“Adjunctive topical amphotericin B in post-transplant surgical-site mucormycosis in an immunocompromised diabetic patient: a case report”

Abstract

Introduction:

Cutaneous mucormycosis is a rapidly progressive and often fatal fungal infection predominantly affecting immunocompromised hosts, with post-transplant patients being particularly vulnerable due to immunosuppressive regimens and metabolic derangements. Despite its high mortality, especially in the context of surgical-site involvement, optimal therapeutic strategies remain underexplored. We present a rare case of surgical-site mucormycosis in a renal transplant recipient with poorly controlled diabetes, successfully managed using adjunctive topical antifungal therapy, highlighting a potential treatment strategy in immunosuppressed populations.

Case discussion:

A middle-aged male with chronic kidney disease, recent renal transplantation, and persistent hyperglycemia developed a non-healing surgical-site wound. Early clinical suspicion led to a bedside potassium hydroxide mount and expedited fungal cultures, which revealed mucormycosis. The patient was promptly initiated on systemic liposomal amphotericin B and, uniquely, adjunctive topical amphotericin B applied directly to the wound bed. Despite the challenges of ongoing immunosuppression, renal dysfunction, and glycemic instability, the patient demonstrated significant local and systemic improvement without the need for disfiguring surgical debridement.

Discussion:

This case underscores the diagnostic value of bedside fungal microscopy in resource-limited and time-sensitive settings, where conventional culture and histopathology may be delayed. The clinical decision to incorporate topical amphotericin B, an underutilized yet mechanistically sound adjunct, was based on the rationale of high local fungal burden, systemic drug toxicity concerns, and limited evidence in immunosuppressed surgical cohorts. This approach not only curtailed disease progression but also preserved graft integrity and patient quality of life. This case highlights the under-recognition of mucormycosis in post-transplant surgical wounds and the absence of standardized topical antifungal protocols, representing a critical gap in transplant infectious disease management.

Conclusion:

This case report highlights that early bedside diagnosis, combined with individualized adjunctive topical amphotericin B, may help control post-transplant surgical-site mucormycosis, reduce the need for morbid surgical interventions, and warrants further evaluation for incorporation into future treatment guidelines for high-risk immunocompromised patients.

Introduction

Mucormycosis is an aggressive, opportunistic, and angioinvasive fungal infection caused by fungi of the order Mucorales, primarily affecting immunocompromised individuals, such as patients with diabetes mellitus, hematologic malignancies, neutropenia, or those undergoing solid organ transplantation. It is characterized by the rapid proliferation of broad, ribbon-like, aseptate hyphae that invade blood vessels, leading to thrombosis, infarction, and tissue necrosis. Among its clinical manifestations, rhino-cerebral and pulmonary mucormycosis are the most prevalent; however, the cutaneous form, while relatively rare, remains a significant contributor to morbidity and mortality when not promptly recognized and treated^[1^].

Cutaneous mucormycosis typically arises from the direct inoculation of spores into disrupted skin or surgical wounds, making it a critical consideration in postoperative or trauma-related infections, particularly among immunocompromised hosts. Postoperative surgical-site mucormycosis in renal transplant recipients is exceedingly rare, with fewer than 15 cases reported in the global literature to date^[2^]. This rarity, combined with its resemblance to common bacterial surgical-site infections – manifesting as erythema, induration, and necrotic eschars – often leads to diagnostic delays, inappropriate antibiotic escalation, and treatment failure. The mortality rate of mucormycosis remains alarmingly high, ranging from 40 to 80%, despite the availability of systemic antifungals such as liposomal amphotericin B^[3^].

In the transplant setting, where patients are maintained on potent immunosuppressive regimens, including calcineurin inhibitors, corticosteroids, and antimetabolites, the risk of invasive fungal infections is significantly elevated. Furthermore, concomitant conditions such as poorly controlled diabetes and chronic kidney disease exacerbate susceptibility and complicate management. These patients often present atypically, and invasive diagnostics like tissue biopsy may be contraindicated due to bleeding risks or poor wound healing. Hence, the role of bedside fungal diagnostics, such as potassium hydroxide (KOH) wet mounts and fungal cultures, becomes pivotal in early detection and guiding antifungal therapy.

Systemic antifungal therapy with amphotericin B remains the cornerstone of treatment; however, its efficacy is often limited by poor penetration into necrotic tissue and systemic toxicity, especially in patients with preexisting renal dysfunction. Surgical debridement of necrotic tissue is, therefore, essential for improving outcomes, yet it may not always suffice in achieving local fungal clearance. In this context, the adjunctive use of topical amphotericin B, directly applied to the debrided wound bed, has emerged as a potentially valuable yet underutilized therapeutic strategy. Topical delivery ensures high local drug concentrations, may bypass systemic toxicity, and could offer enhanced efficacy in poorly vascularized or extensively necrotic tissues^[4^].

Despite its potential, there is a scarcity of documented clinical experiences or standardized protocols regarding the use of topical amphotericin B in surgical wound mucormycosis. Most of the literature comprises isolated case reports or experimental models, with limited translation into clinical practice. This lack of awareness may stem from the rarity of the condition, uncertainty regarding formulation and dosing, or concerns about toxicity.

We present a rare and instructive case of surgical-site mucormycosis in a renal transplant recipient, successfully managed with a multimodal approach involving systemic liposomal amphotericin B, serial surgical debridement, and topical amphotericin B powder applied directly to the wound base. Our report not only underscores the feasibility and potential efficacy of this adjunctive modality but also highlights existing gaps in diagnostic vigilance, therapeutic protocols, and transplant infection management. We propose that early fungal diagnostics and localized antifungal strategies may be pivotal in improving outcomes for immunocompromised patients with suspected fungal surgical-site infections. This manuscript complies with the TITAN 2025 guidelines for responsible reporting, transparency, and ethical AI use in clinical publishing^[5^].

HIGHLIGHTS

• This case presents a rare instance of surgical-site mucormycosis in a renal transplant recipient, a complication reported in fewer than 15 cases globally.

• A novel therapeutic approach was employed, using adjunctive topical amphotericin B applied directly to the wound bed during surgical debridement, in addition to systemic liposomal amphotericin B.

• The early use of bedside potassium hydroxide mount microscopy facilitated rapid diagnosis and timely initiation of targeted antifungal therapy.

• The case underscores the clinical value of localized antifungal delivery in immunocompromised hosts, where systemic therapy alone may be insufficient due to poor tissue penetration.

• This report highlights an underutilized yet potentially impactful strategy with implications for transplant infectious disease protocols and surgical infection management, particularly in high-burden, resource-constrained settings.

Case presentation

A 52-year-old woman with a 15-year history of poorly controlled type 2 diabetes mellitus (HbA1c: 9.7%) and chronic kidney disease stage 4 (baseline serum creatinine: 3.1 mg/dL; eGFR: 22 mL/min/1.73 m²) underwent a deceased-donor renal transplantation in February 2024. Her past medical history was notable for hypertension and anemia of chronic disease, but she had no prior history of opportunistic infections or recent antibiotic exposure.

The patient was initiated on standard triple immunosuppression comprising tacrolimus, mycophenolate mofetil, and intravenous methylprednisolone. Perioperative glycemic control remained suboptimal, with serum glucose levels persistently ranging from 280 to 360 mg/dL despite intravenous insulin infusion protocols. Immediate postoperative recovery was initially unremarkable. Urine output remained adequate, and serum creatinine levels showed a steady decline to 1.4 mg/dL by postoperative day (POD) 7, indicating early graft function.

On POD 13, the patient reported increasing localized pain and swelling over the surgical incision site. Physical examination revealed a 6 × 4 cm indurated, violaceous plaque with central necrosis and a black eschar overlying the transplant incision. There was mild purulent discharge but no systemic signs of sepsis. Empirical broad-spectrum antibiotics (piperacillin–tazobactam and vancomycin) were initiated for a presumed surgical-site infection. However, over the next 24 hours, the lesion rapidly progressed in size with increased necrosis, prompting an urgent surgical evaluation.

Bedside debridement was performed, and tissue scrapings were immediately evaluated with KOH mount microscopy. This revealed broad, aseptate, ribbon-like hyphae consistent with mucormycosis. Figure 1 illustrates the characteristic broad, aseptate, ribbon-like hyphae seen on KOH mount microscopy.

Figure 1.

Broad, aseptate, irregular, ribbon-like hyphae on KOH mount, suggestive of mucormycosis.

Fungal culture on Sabouraud dextrose agar yielded gray–white, cottony colonies, later confirmed by lactophenol cotton blue staining and molecular identification as Rhizopus arrhizus. Figure 2: Gray–white cottony mold with a salt-and-pepper appearance filling tubes and petri plates, characteristic of Rhizopus species. Blood and urine cultures remained sterile. CT imaging of the abdomen and pelvis showed no intra-abdominal collections or systemic dissemination of fungal disease.

Figure 2.

Gray–white cottony mold with a salt-and-pepper appearance filling tubes and petri plates, characteristic of Rhizopus species.

The patient was promptly initiated on intravenous liposomal amphotericin B at a dose of 5 mg/kg/day, which was gradually escalated to 10 mg/kg/day over 72 hours. Nephrology support was sought to monitor and manage renal toxicity. Simultaneously, the patient underwent three staged surgical debridements under general anesthesia, spaced over 10 days, to ensure complete removal of necrotic tissue. The key laboratory trends are summarized in Table 1. Notably, serum creatinine remained stable (1.1–1.3 mg/dL) despite high-dose liposomal amphotericin B therapy, and there was no significant electrolyte derangement. HbA1c decreased from 9.7% at admission to 7.1% at follow-up, reflecting improved glycemic control.

Table 1.

Key laboratory findings during hospitalization.

Parameters	Value	Reference range	Interpretation
HbA1c	9.70%	<5.7%	Poor glycemic control
Serum glucose (random)	280–360 mg/dL	70–140 mg/dL	Persistent hyperglycemia
Serum creatinine (baseline)	3.1 mg/dL (274 µmol/L)	0.6–1.2 mg/dL (53–106 µmol/L)	CKD Stage 4
eGFR	22 mL/min/1.73 m2	> 60 mL/min/1.73 m2	Decreased kidney function
Corrected calcium	9.8 mg/dL (2.45 mmol/L)	8.5–10.2 mg/dL (2.12–2.62 mmol/L)	Normal on follow-up
WBC count	9600 /µL	4000–11 000 /µL	Within normal range
Hemoglobin	9.2 g/dL	12–16 g/dL	Mild anemia
Platelets	180 000 /µL	150 000–450 000 /µL	Normal
Potassium hydroxide mount	Positive for broad aseptate hyphae	N/A	Suggestive of mucormycosis
Fungal culture	Rhizopus arrhizus	No growth	Confirmed mucormycosis
Liver function tests	Normal	–	No hepatotoxicity observed
Blood and urine cultures	No growth	No growth	No systemic spread

Importantly, during each debridement, topical amphotericin B powder (50 mg reconstituted in 10 mL of sterile water) was applied directly to the wound bed, based on a multidisciplinary consensus. The application was performed with meticulous wound irrigation and gauze-packing protocols to ensure local drug retention. No local adverse effects attributable to topical amphotericin B, including wound irritation, delayed healing, or local tissue necrosis, were observed during the treatment course.

Wound cultures performed after the second debridement showed no fungal growth. By the third debridement, the wound base appeared healthy with granulation tissue. Over the subsequent 4 weeks, the patient demonstrated significant clinical improvement. The surgical wound was managed with regular dressing changes and showed progressive healing. Serum creatinine remained stable between 1.1 and 1.3 mg/dL, and there was no recurrence of necrosis or systemic symptoms.

At the 6-week outpatient follow-up, the patient was afebrile and normoglycemic, with improved glycemic control (HbA1c 7.1%), and the surgical wound had healed by secondary intention. Repeat fungal cultures remained negative. Maintenance immunosuppression was gradually tapered to include tacrolimus monotherapy.

Patient perspective

The patient reported gradual improvement in local pain, wound discomfort, and overall functional status following repeated surgical debridement and adjunctive topical amphotericin B application. She expressed reassurance with the visible wound healing progress and the avoidance of more extensive surgical procedures. No treatment-related local discomfort or adverse effects were perceived during topical therapy, and the patient reported satisfaction with the recovery process and outpatient follow-up care.

Discussion

Pathophysiology and risk factors

Mucormycosis is caused by fungi of the order Mucorales, most commonly Rhizopus arrhizus. These organisms are ubiquitous in the environment but typically only cause disease in immunocompromised hosts. The angioinvasive nature of these fungi leads to vascular thrombosis, tissue ischemia, and rapid necrosis – hallmarks of aggressive disease progression. Renal transplant recipients are uniquely predisposed due to multiple risk factors: immunosuppression, poorly controlled diabetes, broad-spectrum antibiotic use, and impaired wound healing^[6^].

In our case, multiple risk factors coexisted – advanced diabetes (HbA1c: 9.7%), CKD, and immunosuppressive therapy – facilitating fungal proliferation and dissemination. Hyperglycemia reduces neutrophilic phagocytic function and provides an iron-rich substrate for fungal growth. Tacrolimus and corticosteroids further suppress innate immunity, creating a permissive environment for opportunistic pathogens^[7^].

Diagnostic challenges

Surgical-site mucormycosis can mimic bacterial wound infections, resulting in delays in diagnosis and inappropriate empirical antibiotic therapy. This case highlights the critical importance of bedside KOH mount microscopy, which enabled rapid visualization of broad, aseptate hyphae suggestive of Mucorales. Figure 1 reinforces the utility of KOH mount as a rapid bedside diagnostic tool. Fungal cultures confirmed the diagnosis. Literature underscores that early mycological diagnosis significantly reduces mortality^[8^]. Histopathology, although useful, may be less accessible in urgent settings or poorly vascularized necrotic wounds.

Therapeutic approach and novelty

Systemic amphotericin B and surgical debridement remain the mainstay of treatment; however, it is often inadequate alone due to poor perfusion of necrotic tissue and the chances of leaving residual fungal foci. The topical application of amphotericin B, as performed in this case, allows direct delivery of high concentrations to the wound bed ^[2–4^]. Importantly, the successful outcome in our patient cannot be attributed to topical therapy alone. Our patient underwent three serial surgical debridements, which were central to achieving adequate source control and removing devitalized tissue. Intraoperative application of amphotericin B powder (50 mg) at each session was intended to enhance local antifungal activity in areas at risk for residual infection. The classic cottony appearance of Rhizopus (Fig. 2) aided in species-level identification and guided targeted antifungal management. A few published reports by Wang et al. and Warren et al. have highlighted the adjunctive role of topical amphotericin B, in combination with wound vacuum-assisted closure dressing and hyperbaric oxygen therapy, showing excellent outcomes in post-transplant surgical-site infections caused by mycoses^[9,10^]. A recent multicenter retrospective analysis also suggested that adjunctive topical antifungals reduced recurrence rates in surgical mucormycosis^[11^]. The combination of timely diagnosis, repeated surgical debridement, systemic antifungal therapy, and adjunctive topical application likely acted synergistically to achieve wound resolution by week eight.

Differential diagnoses considered

The initial differentials included bacterial surgical-site infection, necrotizing fasciitis, and wound dehiscence. However, the presence of a black eschar and rapid tissue necrosis in an immunocompromised host prompted a fungal evaluation. Other possibilities, such as aspergillosis or fusariosis, were excluded based on culture results and morphology.

Gaps in clinical practice and literature

Despite the growing burden of diabetes and immunosuppressive states, current transplant guidelines do not routinely recommend fungal surveillance for surgical wounds. This represents a significant gap. Moreover, topical antifungal therapy remains underreported in major treatment protocols.

Guidelines for cutaneous mucormycosis and randomized trials evaluating its efficacy are lacking. We advocate for early empirical antifungal coverage in non-healing surgical wounds in high-risk patients and recommend the inclusion of topical agents in future clinical protocols^[12^].

Limitations

This case report is inherently limited by being a single-patient experience, lacking comparative controls. While the positive outcome supports the adjunctive role of topical therapy, it cannot conclusively prove efficacy. Additionally, long-term follow-up beyond eight weeks was not available. Furthermore, standardized dosing, formulation, and application protocols for topical amphotericin B are currently lacking, representing an important gap that limits reproducibility and broader clinical adoption.

Implications and recommendations

Clinicians managing solid organ transplant recipients must maintain a high level of suspicion for fungal infections in atypical surgical wound presentations. Early bedside diagnostics, aggressive and repeated surgical debridement, and carefully selected adjunctive therapies, such as topical amphotericin B, may improve outcomes. We urge prospective studies and the inclusion of this therapeutic modality as an adjunct in future consensus guidelines for transplant-associated mucormycosis.

Conclusion

This case represents a rare, well-documented instance of surgical-site mucormycosis in a renal transplant recipient, successfully managed with a combination of systemic and adjunctive topical amphotericin B. Its novelty lies in the early use of bedside fungal diagnostics and repeated intraoperative topical antifungal application – an underutilized strategy with promising outcomes. Despite growing transplant volumes and rising diabetes prevalence, current guidelines lack protocols for early fungal surveillance and omit topical antifungal therapy from standard care. This case underscores the need for heightened clinical suspicion, incorporation of rapid diagnostic tools, and exploration of localized antifungal strategies to improve outcomes in high-risk, immunocompromised patients. Broader awareness and research into adjunctive treatments may shift paradigms in managing invasive cutaneous fungal infections.

Ethical approval

There is no need for ethical approval for a case report according to the local ethical guidelines.

Consent

Written informed consent was obtained from the patient for the publication of this case report and the accompanying images.

Sources of funding

Not applicable.

Author contributions

Conceptualization, data curation, literature review, visualization, writing of the original draft, and final approval: S.N.M.; clinical supervision and validation: S.S.M.; writing of the original draft, review, revision writing and editing, visualization, and validation: A.A.; supervision, review, and editing: S.G.M.; writing of the original draft, revision writing, and editing: A.S.; conceptualization of the study, data collection, literature review, drafting of the manuscript, figure and image preparation, and final approval of the version to be published: S.N.M.; clinical supervision, validation: S.S.M.; manuscript writing, revision, figure and image preparation, and validation: A.A.; supervision, review, and editing: S.G.M.; Manuscript writing, revision, writing, and editing: A.S.

Conflicts of interest disclosure

The authors declare that there are no conflicts of interest regarding the publication of this case report.

Research registration unique identifying number (UIN)

Not applicable.

Gurantor

Ashok Adhikari.

Provenance and peer review

Not commissioned; externally peer reviewed

Data availability statement

The complete data of this research is fully available upon request made to the corresponding author.