Background/Objectives: Postmortem microbiology has traditionally been regarded with caution in forensic practice due to concerns related to contamination, bacterial translocation, and postmortem microbial overgrowth. As a result, microbiological findings obtained after death have often been considered unreliable or of limited diagnostic value. However, growing evidence indicates that, when appropriately interpreted and integrated with autopsy findings, histopathology, and circumstantial information, postmortem microbiology can provide crucial support for cause-of-death determination. This narrative review critically examines the current role of postmortem microbiology in forensic diagnostics, with a focus on its diagnostic applications, interpretative challenges, and future perspectives. Methods/Results: The transition from conventional culture-based techniques to molecular approaches—including polymerase chain reaction, microbiome analysis, and metagenomic methods—is discussed, highlighting both their potential advantages and inherent limitations within the forensic setting. Particular attention is devoted to key interpretative issues such as postmortem interval, sampling strategies, contamination, and bacterial translocation. In addition to cause-of-death attribution, emerging applications—including postmortem interval estimation, trace evidence analysis, and artificial intelligence–based models—are reviewed. Although these approaches show promising research potential, their routine forensic applicability remains limited by methodological heterogeneity, lack of standardization, and interpretative complexity. Conclusions: In conclusion, postmortem microbiology represents a valuable diagnostic tool when applied within a multidisciplinary forensic framework. Its effective use requires cautious interpretation and integration with pathological and contextual evidence, avoiding standalone or automated conclusions. Future progress will depend on standardized methodologies, multidisciplinary collaboration, and a clear distinction between experimental research and routine forensic practice.

Background and Clinical Significance: Cerebral candidiasis (Candida albicans meningoencephalitis) is a rare but severe central nervous system (CNS) infection, usually associated with neurosurgical procedures or indwelling devices. Diagnosis is challenging due to frequent negativity of cerebrospinal fluid (CSF) cultures, and mortality remains high despite antifungal therapy. Case Presentation: We describe a 64-year-old woman who underwent retrosigmoid resection of a left vestibular schwannoma. The early postoperative course was complicated by fever, neurological deterioration, and hydrocephalus requiring external CSF drainage. Multiple lumbar punctures revealed inflammatory CSF profiles but persistently negative cultures. One month post-surgery, intraoperative samples from mastoid repair material grew Candida albicans, prompting antifungal therapy. Despite treatment, the patient experienced fluctuating neurological status and required multiple external ventricular drains. Three months after surgery, she clinically deteriorated and died. Autopsy showed diffuse meningeal thickening and purulent exudates at the brain base and posterior fossa. Histopathology confirmed chronic lympho-histiocytic meningitis with necrotizing foci containing Candida albicans. Conclusions: This case underscores the diagnostic and therapeutic challenges of post-neurosurgical Candida CNS infections. Repeatedly negative CSF cultures delayed diagnosis, emphasizing the value of ancillary tests such as β-d-glucan and molecular assays. Even with antifungal therapy, prognosis is poor. Autopsy remains essential for uncovering fatal healthcare-associated fungal infections and informing clinical vigilance and medico-legal assessment.

Sudden unexpected death in infancy (SUDI) remains a major challenge in pediatric pathology and forensic medicine. Despite advances in diagnostic techniques, many cases are still classified as unexplained and labeled as sudden infant death syndrome (SIDS). Increasing evidence suggests that a proportion of these deaths may be due to “hidden” causes not detectable through routine post-mortem examination. A narrative review of the literature (2000–2026) was conducted using PubMed and Scopus, focusing on under-recognized causes of SUDI and their diagnostic implications. Relevant studies were selected and organized into major pathological and forensic categories. Hidden causes of SUDI include a wide spectrum of conditions. Cardiac disorders—such as myocarditis, cardiomyopathies, and inherited arrhythmogenic syndromes—are frequently implicated and may require molecular autopsy for detection. Infectious diseases, often presenting with minimal or nonspecific findings, represent another important category, particularly viral and bacterial infections. Inborn errors of metabolism, especially fatty acid oxidation defects, may lead to sudden death in the absence of specific autopsy findings, highlighting the role of biochemical analyses. Neuropathological abnormalities involving brainstem regulatory systems may contribute to impaired autonomic control. Environmental, toxicological, and medico-legal factors—including unsafe sleep conditions, toxic exposures, and inflicted injury—must also be considered. SUDI is a multifactorial entity in which many unexplained deaths may be attributable to identifiable but overlooked conditions. A standardized, multidisciplinary approach integrating autopsy, ancillary investigations, and molecular diagnostics is essential to improve diagnostic accuracy and support prevention strategies.

Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is associated with highly aggressive necrotizing pneumonia characterized by rapid clinical deterioration and high mortality. However, the clinicopathological features of fatal cases, particularly in the forensic setting, remain incompletely defined. We report a fatal case of PVL-positive S. aureus necrotizing pneumonia diagnosed through forensic autopsy and molecular analysis. In addition, a systematic review was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE and Scopus were searched from database inception to 12 March 2026 to identify published fatal cases of PVL-positive S. aureus pneumonia. A previously healthy 58-year-old man presented with acute respiratory symptoms and rapidly developed severe respiratory failure and septic shock, resulting in death within 24 h of hospital admission. Blood cultures and bronchoalveolar lavage yielded methicillin-susceptible S. aureus. Autopsy revealed bilateral necrotizing hemorrhagic bronchopneumonia, and molecular analysis confirmed PVL positivity. The literature review identified 31 fatal cases. Most cases were characterized by rapid clinical deterioration, frequent septic shock, and hemoptysis or pulmonary hemorrhage. When autopsy was performed, a consistent pattern of necrotizing and hemorrhagic pulmonary infection was observed. PVL-positive S. aureus pneumonia represents a rare but highly aggressive infection that may rapidly progress to respiratory failure and death. The combination of rapid clinical deterioration, hemoptysis, and necrotizing hemorrhagic pneumonia at autopsy represents a distinctive clinicopathological pattern. Integration of autopsy findings with microbiological and molecular investigations is essential for establishing the diagnosis in rapidly fatal infectious deaths.

Waterhouse–Friderichsen syndrome (WFS) represents a fulminant septic condition characterized by bilateral adrenal hemorrhage and rapid clinical deterioration. Although classically associated with meningococcal infection, fatal cases occur across multiple infectious etiologies and heterogeneous clinical contexts. In forensic practice, diagnosis frequently relies on post-mortem interpretation rather than clinical recognition, making consistent pathological assessment essential. A systematic review was conducted according to PRISMA guidelines to identify autopsy-confirmed fatal cases consistent with WFS. PubMed/MEDLINE and Scopus were searched from database inception to 21 February 2026, with a supplementary search conducted in Google Scholar. Eligible studies included fatal human cases with bilateral adrenal hemorrhage documented at autopsy and sufficient pathological and/or microbiological data. Data were extracted on clinical course, gross and histopathological findings, microbiological investigations, pathogens, and predisposing factors. Owing to marked heterogeneity of case-level reporting, qualitative synthesis and semi-quantitative descriptive analysis were performed. Sixty-five studies, encompassing 86 individual fatal cases, met the inclusion criteria. Bilateral adrenal hemorrhage consistently occurred within a broader systemic septic pattern characterized by multiorgan congestion, hemorrhagic manifestations, and variable disseminated intravascular coagulation-related changes. Histopathological and microbiological findings were heterogeneous, with frequent discrepancies between culture-based and molecular results and recurrent diagnostic limitations related to post-mortem microbiology. The synthesis of evidence supports interpreting WFS as a recurrent forensic-pathological pattern rather than a single morphological diagnosis. Based on key findings identified across cases, practical forensic frameworks were developed to support autopsy interpretation, microbiological sampling, and differential diagnosis. Integration of morphology, histopathology, microbiology, and circumstantial data may improve consistency and reproducibility in the medico-legal evaluation of sudden septic deaths.

Background: Fatal spider envenomation is exceptionally rare in contemporary medical practice; however, sporadic reports continue to appear in the forensic literature, often characterized by diagnostic uncertainty and heterogeneous documentation. This systematic review critically evaluated all published fatal cases attributed to spider envenomation, with emphasis on autopsy findings, histopathological patterns, and medico-legal robustness of causal attribution. Results: A systematic search of PubMed/MEDLINE, Embase, and Scopus was conducted from database inception to 14 February 2026 in accordance with PRISMA 2020 guidelines. Twelve studies met predefined inclusion criteria and were included in the qualitative synthesis. Seven cases (58%) were supported by autopsy findings, while five were clinically well-documented fatalities without post-mortem examination. Loxosceles accounted for most cases (8/12), followed by Latrodectus (3/12) and Atrax (1/12). Three recurrent genus-specific patterns emerged. Loxosceles envenomation showed a hemolytic–coagulopathic profile characterized by intravascular hemolysis, disseminated intravascular coagulation, and acute renal injury. Latrodectus cases demonstrated a predominantly cardiotoxic pattern with myocardial injury and pulmonary edema. Atrax envenomation was associated with a neurotoxic–pulmonary presentation marked by severe pulmonary edema and autonomic instability. Conclusion: Although the number of cases is limited, the recurrence of distinct pathological patterns supports biological plausibility. Nevertheless, substantial risk of misclassification persists, particularly in the absence of entomological confirmation or systematic exclusion of alternative causes of sudden death. Fatal spider envenomation should therefore be interpreted through a structured forensic framework integrating exposure plausibility, clinicopathological coherence, and exclusion of competing causes of death.