Medicine and Pharmacology

Abstract: Sexually transmitted infections (STIs) remain a significant public health challenge due to dynamic epidemiological and behavioral shifts. The diversity of pathogens necessitates complex strategies for screening, diagnosis, and prevention, supported by health education and counseling to mitigate risky sexual behaviors. This narrative review aims to systematize and analyze the educational and counseling competencies of midwives in the prevention of sexually transmitted diseases (STDs) across the distinct stages of a woman's life course. The professional role of the midwife in STI prevention is grounded in clinical knowledge and counseling skills that support women in maintaining optimal sexual and reproductive health. During puberty, age-appropriate history-taking and sensitive communication facilitate the provision of critical information regarding STIs, HPV, and early prophylaxis. Furthermore, STI prevention is vital for ensuring safe pregnancy and childbirth outcomes, with midwifery competencies directly influencing the development of health literacy, informed sexual behavior, and responsible health practices among young people. In early reproductive age, clinical counseling fosters sustainable health habits and responsible attitudes, thereby preserving vital reproductive functions. Particular emphasis is placed on regular prophylactic gynecological check-ups, which enable the early identification of infections and functional anomalies, supporting long-term gynecological well-being. Ultimately, comprehensive care for women of reproductive age incorporates structured professional support to sustain sexual health and strengthen community-based infection prevention.

Abstract: Background: Effective empirical therapy and antimicrobial stewardship rely on up-to-date local data on respiratory pathogens and antimicrobial resistance trends. In Kazakhstan, contemporary microbiological surveillance remains limited, particularly for hospitalized patients with chronic pulmonary disease (COPD) and pneumonia. This study aimed to characterize the microbial profiles and antimicrobial susceptibility patterns in respiratory specimens from these patient groups in Almaty, Kazakhstan. Methods: This retrospective observational study included adult patients hospitalized at a tertiary referral center between January 2024 and December 2025. Respiratory specimens (sputum and bronchoalveolar lavage) underwent bacterial culture, species identification using MALDI-TOF MS, and antimicrobial susceptibility testing via EU-CAST disk diffusion. Susceptibility was interpreted according to EUCAST categories (S, I, R). Group comparisons were performed using Pearson’s chi-square or Fisher’s exact test with Benjamini-Hochberg correction. Results: Among 713 patients (255 COPD exacerbation; 458 pneumonia), Streptococcus pyogenes was the most frequently isolated organism in both groups, followed by viridans group streptococci (VGS) and Streptococcus pneumoniae. Gram-negative isolates included most frequently Klebsiella pneumoniae, Klebsiella aerogenes, and Pseudomonas aeruginosa. After correction for multiple testing, bacterial distribution did not differ significantly between COPD and pneumonia. Streptococcal isolates demonstrated consistently high susceptibility to β-lactams, while susceptibility to macrolides, clindamycin, and doxycycline was lower. Gram-negative organisms demonstrated more variable resistance profiles. MDR phe-notypes were common among K. pneumoniae (16.7% COPD; 31.0% pneumonia) and P. aeruginosa (22.2% COPD; 17.9% pneumonia), with no significant between group dif-ferences. Conclusions: COPD exacerbation and pneumonia patients showed broadly similar bacterial profiles, whereas antimicrobial susceptibility varied substantially across species. High β-lactam activity against streptococci contrasted with complex resistance patterns and notable MDR/XDR phenotypes among Gram-negative organisms. These findings highlight the importance of ongoing institution-specific surveillance to support antimicrobial stewardship and guide empirical treatment decisions.

Abstract: Objectives: To evaluate determinants of vaccine hesitancy among medical students at a Brazilian federal university using the 5C model as a theoretical framework. Methods: A cross-sectional observational study was conducted among medical students at the Federal University of Rio Grande do Sul, Brazil, between December 2024 and March 2025. Data were collected using a self-administered questionnaire conceptually based on the 5C model (confidence, complacency, convenience, communication, and context). The questionnaire was pilot-tested among medical students before application to assess clarity and comprehensibility. Sociodemographic variables and vaccine-related perceptions were analyzed descriptively and inferentially using Pearson’s chi-square, Fisher’s exact, Student’s t, and Mann–Whitney tests. Statistical significance was set at p < 0.05. Results: Out of 809 eligible students, 230 participated in the study (response rate: 28.4%). Most participants reported complete confidence in vaccines (83.5%). Complete confidence in vaccines was more frequently reported among female students than male students (89.4% vs. 75.5%; p = 0.006) and among students from private schools compared with those from public schools (87.7% vs. 78.7%; p = 0.04). Although most participants perceived moderate or high risk for vaccine-preventable diseases, 28.8% reported low risk perception. Higher perceived risk was significantly associated with higher vaccine confidence (p = 0.010). Regarding convenience, 54.0% of participants reported moderate to very high impact of logistical barriers on vaccination decisions. Healthcare professionals (32.3%) and scientific or academic sources (30.1%) were the most frequently reported information sources, although 19.9% identified social media as their primary source. Sociocultural influences on vaccination decisions were considered low or absent by most participants (66.9%). Conclusions: Medical students demonstrated high confidence in vaccines; however, determinants potentially associated with vaccine hesitancy were identified, particularly within the domains of complacency, convenience, and communication. These findings highlight the need for institutional and educational strategies to improve vaccine access, strengthen immunization education, and promote critical appraisal of health information during medical training.

Abstract: Background/Objectives: Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major human pathogen. This study aimed to determine the phenotypic profiles of macrolide resistance in S. pyogenes isolates from southeastern Turkey and to investigate underlying genotypic mechanisms using Oxford Nanopore sequencing. Methods: A total of 83 clinical isolates of S. pyogenes were collected between January 2024 and June 2025. Antimicrobial susceptibility was assessed by disk diffusion following EUCAST guidelines. Macrolide resistance phenotypes (iMLSB, cMLSB, M) were determined by the D‑zone test. Whole‑genome sequencing of erythromycin‑resistant isolates was performed using Oxford Nanopore technology, and resistance determinants were analyzed with the CARD/RGI pipeline.Results: All isolates were susceptible to penicillin. Six isolates (7.2%) exhibited erythromycin resistance: three iMLSB, two cMLSB, and one M phenotype. Adult isolates were exclusively iMLSB, whereas pediatric isolates included one M and two cMLSB phenotypes. Genotypic analysis revealed erm(A) in all iMLSB isolates, mef(A)/msr(D) in the M phenotype, and absence of major resistance genes in cMLSB isolates, which instead carried chromosomal lmrP and mef(E)‑like sequences. Co‑occurrence of tetracycline resistance genes (tetM/O) was observed in several isolates.Conclusions: Penicillin remains the cornerstone of GAS therapy; however, macrolide resistance persists through diverse mechanisms. The coexistence of erm(A)‑mediated iMLSB, mef(A)/msr(D)‑associated M phenotype, and unexplained cMLSB resistance highlights the need for routine D‑testing and genomic surveillance. These findings emphasize the importance of integrating phenotypic and genotypic approaches to monitor resistance evolution in GAS.

Abstract: Background/Objectives: Maternal-birth cohort studies are critical epidemiologic tools to assess patterns, breadth, and duration of immunity derived from influenza vaccines, natural infections, and maternal immunologic contributions. Historically, this study design has been important to the development of well-designed pediatric vaccines. We systematically reviewed international influenza maternal-birth cohort studies to discern commonalities and gaps in their approaches to evaluating influenza immune development. Methods: We performed a scoping review of published maternal-birth cohorts studying influenza virus infections and immunity. Principal themes included, a.) incidence rates and percentages of acute respiratory and influenza infections, b.) sample collection methods, c.) laboratory methods and diagnostic tests, d.) symptomatology and asymptomatic infections, e.) medically attended infections, f.) maternal and child vaccination status, g.) maternal samples and obstetric history, and h.) reported sources of cohort funding. Results: Nine cohorts met the inclusion criteria and were selected for review. Only two cohorts were conducted in countries classified as lower-middle income, and none were conducted in low-income countries. Syndromic definitions, statistical measures, specimen types, and laboratory techniques differed greatly across these cohorts. Most of these cohorts relied on governmental funding. Conclusions: The resource- and time-intensive information obtained from each of these cohorts independently contributes valuable knowledge to the study of influenza exposures and immunity. However, cross-cohort comparisons and analyses are challenged by methodologic variability. Scientific knowledge could be improved by including cohorts of infants at high risk of negative influenza outcomes, by purposeful standardization of core data element collection, timing, and procedures, by standardized analytic measurements, and coordinated reporting of results of scientific interest.

Abstract:

Strains of Campylobacter jejuni are known to produce two distinct diarrheal manifestations in humans: watery, cholera-like diarrhea and bloody, inflammatory diarrhea. Although the inflammatory form has been extensively studied, the mechanisms underlying watery manifestations remain poorly defined, largely due to the limitations of existing animal models. Using a neonatal piglet model, which closely mimics human gastrointestinal physiology, this study characterizes the temporal development of lesions associated with watery diarrhea induced by C. jejuni strain S3 and identifies proteins potentially involved in its pathogenesis. Clinical signs of self-limiting watery diarrhea appeared within 24 h post-infection, peaking at 48 h and largely resolving by 72 h. Gross pathology revealed significant fluid accumulation in the jejunum and colon, whereas histological assessment showed mild villus atrophy and minimal inflammation. Transmission electron microscopy demonstrated marked destruction of colonic microvilli at 24-48 h, followed by evidence of regeneration by 72 h, consistent with transient disruption of fluid absorption. Proteomic analysis of intestinal fluid at 72 h post-infection identified 180 C. jejuni proteins, including three prophage (CJIE4)-encoded proteins predominantly associated with watery diarrheal strains. Together, these findings are consistent with a model in which C. jejuni watery diarrhea results from the combined effects of increased jejunal fluid secretion and transient loss of colonic absorptive capacity. This study provides new insights into the secretory pathogenesis of C. jejuni and highlights phage-derived elements as potential mediators of disease phenotypes.

Abstract: Background: Abdominal sepsis is associated with profound pharmacokinetic (PK) alterations that make standard beta-lactam dosing regimens potentially inadequate in critically ill patients. Increased volume of distribution, hypoalbuminemia, augmented renal clearance (ARC) and acute kidney injury (AKI) collectively impair the ability of conventional dosing to achieve pharmacodynamic (PD) targets. Beta-lactam antibiotics, the cornerstone therapy in intra-abdominal infections (IAIs), are particularly susceptible to these alterations, especially in the context of multidrug-resistant (MDR) pathogens. Methods: We conducted a structured narrative review of the literature published between 2010 and 2026, searching PubMed and Embase using terms related to pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, beta-lactam antibiotics, abdominal sepsis, and intra-abdominal infection in critically ill patients. Additional references were identified through manual bibliography screening, including seminal studies predating the search window. No formal systematic review methodology was applied. Results: PK/PD optimization in abdominal sepsis relies on four pillars: extended or continuous infusion of beta-lactams to maximize the time above the minimum inhibitory concentration; therapeutic drug monitoring (TDM) to guide individualized dose adjustment in the presence of ARC, AKI, or continuous renal replacement therapy (CRRT); dose optimization during CRRT; and target attainment analysis against MDR organisms. Current evidence suggests combining real-time TDM with emerging bi-omarkers provides a rational framework for safe de-escalation and stewardship. Conclusions: In abdominal sepsis, integrating PK/PD principles and TDM-guided dosing represents an evidence-based strategy to optimize beta-lactam exposure, improve target attainment against MDR pathogens, and potentially reduce treatment failure and resistance selection. Prospective studies specifically designed for the IAI population are needed to establish definitive TDM-guided dosing protocols in this high-acuity setting.

Abstract:

Background: Long COVID is clinically heterogeneous; objective biomarkers for diagnosis and biological stratification remain incompletely defined. Methods: We conducted a cross-sectional analysis of 191 de-identified post-COVID participants (158 with long COVID; 33 without sequelae), assessing eight biomarkers. Values below detection limits were imputed as half the assay-specific threshold. Analyses included two-sided Mann–Whitney U tests with Benjamini–Hochberg false-discovery-rate (FDR) correction, logistic regression, receiver operating characteristic analysis with stratified bootstrap confidence intervals (B=1,000), and Ward hierarchical clustering. Results: The long COVID group showed significantly higher IL-6, TNF-α, CXCL9, IP-10, SLAMF1, IL15RA, and IL-18 levels (all FDR q<0.001), whereas IFN-λ3 was not discriminatory (P=0.658). CXCL9 showed the highest single-marker performance (AUC 0.998, 95% confidence interval [CI] 0.989–1.000), followed by IL-6 (AUC 0.991) and IP-10 (AUC 0.973). In the stable multivariable model, higher log10-transformed TNF-α (adjusted odds ratio [aOR] 10.38, 95% CI 1.25–86.36; P=0.030), SLAMF1 (aOR 48.30, 95% CI 4.34–537.16; P=0.002), and IL15RA (aOR 14.45, 95% CI 2.52–82.83; P=0.003) remained independently associated with long COVID, whereas IL-18 was not significant (P=0.207). The model achieved an AUC of 0.995. Clustering identified high-inflammatory and moderate-inflammatory long COVID subtypes (n=79 each). Conclusions: Persistent inflammatory chemokine and cytokine elevation characterizes long COVID, with strong discrimination by CXCL9 and IL-6. Biomarker-defined subtypes support biological heterogeneity and may guide future patient stratification.

Abstract: Background: Chikungunya virus (CHIKV) has circulated in the Philippines for more than six decades. Reviewing the evidence accumulated over this period provides an oppor-tunity to summarize its epidemiology and describe patterns of transmission over time. We systematically reviewed the epidemiology of CHIKV in the Philippines, integrating evidence on transmission, seroprevalence, diagnostics and molecular lineages. Methods: We followed PRISMA 2020 and searched PubMed and Embase to March 2026 for original studies reporting incidence, prevalence, seroprevalence, outbreak characteristics, or surveillance findings in human populations in the Philippines. Grey literature from the Department of Health (DOH) Epidemiology Bureau (2018–March 2026) was included separately. Findings were synthesized narratively because of substantial heterogeneity. Results: Sixteen studies and one national surveillance dataset were included. Serological reconstruction and prospective cohorts indicate approximately four major transmission waves over six decades, separated by intervals of about 17 years. Each wave infected an estimated 23% (16–37%) of remaining susceptible, while more than half remained sus-ceptible thereafter. In Cebu, incidence declined from 12.32 to 2.84 infections per 100 person-years as neutralizing-antibody prevalence increased from 28% to 42%; only about one in five infections was symptomatic. National surveillance recorded 12,662 cases from 2018 to early 2026, including 722 laboratory-confirmed; three deaths. The Asian genotype predominated during the 2011–2013 epidemic, while the Indian Ocean lineage viruses were detected in southern Mindanao. Conclusions: Transmission of CHIKV in the Phil-ippines appears to follow a periodic, recurrent pattern, with outbreaks occurring as population susceptibility accumulates following periods of low-level transmission. Pe-riodic arboviral serosurveys and testing of acute febrile illness are needed to better characterize CHIKV epidemiology in the Philippines.

Abstract: Background and Aim: HDV infection represents one of the most severe forms of chronic viral hepatitis, characterized by rapid fibrosis progression and poor long-term outcomes, and is associated with a markedly increased likelihood of developing liver cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Metabolic dysfunction-associated steatotic liver disease (MASLD), now recognized as the most common chronic liver disorder globally, has been proposed to amplify hepatic injury through overlapping metabolic and inflammatory mechanisms when concurrent with viral hepatitis. To date, however, systematic data on the co-occurrence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) in the setting of chronic HDV infection are remarkably scarce. Accordingly, the present study aimed to characterize the prevalence and severity of MASLD and MASH, as assessed by transient elastography (FibroScan), in a cohort of patients with chronic HDV infection. Methods: A total of 125 anti-HDV seropositive patients were enrolled in this cross-sectional study . HDV-RNA quantification was performed in all participants. Liver stiffness measurement (LSM, kPa) and controlled attenuation parameter (CAP, dB/m) were obtained via FibroScan. Results: The mean patient age was 39.0 years; 74.4% of participants were male (n=93). Of all the patients, 68% (n=85) had received pegylated interferon-alpha (peg-IFN-alpha) therapy for at least 12 months; however, sustained virological response (SVR) was achieved in only 14.1% (n=12). The overall mean LSM was 9.1 kPa, while the mean CAP was 228 dB/m. Liver cirrhosis was identified in 36.8% of patients (n=46; mean LSM 16.2 kPa), with 17.4% of cirrhotic patients (n=8) classified as decompensated and referred for liver transplantation evaluation. HCC was detected in 1.6% (n=2). MASLD was present in 24.0% of patients (n=30; mean CAP 289 dB/m) and MASH in 8.8% (n=11). LSM values were significantly higher in the cirrhotic group compared with non-cirrhotic patients (p< 0.001). No statistically significant difference in CAP was observed between cirrhotic and non-cirrhotic groups (p=0.121). Conclusion: Chronic HDV infection carries a heavy burden of cirrhosis and HCC, further compounded by markedly limited therapeutic efficacy. The presence of MASLD in approximately one in four patients, and MASH in nearly one in ten, underscores the necessity of routine FibroScan-based metabolic liver assessment in this high-risk population.

Abstract: Community-acquired pneumonia carries high mortality in very old adults with multimorbidity, yet preventable medication-related harm is often under-recognised. This case report describes a woman in her late 80s with stage G3a chronic kidney disease who presented with community‑acquired pneumonia to a large multidisciplinary centre. Empiric meropenem was initiated shortly after admission and the dose was increased on day 8 despite persistent renal impairment. Amikacin 1 g once daily was then added. On the same day, the patient received furosemide, intravenous potassium chloride, and glucose infusions as metabolic abnormalities emerged. After temporary stabilisation in the intensive care unit, amikacin was discontinued, linezolid was started, and the patient was transferred to a general ward, where she died four days later. On her final day, life-threatening hyperkalaemia was documented, yet additional potassium was administered, precipitating cardiac arrest. This case illustrates how routine interventions—broad-spectrum antibiotics, aminoglycosides, diuretics, and potassium supplementation—can become iatrogenic in frail older adults when dosing and monitoring are not adjusted for age and kidney function. It underscores the need for strict renal dose adjustment, cautious potassium management, and early geriatric assessment in hospitalised multimorbid older patients.

Abstract: Background: Severe varicella in previously healthy adults is uncommon, and underlying genetic susceptibility is increasingly recognized as a contributing factor in such cases. However, the coexistence of heterozygous variants affecting distinct immunological pathways has rarely been documented. Case presentation: We report a 39-year-old previously healthy Chinese male who presented with a 2-day history of fever and a 1-day history of a generalized vesicular rash after exposure to a patient with herpes zoster. The patient rapidly developed severe pneumonia, acute liver injury (ALT 617.9 U/L, AST 1055.2 U/L), acute myocardial injury (troponin T 17.91 pg/mL), acute kidney injury (creatinine 121.4 μmol/L), and severe thrombocytopenia (36×10⁹/L) with coagulopathy. Lymphocyte subset analysis obtained during acute illness revealed decreased CD4⁺ T cells (373.6/μL), elevated CD8⁺ T cells (1450.3/μL), and an inverted CD4⁺/CD8⁺ ratio, likely reflecting infection-induced perturbations. Whole-exome sequencing identified a heterozygous missense variant in FOXN1 (NM_003593.3) (c.163G>A, p.G55S) and a heterozygous missense variant in PIK3CD (NM_005026.4) (c.1487G>A, p.R496Q), both classified as variants of uncertain significance without functional validation. The patient received high-flow nasal cannula oxygen therapy, intravenous acyclovir, intravenous immunoglobulin, and multiorgan supportive care, and achieved full recovery without sequelae. Conclusions: This case represents the first report of coexisting FOXN1 and PIK3CD concurrent heterozygous variants in an adult presenting with severe varicella and multiorgan dysfunction. As both variants are VUS and lack functional characterization, any attribution of functional impact remains speculative. It is hypothesized that the FOXN1 variant, if pathogenic, might reduce thymic T-cell output, and the PIK3CD variant, if gain-of-function, could cause T- and B-cell dysregulation, potentially impairing antiviral responses. Causality has not been established, and functional studies are required to determine the significance of these variants. This case underscores the importance of genetic evaluation in previously healthy adults who develop unusually severe infections and suggests that concurrent heterozygous variants of uncertain significance may contribute to a "hidden immunodeficiency" phenotype, wherein a baseline vulnerability only becomes clinically apparent upon a potent viral trigger.

Abstract: Clostridioides difficile infection (CDI) has evolved from a sporadic, antibiotic-associated illness into a leading European healthcare-associated infection (HAI). Romania is an instructive case: hypervirulent ribotype 027 (RT027) has dominated locally since 2011–2012, and national surveillance traces four phases — emergence, consolidation, pandemic-era distortion, and recent resurgence. This review synthesises 102 Romanian and pan-European sources (ECDC, ECDIS-Net, COMBACTE-CDI, ESCMID/IDSA-SHEA guidance) to characterise CDI’s epidemiology, molecular typing, and clinical outcomes in Romania relative to Europe. Romanian RT027 prevalence (68–82.6% of typed isolates) far exceeds the 2008 pan-European baseline (5%); national confirmed cases rose from 5,845 in 2015 to a pre-pandemic peak of 12,068 in 2019, fell during the pandemic despite persistently elevated calculated incidence, and resurged to 11,651 in 2022; hospital incidence more than tripled between 2020 and 2023 at one tertiary centre; a 2026 multicentre analysis found CDI caused over half of reported HAIs, amid high antibiotic consumption despite low official HAI rates; and treatment access remains constrained, with limited fidaxomicin reimbursement data and just 31 active faecal microbiota transplantation centres continent-wide. Romania exemplifies a surveillance-bias-masked endemic pattern in which true CDI burden is likely underestimated; priorities include mandatory notification, systematic ribotyping, disciplined antimicrobial stewardship, and equitable access to guideline-recommended therapy.

Abstract: The global emergence of coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 in patients range from asymptomatic disease to severe multiorgan dysfunction and even death. Moreover, the growing population of clinically immunodeficient patients and the use of single clinical antifungal agents have gradually increased the incidence of Aspergillus fumigatus infections, the complex clinical manifestations of which are yet to be fully clarified. The mortality rate among COVID-19 patients coinfected with A. fumigatus has risen significantly. Therefore, a comprehensive understanding of the diagnosis and treatment of A. fumigatus infections, SARS-CoV-2 infections, and their coinfections is crucial. In this review, we first provide a comprehensive description of the life cycle of A. fumigatus, together with an in-depth analysis of its characteristics, diagnosis, and treatment strategies for associated diseases. Then the basic structure of SARS-CoV-2, the evolution of variant strains, and key aspects of its prevention and control was discussed. Finally, the symptoms, diagnosis, and treatment of COVID-19 coinfection with A. fumigatus are summarized. In this paper, we provide methodological references and data to support the clinical prevention and treatment of A. fumigatus and SARS-CoV-2 infections.

Abstract: Background: Gastrointestinal infections remain a major cause of morbidity, mortality, and healthcare utilization worldwide. Although most episodes are self-limiting and require supportive care, antibiotics are essential in selected severe, invasive, or high-risk infections. Inappropriate prescribing contributes to adverse events, microbiome disruption, Clostridioides difficile infection, and antimicrobial resistance. Methods: This narrative review examined evidence on antibiotic use in gastrointestinal infections, emphasizing clinical indications, pathogen-directed therapy, stewardship, resistance, and emerging treatments. PubMed, Scopus, and Google Scholar were searched primarily for publications from 2014 to 2026. Relevant international guidelines and landmark earlier studies were also included. Evidence was selected according to clinical relevance and methodological quality. Results: Antibiotic decisions should be guided by disease severity, host factors, epidemiological exposures, microbiological findings, and local susceptibility patterns. Routine treatment is generally unnecessary for uncomplicated non-typhoidal salmonellosis and campylobacteriosis but may benefit patients with severe disease or increased risk of invasive infection. Treatment is indicated for selected shigellosis, cholera, travelers’ diarrhea, and Clostridioides difficile infection, whereas antibiotics should be avoided in Shiga toxin-producing Escherichia coli infection because of the potential risk of hemolytic uremic syndrome. Rapid molecular diagnostics improve pathogen detection but require careful interpretation and do not replace culture or susceptibility testing. Fidaxomicin, microbiota-based therapies, vaccines, and clinical decision-support systems may further improve outcomes. Conclusion: Effective management requires selective, evidence-based prescribing integrated with prompt rehydration, diagnostic stewardship, and resistance surveillance. Preserving antimicrobial effectiveness and intestinal microbial integrity will require coordinated clinical, public-health, and One Health strategies, alongside equitable access to diagnostics, effective treatments, sanitation, vaccination, and continuing professional education.

Abstract: Background: Clostridioides difficile infection (CDI) is an important healthcare-associated infection associated with substantial morbidity and mortality. This study aimed to characterize the clinical and epidemiological profile of hospitalized CDI patients and identify independent predictors of 90-day all-cause mortality. Methods: We conducted a retrospective observational study of adult patients with CDI admitted to a regional infectious diseases’ hospital in Galați, Romania, during 2024. CDI was defined according to ECDC criteria and diagnosed using a two-step laboratory algorithm. Clinical, epidemiological, and laboratory data were collected. Predictors of 90-day mortality were assessed using multivariable logistic regression. Results: Among 170 patients (median age, 70 years), 74.3% had an age-adjusted Charlson Comorbidity Index >5, and 49.4% had previous antibiotic exposure. Three patients died during hospitalization, while an additional 52 deaths occurred among 167 patients discharged alive. An ATLAS score >4 (adjusted OR, 3.96; 95% CI, 1.78–8.81; p = 0.001) and indwelling urinary catheter use (adjusted OR, 2.89; 95% CI, 1.13–7.35; p = 0.026) were independently associated with 90-day mortality. Conclusions: Ninety-day all-cause mortality was substantial. An ATLAS score >4 and indwelling urinary catheter use were independently associated with mortality, supporting early risk stratification and closer follow-up of high-risk patients.

Abstract: Background: Bromhexine hydrochloride (BRH) has been proposed to functionally inhibit 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 depend on TMPRSS2-mediated proteolytic activation. Emerging evidence suggests that the antiviral activity of BRH against SARS-CoV-2 may extend beyond TMPRSS2 inhibition. BRH may interfere with spike–ACE2 interaction through ACE2-targeted mechanisms, while preliminary molecular and computational evidence suggests probable inhibition of the SARS-CoV-2 main protease (Mpro/3CLpro), potentially affecting viral polyprotein processing and replication. Thus, BRH may exert a three-pronged antiviral effect against SARS-CoV-2—interference with spike–ACE2 binding, inhibition of TMPRSS2-dependent viral entry, and probable inhibition of Mpro/3CLpro-dependent viral replication. Rather than completely preventing infection, such multimodal pharmacological attenuation may reduce viral entry and amplification while preserving sufficient antigen exposure for adaptive immune priming. This strategy may be particularly relevant to personalized prevention according to individual susceptibility, comorbidities, exposure risk, and vulnerability to severe respiratory infection. Methods and Clinical Observations: We describe a 72-year-old man who had received no SARS-CoV-2 vaccination 2021 and had been taking BRH 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, he 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 BRH prophylaxis and presumed household exposure, she remained clinically asymptomatic while demonstrating measurable anti-spike immune reactivity. Additional real-world observations from individuals receiving prolonged BRH prophylaxis—including elderly patients with multiple comorbidities, heavy smokers, and a child receiving seasonal prophylaxis—were characterized by favorable tolerability and absent or markedly attenuated clinically apparent COVID-19 and influenza. Hypothesis and Conclusions: These observations support the hypothesis of Pharmacologically Attenuated Natural Immunization (PANI), whereby pharmacological attenuation of infection reduces viral entry and subsequent amplification sufficiently to limit tissue injury and clinically significant disease without necessarily producing sterilizing protection, thereby preserving antigen presentation and adaptive immune priming. In SARS-CoV-2 infection, the proposed three-pronged activity of BRH—targeting spike–ACE2 interaction, TMPRSS2-dependent entry, and potentially Mpro/3CLpro-dependent replication—provides a mechanistic framework for such controlled attenuation. For influenza, the principal proposed mechanism remains inhibition of TMPRSS2-dependent hemagglutinin activation. Within a personalized medicine framework, this concept raises the possibility of tailoring host-directed prophylaxis according to individual risk profiles. The observations presented here are hypothesis-generating and do not establish causality. Prospective controlled studies incorporating documented viral exposure, serial quantitative virological assessment, neutralizing antibody measurements, cellular immune profiling, and predefined risk stratification are required to determine whether BRH can reproducibly achieve infection sufficient for immune priming but pharmacologically constrained below the threshold for clinically significant disease.

Abstract: Sepsis-associated renal injury involves interacting oxidative, inflammatory, and microvascular mechanisms. Molsidomine, a nitric oxide donor, may modulate these pathways. We investigated whether molsidomine pretreatment attenuates renal injury in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty male Wistar albino rats were randomized to Sham, molsidomine (MOL), CLP, or MOL+CLP groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. At 24 h, renal biochemical, histopathological, and immunohistochemical outcomes were assessed. Seven septic animals died before the endpoint, resulting in outcome-specific numbers of evaluable animals. The primary outcome was total renal histopathological damage score. The total renal histopathological damage score was lower in MOL+CLP than CLP animals [median (IQR), 2 (1–3) vs. 5.5 (5–6); overall p < 0.001], with reductions across all four histopathological components. Renal MDA was lower in MOL+CLP than CLP animals (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), whereas SOD (36.23 ± 4.19 vs. 24.12 ± 2.23 U/g) and GPx (99.43 ± 26.38 vs. 61.54 ± 9.10 U/mg) activities were higher. VEGF and P-selectin H-scores were also markedly lower in MOL+CLP than CLP animals. Conversely, renal NO, GSH, TOS, OSI, and TNF-α and serum creatinine, BUN, and urea did not differ significantly between the two septic groups. Molsidomine pretreatment attenuated renal structural injury, selected redox abnormalities, and VEGF/P-selectin immunoreactivity in experimental polymicrobial sepsis. This renoprotective phenotype was not accompanied by uniform biochemical or renal functional improvement. These proof-of-concept findings warrant evaluation using post-sepsis treatment protocols and longer-term renal outcomes.

Abstract: Invasive fungal diseases (IFD) have become a routine diagnostic and therapeutic challenge in high-acuity hospitals worldwide, and Latin America presents a distinctive scenario in which opportunistic mycoses of tertiary care coexist with endemic dimorphic fungi, heterogeneous diagnostic capacity, and uneven antifungal access. This narrative review organizes a practical, clinically usable pathway for Latin American high-acuity hospitals, from the construction of a “window of suspicion” based on host risk factors, through the diagnostic work-up available in the region (non-culture biomarkers, molecular platforms, imaging, and histopathology), to syndrome-specific clinical pathways for candidemia, invasive aspergillosis, mucormycosis, and cryptococcal meningitis, including antifungal selection, dosing, and stewardship. We highlight where regional diagnostic and therapeutic constraints depart from guidance developed in high-resource settings and where structured clinical suspicion must substitute for advanced biomarkers. We conclude that early, syndrome-directed pathways adapted to local resource availability, rather than uncritical adoption of international algorithms, offer the most realistic route to earlier antifungal therapy and improved outcomes in Latin American high-acuity hospitals.

Abstract: Introduction: Infective endocarditis (IE) remains associated with high mortality, and the optimal timing of surgery in patients without an urgent indication remains uncertain. We evaluated the association between surgical timing, in-hospital mortality, and a study-specific ECHO risk score. Methods: We retrospectively studied 100 adults with definite IE treated at a tertiary care center in Bucharest, Romania. The ECHO score incorporated etiology, blood culture time to positivity, vegetation size, and embolization or surgical indication. Surgical timing was categorized as < 7 days, 7–14 days, or >14 days after hospital admission. The primary outcome was in-hospital mortality. Results: Eighty-two patients had a surgical indication, and 60 underwent surgery. Mortality was lowest after surgery at 7–14 days (23.1%), compared with >14 days (27.3%), no surgery despite indication (36.4%), and < 7 days (56.0%) (p = 0.123). Among patients with a non-urgent surgical indication, intermediate-risk patients had the lowest mortality after surgery at 7–14 days (25%), whereas no deaths occurred among surgically treated high-risk patients. ECHO risk category was not associated with mortality (p = 0.165). Conclusions: Surgery at 7–14 days was associated with the lowest observed mortality. These exploratory findings require confirmation in larger prospective studies.