonas species isolates recovered from blood cultures in 56 European hospitals between January 1st 2020 and December 31st 2024. Epidemiological features and antimicrobial susceptibility profiles were analyzed. A total of 590 Aeromonas isolates were included. Most were recovered from polymicrobial blood cultures (73.1%), and catheter-related bloodstream infections were frequent (21.7%). The most commonly reported species were A. caviae (30.1%), isolates without conclusive species identification (Aeromonas spp., 24.8%), A. hydrophila (20.7%), and A. veronii (19.1%). At the genus level, susceptibility to aztreonam, ceftazidime, and cefepime exceeded 90%. Resistance to fluoroquinolones (&#x223c;10%) and sulfamethoxazole/trimethoprim (up to 11%) was observed. Species-level analyses showed higher resistance rates to fluoroquinolones and sulfamethoxazole/trimethoprim among A. caviae and A. hydrophila, and increased resistance to ceftazidime among Aeromonas spp. Aeromonas species in Europe showed high susceptibility to ceftazidime and cefepime, alongside with emerging resistance to fluoroquinolones and sulfamethoxazole/trimethoprim. Species-specific findings should be interpreted cautiously due to limitations in routine identification methods, underscoring the need for sustained surveillance and harmonised diagnostic standards across Europe.

Gepotidacin (GSK2140944) is a novel triazaacenaphthylene antibiotic that inhibits bacterial DNA gyrase and topoisomerase IV by a distinct binding site, a unique mechanism of action and has been approved for the treatment of urogenital gonorrhea and uncomplicated urinary tract infections. This study assessed the performance of the agar dilution method for gepotidacin, ciprofloxacin and ceftriaxone susceptibility testing against Neisseria gonorrhoeae using four different media and four incubation times (18, 20, 24, 48 hours). A total of 30 N. gonorrhoeae isolates including 14 WHO strains were included. The reference agar media was BD Difco GC medium base supplemented with 1% IsoVitaleX and the comparator agar mediums included Sensitest Agar with 5% horse blood (SAHB), Diagnostic Sensitivity Test Agar with 5% horse blood and 1% Vitox (DST), and Mueller Hinton II agar with 5% lysed sheep blood and 20 mg/mL &#x3b2;-NAD (CHOC). The data generated in this study showed that 1.) for gepotidacin, only Sensitest Agar produced results that were in &#x2265; 90% essential agreement with the reference method, 2.) for ciprofloxacin, &#x2265; 90% essential agreement with the reference method was observed for Diagnostic Test Agar at 48 hours, Mueller Hinton II agar at 24 hours and Sensitest Agar at 20 and 48 hours and 3.) for ceftriaxone, none of the media tested in this study produced results that were in &#x2265; 90% essential agreement with the reference method. These study data reinforce the importance of utilizing standardized methodologies for agar dilution susceptibility testing of N. gonorrhoeae.

Cystoisospora belli is an opportunistic apicomplexan parasite that infects the human gastrointestinal tract and causes cystoisosporiasis, particularly affecting individuals in tropical and subtropical regions and immunocompromised patients. Conventional parasitological diagnosis, although widely used due to its low cost, presents limitations such as low sensitivity and false-negative results. This study evaluated the potential of an aqueous two-phase system (ATPS) composed of polyethylene glycol (PEG) and phosphate for the separation and diagnosis of C. belli oocysts. Twenty assays were conducted based on a full factorial design (2&#x2074;), considering PEG molecular weight, PEG and phosphate concentrations, and pH. The system produced three distinct phases: a PEG-rich top phase, an interface containing lipids and fecal debris, and a phosphate-rich bottom phase. Micromorphological analysis demonstrated that C. belli oocysts preferentially partitioned into the PEG-rich top phase, while the interface retained fecal residues and the bottom phase remained free of oocysts. The method generated slides with high clarity and minimal contamination, enabling clear visualization of oocyst morphology without structural damage. The PEG molecular weight influenced separation performance, with PEG 4000 combined with phosphate at pH 6, both at 10% concentrations, showing the best results. The most efficient system provided clear oocyst recovery in the polymer-rich phase with minimal residual contamination and required only 2 minutes for phase separation. Compared with conventional parasitological techniques, the ATPS approach demonstrated advantages such as faster processing, reduced use of toxic reagents, and improved sample clarification.

Trichomonas vaginalis (T. vaginalis) is a motile, flagellated protozoan that exclusively infects humans. It is a significant etiological agent of vaginitis and has been associated with adverse reproductive outcomes such as preterm birth and infertility. Candida albicans (C. albicans) accounts for approximately 85-90&#x202f;% of fungal vaginitis cases. This study aimed to determine the prevalence of trichomonal and candidal vaginitis among married women attending health centers in Khorramabad, using both conventional laboratory techniques and molecular diagnostics. In this descriptive-analytical study, vaginal specimens were collected from 304 married women attending health centers in Khorramabad during 2024. Samples were analyzed using conventional laboratory methods including direct smear, Giemsa staining, culture on Sabouraud Dextrose Agar (SDA), germ tube test, Corn Meal agar culture, and incubation at 45&#x202f;&#xb0;C as well as molecular techniques (PCR and sequencing). Data were statistically analyzed using SPSS version 27. T. vaginalis was identified in 9 cases (3&#x202f;%) via PCR and in 2 cases (0.7&#x202f;%) via direct smear. The kappa coefficient for agreement between direct smear and PCR was 0.36 (p&#x202f;<&#x202f;0.001), indicating fair concordance. For C. albicans, PCR detected 20 positive cases (6.6&#x202f;%), while conventional methods yielded the following results: direct smear 56 cases (18.4&#x202f;%), SDA culture 65 cases (21.4&#x202f;%), germ tube test 63 cases (20&#x202f;%), Corn Meal agar culture 58 cases (19.1&#x202f;%), and incubation at 45&#x202f;&#xb0;C 12 cases (3.9&#x202f;%). PCR demonstrated superior sensitivity for detecting T. vaginalis, whereas SDA culture exhibited the highest sensitivity for C. albicans. The low prevalence of trichomoniasis (3&#x202f;%) contrasted with the relatively high prevalence of candidiasis (6.6-21.4&#x202f;%), underscoring the need for targeted educational and preventive health programs.

The nation of Timor-Leste has a significant burden of infectious disease but has historically had limited diagnostic capacity and limited availability of microbiology data on human health. Recent developments in the diagnosis and reporting of key pathogens including Staphylococcus aureus have allowed better understanding of the burden of key infectious diseases and their impact on the population of Timor-Leste. A prospective observational study was performed on clinical isolates of S. aureus received at Laborat&#xf3;rio da Sa&#xfa;de in Dili, Timor-Leste between January 2020 and July 2020. Clinical samples were obtained from patients living in 11 of the 13 municipalities in Timor-Leste. Standard microbiology culture, identification, and antimicrobial susceptibility testing were performed, and clinical and demographic data were collected on laboratory-confirmed S. aureus isolates. A total of 59 clinical isolates of S. aureus were identified. Most patients in our study were found to have community-acquired S. aureus (75%), whilst the remaining 25% were hospital-associated infections. Of S. aureus isolates, 25% were found to be methicillin-resistant. This is the first description of S. aureus infections in Timor-Leste. The high MRSA rates identified in this study can be used to better inform guidelines for the empirical treatment of S. aureus infection. Continuous investment in detecting clinically important pathogens and understanding their susceptibility profiles is critical for the development of treatment guidelines and antibiotic stewardship activities.