Medicine and Pharmacology

Abstract: Background: Bromhexine hydrochloride (BRH) is a functional inhibitor of the host serine protease TMPRSS2, a key mediator of viral entry for SARS-CoV-2, influenza A and B viruses, and other respiratory viruses that utilize TMPRSS2-mediated proteolytic activation. While most antiviral strategies aim to prevent infection or suppress viral replication, partial modulation of host-dependent viral entry may represent an alternative approach that attenuates disease severity while preserving sufficient antigen exposure for adaptive immune priming. Methods and Clinical Observations: We describe a 72-year-old man who had received no SARS-CoV-2 vaccination after 2021 and had been taking bromhexine prophylactically (8 mg twice daily) for approximately two weeks before an incidentally diagnosed SARS-CoV-2 infection. The infection remained clinically inapparent apart from mild throat irritation. Despite the absence of clinically significant disease, the patient developed a robust humoral immune response, with an anti-spike antibody concentration of 2,080 BAU/mL three months after infection and persistent anti-spike IgG reactivity nine months later (Vircell anti-S IgG ratio 22.209). A parallel household observation involved his 71-year-old wife, who had multiple established risk factors for severe COVID-19, including chronic obstructive pulmonary disease, previous pancreaticoduodenectomy for pancreatic cancer, severe underweight, and a long history of heavy smoking. Despite continuous bromhexine prophylaxis and presumed household exposure, she remained clinically asymptomatic while demonstrating measurable anti-spike immune reactivity. Additional real-world observations from individuals receiving prolonged bromhexine prophylaxis, including elderly patients with multiple comorbidities, heavy smokers, and a child receiving seasonal prophylaxis, consistently demonstrated favorable tolerability together with absent or markedly attenuated clinically apparent COVID-19 and influenza. Hypothesis and Conclusions: These observations support the hypothesis of pharmacologically attenuated natural immunization, whereby partial inhibition of TMPRSS2 reduces viral entry sufficiently to attenuate disease without completely preventing infection, thereby preserving antigen presentation and promoting durable adaptive immunity. Rather than functioning as a sterilizing antiviral agent, bromhexine may shift the host–virus interaction toward controlled attenuation, reducing tissue injury while maintaining immune memory. These observations are hypothesis-generating and do not establish causality. Prospective controlled studies incorporating documented viral exposure, quantitative virological assessment, neutralizing antibody measurements, and comprehensive cellular immune profiling are required to determine whether TMPRSS2 modulation can reproducibly achieve controlled attenuation of respiratory viral infections while preserving long-term protective immunity.

Abstract: Enteric fever remains a significant public health burden in sub-Saharan Africa, yet the phylogenetic diversity of circulating Salmonella serovars in Nigeria remains incompletely characterized. While typhoidal strains dominate clinical reports, emerging atypical lineages and non-typhoidal serovars may contribute substantially to febrile illness transmission. A health facility-based cross-sectional study enrolled 425 consecutive febrile patients (aged 1–65 years) with suspected enteric fever in Keffi Local Government Area, Nasarawa State, Nigeria. Blood cultures were processed using the BD Bactec™ automated system, followed by sub-culturing on selective media and presumptive phenotypic screening. Molecular confirmation employed PCR amplification of the 16S rRNA gene (27F/1492R) and Sanger sequencing. Sequence analysis utilized BLASTn against the NCBI GenBank database, and phylogenetic trees were constructed in MEGA 11 using the Maximum Likelihood method with 1,000 bootstrap replicates. Sixty-three (14.8%) blood cultures yielded microbial growth, of which 32 (7.5%) were phenotypically identified as Salmonella. Molecular characterization confirmed 25 isolates (5.9%) as Salmonella species. Phylogenetic analysis resolved four major clades dominated by closely related non-typhoidal Salmonella enterica serovars, particularly S. Typhimurium (n=11), with moderate to strong bootstrap support (68–89%). Emerging atypical lineages, including Salmonella bongori (n=1) and Salmonella enterica subsp. diarizonae (n=1), formed distinct divergent branches separate from the core S. enterica lineages. Additional serovars identified included S. Enteritidis (n=1), S. Typhi (n=1), S. Paratyphi B (n=1), S. Heidelberg (n=1), S. Infantis (n=1), S. Livingstone (n=1), and untyped S. enterica strains (n=6). Substantial phylogenetic diversity exists among Salmonella serovars circulating in suspected enteric fever cases in Keffi, with S. Typhimurium representing the predominant lineage and emerging atypical serovars (S. bongori and S. diarizonae) suggest potential zoonotic and environmental transmission pathways. These findings underscore the urgent need for routine molecular surveillance, enhanced diagnostic capacity, and One Health-based interventions for effective disease control in Nigeria.

Abstract: Background/Objectives: Antimicrobial resistance poses a major global health threat, necessitating strict compliance with treatment algorithms. This nationwide audit evaluated prescriber adherence to the National Antimicrobial Guideline (NAG 2019) among multidrug-resistant organism (MDRO) cases in Malaysian public hospitals, identifying key clinical, microbiological, and health-system determinants. Methods: A retrospective national clinical audit of N = 437 MDRO cases were conducted across public hospital tiers. Bivariate associations were evaluated using Pearson Chi-square tests. Multivariable binary logistic regression was performed to identify independent predictors of compliance while controlling confounders and multicollinearity. Results: Overall guideline adherence was 72.1% (315/437). Bivariate analysis showed significant associations between adherence and geographic zone (p = 0.018), infection site (p < 0.001), specimen type (p = 0.035), isolated pathogen (p = 0.007), surveillance year (p < 0.001), and treatment choice (p < 0.001). Gender, hospital category, and isolate colonization status showed no significant association. In multivariable modeling, primary infection site (p = 0.005) and surveillance year (p < 0.001) remained robust independent predictors. High-acuity conditions like hospital-acquired pneumonia (77.4%) and bloodstream infections (76.8%) yielded high compliance, whereas surgical site/soft tissue infections exhibited the lowest adherence (50.0%). Longitudinally, adherence dropped sharply during the 2020 COVID-19 pandemic peak (39.3%) before recovering rapidly in 2021 (88.5%) and 2022 (80.5%). Regional compliance varied from 75.9% (Northern) to 54.5% (Southern). Conclusions: Prescriber adherence to NAG 2019 is high overall, but marked disparities exist across clinical sites, regions, and pandemic stress periods. Antimicrobial stewardship programs should prioritize soft tissue infections, equalize regional resources, and establish crisis-resilient frameworks for future healthcare disruptions.

Abstract: Background: Surgical antimicrobial prophylaxis (SAP) is a cornerstone of surgical site infection (SSI) prevention and represents one of the most cost-effective interventions in perioperative care. However, inappropriate antimicrobial selection, timing, dosing, and duration remain common, compromising clinical outcomes and increasing healthcare costs. This narrative review summarizes the pharmacoeconomic value of SAP and its role in antimicrobial stewardship, value-based healthcare, and healthcare sustainability. Methods: A narrative review was conducted to synthesize current evidence on the clinical and economic impact of SAP. The literature addressing the burden of SSIs, cost-effectiveness of prophylactic strategies, antimicrobial selection and duration, stewardship interventions, and future perspectives for optimizing perioperative infection prevention was reviewed. Results: Evidence consistently demonstrates that appropriate SAP reduces SSI rates, postoperative morbidity, hospital length of stay, readmissions, reoperations, and healthcare expenditures. First-generation cephalosporins, particularly cefazolin, remain the preferred agents for most procedures because of their efficacy, safety, and favorable pharmacoeconomic profile. In contrast, inappropriate antimicrobial selection and prolonged postoperative prophylaxis increase costs, antimicrobial consumption, adverse events, and antimicrobial resistance without improving outcomes. Antimicrobial stewardship programs significantly improve adherence to evidence-based recommendations, optimize antimicrobial use, and enhance both clinical and economic performance. Conclusions: Appropriate SAP is a high-value intervention that improves patient outcomes while reducing healthcare costs. Optimizing antimicrobial selection, timing, dosing, and duration through stewardship initiatives is essential to maximize clinical effectiveness, minimize unnecessary antimicrobial exposure, and promote sustainable healthcare systems. Future studies should incorporate standardized pharmacoeconomic methodologies to strengthen evidence-based decision-making and value-based surgical care.

Abstract: (1) Background: The available literature on sexually transmitted infections in patients with genital molluscum contagiosum is limited. This study aimed to evaluate the serological test results and screening rate for sexually transmitted infections, including human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis, among patients with genital molluscum contagiosum. (2) Methods: This retrospective cross-sectional study reviewed the medical records of patients aged ≥18 years diagnosed with genital molluscum contagiosum at our dermatology outpatient clinic between October 2016 and December 2025. Age, sex, and serological test results for anti-human immunodeficiency virus, hepatitis B surface antigen, anti-hepatitis C virus, and Venereal Disease Research Laboratory/Rapid Plasma Reagin were recorded. (3) Results: Serological screening was performed in 202 of 528 patients (38.3%), and 11 (5.45%) had positive test results for at least one sexually transmitted infection. (4) Conclusions: Our findings support routine screening for sexually transmitted infections in patients with genital molluscum contagiosum, given that a substantial proportion of these patients do not undergo serological screening.

Abstract: Background/Objectives: Ventilator-associated pneumonia (VAP) is the leading indication for antibiotic therapy in intensive care units (ICUs), and patients with traumatic brain injury (TBI) are at particularly high risk of early-onset VAP (eVAP). Antibiotic prophylaxis reduces eVAP but may exert selective pressure favouring multidrug-resistant (MDR) organisms. We assessed whether prophylactic exposure extending beyond 24 h was associated with eVAP and with MDR aetiology of the subsequent pneumonia episode. Methods: Retrospective single-centre cohort of adults with moderate-to-severe TBI (Glasgow Coma Scale ≤12) receiving invasive mechanical ventilation in a Brazilian reference trauma ICU (January–August 2016). Patients were grouped by prophylactic exposure during the first 24 h of ICU admission: no antibiotic or a single dose (Group <24 h) versus ≥24 consecutive hours (Group ≥24 h). The primary outcome was eVAP (48–96 h of ventilation); secondary outcomes included MDR or extensively drug-resistant (XDR) aetiology of the first episode, length of stay (LOS), tracheostomy, mortality and neurological outcome. Multivariable logistic regression with backward selection was complemented by a pre-specified forced-entry sensitivity model. Results: Of 907 admissions, 231 patients were included (123 Group <24 h; 108 Group ≥24 h). Group ≥24 h had less eVAP (19.4% versus 36.6%; adjusted odds ratio [OR] 0.47, 95% confidence interval [CI] 0.25–0.87) and shorter hospital LOS (median 45 versus 61 days), but a higher proportion of MDR/XDR organisms in the first VAP episode (48.6% versus 27.4%; adjusted OR 3.23, 95%CI 1.27–8.33) and more purulent tracheal secretions from day 5 of ventilation onwards. Mortality and neurological outcome did not differ. Conclusions: Prophylaxis beyond 24 h was associated with less eVAP but with greater antimicrobial resistance pressure, supporting a stewardship-guided 24 h exposure ceiling. These hypothesis-generating findings require prospective confirmation.

Abstract: Enterocytozoon bieneusi is a major zoonotic pathogen causing human microsporidiosis, with small ruminants serving as crucial reservoir hosts. Hu sheep and local goats are pillar livestock breeds in Zhejiang Province, yet no parallel comparative epidemiological data on E. bieneusi exist for sympatric small ruminants in southern Zhejiang, and the infection status in Hu sheep remains entirely uncharacterized. Here, a total of 297 fecal samples (159 Hu sheep, 138 goats) were collected from four administrative regions in southern Zhejiang from 2021 to 2023 and screened via nested PCR targeting the ribosomal internal transcribed spacer (ITS) region of the E. bieneusi genome. Overall, the total E. bieneusi prevalence reached 18.18%, and Hu sheep exhibited a significantly higher infection rate (24.53%, 39/159) than sympatric goats (10.87%, 15/138; χ² = 9.27, P = 0.002). Obvious geographical and age-dependent disparities were observed in Hu sheep, with pre-weaning lambs (< 3 months) showing the highest prevalence (60.42%), while adult sheep (> 1 year) had the lowest rate (4.48%). No significant age or regional differences were detected in goats. Five genotypes were identified from Hu sheep: CM7 (n = 25), BEB6 (n = 10), CHG1 (n = 2), Type IV (n = 1), and CHG5 (n = 1). Five genotypes were detected from goats: CHG1 (n = 9), BEB6 (n = 3), Type IV (n = 1), CHG3 (n = 1), and CYG-2 (n = 1). BEB6, Type IV, and CHG1 were shared by both hosts. All genotypes belonged to zoonotic Group 1 and Group 2. This study represents the first systematic parallel survey of E. bieneusi in cohabiting Hu sheep and goats in eastern China, identifies distinct host-specific infection patterns linked to divergent rearing systems, provides molecular evidence for potential cross-species transmission, and underscores the need for breed-tailored biosecurity strategies under a One Health framework.

Abstract: The intestinal microbiome has emerged as a clinically significant modulator of outcomes across multiple domains of cancer care. In hematopoietic stem cell transplantation (HSCT), loss of microbial diversity and depletion of short-chain fatty acid–producing commensals are independently associated with graft-versus-host disease (GvHD), bloodstream infections, transplant-related mortality, and overall survival. Mechanistic studies have identified interconnected pathways — including butyrate-mediated epithelial protection, tryptophan-derived aryl hydrocarbon receptor signaling, bile acid metabolism, and Paneth cell–intestinal stem cell interactions — through which microbial communities regulate intestinal barrier integrity and immune homeostasis. These insights have provided the biological rationale for therapeutic strategies aimed at restoring microbial ecology. Fecal microbiota transplantation (FMT) has demonstrated promising clinical activity in steroid-refractory acute GvHD, with pooled remission rates exceeding 60% in meta-analyses, and proprietary live biotherapeutic products (LBPs) such as MaaT013 have advanced to phase III testing. In parallel, the gut microbiome has been established as a determinant of immune checkpoint inhibitor (ICI) efficacy, with FMT shown to overcome anti-PD-1 resistance in refractory melanoma and enhance response rates in treatment-naive patients with melanoma and non-small cell lung cancer. Defined single-strain approaches, notably Clostridium butyricum CBM588, have demonstrated significant improvements in progression-free survival when combined with ICI in metastatic renal cell carcinoma. Emerging evidence further links antibiotic-induced dysbiosis to impaired chimeric antigen receptor T-cell (CAR-T) therapy outcomes, while short-chain fatty acids have been identified as direct enhancers of CAR-T cell effector function. This review synthesizes the current evidence for microbiome-based therapeutics across HSCT, GvHD, ICI therapy, CAR-T cell therapy, and infection prevention, and addresses cross-cutting translational challenges including antibiotic stewardship, donor selection, safety in immunocompromised populations, and pharmacomicrobiomics. While randomized controlled trial data remain limited and many approaches are investigational, the convergence of mechanistic, observational, and early interventional evidence positions microbiome restoration as a promising frontier in precision oncology.

Abstract: Infective endocarditis (IE) is associated with an in-hospital mortality rate of 15–30%. Standard treatment requires 2 to 6 weeks of intrave-nous (IV) antibiotic therapy, resulting in prolonged hospitalization with its attendant risks, including catheter-related complications, in-creased length of stay, and cost.This review summarizes the current evidence, eligibility criteria, antibiotic regimen selection, and practical aspects of partial oral ibiotic therapy (POAT) for IE. Oral treatment is already recommended for right-sided Staphylococcus aureus IE and IE caused by atypical pathogens. The landmark POET trial (2019) demonstrated the non-inferiority of POAT — initiated after at least 10 days of IV therapy — versus continued IV treatment for left-sided IE caused by streptococci, Enterococcus faecalis, S. aureus, or coagu-lase-negative staphylococci. Long-term follow-up at 5.4 years demon-strated lower all-cause mortality in the POAT group. The 2023 ESC Guidelines now formally endorse POAT for selected patients fulfilling strict criteria. Despite robust evidence, POAT is currently implemented in fewer than half of eligible patients. These findings have since been corroborated by the WikiGuidelines Group consensus statement and the French SPILF-AEPEI position statement, and extended by re-al-world evidence (the ENDO-ORAL study) suggesting that carefully selected patients falling outside strict trial-based eligibility criteria may also benefit from oral step-down therapy. POAT represents a safe, effective, and resource-efficient alternative to prolonged IV therapy in carefully selected patients. Strict adherence to eligibility criteria, ap-propriate antibiotic selection based on pathogen susceptibility, and close clinical follow-up are essential to optimize outcomes.

Abstract: Telomere, also known as a “molecular clock”, is a specific, unique cap-like structure of nucleoprotein with repetitive, noncoding, guanine-rich tandem of nucleotide sequences of DNA-protein located at the ends of chromosomes fashioned in a duplex “D-loop-T-loop” appearance. The dynamic and equilibrium of telomere homeostasis is a function of competing pro-telomere lengthening and pro-telomere shortening factors in determining the telomere length and telomerase activity. While many studies have been done on telomere dynamics, few have been done on telomeres and HIV with a stark gap in knowledge on the impact lifestyle modifications have on the telomeres of people living with HIV. Development of “telomere check kits” in the future will go a long way to put the “molecular clock” within our reach and be directly involved and aware of where we are in the “time or clock” of our life. Having extensively and comprehensively reviewed the healthy lifestyle and the improvement of telomere length and enhancement of telomerase activity that can result in promoting longevity and maximizing health-related quality of life, a full integration of lifestyle modifications as part of the management of HIV disease is long overdue.

Abstract: Background: Dengue is one of the most important mosquito-borne viral diseases in Mexico, where transmission is shaped by complex interactions among environmental, demographic, urban, land-use, and climatic conditions. However, long-term national ecological analyses integrating these factors remain limited. This study evaluated ecological associations between environmental, demographic, urban, land-use, and climatic indicators and dengue incidence trends in Mexico from 1990 to 2021. Methods: A national ecological time-series study was conducted using annual aggregated data obtained from official public databases. Dengue fever and severe dengue incidence rates were analyzed in relation to environmental, land-use, urban, demographic, and climatic indicators. Exploratory simple and multiple linear regression analyses were performed, and autoregressive integrated moving average models with exogenous variables (ARIMAX) were used to evaluate temporal associations while accounting for autocorrelation. Results: In simple regression analyses, urban population, population density, renewable internal freshwater resources, forest area, and average annual temperature were significantly associated with dengue incidence. For severe dengue, renewable internal freshwater resources showed the highest explanatory capacity in simple regression analyses (R² = 0.33). In multivariable models, forest area remained positively associated with severe dengue incidence (β = 64.29; p = 0.006), whereas renewable internal freshwater resources showed an inverse association (β = −0.087; p = 0.002). After accounting for temporal autocorrelation, none of the environmental or demographic indicators remained statistically significant in ARIMAX models; however, renewable internal freshwater resources showed the strongest association with severe dengue incidence (p = 0.062). The severe dengue model included a significant first-order moving-average component (MA(1), p < 0.001), indicating short-term temporal dependence in annual incidence rates. Conclusions: Environmental, demographic, urban, land-use, and climatic indicators were associated with long-term national dengue incidence trends in Mexico. Renewable internal freshwater resources emerged as one of the most consistent ecological indicators across analyses, highlighting the relevance of water availability and management within integrated dengue prevention strategies. The temporal dependence observed for severe dengue suggests that ecological time-series analyses may contribute to improving epidemiological surveillance and generating hypotheses for future regional studies.

Abstract: Preliminary evidence suggests that patients with Enterococcus faecalis bacteremia and infective endocarditis, particularly those without an identifiable source, may have an increased prevalence of colorectal neoplasia. Whether systematic colonoscopy should be recommended in this population remains unresolved. EnteroColonus is a multicenter, prospective, observational matched cohort study that will recruit adults aged 50 years or older with E. faecalis bacteremia and/or infective endocarditis from 22 Spanish centers, together with asymptomatic controls undergoing colorectal cancer screening. Cases will be stratified into E. faecalis bacteremia/endocarditis of unknown origin (EFBEUO) and with suspected source (EFBESS). Planned sample size is 414 participants: 276 cases and 138 matched controls. Core procedures include colonoscopy, histopathology, clinical and microbiological phenotyping, fecal microbiome profiling by shotgun metagenomics, detection of E. faecalis genetic material in colorectal biopsy specimens using 16S sequencing and species-specific qPCR, and whole-genome, SNP, and phylogenetic analyses of clinical isolates. The primary endpoint is the detection of colorectal neoplasia by colonoscopy/histopathology in EFBEUO compared with EFBESS and matched screening controls. Secondary endpoints include microbiome profiles, biopsy positivity for E. faecalis, genomic traits of bloodstream isolates, mortality, relapse/recurrence, and development of a colorectal neoplasia risk score. This protocol is designed to clarify which patients with E. faecalis bloodstream infection might benefit from systematic colonoscopy evaluation and to explore host-microbe mechanisms underlying the observed association with colorectal neoplasia.

Abstract: Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) increasingly combines high-risk clonal expansion, mobile resistance platforms and limited treatment options. We investigated the genomic epidemiology, resistance and virulence architecture, plasmid backbones, and therapeutic vulnerabilities of CRKP circulating in Oman. Methods: Between 2021 and 2024, 135 non-duplicate CRKP isolates were recovered from diverse clinical specimens. New antimicrobial agents were evaluated phenotypically, while 38 representative XDR/PDR isolates underwent WGS for MLST, capsular typing, resistome, virulome, plasmid and MGE analysis. In-vitro synergy of ceftazidime-avibactam/aztreonam, meropenem/fosfomycin and amikacin/fosfomycin was assessed using E-test-based FICI. Results: WGS revealed a striking shift towards OXA-232-producing ST-2096, which dominated the sequenced collection and carried KL64 with a conserved multidrug-resistant backbone. NDM-5/ST147 and NDM-1+KPC-2/ST11 formed distinct high-risk lineages with broader ESBL repertoires, greater plasmid heterogeneity and, in co-producers, the highest MGE burden. Across isolates, resistance was reinforced by widespread blaCTX-M variants, armA, aac(6')-Ib-cr, fosA, porin alterations and fluoroquinolone-resistance mutations, while core virulence and fitness loci including fimH, mrkA, iutA, fyuA and irp2 were widely retained. Cefiderocol showed the most consistent in-vitro activity across carbapenemase groups, and eravacycline remained active, whereas plazomicin and fosfomycin activity was compromised by methyltransferase and fos genes. Ceftazidime-avibactam/aztreonam demonstrated universal synergy, while meropenem/fosfomycin and amikacin/fosfomycin showed limited, carbapenemase-dependent activity. Conclusion: CRKP in Oman is characterized by convergent clonal expansion, plasmid-mediated resistance, retained virulence potential and narrowing therapeutic options. Integrated genomic surveillance with carbapenemase-directed susceptibility and synergy testing is essential to guide precision antimicrobial stewardship in high-risk healthcare settings and inform early infection prevention responses to emerging regional CRKP lineages.

Abstract: Background: Monocyte Distribution Width (MDW) is a hematological parameter automatically generated during routine blood count analysis and currently represents the only blood count-derived biomarker for early sepsis risk assessment in adult emergency department (ED) patients. Evidence regarding its ability to identify blood culture (BC) positivity and bloodstream infection (BSI) remains limited. This cohort study aimed to evaluate its diagnostic accuracy. Methods: Adult patients presenting to the ED of a tertiary hospital with suspected infection and BC request were evaluated. Between March 2022 and December 2024, MDW, C-reactive protein (CRP), and BC results were retrospectively collected from the laboratory information system. Samples were categorized as BC-negative or BC-positive and further stratified into microbiological categories. Diagnostic performance was assessed using ROC curve analysis and decision curve analysis (DCA). Analyses were performed both including and excluding CoNS. Results: A total of 2,748 samples were available. MDW values were significantly higher in BC-positive than in BC-negative samples (25.8±6.7 vs. 23.4±4.7) and were highest in Gram-negative infections (27.7±7.5). When CoNS were excluded, MDW achieved an AUC of 0.65 at the optimal cut-off of 24.5, showing a sensitivity of 58% and specificity of 66.2%. Rule-out thresholds of 17.7 and 18.7 achieved sensitivities of 95% and 92.9%, respectively, whereas rule-in thresholds of 29.4 and 32 achieved specificities of 90.0% and 95.2%. MDW consistently outperformed CRP and demonstrated positive clinical net benefit in DCA. The addition of CRP did not provide improvement in diagnostic accuracy (AUC 0.65). Conclusions: MDW is associated with BC positivity and clinically significant BSI and outperforms CRP in identifying patients with BC-positive in the ED supporting its integration into diagnostic stewardship strategies and early risk stratification pathways.

Abstract: Objectives: To assess the impact of the COVID-19 pandemic on the epidemiology, microbiology, clinical presentation, management, and outcomes of infective endocarditis (IE). Methods: A retrospective cohort study was conducted, including 100 adult patients with definite IE diagnosed between January 2020 and December 2025 at a Romanian tertiary care center. Patients were stratified by year of admission into pandemic (2020–2022) and post-pandemic (2023–2025) groups. Results: Among the 100 patients (47 in the pandemic period and 53 in the post-pandemic period), the time from symptom onset to diagnosis was significantly shorter in the post-pandemic period (median of 24 days versus 40 days; p < 0.01). The microbiological etiology shifted from a predominance of staphylococci during the pandemic to a more balanced distribution of enterococci and streptococci in the post-pandemic period (p = 0.03). In-hospital mortality decreased significantly from 51.1% to 24.5% (p = 0.007), and survival improved from 48.9% to 75.5% (p = 0.007). Embolic events were more frequent in the post-pandemic period (62.3% vs. 38.3%; p = 0.028). Vegetation size was associated with embolic risk (OR: 1.05 per mm; p < 0.01). Conclusions: The COVID-19 pandemic was associated with delayed presentation and worse outcomes in IE. Post-pandemic improvements likely reflect healthcare system adaptation and earlier diagnosis. Microbiological etiology remains a key determinant of prognosis.

Abstract: Abstract Coronavirus disease 2019 (COVID-19) and influenza share key pathogenic mechanisms, including viral invasion, dysregulated innate immune activation, and the development of severe systemic complications. A central mediator of disease progression in both infections is the hyperactivation of the NLRP3 inflammasome, which drives excessive production of pro-inflammatory cytokines, immunothrombosis, multiorgan injury, and increased mortality. Colchicine possesses a unique pharmacokinetic property of preferential accumulation within myeloid cells, where sufficiently high intracellular concentrations inhibit NLRP3 inflammasome activation. This mechanism provides a biological rationale for preventing the cytokine storm and its downstream consequences when colchicine is administered early during infection. Available pharmacokinetic, toxicological, and clinical evidence suggests that loading doses of colchicine up to approximately 0.05 mg/kg body weight can be administered safely in appropriately selected patients, provided that clinically significant drug–drug interactions and hepatic or renal impairment are carefully excluded. The widely accepted belief that total doses of 7–7.5 mg are inherently lethal appears to reflect historical cases complicated by drug interactions and/or hepatic or renal impairment, rather than toxicity attributable to colchicine dose alone. These observations support reconsideration of current guideline recommendations regarding colchicine dosing. In particular, cumulative doses below 0.1 mg/kg appear to be consistently safe, whereas doses between 0.1 and 0.2 mg/kg are associated with only a low risk of toxicity and rarely with severe intoxication. Reassessment of colchicine dosing strategies may therefore be warranted to optimize NLRP3 inflammasome inhibition and improve outcomes in patients with COVID-19 and influenza.

Abstract: Background/Objectives: Healthcare-associated infections (HAIs) remain a pressing patient-safety challenge, disproportionately burdening low- and middle-income countries. Uzbekistan's national sanitary regulations govern HAI prevention, but their alignment with World Health Organization (WHO) standards has not been systematically assessed. The primary aim of this study was to evaluate the alignment of Uzbekistan's national regulatory framework with the WHO Core Components (CC1–CC8) of infection prevention and control (IPC), using a decade of national HAI surveillance data (2015–2024) as descriptive context. Methods: We performed a retrospective analysis of officially registered HAI cases (2015–2024) using national surveillance and population data. We compared national regulations (SanPiN No. 0342-17 and No. 0317-15) against the eight WHO Core Components using a qualitative method, with two authors independently classifying alignment as full, partial, or weak. Results: National HAI incidence declined from 3.95 to 2.16 per 100,000 population (45.3% reduction; Mann–Kendall p = 0.007; average annual percentage change [AAPC] −6.36%/year, 2020 excluded). Tashkent city accounted for the largest 2024 share (31.7%); surgical site infections predominated (44.1%). Full WHO alignment was found for guidelines (CC2), training (CC3), and environment/equipment (CC8); partial or weak alignment for staffing (CC1, CC7), surveillance (CC4), and audit (CC6). Conclusions: HAI incidence has declined over the past decade, though this should be interpreted cautiously given likely 2020 reporting artefacts. The framework is strong in waste-management provisions but would benefit from mandatory epidemiologist staffing, electronic real-time surveillance, and more frequent audits. This is, to our knowledge, the first such regulatory-to-WHO benchmarking reported from Central Asia, offering a transferable template for similar evaluations in other low- and middle-income countries.

Abstract: Background and Objectives: Balamuthia mandrillaris granulomatous amoebic encephalitis (GAE) is a rare, frequently fatal central nervous system infection in which delayed recognition remains a major determinant of outcome. The increasing use of metagenomic next-generation sequencing (mNGS), plasma microbial cell-free DNA sequencing and targeted sequencing has changed the diagnostic pathway for unexplained encephalitis, but the survival implications of earlier molecular diagnosis remain unclear. Materials and Methods: A systematic review of peer-reviewed reports published from January 2015 to June 2026 was designed according to PRISMA 2020. Eligible records reported human B. mandrillaris GAE, encephalitis, meningoencephalitis or encephalomyelitis with extractable patient-level diagnostic, treatment or outcome information. Data were narratively synthesised because case definitions, sample types, timing of testing and follow-up were heterogeneous. Results: The evidence base consisted mainly of case reports, small case series and retrospective clinical summaries. Across recent reports, B. mandrillaris GAE commonly mimicked malignancy, tuberculosis, fungal infection, autoimmune encephalitis or bacterial brain abscess. Diagnostic delay was driven by nonspecific symptoms, ring-enhancing lesions, negative routine cultures and limited clinician familiarity with free-living amoebae. Molecular methods, particularly mNGS/NGS applied to cerebrospinal fluid, plasma, blood, brain tissue or bronchoalveolar lavage fluid, repeatedly enabled antemortem diagnosis when routine tests were unrevealing. Survival reports shared a pattern of earlier tissue diagnosis or molecular identification, neurosurgical intervention when feasible, and prolonged multidrug therapy, sometimes including miltefosine or nitroxoline. Conclusions: B. mandrillaris GAE should be considered in subacute encephalitis with mass-like or multifocal enhancing lesions and negative conventional investigations. Early biopsy or non-invasive sequencing, followed by confirmatory testing and expert-guided combination therapy, represents the most actionable strategy to reduce diagnostic delay.

Abstract: Background: Melioidosis correlates strongly with rainfall, but there is substantial di-versity in climate between melioidosis-endemic locations. The Northern Territory of Aus-tralia epitomises the “wet/dry” tropics, with a prolonged dry season from May to October. We analysed dry season cases of melioidosis during 35 consecutive years and compared these with wet season cases. We aimed to provide insights into how dry season cases of melioidosis may occur in this region. Methods: Case epidemiological and clinical data were extracted from the Darwin Prospective Melioidosis Study. Weather parameters, in-cluding daily rainfall, were analysed using generalised additive models and conditional logistic regressions to assess associations between dry season cases and preceding rain-fall. Results: Of 1520 melioidosis cases between 1989 and 2024, there were 325 (21%) in the dry season. While the well-recognised clinical diversity of melioidosis was also seen amongst dry season cases, pneumonia was proportionally less common and cutaneous melioidosis was more common than in the wet season. A higher proportion of dry season patients (23%) had no identified clinical risk factors for melioidosis, and mortality in the dry season was 8%. There was a range of plausible explanations for many of the dry sea-son cases, including unseasonal rainfall prior to infection. Infections in urban settings were notable, with anthropogenic factors such as irrigation and construction resulting in persistence of Burkholderia pseudomallei in the environment during the dry season. 3% of cases remained unexplained. Conclusion: Further prospective studies are needed to better define the infecting events resulting in melioidosis, especially in the dry season. These studies should include a timely history taking from the case and their family and selected environmental sampling for B. pseudomallei.

Abstract: The increase in antimicrobial resistant infections has fueled a resurgent interest in bacteriophage (phage) therapy. We conducted a systematic review of personalized phage therapy cases in the peer-reviewed, English-language literature reported between 1/1/2005, to 8/31/2025 for which individual patient data were available, for a total of 323 patients in 83 studies. Most patients (68%, 221/323) were treated with ≥2 phages (a phage cocktail). The median concentrations of phages was 108 PFU/mL (IQR 107-109). Most patients (76%, 246/323) received antibiotics concurrent with phage therapy. The median duration of therapy was 10 days (IQR 5-21). The most common indications for phage therapy were skin/soft tissue, pulmonary, orthopedic, osteoarticular, and genitourinary infections. 144 patients received fixed (off-the shelf) phage preparations whereas 179 received bespoke phage preparations in which all of these were screened for in vitro efficacy against the patient’s clinical isolates prior to treatment initiation (e.g. personalized therapy). For cases where outcomes data were available, 78% (253/323), experienced clinical improvement while the targeted pathogen was eradicated in 61% (177/290) of cases. Nine patients had treatment withdrawn due to tolerability concerns. These data indicate that there is substantial heterogeneity in current personalized phage therapy clinical practices but that this approach can be successful.