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: Liu, J., Zhang, W., & Chen, H. (2026). Case report: Fatal hematogenous gastrosplenic mucormycosis in an immunocompetent adult following sigmoid perforation, septic shock, and short-term stress glucocorticoids. Frontiers in Fungal Biology, 7, Article 1940494. 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

Now, a new study published in Frontiers in Health Services has examined how these patients were actually treated and what happened to them after they left the hospital. Researchers led by Ruchi Baghel and Megha Sharma at R. D. Gardi Medical College in Ujjain, Madhya Pradesh, in collaboration with Karolinska Institutet in Stockholm, extracted clinical data from the medical records of 108 biopsy-proven ROCM inpatients admitted between May and July 2021 at two COVID-19-dedicated hospitals, one private and one public, in Central India. Two years later, in early 2023, the team conducted a Mobile-Based Post-Discharge follow-up, telephoning survivors using a structured 27-question instrument drafted in Hindi and validated through pilot testing and back-translation. The ambispective design, reported according to the STROBE statement, integrated retrospective record analysis with prospective patient-reported experiences, aiming to fill a critical gap: post-discharge follow-up is rarely part of mucormycosis treatment strategies, despite the long-term sequelae survivors face, including facial deformities, neurological deficits, and psychological impacts.

The pharmacological picture that emerged from the medical records was dominated by two antifungal agents. Of the 108 patients, 90 received at least one antifungal: 71 percent were prescribed liposomal amphotericin B, the guideline-recommended drug of choice with broad-spectrum activity against Mucorales, and 75 percent received posaconazole, which was often used as an alternative or step-down therapy amid supply shortages and the nephrotoxicity associated with amphotericin formulations. The mean duration of treatment with both agents was 16 days. Notably, 64 percent of patients received a combination of two or more antifungals, even though current global and national guidelines do not recommend concurrent use of two systemic antifungal agents for mucormycosis, because robust clinical data supporting combination therapy are lacking. A propensity score analysis of 106 patients with hematologic malignancies had previously shown that combination therapy did not improve outcomes compared with monotherapy, while unavoidably increasing the incidence of adverse drug reactions. The researchers suggest that the prescribing patterns in their cohort reflected real-world treatment constraints during the pandemic, guided by drug availability, patient tolerance, and evolving consensus rather than evidence-based preference.

Antibiotic prescribing was equally revealing. The study population received an average of two antibiotics per patient, with ceftriaxone and its fixed-dose combination with sulbactam the most frequently prescribed substances. Nearly half of the antibiotics were administered parenterally, reflecting the preference for intravenous therapy in severe infections. When the prescriptions were audited against the WHO AWaRe classification, which categorizes antibiotics into Access, Watch, and Reserve groups based on their potential to drive antimicrobial resistance, Access antibiotics constituted only 40 percent of prescriptions, well below the WHO target of at least 60 percent. Watch antibiotics accounted for 39 percent and Reserve antibiotics 8 percent, while 13 percent of prescriptions were WHO Not Recommended fixed-dose combinations that lack evidence-based indications in international guidelines. The authors attribute this pattern to the exceptional circumstances of the pandemic, including diagnostic uncertainty, high patient burden, and empiric treatment of suspected secondary bacterial infections, and call for pandemic-specific antimicrobial stewardship policies to promote rational antibiotic use during future public health emergencies.

Adverse drug reactions were identified through active surveillance of deranged laboratory parameters, as no spontaneous reports reached the ADR Monitoring Center during the study period. Among the 108 inpatients, 68 percent had deranged laboratory values, with hyponatremia in 46 percent and hypokalemia in 44 percent. Overall, 97 ADRs were observed in 73 patients, an average of 1.3 per patient. All were categorized as possible on the WHO causality assessment scale, since limited clinical information and concomitant polypharmacy made it difficult to establish definite causal relationships with individual drugs. On the modified Hartwig and Siegel severity scale, 72 percent of the reactions were mild and 28 percent moderate. Hypokalemia is a well-recognized effect of liposomal amphotericin B and has also been reported with posaconazole, along with hepatic enzyme elevations. Because both antifungals were often administered concomitantly, the laboratory abnormalities could not be attributed to either drug individually, underscoring the importance of daily monitoring of electrolytes, renal function, and liver enzymes during therapy, which the study hospitals did perform.

The comorbidity profile highlighted the central role of hyperglycemia. Diabetes mellitus, alone or with other conditions, was present in 32 percent of patients, while 42 percent had a history of COVID-19 infection and only 14 percent had documented steroid use before admission. The relatively low steroid prevalence suggests that diabetes, rather than corticosteroid exposure, may have been the dominant driver of mucormycosis pathogenesis in this Central Indian cohort, consistent with multicentric evidence that diabetes prevalence is rising rapidly in the region. Diabetes-related immune dysfunction creates a favorable environment for Mucorales fungi to grow. All 108 patients underwent endoscopic surgical debridement, including Denker’s and Modified Denker’s procedures, with orbital exenteration in 23 percent of cases. The median length of hospital stay was 14 days, shorter than the 22 to 24.5 days reported in other Indian and United States studies, which the authors attribute to the rhino-orbital disease spectrum, timely intervention, and the fact that about a quarter of patients were referred elsewhere to continue treatment.

The most striking findings came from the mobile-based follow-up conducted two years after hospitalization. Of the 97 survivors, 17 had incomplete or incorrect phone numbers in their records, and 19 of the remaining 80 never answered despite repeated attempts. Ultimately, 61 of the 80 contacted respondents consented to participate, a 76 percent response rate, with 51 calls answered by patients themselves and 10 by family members. Fifty-two of the 61 respondents reported 123 post-discharge adversities, averaging 2.4 per patient. The most frequent were hypokalemia at 22 percent, vomiting at 13 percent, and nausea at 11 percent. Nine respondents, 7 percent of the cohort, confirmed deaths after discharge, revealing post-discharge mortality that likely would have gone unreported without the follow-up calls. Nine patients also developed new-onset diabetes after receiving mucormycosis treatment, and others reported loss of vision, eye pain, headache, memory loss, and loose teeth. Six respondents described financial burdens from medical expenses, even though the government had supplied antifungal drugs free of cost to both hospitals during the pandemic.

Statistical analysis using multivariable Firth-penalized logistic regression, chosen to handle the modest cohort size and sparse outcome distribution, found that receipt of any antifungal prescription was independently associated with nearly six-fold higher odds of adversity, with an adjusted odds ratio of 5.82 and a 95 percent confidence interval of 1.56 to 21.71, statistically significant at p equals 0.009. This finding is consistent with the pharmacodynamic profile of systemic antifungal agents, including hepatotoxicity, nephrotoxicity, gastrointestinal effects, and drug-drug interactions. Patients older than 60 years showed almost four times the odds of adversity compared with younger adults, a borderline association that is biologically plausible given age-related physiological changes, multimorbidity, and altered pharmacokinetics. The overall model was statistically significant, and the authors recommend a contextual drug-use policy alongside vigilant monitoring and structured follow-up to mitigate these risks.

Perhaps the most human dimension of the study was the response to the follow-up calls themselves. Survivors and grieving family members expressed surprise and gratitude that anyone had called. One respondent who lost her mother said the call felt like someone cared about her, while another patient wrote that he never thought someone would ask how he was feeling now, describing the pandemic period as days of bad dreams. One participant suggested that a government scheme to call and follow up patients with serious illness would give a sense of being cared for and help those unable to visit a doctor. The mean call duration of 7.33 minutes suggests the intervention was operationally feasible and efficient, and the authors argue that such mobile-based follow-up could be regularized to monitor recovery, identify health needs, and provide psychological support, particularly in resource-constrained settings where access to in-person follow-up is limited.

The study is the first comprehensive analysis of mucormycosis cases in Central India, a region scarcely represented in the existing literature despite facing rising diabetes prevalence and resource constraints. The authors acknowledge limitations, including reliance on medical record completeness, the two-year recall gap between hospitalization and follow-up, potential survivor and non-response bias, and the unknown survival status of the 36 non-respondents, which may have produced overly optimistic outcome estimates. Notably, the length of hospital stay reported by respondents was twice that documented in medical records, possibly reflecting referral to other facilities and recall bias. Despite these caveats, the findings provide real-world evidence on mucormycosis management and survivorship, highlight the persistent risk of death and complications after discharge, and demonstrate the feasibility of mobile-based post-discharge follow-up as a scalable surveillance and support strategy. The authors call for survivor-centred care models that extend monitoring beyond one year, encompassing psychosocial well-being, quality of life, functional outcomes, and reconstructive needs, to inform targeted interventions and optimize care pathways for mucormycosis survivors within global public health systems.

Subject of Research: Health

Article Title: Pharmacological treatment, adversities, and mobile-based post-discharge follow-up of mucormycosis survivors in Central India: strengthening patient care

Article References: Baghel, R., Acharya, P., Verma, A., & Sharma, M. (2026). Pharmacological treatment, adversities, and mobile-based post-discharge follow-up of mucormycosis survivors in Central India: strengthening patient care. Frontiers in Health Services, 6, Article 1911647. https://doi.org/10.3389/frhs.2026.1911647

Image Credits: AI Generated

DOI: 10.3389/frhs.2026.1911647

Keywords: Pharmacological, treatment, adversities, mobile-based, post-discharge, follow-up, mucormycosis, survivors, Central, India, strengthening, patient

The research, published in BMC Nursing, was conducted at the Children’s Cancer Hospital Egypt (CCHE) 57357, one of the largest pediatric oncology centers in the Middle East. A team of nursing researchers led by Amira El-Sayed of October 6 University in Giza set out to answer a deceptively simple question: if you teach pediatric oncology nurses about mucormycosis in a systematic way, do their knowledge and their actual bedside practices improve? The answer, measured with rigorous before-and-after assessments, was a resounding yes, at least in the short term. The findings arrive at a moment when clinicians worldwide are paying renewed attention to fungal infections, which are increasingly recognized as a growing danger for patients whose immunity has been compromised by cancer therapy, transplantation, or other modern medical interventions.

Mucormycosis is caused by fungi in the order Mucorales, ubiquitous organisms that most healthy people encounter daily without consequence. In an immunocompromised host, however, these molds can germinate and invade blood vessels, causing tissue death, a process known as angioinvasion. The disease can manifest in the rhinocerebral form, attacking the sinuses and brain; the pulmonary form, destroying lung tissue; or the gastrointestinal and cutaneous forms, each carrying substantial mortality. Children with hematologic malignancies such as leukemia, and those undergoing hematopoietic stem cell transplantation, sit squarely in the highest-risk category. Neutropenia, the depletion of infection-fighting white blood cells induced by chemotherapy, removes the body’s primary cellular defense against these fungi. Because early diagnosis is difficult and treatment options are limited, prevention becomes paramount, and prevention in a hospital setting depends heavily on the vigilance of nursing staff.

Nurses occupy a uniquely influential position in infection prevention. They control the environment around the patient, from the cleanliness of surfaces and equipment to the handling of food, the management of personal protective equipment, and the early recognition of warning signs. Yet studies have repeatedly shown that knowledge about rare fungal infections among nursing staff can be patchy, particularly in resource-limited settings where formal training on emerging pathogens may be scarce. The Egyptian research team recognized this gap and designed a quasi-experimental study to test whether targeted education could close it. They enrolled 81 pediatric oncology nurses at CCHE 57357, measuring their baseline knowledge with a structured questionnaire and their actual infection-control behaviors with an observational checklist completed at the bedside.

The educational intervention itself consisted of three structured sessions covering the risk factors for mucormycosis, its pathophysiology, and the infection control measures that nurses can implement in daily practice. This content was not exotic. It included fundamentals such as environmental hygiene, appropriate use of personal protective equipment, meticulous hand hygiene, safe food handling for neutropenic patients, and surveillance for early signs of infection. But the study’s design ensured that the effect of this teaching could be quantified. Every participant completed the same knowledge assessment before and after the program, and trained observers evaluated the same set of practices using the same checklist at both time points, allowing direct comparison of scores across the intervention.

The results were striking. The mean knowledge score nearly doubled, rising from 5.82 plus or minus 0.91 before the program to 12.1 plus or minus 0.76 afterward, a difference that was statistically significant with a p-value below 0.001. The mean practice score, reflecting what observers actually saw nurses do rather than what they claimed to know, climbed from 3.86 plus or minus 1.13 to 7.58 plus or minus 1.02, also highly significant. In other words, the training did not merely fill heads with facts; it changed hands-on behavior at the bedside. Nurses who had completed the sessions were demonstrably more likely to perform the preventive measures that the checklist captured, from environmental controls to protective equipment use.

Equally interesting was the relationship between knowledge and practice. The researchers found a positive correlation between the two at both time points: before the intervention, the correlation coefficient was 0.348 with a p-value of 0.001, and after the intervention it was 0.382 with a p-value below 0.001. This suggests that what nurses know is linked to what they do, and that strengthening knowledge may be a viable pathway to strengthening practice. The correlation is moderate rather than perfect, which is a familiar pattern in health-services research; knowing the right thing does not always translate into doing it, particularly under the time pressures and staffing constraints of a busy oncology ward. But the consistency of the association before and after training reinforces the case for education as a lever for behavioral change.

The authors are careful, and rightly so, about the limits of what their study can claim. Because the design was a one-group pretest-posttest study without a control group, and because patient outcomes were not tracked, the findings cannot be interpreted as evidence that the training reduced actual mucormycosis infection rates. No children were followed to see whether their risk of fungal infection declined. The improvements measured were in nurse knowledge and observed practice, over a short-term horizon, and the study cannot rule out other explanations for the change, such as heightened attention from being observed or the general effect of participating in a research project. These are standard caveats for this study design, but they matter for anyone hoping to translate the results into policy.

Nevertheless, the study carries real weight for a field that urgently needs practical solutions. Invasive fungal infections in pediatric cancer patients are associated with prolonged hospitalizations, expensive antifungal therapy, and significant mortality, and the arsenal of preventive tools is limited. Environmental measures and vigilant nursing care are among the few interventions available on the front lines, and they cost far less than new drugs. If a three-session educational program can nearly double knowledge scores and substantially improve observed infection-control behavior among nurses caring for the most vulnerable children, that is an intervention worth replicating and testing more rigorously. The Egyptian team’s work provides a template: a structured curriculum, validated assessment tools, and an observational checklist that other institutions could adapt.

The broader lesson extends beyond mucormycosis. As fungal infections gain prominence in global health discussions, driven by rising numbers of immunocompromised patients and growing awareness of fungal threats, the healthcare workforce’s preparedness becomes a critical variable. This study demonstrates that targeted, relatively brief professional education can move the needle on both knowledge and practice in a specialized nursing population. The authors call for continuous professional development and targeted training to sustain and build on these gains, a reminder that a single educational burst is unlikely to be enough. For the nurses of CCHE 57357 and the children they care for, the message is clear: understanding the enemy is the first step in defending against it, and that understanding can be taught.

Subject of Research: Effect of a structured educational program on pediatric oncology nurses' knowledge and mucormycosis-prevention practices

Article Title: Changes in pediatric oncology nurses’ knowledge and observed mucormycosis-prevention practices following an educational programme: a one-group pretest-posttest study

Article References: El-Sayed, A., Alsharkawy, S., Hassan, E. A., Wahid, H., Ragab, N., & El-Hamid, H. A. (2026). Changes in pediatric oncology nurses’ knowledge and observed mucormycosis-prevention practices following an educational programme: a one-group pretest-posttest study. BMC Nursing, 25(1), Article 966. https://doi.org/10.1186/s12912-026-05382-5

Image Credits: AI Generated

DOI: 10.1186/s12912-026-05382-5

Keywords: mucormycosis, pediatric oncology, nursing education, infection control, fungal infection, chemotherapy, immunocompromised children, quasi-experimental study, Egypt, nurse training, knowledge and practice, BMC Nursing

The biology behind the problem is deceptively simple. Mucorales, the order of molds responsible for mucormycosis, are ubiquitous in the environment, abundant in air, soil and water, and encountered constantly in daily life. In an immunologically intact host, inhaled spores are dispatched swiftly by innate immune defenses, particularly airway epithelial barriers, alveolar macrophages and neutrophils. Respiratory viral infections disrupt this arrangement at multiple levels. Viral replication damages the respiratory epithelium, stripping away the physical barrier that prevents fungal access to deeper tissue. At the same time, antiviral immune responses and the treatments used to modulate them, most notably systemic corticosteroids and other immunosuppressive agents, can blunt the very cellular machinery required to kill fungal hyphae. The result is a window of vulnerability in which an environmental mold can establish rapidly progressive, angioinvasive disease with high mortality.

Recognizing that this vulnerability is predictable, an international panel set out to define who is most at risk and what can realistically be done to protect them. The effort was coordinated from West China Hospital, Sichuan University, and brought together 49 experts drawn from 44 institutions across eight countries. The panel conducted systematic searches of PubMed, Embase, the Cochrane Library, CNKI and the Wanfang Database through February 2025, and then evaluated proposed statements on high-risk groups and preventive measures through a two-round modified Delphi process, a structured method for building consensus among experts independent of geography and specialty. The threshold for adoption was set at 80 percent agreement. In the event, after revisions between rounds, all twelve final recommendations achieved 100 percent agreement, a level of unanimity that underscores how uncontroversial the core preventive principles are, even where the underlying evidence remains thin. Evidence for each statement was graded using the 2009 Oxford Centre for Evidence-Based Medicine system.

A central contribution of the consensus is its explicit definition of the populations that should be considered at principal risk. Four groups are identified. The first comprises critically ill patients requiring mechanical ventilation, in whom prolonged intubation, sedation and intensive care environments converge with severe illness. The second encompasses immunocompromised patients, a category that includes individuals with poorly controlled diabetes, hematological disease, solid organ or stem cell transplantation, ongoing immunosuppressive treatment and uncontrolled HIV/AIDS. The third consists of patients with stage 4 or 5 chronic kidney disease, a population whose impaired immune function and frequent hospital exposure elevate susceptibility. The fourth covers patients with structural lung disease, such as bronchiectasis, in whom the architectural damage to airways provides both a portal of entry and a reservoir where inhaled spores can persist. Beyond these principal groups, the panel noted that several factors may further increase risk: solid tumors and anticancer treatment, exposure to mold-contaminated environments, prolonged central oxygen use, broad-spectrum antibiotics combined with invasive procedures, and severe malnutrition.

The twelve recommendations are organized into four thematic blocks. Recommendations one through four address education and personal protection. High-risk patients and their families should be informed about exposure risks and practical preventive measures, while healthcare workers should be trained to recognize vulnerable patients and the early warning signs of invasive fungal disease. Vaccination against influenza and COVID-19 is recommended for high-risk patients whenever not contraindicated, a measure that reduces the likelihood of the inciting viral illness itself. Mask use in public settings is advised according to local guidance and availability, reflecting the reality that recommendations must be implementable in widely varying health systems rather than only in well-resourced tertiary centers.

Recommendations five through seven target the timeliness of diagnosis and antiviral therapy, the point at which prevention intersects most directly with clinical practice. Patients with suspected respiratory infection should be tested promptly, with particular attention to influenza virus and SARS-CoV-2, and effective antiviral treatment should begin early. The consensus goes a step further for influenza season: high-risk patients presenting with influenza-like illness may receive empiric antiviral treatment before laboratory confirmation is available, an acknowledgment that delays in testing should not translate into delays in protecting the airway epithelium and preserving antifungal immunity. On the diagnostic infrastructure side, tertiary hospitals are expected to provide testing capability for mucormycosis itself, while secondary hospitals should establish testing services, specimen-transfer arrangements or referral pathways so that suspected cases are not lost in transit between levels of care.

Recommendations eight through eleven concern hospital infection control, an area where mucormycosis prevention differs in practical detail from many other nosocomial threats. Because Mucorales thrive in soil and organic matter, soil-containing items should be excluded from rooms housing high-risk patients, and vulnerable individuals should be protected from dust generated by construction and renovation work, a recognized source of fungal spore aerosols in healthcare facilities. Bed linen should be handled gently to avoid dispersing spores into the air and transported in closed containers. Ventilation systems require proper maintenance to ensure that air handling does not become a vector for fungal dissemination. Standard precautions apply to patients with confirmed mucormycosis, and when a suspected healthcare-associated outbreak occurs, the panel recommends systematic investigation of non-sterile products, invasive procedures and environmental sources, the three routes by which hospital outbreaks of mucormycosis have historically been traced.

The twelfth recommendation addresses the resource-limited settings where the burden of disease is often greatest and where sophisticated diagnostic and air-handling infrastructure may be unavailable. The panel prioritizes screening of high-risk patients, direct microscopy and other affordable diagnostic tests, referral and teleconsultation networks, training for primary healthcare workers, hand hygiene, diabetes management and environmental education. This tiered approach reflects a deliberate design choice: rather than prescribing a single standard that only wealthy health systems could meet, the consensus offers a ladder of interventions that can be adapted to local capacity. Given that the 2021 Indian outbreak unfolded largely in settings of variable resources, this pragmatism is likely to determine the document’s real-world influence.

Notably, the panel declined to recommend routine antifungal prophylaxis for all high-risk patients, a decision that will attract scrutiny given the severity of the disease. Patients with hematological malignancies may be assessed individually according to existing invasive fungal disease guidelines, but the consensus states plainly that current evidence is insufficient to define specific indications, drug choice, timing, dose or duration of prophylaxis following respiratory viral infection. Evidence gaps also extend to immunomodulatory treatment, filtration in central oxygen systems and formal risk-prediction models, all of which remain promising but unvalidated. The authors are candid about the limitations of their evidence base: most available data are retrospective or observational, and the clinical effects of several recommendations require prospective and real-world validation. They identify surveillance, faster diagnostics, environmental monitoring, validated early-warning models and carefully designed prophylaxis studies as the priority research agenda.

The consensus, published as Qu and colleagues in iFungi with corresponding authors including Zhiyong Zong, Junyan Qu and Xinyao Liu of West China Hospital, was supported by the National Key Research and Development Program of China, and all participating experts declared no conflicts of interest. Its significance lies less in any single novel intervention than in its framing: it defines precisely which patients require targeted prevention after respiratory viral infection and translates limited evidence into actionable steps that hospitals and primary care systems can adapt. As respiratory viruses continue to circulate globally and immunosuppressive therapies expand, the document offers clinicians a structured answer to a question that the COVID-19 era made impossible to ignore, namely how to stop an environmental mold from exploiting the damage a virus leaves behind.

Subject of Research: Prevention of secondary mucormycosis following respiratory viral infections

Article Title: Expert consensus outlines 12 recommendations to prevent secondary mucormycosis after respiratory viral infections

Article References: Expert consensus outlines 12 recommendations to prevent secondary mucormycosis after respiratory viral infections. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: mucormycosis, Mucorales, respiratory viral infections, COVID-19, influenza, expert consensus, infection control, immunocompromised patients, antifungal prophylaxis, Delphi process, diabetes, hospital hygiene

Mucormycosis is caused by environmental molds belonging to the order Mucorales, most notoriously the genus Rhizopus, whose spores float freely in soil, decaying organic matter, and damp air. In most people, inhaled spores are simply engulfed and destroyed by neutrophils and macrophages, the innate immune cells that patrol the airways. But when those defenses falter, as in diabetes, cancer, or organ transplantation, the spores germinate into broad, ribbon-like fungal hyphae that invade blood vessels with terrifying speed. This angioinvasion triggers thrombosis and tissue death, driving a fulminant infection that kills 40 to 50 percent of affected patients even with treatment. Diabetes remains the most common predisposing factor, associated with an overall mortality of roughly 46 percent, and more than half of all mucormycosis cases in large reviews occur in people with overt immunosuppression.

The Iranian patient’s initial symptoms were strikingly atypical, which is precisely why the diagnosis proved so treacherous. He complained of severe right-sided epigastric pain and excessive watering of the right eye, with no nasal congestion, no fever, and no neurological signs. His doctor prescribed topical ketorolac eye drops for presumed conjunctivitis. Instead of improving, he deteriorated: marked redness around the eye progressed to bruising-like ecchymosis and swelling, prompting admission to Prophet Azam Hospital at Kerman University of Medical Sciences. The authors of the report suggest that the abdominal pain may have reflected inadvertent ingestion of fungal spores, since gastrointestinal acquisition of Mucorales is well documented and greenhouse workers handle contaminated material constantly, though it may equally have been an incidental finding that contributed to the dangerous delay.

On admission, the man was alert, oriented, and afebrile, with intact vision and no cranial nerve deficits, findings that could easily have reassured clinicians. But computed tomography and magnetic resonance imaging of his sinuses and orbits told a more alarming story: right-sided proptosis, meaning the eye was being pushed forward, together with significant edema and infiltration of both the intraconal and extraconal fat spaces inside the orbit. T2-weighted MRI sequences showed the bright signal characteristic of acute inflammatory change, though without definite evidence of intracranial extension or cavernous sinus thrombosis. Such imaging findings are non-specific and can appear in severe bacterial cellulitis, but the combination of rapid deterioration, extensive orbital involvement, and the patient’s occupational history in a high-risk environment raised immediate suspicion of invasive fungal disease and guided the urgent biopsy that followed.

The laboratory work-up was equally revealing for what it did not find. The patient’s white blood cell count was mildly elevated at 12.6 × 10³ per microliter with 95 percent neutrophils, C-reactive protein stood at 37 mg/L, and his erythrocyte sedimentation rate was 21 mm/h, all consistent with a robust systemic inflammatory response. Yet targeted immunological testing, including HbA1c of 5.3 percent, negative HIV serology, and normal immunoglobulin G, A, and M levels, confirmed that he was genuinely immunocompetent. His fasting glucose of 110 mg/dL represented only an impaired fasting glucose, a subtle metabolic derangement. The authors note that even mild hyperglycemia can upregulate endothelial receptors such as GRP78, enhancing fungal adhesion and angioinvasion, and emerging evidence suggests that transient or subclinical dysglycemia can predispose otherwise healthy individuals to opportunistic mycoses.

Definitive diagnosis came from the mycology laboratory. During drainage of the eye discharge, necrotic tissue and purulent secretions were sampled and examined under potassium hydroxide preparation, hematoxylin and eosin staining, and Giemsa staining. All three revealed the pathognomonic signature of Mucorales: broad, aseptate, ribbon-like hyphae branching at wide angles. Culture on Sabouraud dextrose agar produced luxuriant, fluffy, grayish-white to brown colonies within seven days at 30 degrees Celsius, and lactophenol cotton blue microscopy of the isolate, showing sporangiophores with rhizoids at their base and a columella, identified the culprit as a Rhizopus species. Repeat sampling from the skull base again yielded positive results. Critically, treatment was initiated on the basis of microscopy alone, because fungal culture sensitivity is only 30 to 50 percent and its slow turnaround makes it useless for guiding urgent therapy.

What followed was an aggressive multimodal assault on the infection. Surgeons performed an urgent orbital exenteration, the radical removal of the entire contents of the eye socket, after intraoperative inspection revealed extensive necrotic tissue that had to be excised to prevent extension to the skull base, a complication carrying a mortality above 80 percent. Simultaneously, the patient received intravenous liposomal amphotericin B at 5.0 to 10 mg/kg per day, continued for a total of three weeks. The combined medical-surgical approach was well tolerated and produced a favorable clinical response. He was discharged in stable condition upon completing the antifungal course, and final culture results corroborated the diagnosis seven days after discharge. At follow-up three months later, he remained asymptomatic with no signs of recurrence, though he has been counseled on occupational safety measures should he return to greenhouse work.

The case fits a growing pattern in which occupational and environmental exposure, rather than host immunosuppression, precipitates invasive disease. A cohort study of cucumber greenhouse workers documented substantial exposure to airborne fungi, including Mucorales species, using next-generation sequencing alongside biomarkers of systemic inflammation, lending biological plausibility to the exposure route even though invasive disease was not observed in that cohort. Comparable risk has been described after natural disasters, including a case of rhino-orbital mucormycosis in an immunocompetent adult following prolonged mold exposure during post-hurricane cleanup, and rural living or contact with organic matter has been implicated in pediatric orbital mucormycosis without underlying immunodeficiency. The authors argue that a sufficiently high inoculum of spores can simply overwhelm innate defenses, particularly phagocytosis by neutrophils and macrophages, which are typically effective against Mucorales.

A literature search across PubMed, Scopus, and Web of Science covering January 2000 to October 2025, summarized by the authors, shows how consistently diagnostic delay haunts immunocompetent patients. A 67-year-old woman who developed headache, diplopia, and vision loss after post-hurricane mold cleanup recovered fully after multiple debridements and amphotericin B. A 12-year-old girl with a nasal foreign body and Rhizopus oryzae infection survived after surgery and antifungal therapy, as did a 22-year-old man with a minor skin lesion who required exenteration. But a 59-year-old woman with no identified risk factors died of multiple organ failure, diagnosed only at post-mortem, and a 32-year-old man died after treatment non-compliance, a reminder that even favorable biology depends on adherence to therapy. Across these reports, the absence of classic risk factors and the non-specific nature of early symptoms repeatedly misled clinicians.

For physicians on the front lines, the message is stark: progressive orbital infections deserve consideration of mucormycosis even in patients with no diabetes, no malignancy, and no immunosuppressive drugs, particularly when their work or environment involves soil, decaying vegetation, or mold-laden air. Interestingly, angioinvasion in immunocompetent hosts may follow a somewhat less fulminant course than in diabetic patients, offering a window for recovery if clinicians act quickly. High clinical suspicion, prompt histopathological diagnosis using KOH preparations and tissue staining, and aggressive combined surgical and antifungal treatment remain the pillars of survival, with combined approaches yielding roughly 60 percent survival in rhino-orbital-cerebral disease compared with more than 90 percent mortality in disseminated infection. As greenhouse agriculture expands worldwide, this single case suggests that the boundary between harmless environmental mold and life-threatening invasion may be thinner than the immune status of the host alone would suggest.

Subject of Research: Rhino-orbital mucormycosis in an immunocompetent adult linked to occupational greenhouse mold exposure

Article Title: Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges

Article References: Mousavi, S. M., Mousavi, S. A. A., Faryabi, O., Sharifi, I., Kamyab, H., & Shirazi, Z. (2026). Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges. Clinical Case Reports, 14(10), Article e73683. https://doi.org/10.1002/ccr3.73683

Image Credits: AI Generated

DOI: 10.1002/ccr3.73683

Keywords: mucormycosis, Rhizopus, orbital exenteration, immunocompetent patient, greenhouse workers, occupational exposure, liposomal amphotericin B, fungal infection, angioinvasion, diagnostic delay, Mucorales, Iran