The patient arrived at the emergency department of the 900th Hospital of the PLA Joint Logistic Support Force in Fuzhou, China, in September 2025 with two days of left-sided abdominal pain, fever of 39 degrees Celsius, and confusion. His blood pressure had collapsed to 76/45 mmHg, his heart raced at 123 beats per minute, and laboratory results revealed a lactate of 5.4 mmol/L — a marker of profound tissue oxygen starvation — alongside a procalcitonin level of 78.34 ng/mL, indicating overwhelming bacterial sepsis. Computed tomography showed free air in the abdominal cavity and fecal ascites, the signature of a ruptured bowel. Surgeons found an 0.8-centimeter perforation on the sigmoid colon and performed an emergency partial colectomy with colostomy.

What followed was a cascade that the case authors, led by Jiewei Liu, Wei Zhang, and Hua Chen, describe as unprecedented. Postoperatively, the man remained in refractory septic shock and received intravenous hydrocortisone at 200 milligrams daily for three days — a standard, guideline-endorsed measure for septic shock that supports blood pressure when fluids and vasopressors fail. He stabilized briefly, was extubated on postoperative day 4, but fever returned the next day. Drainage fluid cultures grew only the bacterium Proteus mirabilis, and a serum 1,3-β-D-glucan test — a common fungal screening assay — came back negative. Based on the suspicion of intra-abdominal candidiasis, a frequent complication after fecal peritonitis, clinicians added micafungin, an echinocandin antifungal.

That choice would prove fatal. Echinocandins, which inhibit fungal cell wall synthesis, have no meaningful activity against Mucorales — the order of molds that includes Rhizopus, Mucor, and Lichtheimia, the causative agents of mucormycosis. For eight days the patient received ineffective antifungal coverage while the infection advanced silently. On postoperative day 10, dark brown fluid began draining from his abdominal tubes, and an emergency second laparotomy revealed the source: a 6.0 by 8.0-centimeter full-thickness rupture on the posterior wall of his stomach and a spleen that had turned ischemic and necrotic. Surgeons removed the entire stomach and spleen, but it was too late.

Histopathology delivered the definitive answer on postoperative day 13. Microscopic examination of the gastric and splenic tissue revealed broad, ribbon-like, aseptate hyphae branching at right angles — the pathognomonic appearance of Mucorales — invading blood vessel walls and triggering thrombosis, the hallmark of angioinvasive mucormycosis. The gastric specimen showed full-thickness hemorrhagic infarction with fungal elements throughout the mucosa, while the spleen exhibited acute inflammation, fungal invasion, and infarction. Liposomal amphotericin B, the gold-standard first-line agent for mucormycosis, was initiated immediately upon diagnosis, but the patient succumbed to refractory shock and systemic capillary leak syndrome the same day.

The most striking finding, however, was what the pathologists did not see. Multiple-level serial sections of the resected sigmoid colon — the original site of perforation — contained no fungal elements whatsoever, a result confirmed independently by two pathologists reviewing all hematoxylin-eosin-stained slides. In classic primary gastrointestinal mucormycosis, ingested spores germinate on injured intestinal mucosa and invade contiguously, so the primary bowel lesion is almost always fungus-laden. Here, the colon was sterile while the stomach and spleen were overrun. The authors conclude that the fungi reached these organs through the bloodstream — a hematogenous dissemination pathway never before documented in comparable visceral perforation cases.

To explain how the fungi selectively colonized the gastric and splenic vasculature, the authors point to the CotH3–GRP78 virulence axis, a molecular interaction well characterized in laboratory and animal studies. Mucorales hyphae express CotH3, a surface adhesin from the CotH family of proteins, which binds GRP78 (glucose-regulated protein 78 kDa), a receptor on the surface of human endothelial cells lining blood vessels. Stress-induced hyperglycemia, lactic acidosis from severe sepsis, and exogenous glucocorticoids each independently upregulate endothelial GRP78 expression. In this patient, all three factors converged within days, potentially creating a transient

The diagnostic delays documented in this case reflect a broader and well-recognized blind spot in the management of postoperative intra-abdominal sepsis. Serum 1,3-β-D-glucan, the fungal biomarker used in this patient, is validated primarily for the detection of invasive Candida and certain mold species, but it is consistently negative in mucormycosis because Mucorales possess cell walls whose glucan content differs structurally from that of the fungi the assay was designed to detect. Peritoneal fungal cultures perform similarly poorly, since Mucorales are fastidious in culture, grow slowly on standard media, and are frequently killed by routine specimen processing. The result is a diagnostic landscape in which a patient can harbor a rapidly advancing angioinvasive mold infection while every routinely ordered test returns reassuringly negative results. The authors argue that this reality should lower the threshold for surgical re-exploration and tissue biopsy in deteriorating postoperative patients, because histopathology remains the only reliably definitive diagnostic modality for intra-abdominal mucormycosis.

The therapeutic pitfall highlighted by the case is equally instructive. Micafungin and the other echinocandins inhibit β-1,3-glucan synthase, an enzyme essential to the cell wall architecture of Candida and Aspergillus species, but Mucorales are intrinsically resistant to this class because their cell wall composition and target enzyme structure differ sufficiently to confer no meaningful susceptibility. Empirical echinocandin coverage is a rational and widely endorsed strategy for patients with fecal peritonitis at risk of candidemia, which makes the eight-day window of ineffective therapy in this case less a failure of individual judgment than a predictable consequence of a common ICU protocol colliding with an uncommon pathogen. The authors emphasize that once mucormycosis enters the differential — particularly in a deteriorating patient with unexplained visceral infarction — the empirical regimen should be escalated promptly to liposomal amphotericin B, the agent with the most established activity against Mucorales, rather than waiting for microbiological or histological confirmation that may arrive too late.

The immunological dimension of the case also merits careful interpretation. The authors are explicit that three days of stress-dose hydrocortisone should be understood as one potential contributing factor within a broader state of sepsis-associated immune dysfunction, not as a standalone cause. Critical illness itself induces profound immune perturbations, including impaired neutrophil chemotaxis and phagocytosis, monocyte deactivation, and lymphocyte exhaustion, and these defects are compounded by the metabolic and hormonal stress of major abdominal surgery. Glucocorticoids add a further layer by suppressing phagocyte function and, as the authors note, upregulating endothelial GRP78 expression, which may enhance the ability of circulating Mucorales spores and hyphal fragments to adhere to and invade blood vessel walls. The convergence of these mechanisms within a matter of days may explain how a previously immunocompetent host became permissive to an infection classically reserved for the chronically immunosuppressed.

The CotH3–GRP78 axis, invoked by the authors to explain the selective pattern of organ involvement, has emerged in recent years as the central molecular paradigm of Mucorales pathogenesis. CotH3 is a surface protein expressed by Rhizopus, Mucor, and related genera that functions as a ligand for GRP78, a host stress-response chaperone normally resident in the endoplasmic reticulum but translocated to the endothelial cell surface under conditions of hyperglycemia, acidosis, iron overload, and glucocorticoid exposure. Binding of CotH3 to endothelial GRP78 triggers invasion of the vessel wall, endocytosis of the fungal element, and subsequent thrombosis, producing the hemorrhagic infarction that characterizes angioinvasive disease. The distribution of GRP78 expression across vascular beds may partly account for the preferential involvement of the gastric and splenic circulation observed in this patient, although the authors present this as a biologically plausible framework rather than a definitively proven mechanism in this specific case.

The hematogenous route of dissemination, confirmed by the complete absence of fungal elements in the resected sigmoid colon, carries important implications for how clinicians conceptualize postoperative fungal sepsis. In classic gastrointestinal mucormycosis, ingested spores colonize injured mucosa and spread contiguously through the bowel wall, so the primary lesion is invariably fungus-laden and the disease tends to remain anatomically localized until late stages. By contrast, a bloodstream route implies that fungal elements seeded distant organs early and silently, potentially before any localizing signs appeared, and that the visible gastric rupture and splenic infarction were downstream consequences of vascular invasion rather than the leading edge of the infection. This distinction matters prognostically, because hematogenous dissemination is associated with a higher fungal burden, more extensive vascular thrombosis, and a narrower window for effective surgical and antifungal intervention.

For clinicians managing postoperative patients with fecal peritonitis, the case suggests several practical considerations. Unexplained deterioration after apparent source control, particularly when accompanied by signs of visceral ischemia such as rising lactate, new organ dysfunction, or dark drainage fluid, should prompt consideration of angioinvasive fungal infection even in the absence of traditional risk factors. Imaging findings of gastric wall thickening or splenic hypoperfusion in this context warrant urgent surgical consultation rather than watchful waiting. And when tissue is obtained, the pathology laboratory should be alerted to the possibility of mucormycosis, since the broad, aseptate, right-angle branching hyphae that define the infection can be distinguished from Aspergillus and other septate molds only by careful morphological assessment. The authors conclude that early re-laparotomy for histopathological biopsy, rather than reliance on negative cultures and biomarkers, is the decisive step in refractory cases of this kind.

Subject of Research: Hematogenous dissemination of Mucorales causing fatal gastric perforation and splenic infarction in an immunocompetent adult after brief stress-dose glucocorticoid therapy

Article Title: Case report: Fatal hematogenous gastrosplenic mucormycosis in an immunocompetent adult following sigmoid perforation, septic shock, and short-term stress glucocorticoids

Article References: Case report: Fatal hematogenous gastrosplenic mucormycosis in an immunocompetent adult following sigmoid perforation, septic shock, and short-term stress glucocorticoids. (n.d.). https://doi.org/10.3389/ffunb.2026.1940494

Image Credits: AI Generated

DOI: 10.3389/ffunb.2026.1940494

Keywords: mucormycosis, Mucorales, gastric perforation, splenic infarction, septic shock, glucocorticoids, liposomal amphotericin B, echinocandins, CotH3, GRP78, immunocompetent host, intra-abdominal sepsis