Humicola Trauma-related Invasive Fungal Infection in an Immunocompetent Patient

Summary:

The majority of invasive fungal infections arise in immunocompromised patients; however, there exist many clinical interventions and physiologic phenomena in the setting of traumatic injury that induce immunosuppressant states. Enhanced clinical suspicion and early detection of invasive fungal infections has played an increasingly pertinent role in clinical management of patients admitted for traumatic injury, given its substantial morbidity and mortality rates. In this case report, we discuss a case of trauma-related invasive fungal infection by a rare humicola pathogen in a previously immunocompetent patient. We present this case in hopes of instilling a high index of clinical suspicion for trauma-related invasive fungal infections. We also discuss the role of negative pressure wound therapy and aggressive surgical management, including debridement and various levels of amputation to optimize patient outcomes. Clinical management of trauma-related IFI has adopted increasingly aggressive approaches with respect to its formidable morbidity and mortality rates. Multidisciplinary discussions and patient-centered care are essential when making surgical decisions that impact quality of life such as amputation level.

INTRODUCTION

Enhanced clinical suspicion and early detection of invasive fungal infection (IFI) has played an increasingly pertinent role in clinical management of patients admitted for traumatic injury. Due to severely impaired wound healing, IFI patients are more likely to require revision to a more proximal amputation,^1,2 hemipelvectomies or hip disarticulations,^1,3 a higher number of operative procedures,^1,2 and longer intervals preceding initial wound closure.¹ Prior investigations have shown mortality rates as high as 38% for patients with trauma-related IFI.^1,4

The majority of IFI cases arise in immunocompromised patients.⁵ Many clinical interventions and physiologic phenomena in the setting of traumatic injury induce immunosuppressant states. Notably, large-volume blood transfusion induces a transient immunosuppressive state, facilitating opportunistic fungal and bacterial infections.^1,6

We present a previously immunocompetent 62-year-old man whose care was complicated by infection with humicola species, a rare cause of IFI. Only 16 cases of humicola infection have been reported, with none of these cases having originated in immunocompetent patients.⁵ We present this case to report a rare invasive fungal infection in a previously immunocompetent patient. We also discuss how IFI impacts surgical management of patients with traumatic injuries.

CASE REPORT

A 62-year-old man with no pertinent medical history presented after sustaining extensive polytrauma when he was hit by a car while riding his motorcycle. He developed hemorrhagic shock secondary to traumatic liver laceration, treated with massive blood transfusion. He also sustained multiple severe orthopedic injuries, and guillotine below-knee amputation (BKA) of right lower extremity was performed (Fig. 1). Two weeks later, he was transferred to our facility for multidisciplinary surgical consultation given the complexity of his injuries.

Fig. 1.

Grossly infected amputation site and traumatic knee injuries prior to debridement. A, Guillotine BKA of the right lower extremity, with the patient in the supine position. B, Right traumatic knee wound sustained in the traumatic collision.

Soon after arrival, the patient underwent additional debridement of the guillotine BKA. Wound cultures from both stump and right traumatic knee wounds grew a rare, unidentifiable fungus, necessitating initiation of empiric intravenous amphotericin B. The stump culture additionally grew Candida parapsilosis. One week later, the BKA was partially closed with a posterior advancement flap. A small area was left open laterally and dressed with negative pressure wound therapy (NPWT) to promote wound drainage and bacterial clearance in the setting of persistent positive wound cultures without gross infection or purulence. NPWT dressing changes were scheduled every other day, at which time his wounds were assessed for granulation tissue and IFI clearance.

Due to concerns of skin graft failure and IFI exacerbation, NPWT was applied for longer intervals between revision surgeries and closure compared with management of traumatic wounds not affected by IFI. Additionally, conservative advancement of amputation level for definitive clearance of IFI was considered. There were several multidisciplinary discussions among the infectious disease, orthopedic and plastic surgery services pertaining to the persistence of IFI at the knee wound. The mainstay of these discussions was the efficacy of surgical debridements and antifungal therapy versus surgical advancement to an above-knee amputation to definitively clear the infection. Based on discussions with the patient and his stable clinical status, our primary goal was salvage of BKA to better support ambulation with a prosthesis in the future.

Six weeks after positive fungal cultures from our patient’s initial revision surgery, the fungus was identified as humicola species by DNA sequencing at an external laboratory. A few days later, the wound sites exhibited healthy granulation tissue (Fig. 2). Wound cultures confirmed resolution of the fungal infection at the knee wound, and split-thickness skin grafting was deemed an appropriate reconstruction due to absent exposed bone or tendon. Split-thickness skin grafting was performed at the knee wound, and the stump wound underwent definitive closure. The patient has followed up for outpatient wound care and antifungal therapy and is being fitted for a prosthesis (Fig. 3).

Fig. 2.

Healthy granulation tissue at the patient’s right traumatic knee wound following debridement and NPWT.

Fig. 3.

Postoperative wound site healing well after split-thickness skin grafting, harvested from a right anterolateral thigh autogenous donor site.

DISCUSSION

High index of clinical suspicion is essential to promptly diagnose trauma-related IFI and prevent significant morbidity and mortality. Treatment of IFI is often delayed due to low clinical suspicion afforded to previously immunocompetent patients followed by protracted confirmational laboratory testing. According to the Trauma Infectious Disease Outcomes Study Investigative Team, the diagnostic criteria for trauma-related IFI include (1) presence of traumatic wound(s), (2) recurrent necrosis following serial surgical debridements, and (3) laboratory evidence of fungal infection.^3,7 In our case, a rare fungus necessitated DNA sequencing at an external laboratory over the course of 6 weeks. We suggest initiating aggressive IFI treatment with ongoing wound necrosis after two surgical debridements.^3,7

Three pillars of IFI management include (1) prompt and aggressive surgical debridement, (2) limiting immunosuppressant therapies, and (3) empiric dual antifungal therapy (amphotericin B and broad-spectrum triazole).³ Aggressive surgical debridement is defined as debridement beyond the area of gangrenous demarcation every 24–48 hours until there is no further evidence of necrosis.⁸ Angioinvasive potential is an important indicator for aggressive surgical debridement, as these mycoses often extend beyond visible infectious wound demarcations. Debridement is also an essential adjunct to systemic antifungal therapy to improve wound penetration in the setting of local border ischemia. Wound closure should be delayed until the wound is clean and granulation tissue is evident.^3,7

Healthy and immunocompetent patients who undergo traumatic injury are at risk for trauma-related IFI. Trauma leads to cortisol-dependent immunosuppression, and patients can also experience transfusion-related immunomodulation.^6,9 In a case-control study investigating IFI arising from combat casualties in Afghanistan, 97.2% of cases had been treated with massive blood transfusion.² This consequence is dose-dependent, with a 5% increased risk of infection for each unit transfused.⁶

To date, little is known about the effectiveness of antifungal medications in treating trauma-related IFI. Plasma drug concentration is the primary indicator for monitoring treatment efficacy. In a case series describing two patients with trauma-related IFI, Akers et al found amphotericin B to be undetectable in wound effluent collected by NPWT despite high concurrent plasma concentrations.¹⁰ Thus, it is imperative that surgical and infectious disease teams collaborate to develop comprehensive, multidisciplinary treatment plans.

CONCLUSIONS

Clinical management of trauma-related IFI has adopted increasingly aggressive approaches with respect to its substantial morbidity and mortality rates. We present this case in hope of instilling a high index of clinical suspicion and to discuss surgical management of trauma-related IFI.