Medicine and Pharmacology

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.

Abstract: Background: Candidemia carries case-fatality rates exceeding 30% in pediatric oncology cohorts from low- and middle-income countries. We describe a temporal cluster of culture-confirmed candidemia cases at King Hussein Cancer Center (KHCC), Amman, Jordan, coinciding with a novel environmental event, and the multidisciplinary infection prevention and control (IPC) response undertaken. Methods: Retrospective case series of 7 pediatric inpatients with culture-confirmed candidemia identified between June 1 and September 23, 2025, at a 330-bed tertiary oncology center, against a background rate of 1 confirmed case in the preceding 6 months. An additional 5 patients with clinically suspected invasive fungal infection (IFI) but negative blood cultures are described separately. Species identification was performed using the BioFire FilmArray Blood Culture Identification (BCID) panel (multiplex PCR); MALDI-TOF MS was additionally available; antifungal susceptibility was determined by Etest gradient diffusion. Results: The 7 confirmed cases comprised 6 males and 1 female (median age 12 years; range 1–17 years). Underlying diagnoses were predominantly leukemia (71%). All patients had a central venous catheter (CVC) in situ and recent broad-spectrum antibiotic exposure. Candida tropicalis was the predominant species (71%), with azole resistance identified in 40% of tested isolates. A plumbing infrastructure failure with an associated water leak was identified in late August 2025 during the cluster investigation; structural repair was completed in September 2025. The last confirmed case was recorded on September 23, 2025. All patients received guideline-concordant echinocandin- or amphotericin-based therapy. Candidemia-attributable mortality was 14% (1/7). Conclusions: A temporal cluster of 7 culture-confirmed candidemia cases — representing a 7-fold increase above background incidence — was identified at a Jordanian pediatric oncology center. The cluster coincided with a documented environmental water leak. Individual single-room isolation, geographic ward sectioning, contact precautions, hand hygiene monitoring, expanded antifungal prophylaxis with real-time protocol adjustment, and environmental remediation were all implemented and documented with defined operational criteria. These data demonstrate that a structured, criteria-driven IPC bundle is operationally feasible at a resource-limited tertiary oncology center.

Abstract: Gut‑associated lymph nodes (GALNs) constitute an important anatomical reservoir during early and chronic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, but the fate of this compartment during terminal AIDS remains unclear. This study investigated viral persistence and lymph node injury in a rhesus macaque with long‑term SIVmac239 infection and end-stage AIDS, characterized by profound CD4+ T cell depletion (30 cells/μL) and persistent viremia (1 192 copies/mL). At necropsy, GALNs, including mesenteric, paracolic, and ileocecal lymph nodes, and non‑gut‑associated lymph nodes (NGALNs), including hepatic hilar, common iliac, and inguinal lymph nodes, were collected for viral RNA/DNA quantification, histopathology, immunofluorescence, and transcriptomics. SIV DNA was markedly lower in GALNs than in NGALNs, whereas SIV RNA was detectable only in NGALNs. GALNs exhibited extensive fibrotic remodeling, paracortical collapse, severe CD4+ T cell loss across B cell and paracortical regions, and pronounced CD8+ T cell accumulation within B cell zones. Transcriptomic profiling further revealed an exhaustion signature in GALNs, with reduced DNA replication and repair, impaired cell-cycle activity, and suppressed RNA processing, accompanied by activation of innate immune programs and attenuation of adaptive immune responses. These findings indicate that, during terminal AIDS, GALNs no longer serve as the predominant viral reservoir but instead undergo preferential and severe structural and functional exhaustion. This case highlights marked anatomical heterogeneity in lymph node vulnerability during advanced disease and supports a model in which collapse of the gut‑associated immune barrier contributes to disease progression toward terminal AIDS.

Abstract: A pair of recent case–control studies (Bittoni et al., 2024, 2026) reported that dual use of combustible cigarettes (CC) and electronic cigarettes (EC) carries a substantially elevated risk of lung cancer relative to smoking alone, including for early-onset lung disease. We argue that these findings are likely strongly influenced by differential exposure ascertainment. In both studies, lung cancer cases were identified through hospital encounters in which risk-factor documentation was likely systematic, whereas EC use among controls was captured through routine outpatient records, where EC exposure was incomplete. The documented prevalence of EC use among controls was several-fold lower than contemporaneous U.S. and Ohio population estimates matched by age and geography, while cigarette smoking prevalence was high. This pattern is consistent with under-ascertainment of EC use in controls and consequent inflation of the reported dual-use odds ratios. In contrast, the ratio of dual use to cigarette smoking among cases was not elevated relative to comparable CDC general-population estimates. National SEER trends also do not support the hypothesis that EC use has produced an emerging signal of early-onset lung cancer: incidence has declined across major histologic subtypes and age strata since 2000, with the steepest declines observed among adults under 50 during the period of greatest EC market growth. Future studies should validate electronic medical record–based EC exposure capture and more precisely characterize EC use prevalence, timing, duration, intensity, former smoking, and exclusive EC use before drawing causal inferences about lung cancer risk.

Abstract: Objectives: This study aimed to characterize cefiderocol susceptibility distribution among Enterobacterales in Japan—specifically indigenous imipenemase (IMP)-producing strains—and explore the effect of IMP in mediating resistance. Methods: The susceptibility of 560 Enterobacterales isolates to cefiderocol was assessed using disk diffusion and broth microdilution methods based on Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) distributions across groups were compared using Kruskal–Wallis and Mann–Whitney U tests. Results: A total of 556 isolates yielded evaluable results. The cefiderocol susceptibility rate was 99.5 and 98.7 % based on CLSI and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. Notably, under both criteria, IMP-producing isolates exhibited a susceptibility rate of 99.6 %, whereas non-carbapenem-resistant Enterobacterales (CRE) and non-extended-spectrum β-lactamase (ESBL) exhibited 99.4 %. Statistical analysis revealed that the ESBL-only group had higher MICs than the non-CRE/non-ESBL and IMP-only groups (both p < 0.001), whereas no significant difference was observed between the latter two (p = 0.083). Notably, the ESBL-only group exhibited higher MICs than that of isolates harboring both IMP-type carbapenemase and ESBL. Conclusions: These findings indicate a non-additive effect, where the coexistence of multiple resistance enzymes does not necessarily increase cefiderocol resistance. The association between IMP and cefiderocol resistance may be limited. In specific enzyme combinations, its presence was even associated with lower MICs.

Abstract: Rabies remains a fatal zoonotic disease of major public health and veterinary importance in Latin America. Although canine-mediated rabies has markedly declined in Colombia, sylvatic transmission persists in rural regions, and information on equine rabies in Putumayo is scarce. This study aimed to describe the epidemiological, clinical, pathological, and surveillance characteristics of laboratory-confirmed equine rabies cases in Putumayo, southern Colombia, during 2024–2025. A retrospective descriptive study was conducted using national surveillance data. Thirteen equids exposed to the virus were identified. Five were classified as suspected cases, and all of them died; four were laboratory-confirmed. The remaining animals also died but were not reported to the Colombian Agricultural Institute (ICA) for sample collection; however, they exhibited clinical signs consistent with rabies. Epidemiological and clinical variables, necropsy findings, and diagnostic timelines were analyzed. Laboratory confirmation was performed using direct immunofluorescence and histopathology. The four confirmed cases occurred in four separate outbreaks. All affected equines were unvaccinated and raised under extensive management systems. Progressive neurological deterioration led to 100% case fatality. Pathological findings consistently demonstrated central nervous system involvement. The median times from symptom onset to notification were 7.5 days, and from notification to laboratory diagnosis were 9.0 days. This study provides the first detailed characterization of equine rabies in Putumayo, suggesting ongoing sylvatic transmission and gaps in preventive vaccination. Strengthening integrated surveillance and One Health strategies is essential to reduce the rabies burden.

Abstract: The association between obesity and a distinct, non-allergic, late-onset, neutrophilic asthma phenotype has been recognised for over two decades. However, establishing obesity as a causal factor rather than a comorbidity remains methodologically chal-lenging. Randomised allocation to obesity is neither feasible nor ethical. The relationship is mediated by a complex network of mechanical, immunometabolic, microbial, hor-monal, and epigenetic mechanisms. This review applies Sir Austin Bradford Hill’s nine viewpoints (1965) as a structured framework for causal inference to the 2020–2026 evi-dence linking obesity to non-T2 asthma. Evidence for strength (effect sizes 1.4–6.8; E-values 4.8–13.4; Mendelian-randomisation summary risk ratio 1.05 per 1 kg/m²), con-sistency (replication across continents, age groups, sexes, and study designs), temporality (cohort and life-course Mendelian-randomisation evidence), biological gradient (BMI dose–response with TNFα, IL-17A, and Th17 frequency), plausibility (a twelve-layer architecture from adipose dysfunction to bronchial epithelium), coherence with the natural history of the phenotype, experimental support (bariatric surgery, lifestyle weight loss, GLP-1 receptor agonist pharmaco-epidemiology, murine and in vitro stud-ies), and analogy with other obesity-related Th17 diseases collectively support a causal interpretation. Specificity, the weakest of Hill’s viewpoints, is satisfied at the phenotype level. Hill’s viewpoints are situated within the context of the 1964 U.S. Surgeon General’s Report, the GRADE framework, and contemporary counterfactual, directed acyclic graph, and Mendelian-randomisation methodologies, which serve as complementary tools. The cumulative evidence supports treating obesity as a cause of the late-onset, non-allergic asthma phenotype, with implications for primary prevention, endo-type-targeted therapy, and longitudinal research.

Abstract:

Septic arthritis due to non-typhoidal Salmonella (NTS) species is an exceptionally rare extraintestinal manifestation, accounting for less than 1% of invasive syndromes caused by this pathogen. It predominantly targets individuals with severe hematological malignancies or underlying osteoarticular vulnerabilities. A 69-year-old male with a history of primary myelofibrosis treated with chronic corticosteroids and Rituximab presented to the emergency department in septic shock secondary to acute monoarthritis of the left elbow. A diagnostic percutaneous joint aspiration was promptly performed, and cultures isolated Salmonella spp. The automated antimicrobial susceptibility report revealed a paradoxical phenotypic resistance profile (cefoxitin and amikacin resistance despite apparent third-generation cephalosporin susceptibility), suggesting plasmid-mediated AmpC production. Targeted antimicrobial therapy was successfully optimized with intravenous Meropenem to satisfy pharmacokinetic/pharmacodynamic (PK/PD) requirements within the inflamed synovial space, resulting in full clinical recovery and complete resolution of the infectious process.Primary myelofibrosis, compounded by targeted biological immunosuppression, induces a profound immunological breakdown that exponentially increases the risk of invasive NTS (iNTS) tissue seeding from transient gastrointestinal breaches. Clinicians operating in endemic areas of foodborne pathogens must maintain high suspicion for atypical focal infections. Furthermore, this case underscores the critical importance of diagnostic stewardship, demonstrating that looking beyond automated susceptibility labels is mandatory to prevent therapeutic failure in deep-seated, high-inoculum extraintestinal salmonellosis.

Abstract: Andes virus (ANDV) is unique among hantaviruses because person-to-person transmission ispossible. This raises questions on the relevance of post-exposure prophylaxis (PEP), particularlyfollowing high-risk household, healthcare-associated, or laboratory exposures, considering itshigh case fatality rate. Ribavirin has demonstrated antiviral activity against hantaviruses in vitroand in animal models, although clinical evidence supporting its use as treatment or PEP forANDV remains extremely limited. The available evidence consists primarily of cell cultureexperiments, Syrian hamster studies, pharmacokinetic and pharmacodynamic extrapolationsfrom other virusses, limited clinical data, and indirect clinical experience with other viralhemorrhagic fevers. This viewpoint summarizes the currently available evidence regardingribavirin as PEP after potential ANDV exposure. We discuss the knowledge gaps that may limitthe applicability of ribavirin PEP, to make informed decisions on the use of ribavirin in thesetting of PEP. Potential dosing strategies are visualized by modeling and simulation, andpotential dose and duration are discussed. Although the biologic rationale for ribavirin PEPappears compelling, the absence of controlled human studies and the potential toxicityassociated with ribavirin currently limit its role to highly selected exposure scenarios and useshortly after exposure.

Abstract: Background: Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. Despite several worldwide outbreaks, it is now considered as a rare disease by industrialized countries. Clinical manifestations usually account for oropharyngeal lesions but rare cases of systemic involvement (mainly endocarditis) had been described among non-toxigenic strains. Case description: We report the case of a patient who experienced septic shock, disseminated intravascular coagulation and multiorgan failure due to Corynebacterium diphtheriae infection. The pathogen was further characterized as a highly toxigenic strain. Infective endocarditis with mitral and aortic valves vegetations led to early multiorgan septic embolization. Major stroke, liver function impairment, heart failure and acute kidney injury were the main findings. Unlike the typical forms of infection caused by this pathogen, there was no evidence of airways or skin involvement. Furthermore, apart from hemocultures, none of the other investigations (pharyngeal swabs, bronchoalveolar lavages, urine culture) ever tested positive for the bacteria. Conclusions: The report we present describes a case of C. diphtheriae infection with much atypical characteristics: (i) lack of any pathognomonic signs or symptoms; (ii) extensive endocarditic process (very uncommon for toxigenic strains); (iii) early septic emboli development, with rapid evolution to multiorgan failure; (v) detection of disseminated intravascular coagulation. Despite disseminated intravascular coagulation is a known complication of septic shock, regardless for the etiological agent, by our literature research this is the first known case driven by C. diphtheriae infection in the adult.

Abstract: Background/Objectives: To our knowledge, this is the first study to simultaneously investigate the prognostic value of serum ferritin and procalcitonin (PCT) in relation to (SOFA)-2 score-based organ dysfunction severity in intensive care patients diagnosed with COVID-19-associated sepsis. Methods: Patients were stratified based on day 5 ferritin (ng/mL) and PCT levels (μg/L). Prognostic performance was analysed across severity groups defined by (SOFA)-2 score of &lt;5 (mild) and ≥5 (severe). Results: Day 5 PCT levels did not significantly predict (SOFA)-2 score (p &gt; 0.05). The optimal day 5 ferritin cut-off was &gt;1,191 ng/mL, with 35.78% sensitivity and 82.38% specificity (AUC = 0.608). Elevated ferritin levels may help identify patients at higher risk of adverse outcomes who may benefit from closer monitoring or intensive care escalation. By contrast, PCT did not provide additional predictive value for organ dysfunction severity in COVID-19 beyond existing inflammatory markers, consistent with its known suppression during primary viral infections. Conclusions: Serum ferritin showed a significant positive association with (SOFA)-2 score, supporting its role as a clinically relevant biomarker for disease stratification in COVID-19-associated sepsis. These findings may extend to non-COVID sepsis populations where macrophage activation and iron dysregulation drive organ dysfunction.

Abstract:

Osteoarticular infections (OAIs) present a significant diagnostic and therapeutic challenge to paediatric clinical practice. When evaluating suspected paediatric OAIs, the principal pathogens commonly considered are Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Kingella kingae. Osteoarticular infections (OAIs) present a significant diagnostic and therapeutic challenge to paediatric clinical practice. When evaluating suspected paediatric OAIs, the principal pathogens commonly considered are Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Kingella kingae. Consequently, comprehensive knowledge about these emerging, atypical bacterial pathogens is essential to ensure accurate diagnoses and appropriate therapeutic interventions. This review summarises uncommon, fastidious, and emerging bacterial pathogens responsible for OAIs in immunocompetent children. We describe their microbiological characteristics and clinical phenotypes and examine potential diagnostic pitfalls and organism-specific diagnostic strategies.

Abstract: Hantaviruses are emerging rodent-borne pathogens that pose increasing global public health concerns due to their association with hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), both of which can result in substantial morbidity and mortality. Environmental change, climate variability, urbanization, and land-use transformation are increasingly recognized as critical drivers of hantavirus emergence and transmission. This review summarizes current evidence regarding hantavirus virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, surveillance systems, prevention strategies, and One Health preparedness approaches. Emphasis is placed on the influence of climate change and ecological disruption on rodent reservoir dynamics and spillover risk, as well as major surveillance and diagnostic gaps in tropical and Caribbean regions where hantavirus circulation may be underrecognized. Advances in molecular diagnostics, genomic surveillance, vaccine development, monoclonal antibody therapies, and climate-based early warning systems are also discussed. Existing evidence highlights the importance of integrated One Health surveillance systems that combine human, animal, and environmental monitoring to improve early detection and outbreak preparedness. Strengthening laboratory capacity, ecological surveillance, regional collaboration, and public health infrastructure will be essential for reducing the global burden of hantavirus infections and improving preparedness for future zoonotic disease threats.

Abstract: Background: African Union (AU) guidance identifies decentralized diagnostics as central to epidemic preparedness. However, the epidemiological role of self-testing across epidemic-prone diseases remains underexplored. Drivers for potential impact of self-testing impact were examined conceptually using a transmission model. Methods: A deterministic SEIR model compared standard-of-care testing with additional self-testing. Global sensitivity analysis using Latin Hypercube sampling and partial rank correlation coefficients (PRCCs) examined parameters influencing reductions in peak disease prevalence (mitigation). Dynamics were illustrated using AU pathogen archetypes (Ebola, Influenza A, Cholera, Coronavirus, and Mpox), estimating the number needed to self-test (NNST) to avert one death as a measure of marginal efficiency. Results: Epidemic mitigation was minimal (median 1.9%; IQR: 0.4%–5.8%); correlated with isolation adherence (PRCC = 0.784), self-testing intensity (PRCC = 0.617), lower R0 (basic reproductive number; PRCC = -0.607) and greater duration of infectiousness (PRCC = 0.370). Achieving a 10% reduction in peak prevalence at R₀ = 1.1 required 34 self-tests per 10,000 people per day, exceeding AU COVID-19 operational benchmark of 10 per 10,000 per week. High-mortality, moderate-transmission archetypes (e.g., Ebola) were most responsive to mortality reductions (Median 1,512 NNST/death averted) compared to Mpox (Median 355,708 NNST/death averted). Adherence to post-test isolation exerted greater epidemiological impact than diagnostic accuracy. Conclusions: The epidemiological value of untargeted self-testing depends on pathogen characteristics and post-test behavioral adherence. Epidemic mitigation effects were generally limited under constrained health-system capacity. However, future demonstration studies evaluating rapid, early decentralized self-testing deployment during Ebola-archetype outbreaks may help identify operationally feasible targeted deployment strategies to support mitigation and mortality reduction.

Abstract: Background: Skin grafts including split-thickness skin grafts (SSG) and full-thickness skin grafts (FTSG) are widely used in reconstructive surgery. Infection following grafting can compromise graft take and prolong hospitalisation, yet contemporary cohort data describing incidence, microbiology and graft-specific risk factors remain limited. Methods: We conducted a retrospective observational cohort study of 977 consecutive skin graft procedures performed in 116 patients at two hospitals in New South Wales, Australia, between 1 July 2021 and 13 August 2024. Post-graft infection was defined as a clinician-diagnosed graft site infection with microbiological confirmation. Infection incidence was estimated with exact 95% confidence intervals. Associations between graft characteristics and infection were explored using chi-square testing and binomial regression to estimate relative risks. Length of stay (LOS) was assigned to the index admission corresponding to each procedure and analysed using negative binomial regression to account for overdispersion. Results: Among 977 graft procedures, 66 infections occurred, giving an overall infection incidence of 6.8% (95% CI 5.3–8.5%). Median LOS was substantially longer in infected cases than non-infected cases (34 vs 3 days, p < 0.001). Full-thickness grafts to the face (RR 0.083, 95% CI 0.008–0.827) and nose (RR 0.038, 95% CI 0.004–0.378) were associated with a reduced incidence of infection, although estimates were imprecise because of sparse data. Among infections, Staphylococcus aureus accounted for approximately 47% of cases and Pseudomonas aeruginosa for approximately 20%. In a nested antimicrobial audit cohort of 111 split-thickness skin graft procedures, peri-operative prophylaxis was common, postoperative antibiotics were frequently prescribed, and postoperative antibiotic prescribing was not associated with reduced infection, although the analysis was underpowered. Conclusions: Post-graft infection occurred in 6.8% of procedures. This rate is comparable with contemporary literature and was associated with substantial morbidity. S. aureus and P. aeruginosa predominated. These findings support consideration of targeted preventive strategies, microbiology-informed empiric therapy and antimicrobial stewardship, while highlighting the need for prospective studies with more comprehensive risk adjustment.

Abstract: Background: Staphylococcus argenteus is a recently recognized member of the Staphylococcus aureus complex that is almost identical to S. aureus phenotypically and by 16S rRNA gene sequences. Although genomic analyses demonstrate that S. argenteus is phylogenetically distinct from S. aureus, the two species exhibit more than 90% nucleotide identity and routine identification methods—including routine biochemical assays and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)—cannot reliably distinguish between the two. Objectives: We develop and validate a MALDI-TOF MS–based model for accurate identification of S. argenteus. Methods: A multiplex PCR assay targeting crtM and NRPS genes served as the reference standard. MALDI-TOF MS spectra from 25 S. argenteus and 25 methicillin-susceptible S. aureus (MSSA) isolates were analyzed using ClinProTools to identify characteristic peaks and develop the identification model. The model was validated using 40 S. argenteus and 80 MSSA isolates, then applied to 130 randomly selected clinical isolates. Results: Five characteristic peaks—m/z values 5005, 5285, 5323, 6440, and 6526—were identified. Isolates exhibiting at least 4 of these 5 peaks were classified as S. argenteus; those exhibiting fewer than 4 were classified as S. aureus. The model achieved 100% specificity and 100% sensitivity in both the development and validation phases. In the clinical application phase, the model correctly classified all isolates, whereas conventional MALDI-TOF MS yielded several misidentifications. Conclusions: The identification model, and the simple peak-based rule it is based on, can accurately distinguish S. argenteus from MSSA, offering a practical diagnostic tool for clinical microbiology laboratories.

Abstract: Isavuconazole is increasingly being used for the treatment of invasive fungal disease (IFD), although real-world pediatric data remain limited. We retrospectively reviewed patients aged ≤18 years who received isavuconazole for fungal infection at two tertiary centers in Chile between 2021 and 2025. Twenty patients were included, with a median age of 13.7 years (IQR, 9.4–15.5); 14 (70%) had an underlying malignancy, and 6 (30%) were allogeneic hematopoietic cell transplant recipients. Isavuconazole was used for treatment in 16 patients and for prophylaxis in 4, predominantly as second-line therapy due to prior antifungal intolerance, inadequate response, drug–drug interactions, or QT prolongation. Fifteen patients had IFD, with Mucorales (n=3) being the most frequently identified pathogens in proven cases and pulmonary involvement predominating in probable IFD. A succesful response at 90 days was achieved in 60% (6/10) of evaluable cases. No breakthrough fungal infections occurred during treatment or prophylaxis. Hepatic enzyme elevations were observed in four patients. Isavuconazole was associated with favorable outcomes and an acceptable safety profile, supporting its use as an alternative antifungal in pediatric patients.

Abstract: Background: Respiratory infections in critically ill patients remain a major challenge in intensive care units (ICUs), with high morbidity and mortality. Conventional microbiological methods often fail to identify the causative pathogen promptly, particularly in patients previously exposed to antibiotics. Multiplex molecular platforms, such as the BioFire FilmArray® Pneumonia Panel Plus (FAPP), allow rapid detection of multiple respiratory pathogens and resistance markers, potentially improving early therapeutic decision-making. Objectives: To evaluate the impact of implementing FAPP on antimicrobial therapeutic decisions in critically ill patients with suspected respiratory infection. Methods: We conducted a retrospective cohort study in two mixed ICUs between 2023 and 2024. All respiratory samples in which FAPP was requested were analyzed. Results were compared with conventional cultures, and changes in antimicrobial therapy following FAPP results were assessed, classified as escalation/initiation or de-escalation/discontinuation. Concordance between FAPP and culture was evaluated, and clinical and demographic variables were analyzed. Differences between groups were assessed using p-values obtained from the chi-square test or the Mann–Whitney test. Results: A total of 363 respiratory samples were included, 88.4% from mechanically ventilated patients. FAPP was positive in 65.3% of samples, whereas cultures were positive in 23.1%. Overall concordance between FAPP and culture was 57.3%. In 42.4% of cases, pathogens were detected exclusively by FAPP. Antimicrobial therapy was modified in 29.8% of patients, predominantly through de-escalation or discontinuation (69.4% of changes). Therapeutic modifications were more frequent in nosocomial infections and in patients with a positive FAPP result. Conclusions: The use of FAPP in critically ill patients with suspected respiratory infection provides rapid microbiological information that significantly influences antimicrobial decision-making, particularly by facilitating antibiotic de-escalation. Although discrepancies with conventional cultures remain and require careful clinical interpretation, FAPP represents a valuable tool for antimicrobial stewardship in the ICU setting.