Search Results (388)

Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by diagnostic uncertainty, corticosteroid-modified disease, reinfection, inadequate exposure, poor adherence, and limited drug delivery within keratinized tissues. This narrative review was developed to clarify the distinction between true antifungal resistance and clinical recalcitrance, with particular attention to terbinafine-resistant Trichophyton species, Trichophyton indotineae, tinea incognito, onychomycosis, dermatophytoma, and high-barrier skin and nail infections. We synthesized peer-reviewed literature and guideline-level evidence addressing epidemiology, molecular mechanisms of resistance, clinical phenotypes of recalcitrance, diagnostic escalation, therapeutic decision-making, and antifungal delivery in keratinized tissues. The review contributes a dermatology-centered conceptual framework in which persistent dermatophytosis is interpreted through both microbiological resistance and modifiable recalcitrance drivers. This approach emphasizes confirmation of fungal disease when indicated, phenotypic and anatomic classification, avoidance of inappropriate corticosteroid combinations, optimization of dose, duration, vehicle, and adherence, measures to improve drug access and reduce protected fungal burden in high-barrier disease, and prevention of reinfection from reservoirs. The proposed framework may support more rational antifungal use and reduce unnecessary escalation; however, it is based on narrative synthesis rather than a systematic review or prospective validation. Additional studies are needed to determine how such structured clinical approaches affect clinical outcomes, relapse rates, antifungal exposure, and resistance emergence in real-world dermatology practice. Full article

Background/Objectives: This preliminary, single-centre study evaluated infectious diseases consultation (IDC) patterns as indicators of hospital workflow and care complexity, aiming to characterise routinely available variables that may inform future organisational research and EHR-based clinical decision support development. Methods: In this retrospective study, 39,275 IDC requests from 16,430 patients were analysed using hospital information management system records. Paediatric patients and specialised immunosuppressed patient units were excluded. Request volumes, diagnostic categories, consultation purposes, and factors associated with in-hospital mortality were evaluated. Multivariable logistic regression models were constructed separately for two hospital blocks. Results: A total of 39,275 IDC records for 16,430 unique patients were reviewed. Mean consultation access time was 82.2 ± 64.3 min. Requests originated from surgical clinics (43.8%), followed by intensive care units (37.6%) and medical/internal clinics (18.6%). Pneumonia was the most common indication (30.5%), followed by unspecified infections (25.4%) and skin/soft tissue infections (17.2%). Consultation objectives included treatment, diagnostic assessment, and clinical guidance as non-mutually exclusive components. Significant block-level differences were observed in consultation timing, ICU-related consultation, diagnostic profiles, consultation purposes, and mortality. Age and ICU-related consultation were independently associated with mortality in both blocks, whereas consultation access time and COVID-19 diagnosis showed block-specific associations. Conclusions: IDC patterns may reflect not only diagnostic demand but also case severity, ICU-related care, consultation timing, and hospital location. As a preliminary single-centre study, these hypothesis-generating findings highlight the importance of integrating clinical, organisational, and contextual variables in future prospective, multi-centre studies aimed at developing EHR-based decision-support models. External validation, incorporation of comorbidity indices and microbiological data, and assessment of explainability are required before clinical implementation. Full article

Dental caries is a biofilm-mediated dysbiotic disease characterized by ecological shifts within the oral microbiome and progressive demineralization of dental hard tissues. The microbiological composition of carious dentin and the impact of minimally invasive excavation techniques on residual microbial communities remain subjects of ongoing investigation due to methodological heterogeneity and inconsistencies among published studies. This narrative review aimed to summarize current evidence regarding the microbial ecology of carious dentin, compare culture-based and molecular methods for microbiological assessment, and evaluate the microbiological outcomes associated with contemporary approaches to managing minimally invasive caries. The relevant literature on dentinal caries microbiology, microbial detection methods, and excavation techniques was analyzed. The available evidence indicates that carious dentin contains a highly diverse polymicrobial community composed of acidogenic, aciduric, anaerobic, and proteolytic microorganisms. Culture-based methods primarily detect viable and cultivable taxa, whereas molecular approaches reveal substantially greater microbial diversity, including uncultivable and low-abundance species. Comparative studies demonstrate that minimally invasive excavation techniques significantly reduce microbial load but rarely achieve complete microbial elimination. The available evidence suggests that successful caries management is associated with a reduction in and ecological modulation of the residual microbiota within a sealed environment. The integration of culture-based and molecular findings provides a more comprehensive understanding of the microbiology of carious dentin and supports biologically oriented, minimally invasive strategies for caries management. Full article

Background/Objectives: Pregnancy is characterized by complex physiological, hormonal, and immunological changes that influence the oral environment and the microbial composition of the oral cavity. Emerging evidence suggests that maternal oral dysbiosis may be associated with systemic inflammatory responses and may potentially influence pregnancy outcomes. This systematic review aimed to evaluate the current clinical evidence regarding the association between maternal oral dysbiosis and adverse pregnancy outcomes, including preterm birth, low birth weight, and gestational complications. Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted for studies published between January 2013 and September 2025. Observational studies and clinical trials examining the relationship between maternal oral dysbiosis or periodontal pathogens and pregnancy outcomes in pregnant women were included. Study selection was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, and the review was prospectively registered in PROSPERO (CRD420261383855). Data were extracted on the study design, population characteristics, microbiological assessment methods, and reported pregnancy outcomes. Ten studies met the inclusion criteria of this review. Results: Seven of the ten included studies reported significant associations between the increased prevalence of periodontal pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia, and adverse pregnancy outcomes, particularly preterm birth and low birth weight (LBW). Several studies have identified oral bacterial DNA in placental tissues, supporting the potential hematogenous microbial translocation pathways. However, heterogeneity in microbiological assessment techniques and study designs limits the comparability of the findings. Conclusions: Current evidence suggests that maternal oral dysbiosis may be associated with the inflammatory pathways linked to adverse pregnancy outcomes. Further prospective studies and standardized microbiome analyses are required to clarify the role of the oral microbiome in maternal and fetal health. Integrating oral health assessments into prenatal care may be an important strategy for improving maternal and neonatal outcomes. Full article

Fever of unknown origin (FUO) remains a persistent diagnostic challenge in clinical medicine despite significant advances in laboratory testing and imaging techniques. The definition of FUO has evolved since the original criteria proposed in 1961 and currently refers to persistent fever exceeding approximately 38.2–38.3 °C without a definitive diagnosis after an adequate diagnostic evaluation. Gastrointestinal diseases represent an important but often underrecognized group of conditions associated with FUO. The aim of this review is to synthesize current evidence on the gastroenterological causes of FUO, with particular emphasis on pathophysiological mechanisms, diagnostic strategies, and therapeutic management. The analysis highlights the role of inflammatory, infectious, and neoplastic gastrointestinal disorders in the etiology of prolonged fever. Key mechanisms involve systemic inflammatory responses mediated by cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor, as well as immune processes associated with the gut-associated lymphoid tissue (GALT) and interactions between intestinal microbiota and host immunity. Among the most frequently reported gastroenterological causes of FUO are inflammatory bowel diseases, intra-abdominal infections and abscesses, hepatobiliary disorders, pancreatitis, and gastrointestinal malignancies. Diagnostic evaluation requires a stepwise approach integrating laboratory testing, microbiological studies, imaging modalities, and endoscopic procedures, with advanced techniques such as computed tomography and fluorodeoxyglucose positron emission tomography improving detection of occult inflammatory or neoplastic processes. Therapeutic management is primarily guided by the identification of the underlying cause, while empirical treatment should be carefully considered to avoid masking diagnostic clues. A better understanding of the gastrointestinal mechanisms underlying FUO and the development of more efficient diagnostic algorithms may improve clinical outcomes and reduce the number of undiagnosed cases. Full article

Nocardia spp. and Mycobacterium spp. are known etiological agents of granulomatous pulmonary infections in humans and animals; however, co-infections involving these pathogens have not previously been reported in veterinary medicine. This paper describes the first documented case of co-infection with Mycobacterium bovis and Nocardia spp. in a captive roan antelope (Hippotragus equinus). The animal was a 9-year-old female roan antelope from a safari park in northern Italy that died suddenly with a one-month history of weight loss. Post-mortem examination revealed severe, diffuse, chronic granulomatous pneumonia associated with fibrino-granulomatous pleuritis and granulomatous pericarditis. Histologically, multifocal to coalescing necrotizing granulomas were observed, with intralesional acid-fast bacteria. Microbiological culture and biomolecular analyses allowed the identification of M. bovis and Nocardia spp. in lung tissue samples. The Nocardia genome sequence was 98.5% similar to N. tengchongensis, a recently discovered species. The findings emphasize the importance of comprehensive diagnostic approaches in animal granulomatous lung disease. Mixed infections in captive wildlife represent a One Health concern, as the potential for zoonotic adaptation and transmission to humans cannot be excluded. Therefore, pathogen surveillance is of particular importance within zoological collections. Full article

Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings suggestive of systemic dissemination and public health implications. This study aimed to investigate a fatal case of C. difficile infection in a farmed rabbit and to characterize the pathogen’s microbiological, toxigenic, and antimicrobial profile. Methods: An 11-month-old male German Giant Spotted rabbit presenting acute diarrhea, anorexia, and rapid deterioration after unsupervised administration of enrofloxacin and sulfaquinoxaline was submitted postmortem. Necropsy was performed, and samples from cecum, colon, liver, spleen, mesenteric lymph nodes, lungs, and femoral bone marrow were collected. Microbiological analysis included selective culture on CCFA medium, ELISA for toxin A and B detection, MALDI-TOF MS identification, PCR confirmation, and antimicrobial susceptibility testing with the VITEK 2 system. Histopathological examination was conducted on intestinal and parenchymal tissues. Results: Necropsy revealed severe congestion and necrosis of the cecal and colonic mucosa, hepatomegaly, splenic congestion, and petechial hemorrhages. C. difficile was isolated from intestinal sites, confirmed as toxigenic by ELISA and PCR. Histopathology showed necrotizing colitis with epithelial desquamation, fibrin deposition, and heterophilic infiltration. The strain exhibited resistance to clindamycin, ampicillin, and tetracycline, with susceptibility to vancomycin, linezolid, and tigecycline. Conclusions: This case demonstrates that C. difficile can cause severe disease in rabbits, particularly following antimicrobial-induced dysbiosis. The findings underscore the importance of prudent antibiotic use, monitoring of toxigenic strains in rabbit populations, and implementation of preventive strategies to mitigate health risks in both animals and potentially humans. Full article

Post-acute sequelae of SARS-CoV-2 infection (PASC) extend well beyond the acute respiratory phase, with accumulating virological evidence that SARS-CoV-2 RNA, viral antigens, and proteolytic fragments may persist in cardiovascular and other extrapulmonary tissues, although the extent to which such detection represents replication-competent reservoirs versus residual viral material with uncertain pathological relevance remains under active investigation. Sudden cardiac death (SCD) and fatal pulmonary thromboembolism (PTE) have emerged as forensically and epidemiologically significant outcomes in individuals with prior infection, situated at the intersection of microbiology, public health, and forensic medicine. To synthesize current evidence on the virological mechanisms by which SARS-CoV-2 may contribute to post-acute sudden cardiac death (SCD) and pulmonary thromboembolism (PTE), the population-level epidemiology of these outcomes, and their implications for public health surveillance and forensic practice, we conducted a narrative review of PubMed (MEDLINE), Scopus, and Web of Science Core Collection. The search covered publications from January 2020 to December 2025 and focused on SARS-CoV-2 cellular tropism and tissue persistence, immune-mediated and thromboinflammatory mechanisms, excess cardiovascular and thromboembolic mortality, and autopsy-based pathological findings. After de-duplication of 1837 initially identified records (412 duplicates removed) and screening of 1425 unique records, 78 studies were retained for final synthesis based on virological, epidemiological, and forensic relevance. SARS-CoV-2 enters cardiomyocytes, pericytes, and vascular endothelial cells through ACE2-dependent mechanisms, with cathepsin L compensating for the limited cardiac expression of TMPRSS2. Viral RNA and antigen have been detected in cardiovascular and other extrapulmonary tissues months after symptom onset in selected autopsy series, although persistent detection of viral components does not necessarily indicate ongoing productive infection or direct tissue injury. Endothelial dysfunction, neutrophil extracellular trap (NET) formation, complement activation, and persistent thromboinflammation have been proposed as plausible mechanistic substrates for arrhythmogenic remodelling and thromboembolic events, although definitive causal pathways remain incompletely understood. Population-based studies document persistent excess cardiovascular mortality across multiple jurisdictions, with hazard ratios for pulmonary embolism remaining elevated months after acute infection, particularly in unvaccinated individuals. Autopsy series identify mixed pathological patterns including focal lymphocytic infiltrates, microvascular thrombosis, contraction-band necrosis, and cardiomyocyte vacuolation, although fulminant lymphocytic myocarditis fulfilling Dallas criteria remains uncommon. A microbiology-informed framework uniting tissue-based viral detection, standardized cardiac and pulmonary sampling protocols, and prospective post-mortem registries is needed to better characterize the potential contribution of SARS-CoV-2 to post-acute cardiovascular mortality and to support cause-of-death certification, public health surveillance, and medicolegal practice in the post-pandemic era. Many of the proposed mechanisms remain under active investigation, and definitive causal relationships between viral persistence and adverse cardiovascular outcomes have not yet been conclusively established. Full article

Background/Objectives: The increasing emergence of antimicrobial-resistant Staphylococcus pseudintermedius has limited the effectiveness of conventional therapies for canine pyoderma, highlighting the need for alternative topical strategies. This study aimed to develop hydrogels incorporating essential oils (EOs) from Peumo (Cryptocarya alba) and Tepa (Laureliopsis philippiana) as potential topical treatments against Staphylococcus pseudintermedius skin infections in veterinary medicine. Methods: EOs were obtained by steam distillation, chemically characterized by gas chromatography–mass spectrometry (GC–MS), and evaluated for antibacterial activity against S. pseudintermedius strains. Carbopol^®-based hydrogels incorporating the EOs of C. alba (HCA), L. philippiana (HLP), and a control vehicle (HVE) were formulated and characterized in terms of physicochemical properties, microbiological safety, and stability under accelerated and refrigerated conditions. Preclinical dermal safety was evaluated in BALB/c mice by repeated topical administration for five days. The analysis included clinical observation, skin irritation scoring, and histological analysis. Additionally, a preliminary microbiological evaluation was conducted in client-owned dogs with superficial pyoderma to assess the performance of the formulations in the target species. Skin lesion swabs were collected at baseline and after 21 days of treatment, followed by bacterial culture and automated identification using the VITEK^® system. Bacterial detection and bacterial load were evaluated to determine changes in microbiological status over the treatment period. Results: GC–MS analysis identified sabinene and eucalyptol as the main compounds in CA-EO, and linalool, eucalyptol, and safrole in L. philippiana EO. Both EOs exhibited moderate antibacterial activity against S. pseudintermedius (inhibition zones 4.9–10.8 mm; MIC ≥ 2.048 mg mL⁻¹). The hydrogels were microbiologically safe. Among formulations, HLP demonstrated superior physical stability and comparable rheological properties to the vehicle. In vivo safety evaluation demonstrated no signs of systemic toxicity, behavioral alterations, or skin irritation, and histological analysis confirmed preserved skin architecture without evidence of inflammation or tissue damage. In the preliminary microbiological evaluation in dogs, all animals were positive for Staphylococcus spp. at baseline. On Day 21, bacterial elimination was observed in the active treatment groups, but not in the HVE group, with elimination rates of 50.0% for Inveclor^® and 25.0% for both HCA and HLP. In parallel, HLP showed the highest proportion of dogs reaching minimal bacterial load levels (75%), followed by Inveclor^® (50.0%) and HCA (37.5%), whereas no dogs in the vehicle group reached this category. Conclusions: EOs from C. alba and L. philippiana presented antibacterial activity and were successfully incorporated into microbiologically safe hydrogel formulations. Notably, HLP demonstrated superior stability and a favorable preclinical safety profile, supporting its potential. In the preliminary microbiological evaluation in dogs, numerical differences in bacterial elimination and bacterial load categories were observed among groups; however, these differences were not statistically significant and should be interpreted as exploratory. Full article

Agricultural soils worldwide are facing escalating contamination by heavy metals, which present high risks for health due to their persistence, being non-biodegradable, accumulating across the soil profile, and being easily transferred into edible plant tissues, thus propagating through the food chain, with serious consequences for human health and ecosystem integrity. Conventional physical and chemical remediation approaches are costly, ecologically disruptive and operationally complex for the extent of contamination of agricultural land. Thus, there is an urgent need for sustainable and scalable alternatives. This review addresses the need by providing an integrated, mechanistically grounded synthesis of plant-based bioremediation strategies for heavy metal contamination removal, emphasizing the links between soil chemistry, plant physiology, and soil microbiology. First, the principal contamination pathways and controls on metal speciation and bioavailability are summarized, highlighting how parameters such as pH, organic matter, clay minerals, and redox conditions govern the metal fraction available for the plants. The molecular basis of plant heavy metal uptake, translocation and detoxification is examined in detail, including transporter-mediated root uptake, xylem loading and long-distance transport, and chelation by phytochelatins and metallothioneins. The performance and limitations of the main phytoremedation strategies are evaluated across representative hyperaccumulator species, then two major enhancement solutions are discussed: chemical enhancement using synthetic and biodegradable agents, and biological enhancement through plant growth-promoting rhizobacteria, arbuscular mycorrhizal fungi, and mycoremediation fungi. Integrating these perspectives, this review provides a critical assessment of when and how phytoremediation can offer a realistic and agronomically compatible route for managing heavy metal contamination in agricultural soils. Full article

Brucellosis remains a significant zoonotic disease globally, causing considerable economic and public health consequences, particularly in high-risk areas of South Africa (SA) with extensive animal production, including the Limpopo and Free State provinces. This study used a combination of serological, microbiological, and molecular assays to investigate the prevalence and characteristics of Brucella in 580 slaughtered livestock (384 cattle and 196 sheep) in Limpopo and the Free State (192 cattle and 98 sheep in each province) and to compare the diagnostic findings obtained using these assays. Tissue samples collected from each animal included liver, lung, spleen, and lymph nodes. Using the standard diagnostic rose Bengal test (RBT) and complement fixation test (CFT) in series (RBT-CFT), only 2.6% (10/384) of cattle were positive, with 2.1% (95% CI: 0.7–4.9) and 3.1% (95% CI: 1.3–6.3) in the Free State and Limpopo, respectively, while 4.7% (18/384) were positive by RBT-indirect enzyme-linked immunosorbent assay (iELISA), with 5.2% (95% CI: 2.7–9.0) and 4.2% (95% CI: 2.0–7.7) in the Free State and Limpopo, respectively. The molecular prevalence was 18.5% for Brucella deoxyribonucleic acid (DNA), while 97% of PCR-positive cattle tested seronegative in both provinces. Ovine samples were largely seronegative despite showing higher polymerase chain reaction (PCR) positivity (28.6%). Brucella abortus predominated in both species, with B. melitensis and occasional mixed infections also detected. Mixed infections in this study were defined as samples producing multiple species-specific bands within the same sample, consistent with the presence of more than one Brucella species during multiplex PCR analysis. While liver and spleen tissue provided reliable PCR detection, bacterial culture yielded a 0% isolation rate. These findings, together with reports from studies in brucellosis-endemic areas in sub-Saharan Africa, demonstrate discrepancies between traditional serological methods and molecular methods, including detection of Brucella DNA in seronegative animals. This may indicate that some infected animals (chronic or latent carriers) are not identified by conventional serological assays alone, particularly in endemic settings. To strengthen surveillance and enhance the detection of exposed animals, the incorporation of iELISA as a complementary tool into South Africa’s routine surveillance programmes may be beneficial, particularly when combined with regular testing of all animals. Full article

The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4⁺ T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome–HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions—including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics—and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication. Full article

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacterium (NTM) that can infect both immunocompetent and immunocompromised hosts. Cutaneous and soft tissue infections are the most common manifestations and occur more frequently in individuals with underlying immune dysfunction. Patients with chronic lymphocytic leukemia (CLL), particularly those receiving targeted therapies such as ibrutinib, may be at increased risk of opportunistic infections. The diagnostic workup, microbiological findings, antimicrobial susceptibility testing, and therapeutic approach adopted for a cutaneous M. chelonae infection arising in a CLL patient four months after the introduction of ibrutinib were described. Clinical course and surgical management are also reported. A 60-year-old beekeeper with B-cell CLL developed a progressive cutaneous lesion on the left lower limb within four months of starting ibrutinib. Culture of a skin biopsy identified M. chelonae. Antimicrobial therapy was initiated based on in vitro susceptibility testing, resulting in partial clinical improvement. Complete resolution required surgical excision of the infected tissue followed by skin grafting. The patient’s underlying hematologic disease, ongoing immunosuppression, and recent exposure to ibrutinib likely contributed to susceptibility and persistence of infection. This case highlights the increasing recognition of nontuberculous mycobacterial infections in immunocompromised individuals and underscores the importance of early diagnosis and susceptibility- guided therapy. Clinical response may be incomplete, and combined medical and surgical approaches may be required in selected cases. NTM infections should be considered in patients receiving Bruton’s tyrosine kinase inhibitors who present with persistent, atypical, or non-healing cutaneous lesions. However, the association between ibrutinib therapy and susceptibility to infection remains uncertain, as multiple predisposing factors may coexist. Increased awareness of this possible association, together with careful clinical evaluation, may facilitate earlier diagnosis and improved management. Full article

Background: Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue infection characterized by fascial necrosis, with mortality rates of 20–30%. Despite its rarity, NF is increasingly encountered due to the rising prevalence of predisposing factors. Data from Southern European tertiary centers remain scarce. Methods: We retrospectively reviewed all patients ≥18 years with radiological and/or surgical diagnosis of NF managed at IRCCS Policlinico San Matteo, Pavia, Italy, between November 2018 and August 2023. Clinical, microbiological, and treatment data were extracted from electronic medical records. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated retrospectively. The Charlson Comorbidity Index was computed for each patient. Given the small sample size, we adopted a purely descriptive analytical approach without inferential testing. Results: Thirteen patients met inclusion criteria (median age 58 years, IQR 44.5–79.5; 69.2% male). The most common comorbidities were diabetes mellitus (6/13, 46.2%), renal failure (4/13, 30.8%), and chronic liver disease (4/13, 30.8%). The age-adjusted Charlson Index ranged from 0 to 11 (median 4). Lower limbs were the most frequently affected anatomic site (5/13, 38.5%), followed by the perineal/genital region (Fournier gangrene, 4/13, 30.8%). Type II (monomicrobial) NF predominated (9/13, 69.2%). Microbiological cultures were positive in 8/13 patients (61.5%): Gram-positive cocci were isolated in 5/8 (62.5%) and mixed aerobic/anaerobic flora in 3/8 (37.5%). Empirical antibiotic regimens included a piperacillin–tazobactam backbone in 6/12 (50.0%) patients and a meropenem-based combination in 5/12 (41.7%); 6/12 patients underwent targeted de-escalation after culture results. Two patients (15.4%) died in hospital, both with Fournier gangrene and Type I infection (mortality 2/4, 50.0% in Type I vs. 0/9 in Type II). The median length of stay was 26 days (IQR 17–28.5). All patients had LRINEC ≥6 at admission, with 9/13 (69.2%) classified as high risk (≥8). Conclusions: In this small retrospective Italian cohort, NF was most frequently associated with diabetes and high comorbidity burden. Type I (polymicrobial) infections, predominantly involving the perineal region, showed worse outcomes than Type II infections. The clinical experience accumulated during this study period subsequently informed the development of an institutional empirical antimicrobial protocol for skin and soft tissue infections at our hospital. Full article

Microbiological culture and histology of deep tissue specimens are independent diagnostic criteria in fracture-related infection (FRI). However, the association between these tests has rarely been investigated, particularly in relation to clinical outcome after treatment. Patients undergoing surgery for International Consensus-confirmed FRI were included. All had ≥5 tissue specimens taken for microbiological culture and 2–3 for histology. The correlation between cultured pathogen, histological positivity (defined as ≥5 polymorphonuclear neutrophils/high power field), and outcome at one year after surgery was explored. FRI was confirmed in 430 patients, predominantly in the tibia (194), femur (111), upper limb (70), and ankle (40). A total of 321 (74.7%) were culture-positive and 334 (77.7%) were histology positive, while 265 (61.6%) were positive for both tests. Staphylococcus aureus was cultured in 169 (42.5%), coagulase-negative Staphylococci (CoNS) in 61 (15.3%), and Gram-negatives in 145 (36.3%) cases. Virulent microorganisms were strongly associated with positive histology (odds ratio 2.72; 95% CI 1.61–4.58) but not with clinical failure (OR 1.08; 0.42–2.75). Isolation of S. aureus was significantly associated with positive histology compared to other microorganisms (OR 2.21; 1.27–3.87). Surgery succeeded in 390 (90.7%) patients. Treatment failure was weakly associated with positive microbiology alone (OR 2.03; 0.83–4.96) or positive histology alone (OR 2.13; 0.81–5.6). Combined positive culture and histology was strongly associated with clinical failure (OR 2.3; 1.06–4.96). There was no difference in outcome between virulent and non-virulent bacteria when histology was positive, but both had higher failure rates compared to patients with negative culture or histology. A pronounced inflammatory response, as seen in histology, is a feature of virulent bacterial FRI. However, the presence of virulent infection alone does not dictate clinical outcome without marked inflammation. This suggests that outcome is at least as much related to the host response as to the bacterium. When the pathological response is prominent, this may lead to tissue necrosis, further bacterial invasion of adjacent tissues, osteolysis and loss of fracture stability, contributing to treatment failure. This deserves further study to understand the mechanisms behind this interplay and clinical outcome. Full article