Abstract: Background/Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified as an urgent-threat pathogen because of its resistance to nearly all available antibiotics, resulting in high morbidity and mortality rates. However, data on the molecular epidemiology of CRAB isolates in southern Thailand are limited. This study aimed to investigate the genomic epidemiology of CRAB isolates within a hospital network in lower southern Thailand. Methods: Whole-genome sequencing data of CRAB clinical isolates (n = 224) were obtained from a previous study. Additional CRAB clinical isolates (n = 70) were included, and their genomic DNA was extracted and sequenced. A total of 294 genomes were analyzed using several bioinformatic tools. Results: A high proportion of isolates were obtained from sputum samples of patients with CRAB infection or colonization. Sequence type (ST) 2 was the most frequent ST and was classified in the quadrant with high resistance and virulence. The Sankey diagram showed that ST2 was the dominant and most versatile CRAB lineage circulating across major hospitals, commonly associated with pneumonia, and that diverse resistance genes and plasmid combinations were dominated by blaOXA-23. The core single-nucleotide polymorphism (SNP)-based phylogenetic tree revealed clades A1 (ST215), A2 (multiple STs), and B (ST2). Bloodstream, skin, and soft tissue infections were predominantly observed in clade B. Conclusions: Our analysis revealed widespread circulation of a high-risk ST2 CRAB lineage with enhanced resistance and virulence across hospital networks in the studied region, highlighting the importance of genomics-informed surveillance for controlling CRAB dissemination.

Abstract: Background/Objectives: The rising prevalence of extended-spectrum beta-lactamase (ESBL)–producing pathogens has emerged as a significant challenge in the treatment of pyelonephritis. This study aimed to determine the frequency of ESBL-producing agents in hospitalized patients with pyelonephritis, identify associated risk factors, and assess the appropriateness of empirical antimicrobial therapy. Methods: This prospective study included patients hospitalized with pyelonephritis in the Infectious Diseases Clinic of Ankara Training and Research Hospital between October 1, 2022, and February 29, 2024. Demographic features, comorbidities, urinary system pathologies, history of urinary tract interventions, recent hospitalization, antibiotic use within the previous three months, and prior urinary tract infections were compared between patients infected with ESBL-producing and non-ESBL-producing organisms. Antimicrobial susceptibility pro-files and the appropriateness of empirical treatments were evaluated. Statistical analyses were performed using SPSS version 25.0, with p< 0.05 considered statistically significant. Results: Escherichia coli (n=142) and Klebsiella spp. (n=43) were isolated in 180 of 204 patients. ESBL positivity was detected in 95 patients (52.7%). Male sex (p=0.007), history of urinary intervention (p=0.019), hospitalization within the previous month (p< 0.001), and antibiotic use in the last three months (p=0.002) were identified as significant risk factors for ESBL positivity. ESBL production was not associated with prolonged hospitalization; however, bacteremia significantly increased length of stay (p< 0.001). Antimicrobial susceptibility rates were markedly lower in the ESBL-positive group. The appropriateness of empirical therapy was also significantly reduced, with piperacillin–tazobactam being the most frequently inappropriate agent due to high resistance rates and unnecessary broad-spectrum use. Conclusions: ESBL-producing pathogens were highly prevalent among hospitalized patients with pyelonephritis. The low appropriateness of empirical therapy in ESBL-positive cases underscores the need for careful evaluation of ESBL risk factors prior to treatment initiation, as ESBL rates may approach 50%.

Abstract: Background: Use of ART as the only effective way to control HIV infection results in HIV drug resistance. NGS became the common method for identifying drug-resistant variants and reducing analysis costs. The aim of the study was to develop the NGS based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Methods: Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using Illumina NextSeq NGS. HIV-1 drug resistance analysis was conducted using Stanford University HIVdb database. CXCR4 cell tropism was predicted using empirical rule classifier. Results: The protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. In treatment-experienced patients, high levels of resistance were observed to NNRTIs and NRTIs, and in treatment-naive— to NNRTIs. Low levels of resistance were observed to protease and integrase inhibitors. CXCR4 cell tropism was extremely rare. Conclusion: NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS based protocols allows performing ART efficiency and tropism monitoring at scale.

Abstract: Measles resurgence threatens elimination achievements in the Americas. We conducted a nationwide analysis of Mexico's 2025 measles outbreak, integrating individual-level surveillance data from the Special Surveillance System for Febrile Exanthematous Dis-eases with municipal-level social determinants from eight national databases, comple-mented by molecular surveillance data. We analyzed 6151 confirmed cases (epidemio-logical weeks 8–52, 2025) using spatial autocorrelation (Moran’s I, LISA), effective re-production number estimation, negative binomial regression, and logistic regression for risk factors. Cases concentrated in Chihuahua (73%), with 45 LISA hot-spot municipalities containing 71.68% of cases. Molecular surveillance confirmed two independent intro-ductions: D8/MVs/Ontario.CAN/47.24 (98.1%) linked to the Canadian outbreak, and B3 (1.9%) in Oaxaca. Transmission followed a three-stage pattern: introduction through seasonal agricultural worker networks, amplification in undervaccinated communities, and diffusion to marginalized indigenous populations. Vaccine effectiveness was 98.2%, with 83.4% of cases in pockets of susceptibles (municipalities with ≥80% unvaccinated). Risk factors for complications included age < 5 years (aOR 3.59), indigenous status (aOR 2.35), and unvaccinated status (aOR 2.03). Indigenous individuals comprised 30% of cases but 76% of deaths. This outbreak demonstrates that national vaccination thresholds are insufficient when marginalized populations remain systematically underserved.

Abstract: Background: Despite highly efficacious long-acting injectable pre-exposure prophylaxis (LAI-PrEP) achieving >99% efficacy in clinical trials, people who inject drugs (PWID) experience near-zero population-level HIV prevention effectiveness. We hypothesized that nested structural barriers, not pharmacological limitations, explain this disparity. Methods: We developed a Monte Carlo simulation modeling an 8-step LAI-PrEP cascade for PWID under current U.S. policy conditions (n=100,000 per scenario). We decomposed barriers into three layers: pathogen biology, HIV testing gaps, and architectural barriers (policy, stigma, infrastructure, research exclusion, algorithmic deprioritization). We compared PWID outcomes to men who have sex with men (MSM) receiving identical pharmacological interventions and modeled stochastic avoidance failure using network density dynamics. Results: Under current policy, PWID achieved P(R0=0) = 0.003% (95% CI: 0.000-0.006%) compared to 16.3% for MSM—a 5,433-fold disparity. Architectural barriers accounted for 93.2% of cascade failure (policy 38.4%, infrastructure 21.9%, stigma 20.5%, algorithmic bias 8.2%, research exclusion 4.1%), while HIV testing gaps contributed 6.8%. Even theoretical maximum intervention achieved only 19.7% effectiveness. Stochastic avoidance modeling predicted 73.8% probability of major outbreak within 5 years (median: 3.0 years). Conclusions: Current HIV prevention for PWID relies on probability rather than intervention. Structural barriers—particularly criminalization and MSM-centric infrastructure—create conditions where effective prevention is mathematically impossible regardless of drug efficacy. Policy reform addressing these architectural barriers is essential to prevent predictable outbreaks.

Abstract: Background/Objectives: Influenza B virus contributes substantially to annual morbidity and mortality, accounting for 20% to 30% of all influenza-associated deaths globally. Vaccination prevents severe disease, yet widely used inactivated influenza vaccines fail to reduce virus transmission. Also, influenza B viruses are less susceptible to commonly used antivirals than influenza A viruses. Therefore, new approaches are needed to decrease disease burden and limit virus spread. Neomycin, an aminoglycoside antibiotic, has recently been shown to mitigate SARS-CoV-2 transmission in a hamster model. In this study, we investigated the impact of neomycin on the transmission of influenza B virus. Methods: We used an influenza contact transmission model in guinea pigs and an aerosol transmission model in ferrets. Animals in experimental groups received intranasal neomycin sulphate (5 mg/guinea pig, 20 mg/ferret) or placebo one day before contact with infected animals and for four days thereafter. In the guinea pig experiment, an additional control group of animals was treated intranasally with interferon alpha. The virus spread from infected to contact animals was assessed by RT-PCR and viral culture of nasal washes during two weeks. Clinical signs and body weight were monitored daily. Results: In the guinea pig model, 75% of contact animals became infected with influenza B virus regardless of treatment. Neither neomycin nor interferon alpha prevented infection, although both delayed the onset of viral shedding in contact animals. In the ferret model, 33% of contact animals in the placebo group became infected, whereas no viral shedding was detected in the neomycin-treated group. Conclusions: Prophylactic intranasal neomycin treatment has the potential to protect exposed subjects from aerosol transmission of influenza B virus during flu outbreaks.

Abstract: The global rise of multidrug-resistant (MDR) bacterial infections in pediatric populations poses an alarming challenge to effective clinical management and antimicrobial stewardship. Two-component systems (TCSs), comprising sensor kinases and response regulators, play a pivotal role in bacterial adaptation, virulence, and resistance mechanisms, making them promising targets for diagnostic and therapeutic innovation. This study employs a machine learning-driven bioinformatics pipeline to identify and prioritize potential TCS biomarkers across MDR pediatric pathogens for integration into next-generation diagnostic biosensors. Genomic datasets from clinically relevant MDR bacteria were curated and analyzed to extract TCS-associated gene and protein signatures. Using Pfam domain features, multiple supervised learning models were trained, with XGBoost, Random Forest, and a Stacking Ensemble achieving high overall accuracies (0.9883-0.9885). While the dominant Non-TCS class was predicted with near-perfect accuracy, minority subclasses exhibited variable detection due to severe class imbalance, particularly for rare groups such as CpxA-like and EnvZ-like proteins (n=2 each). Moderate F1-scores were obtained for generic response regulators and OmpR-like proteins. Feature importance analysis identified a small set of highly discriminative domains, including PF01339, PF00702, PF07679, PF03997, and PF04886, associated with conserved regulatory and signaling motifs. These results demonstrate that Pfam domain signatures offer biologically meaningful features for TCS classification, while highlighting the need for expanded datasets or embedding-based features to improve minority-class prediction. Overall, this work provides a scalable, AI-driven foundation for TCS biomarker discovery, aiming to develop diagnostic biosensors for MDR pediatric pathogens.

Abstract: Background/Objectives: The optimal duration of postoperative antibiotic therapy for bone and orthopaedic implant infections remains undefined. The SALATIO Trials are prospective randomised trials investigating whether shorter antibiotic courses are non-inferior to standard durations across different infection strata. This report presents the second interim analysis. Methods: Two unblinded non-inferiority RCTs were conducted (intention-to-treat population). Primary outcomes were remission, clinical failure, and microbiologically identical recurrence. In SALATIO 1 (material arm), participants with infected implants, retained or replaced during initial surgery, were randomised to short-course (six weeks) or long-course (twelve weeks) targeted systemic antibiotic therapy following debridement. In SALATIO 2 (non-material arm), participants undergoing implant removal or two-stage exchange were randomised to either a short-course (three weeks) or a long-course (six weeks) of antibiotic therapy. Results: We analysed 175 infections with a minimum follow-up period of one-year from October 2022 until July 2025: 69 (39%) in the material arm (38 short-course [55%], 31 long-course [45%]) and 106 (61%) in the non-material arm (44 short-course [42%], 62 long-course [58%]). No significant differences in clinical failure (19% overall) or microbiological recurrence (7%) were observed between treatment arms in either stratum. Multivariate analysis identified diabetes mellitus and number of debridements—but not antibiotic duration—as independent risk factors for clinical failure. Patients receiving short-course therapy experienced significantly fewer adverse events (median 0 versus 1; p=0.01). Formal non-inferiority has not yet been achieved due to limited statistical power. Conclusion: This interim analysis suggests no disadvantage of shorter antibiotic regimens in surgically treated orthopaedic infections, whilst reducing adverse events. Patient comorbidities and surgical factors appear to be more relevant to treatment outcomes than antibiotic duration. The SALATIO Trials are ongoing and may support improved antibiotic stewardship without compromising outcomes. Trials Registration: NCT05499481.

Abstract: Background: Cryptococcal meningitis (CM) remains a leading cause of mortality among people with advanced HIV disease (AHD) in sub-Saharan Africa. Current guidelines recommend induction therapy with amphotericin B and flucytosine, typically administered in an inpatient setting due to concerns over severe clinical presentation and drug-related toxicities. This requirement poses a significant burden on resource-limited health systems. We evaluated the real-world outcomes of a fully outpatient model for CM therapy in Maputo, Mozambique. Methods: A longitudinal retrospective cohort study was conducted at the Centro de Referência de Alto-Maé (CRAM), a specialized AHD outpatient clinic. We included 83 PLWH with laboratory-confirmed CM treated between October 2020 and December 2024. The primary outcome was hospitalization-free survival (HFS) within the first 10 weeks of treatment. Secondary outcomes included the frequency and severity of adverse drug reactions (ADRs), analysed by tracking haemoglobin (Hgb), potassium (K+), and creatinine (Creat) levels on days 1, 3, and 7 of induction therapy, and retention in care (RIC) at 6, 12, and 24 months. Statistical analyses included Kaplan-Meier survival estimates and paired t-tests. Results: The median age was 37 years (IQR: 27-42), 63.9% were male, and the median CD4 count was 62 cells/µL (IQR: 27-105). Most patients (95.2%) were symptomatic at presentation, and 56.6% had concurrent tuberculosis. For the 52 patients who completed the full induction protocol at CRAM, the HFS rate at 10 weeks was 84.6% (44/52), with an overall survival of 90.4% (47/52). ADR analysis (n=52) showed a predictable pattern of mild, manageable toxicity: a significant decline in Hgb (11.2 ± 1.8 to 10.6 ± 2.0 g/dL, p&lt;0.001) and K+ (4.27 ± 0.66 to 3.86 ± 0.78 mmol/L, p=0.008), and a transient increase in Creat (0.83 ± 0.42 to 1.13 ± 0.64 mg/dL, p=0.001) from day 1 to day 3, with stabilization or trend toward recovery by day 7. No significant differences in ADRs were found between single-dose (47%) and multiple-dose (53%) L-AmB regimens. RIC for the entire cohort (n=83) was high, at 81.9% at 6 months, declining to 74.0% at 12 months and 70.4% at 24 months. Conclusion: An ambulatory model for CM therapy is feasible and effective in a resource-limited setting, demonstrating high hospitalization-free survival, manageable and reversible adverse drug reactions, and excellent medium-term retention in care. These findings provide compelling evidence to reconsider the standard of inpatient care and support the integration of outpatient CM management into AHD care packages to alleviate health system burdens and improve patient outcomesAn integrated care approach is essential to improving survival in resource-limited settings.

Abstract: Background/Objectives: Angiosarcoma of the thorax is a very rare and malignant disease. We studied the incidence and survival of thoracic angiosarcomas with special focus on primary and secondary angiosarcoma. Methods: We analyzed data from the population-based cancer registry North Rhine-Westphalia (NRW), Germany, of the years 2008–2023. We included primary and secondary angiosarcoma of the thorax (ICD-O-3: morphology 9120/3, topography C34, C38, C44.51, C49.3, C50) and report age-standardized (Old European Standard population) incidence rates and survival (Kaplan-Meier Curves). Results: We analyzed 421 cases of thoracic angiosarcoma. 90.0% were female (n = 379). The age-standardized incidence rates of angiosarcoma of the thorax were 0.25 per million and year for male patients (SE 0.0) and 1.5 per million and year for female patients (SE 0.1). All male patients had primary angiosarcoma (n = 42). The majority of thoracic angiosarcoma among females were second primary tumors (n=262, 69.1%). The 5-year overall survival (OS) was 38.5% (SE 2.6). OS for women was 41.4% (SE 2.8) and for men was 12.0% (SE 5.4). OS for female patients was 40.9% (SE 4.1) and 41.8% (SE 3.8) for primary and second primary angiosarcoma respectively. The worst OS had patients with angiosarcoma of the lung (men 20.0% (SE 12.7) and mediastinum, heart and pleura (men 4.7% (SE 4.5). The OS for women was 0%, all females died within 2.2 years after diagnosis of angiosarcoma with these topographies. Conclusions: Angiosarcoma of the thorax is a rare condition with poor prognosis. Irrespective of the classification into primary and second primary, women with angiosarcoma have a better prognosis than men. Topography seems to be the most determining prognostic factor in this disease.

Abstract: This study aims to characterizing both the pre-existing conditions that increase susceptibility and the long-term, post-acute sequelae ("long flu") following influenza. A longitudinal cohort study was conducted using data from the FinnGen cohort of 429,209 individuals including 9,204 influenza cases. A disease-wide association study (DWAS) framework was employed, using Cox proportional hazards models adjusted for age and sex to analyze 110 influenza-comorbid clinical endpoints. Pre-existing conditions, most notably cardiovascular diseases such as heart failure, coronary atherosclerosis, atrial fibrillation, and stroke, were significantly associated with an increased likelihood of a subsequent influenza diagnosis. Following influenza, individuals had a substantially elevated risk for a durable, multi-system "long flu" syndrome. The most robust and persistent risks were for new-onset cardiovascular and neurological diseases. Risks for thromboembolic events, heart failure, atrial fibrillation, stroke, and myocardial infarction remained significantly elevated for one to five years following influenza. Similarly, influenza was associated with a long-term increased incidence of neurodegenerative disorders, including migraine (with and without aura), Alzheimer's disease, and dementia. These findings underscore the urgent need to intensify preventive strategies, particularly through targeted vaccination of at-risk individuals, and to develop integrated care pathways to manage the multi-organ sequelae of long flu.

Abstract: Background. Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALS). We aimed to evaluate whether ALS could remain effective with extended dwell times of up to 10 days. Methods. In this randomized clinical trial, patients with noninfected, recently implanted ports were assigned to one of five ALS dwell-time groups, ranging from 1 to 10 days. Each ALS contained heparin plus an antimicrobial at standard intraluminal concentrations: vancomycin 2 mg/mL, teicoplanin 10 mg/mL, linezolid 1.8 mg/mL, daptomycin 5 mg/mL, or tigecycline 4.5 mg/mL. The primary endpoint was the time at which intraluminal drug concentrations decreased below 1 mg/mL (ClinicalTrials.gov NCT01592032). Results. Vancomycin and linezolid concentrations fell significantly below 1 mg/mL after 3 days of dwell time. Daptomycin and tigecycline concentrations decreased significantly after 7 days but remained above 1 mg/mL. Teicoplanin concentrations did not decline significantly after 7 days. Conclusions. Optimal ALS dwell time depends on the antimicrobial agent. Vancomycin and linezolid locks require daily replacement, whereas daptomycin, tigecycline, and teicoplanin locks maintain therapeutic concentrations for up to 7 days. These findings support individualized ALS replacement strategies, potentially reducing the need for daily interventions.

Abstract:

Background: The outer membrane impermeability of multidrug-resistant (MDR) Gram-negative bacteria, particularly Escherichia coli, remains a primary barrier to antibiotic efficacy. Overcoming this challenge requires strategies that transcend traditional lipophilicity-driven drug design. Methods: This study presents the rational design and in silico validation of ‘Armored-Trojan-1,’ a novel siderophore–beta-lactam conjugate engineered to exploit the bacterial iron-acquisition pathway. Using a generative in silico approach, we designed a high-affinity catechol siderophore with a beta-lactam warhead. To address the metabolic instability limiting previous "Trojan Horse" candidates, we introduced a sterically hindered alpha-methyl ether linker designed to prevent premature periplasmic hydrolysis. Results: Physicochemical profiling indicates that while the candidate exceeds standard passive diffusion thresholds (TPSA > 190 Ų), its polarity is optimized for active transport via the FhuA receptor. A steric and dimensional compatibility audit demonstrates that the molecule fits within the transporter channel without occlusion. Furthermore, structure-based database analysis validates the candidate as a previously undescribed chemical entity. Conclusion: These findings provide a validated computational blueprint for the development of sterically stabilized conjugates, offering a viable strategy to bypass intrinsic resistance mechanisms in Gram-negative pathogens.

Abstract: Background/Objectives: Research has shown consistent excess all-cause mortality since the COVID-19 pandemic, but without a clear explanation. In parallel, research has shown side effects from COVID-19 vaccination and increased deaths. Therefore, one cannot rule out COVID-19 vaccination as an explanation for the excess mortality. Methods: US county-level data were used to model 2022 and 2023 all-cause excess mortality as dependent variables and per capita COVID-19 vaccine uptake by the end of 2021 and 2022 as independent variables. I included lagged dependent variables as controls. The data includes over 3,000 US counties with over 320 million people. Re-sults: A one-unit increase in per-capita vaccination uptake was significantly associat-ed with a .033 (95% CI: .021–.045) increase in 2022 all-cause excess mortality, and sig-nificantly associated with a .027 (95% CI: .021–.033) increase in 2023. Average vaccine uptake was associated with 4.39% (95% CI: 2.78–6.00) higher mortality in 2022 com-pared to assuming zero vaccine uptake, and 137,900 (95% CI: 89,537–186,262) addi-tional deaths. For 2023, there were 5.16% (95% CI: 4.01–6.31) higher mortality and 151,543 (95% CI: 119,397–183,690) additional deaths. Conclusions: COVID-19 vaccine uptake was significantly positively associated with all-cause excess mortality. Given the time asymmetry between vaccine uptake and all-cause excess mortality, the inclu-sion of lagged dependent variables as controls, the large number of observations, and the strongly significant effects, the study has strong internal validity. I.e., vaccine up-take has genuinely caused increased mortality. Also, the study has strong external va-lidity since it covers almost every US county.

Abstract: Background: Infective endocarditis (IE) is a rare yet serious condition affecting the heart valves and the endocardium. Notably, there has been a shift in the risk-factor profile from traditional factors such as rheumatic heart disease and poor dental health to more iatrogenic causes such as prosthetic heart valves, cardiac devices, foreign body implants, haemodialysis, and immunosuppression. Purpose: While IE has been extensively studied in the past, the evolving landscape prompts an epidemiological re-evaluation of vulnerable patient populations. Our primary objective is to examine the trends in microbiological and echocardiographic diagnostics over two decades and to compare them across native valve endocarditis (NVE), prosthetic valve endocarditis (PVE), and cardiac implantable electronic device-related IE (CIED-IE). Methods: We conducted a retrospective analysis of longitudinal data encompassing 912 patients admitted with either a possible or definite IE diagnosis between 2001 and 2023. Results: The incidence of IE increased over the study duration (p<0.01) with octogenarians most affected (21%). Iatrogenic risk factors were associated with nearly two-thirds (63%) of patients diagnosed with IE, while traditional risk factors were evident in almost one-eighth (13%). Blood culture-negative endocarditis increased over the study duration (19% versus 27%, p<0.01) and Staphylococcus aureus (29%, p<0.01) became the dominant pathogen over Viridans group streptococci (14%, p=0.001). Imaging with transthoracic (56% in 2004 versus 75% in 2023) and transoesophageal echocardiography (57% in 2004 versus 79% in 2023) had an increasing contribution in the diagnosis of IE over the two decades. The subgroup analysis suggested that PVE and CIED-IE were more likely to have negative blood cultures (OR=3.7, CI [1.2-6.8] & OR=4.9, CI [1.3-8]) compared to NVE (OR=0.04, CI [0.02-0.8]). PVE and CIED-IE were more likely to have inconclusive echocardiographic imaging (OR=3.7, CI [1.2-6.6] & OR=2.2, CI [0.07-7.8]) compared to NVE (OR=0.63, CI [0.3-3.2]). Conclusion: Our study underscores the evolving nature of IE, now predominantly a healthcare-related disease. Diagnostic challenges persist due to the heterogeneity of the disease, with the emergence of distinct entities such as PVE and CIED-IE.

Abstract: Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) demonstrates superior efficacy and persistence compared to daily oral PrEP. However, real-world implementation reveals that only 52.9% of prescribed individuals initiate treatment with their first injection. This implementation barrier stems from a fundamental mismatch between the traditional PrEP cascade—designed for oral formulations allowing same-day initiation—and LAI-PrEP’s unique requirements involving a 2–8 week “bridge period” between prescription and first injection to establish HIV-negative status. We synthesize data from major clinical trials (HPTN 083, HPTN 084, PURPOSE-1/2; >15,000 participants) with real-world implementation studies to characterize bridge period navigation as the critical implementation barrier. This review proposes a reconceptualized PrEP cascade explicitly recognizing the bridge period as a distinct, measurable step requiring dedicated management strategies. We examine pharmacological bases for conservative initiation protocols, quantify population-specific barriers to bridge period completion, and synthesize evidence on strategies to improve initiation success. This paradigm shift from individual behavioral adherence to structural healthcare system factors requires parallel innovations in cascade conceptualization, measurement frameworks, and implementation approaches. Addressing this structural barrier is essential to translate LAI-PrEP’s extraordinary clinical efficacy (>96%) into meaningful public health impact, particularly for populations experiencing the highest HIV burden.

Abstract:

Background: Intensive poultry production systems can act as reservoirs for antibiotic-resistant and multidrug-resistant (MDR) Escherichia coli, posing a public health risk through food and environmental transmission.Methods: This study investigated the genomic characteristics of antibiotic-resistant E. coli isolated from an intensive poultry production system in the uMgungundlovu District, KwaZulu-Natal, South Africa. Chicken litter, wastewater, and floor swab samples were collected over three consecutive production cycles. Putative E. coli isolates were detected using the Colilert-18 system, cultured on eosin methylene blue agar, and genomically confirmed by quantitative PCR (q-PCR) targeting the uidA gene. Whole-genome sequencing was performed using the Illumina MiSeq platform, followed by bioinformatic analyses to assess resistance genes, mobile genetic elements, and phylogenetic relationships. Results: Of 150 isolates, 70 were genomically confirmed as E. coli and resistant to at least one antibiotic, with 74% exhibiting multidrug resistance. Resistance was highest to tetracycline (100%), ampicillin (94%), and trimethoprim-sulfamethoxazole (76%), while ciprofloxacin resistance was rare (3%). Genomic analysis identified multiple antibiotic resistance genes conferring resistance to fluoroquinolones, β-lactams, aminoglycosides, amphenicols, fosfomycin, and sulfonamides, as well as the disinfectant resistance gene qacI. These genes were frequently associated with mobile genetic elements, including plasmids, integrons, transposons, and insertion sequences. Predominant sequence types included ST155, ST48, ST1286, and ST602, with phylogenetic relatedness to poultry-associated isolates from Cameroon, Ghana, Nigeria, and Tanzania, as well as environmental E. coli strains previously identified in South Africa and Ghana. The detection of diverse, mobile MDR E. coli lineages in poultry environments clearly signals a substantial risk for resistance gene dissemination into the food chain and surrounding ecosystems. Immediate attention and intervention are warranted to mitigate public health threats.

Abstract: Background/Objective: Carbapenem resistant Acinetobacter baumannii (CRAB) pneumonia has limited treatment options, and sulbactam MIC interpretation varies by antimicrobial susceptibility testing (AST) method. This study compared sulbactam MICs determined by broth microdilution (BMD) and E-test and examined their associations with 28-day mortality. Methods: This secondary analysis used data from a randomized controlled trial comparing colistin plus sulbactam at 9 g/day versus 12 g/day in adults with CRAB pneumonia. Sulbactam MICs of 134 isolates were determined by BMD and E-test. Agreement between methods across MIC ranges and associations between MICs, dosing, and 28-day mortality were analyzed. Results: Sulbactam MICs determined by BMD were lower than those obtained by E-test (MIC50/90: 32/128 µg/mL vs. 96/≥256 µg/mL). Overall agreement between methods was limited and depended on MIC level, with better agreement at lower MICs and marked discrepancies at higher MICs, where E-test frequently overestimated MICs. Using the IDSA breakpoint (MIC ≤4 µg/mL), susceptibility was identified in 6% of isolates by BMD and 3% by E-test. A significant survival benefit with high-dose sulbactam (12 g/day) was observed in patients with BMD-determined MICs ≥128 µg/mL (HR 0.27; 95% CI, 0.077–0.956; p=0.042), whereas no mortality association was seen when MICs were categorized using E-test results. Conclusions: AST method selection substantially affects sulbactam MIC interpretation in CRAB pneumonia. BMD shows stronger correlation with clinical outcomes than E-test, particularly at high MIC levels. High dose sulbactam may benefit patients with highly resistant isolates, underscoring the need for accurate and standardized AST methods.

Abstract: Dermatophytes are a group of keratinophilic fungi belonging to either of the genera Trichophyton, Microsporum, or Epidermophyton. These fungi are involved in the superficial fungal infections of skin, hair, and nails in humans as well as animals. Dermatophytosis is one of the most prevalent fungal diseases worldwide, and it does not discriminate any age or sex. The basis of taxonomy and classification of these pathogens has changed many times over time, from a traditional morphological and physiological basis to modern molecular methods. Dermatophytes have an interesting historical perspective, epidemiological trends over time and geography, pathogenesis, different clinical manifestations, and advances in diagnostic technology. This review outlines the modalities of diagnosis and classification of the dermatophytes from culture and microscopy to advanced molecular technology, with highlights on their working principle, advantages, limitations, and disadvantages. This review offers a framework for clinicians, researchers, scientists, and students with insights about the most common yet significant fungal pathogens.

Abstract: Respiratory infections represent one of the leading causes of pediatric consultations and hospitalizations in Chile, where rapid etiological identification is essential for clinical decision-making. We evaluated the impact of implementing the, BIOFIRE® SPOTFIRE® Respiratory (R) Panel in the pediatric Emergency Department of a public referral hospital in Santiago, using a pre-post cross-sectional design comparing two winter periods (July 2023 vs. July 2024). Clinical records, laboratory data, and operational indicators were analyzed to assess changes in diagnostic yield, turnaround time, hospitalizations, discharges, ancillary test requests, and antimicrobial use. A total of 470 patients were included (224 in 2023; 246 in 2024). The etiological detection rate increased from 58.0% to 87.8% after the implementation of Spotfire® (p < 0.0001), with marked increases in the identification of adenovirus, RSV, rhinovirus/enterovirus, and seasonal coronaviruses. Rapid molecular testing was associated with a significant rise in emergency department discharges (23.7% vs. 57.3%; p < 0.0001) and a reduction in hospitalizations (76.3% vs. 42.7%; p < 0.0001) and readmissions (9.2% vs. 0.5%; p < 0.0001). Requests for complete blood counts, chest X-rays, and antimicrobial prescriptions at discharge also decreased significantly. These effects persisted in key subgroups, including infants and children with comorbidities. In this high-demand winter setting, BIOFIRE SPOTFIRE R Panel improved diagnostic performance and supported more efficient and targeted clinical management.