Diagnosis and Treatment of Invasive Aspergillus fumigatus Wound Infection Following Subtotal Colectomy for Perforated Toxic Megacolon in an Immunosuppressed Patient

Introduction. Aspergillus is a rare cause of surgical site infection most often seen in immunocompromised patients undergoing cardiac, transplant, ophthalmologic, or burn operations; an unusual case following a colon resection is presented here. Case Report. The authors report a case of an invasive Aspergillus fumigatus infection following a subtotal colectomy for toxic megacolon. The patient was on antibiotics following the operation and chronic immunosuppression with steroids and infliximab. This was an unusual cause of a postoperative wound infection. Conclusions. This case highlights the importance of early and accurate identification, debridement, and systemic antifungals to prevent widespread infection. With changes in antifungal care over recent years, engaging infectious disease physicians during treatment is recommended.

Aspergillus surgical site infections are very rare, with an estimated rate of 2 in 10 000 cases.¹ General surgery cases only account for 2% of these, with the majority occurring in cardiac, transplant, ophthalmologic, or burn patients.² The authors found a single case of Aspergillus infection following exploratory laparotomy in the literature that was reported more than 20 years ago.³

The case reported herein highlights the risk factors, diagnosis, and treatment of an Aspergillus fumigatus wound infection following a subtotal colectomy.

A 37-year-old woman diagnosed with ulcerative colitis after developing abdominal pain and bloody diarrhea 2 months prior presented to the Swedish Medical Center surgical service (Seattle, WA) with feculent peritonitis from a perforated transverse colon, secondary to toxic megacolon. Her treatment regimen included methylprednisolone 20 mg every 8 hours for the past 6 weeks, with a recent initial dose of infliximab 5 mg/kg. She was brought to the operating room emergently for a subtotal colectomy with end ileostomy. Her fascia was closed, but a superficial wound was left open due to gross contamination during the case.

Postoperatively, she was treated with piperacillin-tazobactam 3.375 mg every 8 hours for 7 days; methylprednisolone 60 mg daily, which was tapered off over 10 days; vitamin A 25 000 units daily throughout steroid taper; and enteral nutrition via nasogastric tube. On postoperative day 7, during the dressing change, there was an acute change in her wound as she was noted to have mold growing (Figure 1). She returned to the operating room where 1 cm to 2 cm of necrotic subcutaneous tissue surrounding the wound was found. This was debrided down to normal appearing subcutaneous fat, and cultures were collected from the wound (Figure 2). Septate hyphae were seen on gram stain, and later A fumigatus grew. Prior to culture results, a serum Aspergillus galactomannan assay was positive. The patient was started on intravenous voriconazole 4 mg/kg every 12 hours and was continued for 8 days.

At 8-days postop from her debridement, voriconazole was converted to oral posaconazole 200 mg three times daily, which was continued until postoperative day 35, and her wound dressing was transitioned from wet-to-dry dressing with Dakin’s solution to negative pressure wound therapy (NPWT; V.A.C. Therapy; KCI, an Acelity Company, San Antonio, TX) at -100 mm Hg continuous pressure with the input of both infectious disease and plastic surgery.

A fungal swab taken from the wound on postoperative day 15 showed no growth. She was discharged to a skilled nursing facility on hospital day 30 with NPWT in place at -100 mm Hg pressure. She continued to take oral posaconazole at 200 mg three times daily and was tapered off steroids by the time of hospital discharge.

At 35-days postop following debridement, she had no signs of infection and the posaconazole was discontinued.

Invasive Aspergillus infection after surgery is estimated to affect 2 in 10 000 cases.¹ The literature consists of a handful of case reports and case series over recent decades.² The majority of these infections are caused by A fumigatus and occurred in burn, cardiac, and transplant operations.^2,4-7 Often, these infections occur in immunocompromised patients, but immunocompetent patients also are susceptible when the skin barrier is broken and tissue is exposed to the environment as in cases of burns or surgery.^1,8 In addition, fungal infections presented at a higher rate in trauma patients, especially when exposed to soil during the trauma such as a farming accident.^9,10

The rare case presented here is of Aspergillus infection following emergent abdominal surgery, which was an isolated incident in the authors’ surgical department, but outbreaks of surgical Aspergillus infections have been reported^7,8 and are thought to be due to airborne Aspergillus conidia. These conidia have been isolated from air in the intensive care unit and operating room where patients became infected.^7,8

Diagnosis of invasive A fumigatus requires histological evidence and positive cultures. This case was unusual with the acute onset of visible mold in the wound (Figure 1). Cultures confirm the diagnosis and allow testing of antifungal sensitivity. Galactomannan antigen assay has increased the efficacy of diagnosis of Aspergillus in recent years and is commonly performed.¹¹

As the present case highlights, treatment consists of debridement and systemic antifungals. Debridement is essential as the large area of wound necrosis has poor penetration of antifungals. In a review of case reports of traumatic filamentous fungal infection, outcomes were improved with surgery and antifungals compared with either treatment alone.¹⁰ Systemic therapy traditionally consisted of amphotericin B or itraconazole. Currently, second-generation triazoles, such as voriconazole or posaconazole, are the treatment of choice due to improved efficacy and reduced toxicity. However, A calidoustus has shown resistance to triazoles.¹² Liposomal amphotericin B may be the best choice for this species.¹² Volkmer et al¹³ reported a case of invasive Aspergillus infection following trauma that failed to respond to systemic antifungals, but the infection regressed with the addition of topical nystatin powder.Caspofungin also has demonstrated efficacy in invasive Aspergillus^10,14 and has been used alongside voriconazole in cases of mediastinitis with a mechanical heart valve⁴ because this combination has been shown to inhibit the formation of Aspergillus biofilms in vitro.¹⁴

In this case, antifungals were stopped after 30 days due to the patient’s clinical improvement. The duration of treatment ranges in the literature, with most studies reporting between 6 weeks and 12 weeks of antifungal treatment.^1,4,10,12 However, these patients often have longer, complicated postoperative courses than the patient presented herein. Beyond debridement and antifungals, case reports suggest that in certain circumstances hyperbaric oxygen (HBOT) may serve as an adjunct to treatment, but definitive data in humans are lacking.^15,16 Aspergillus has the ability to survive in low oxygen states, which are common during infection. A recent study in mice¹⁷ showed increased survival in those treated with HBOT for their Aspergillus infection compared with mice that did not undergo HBOT. The present patient improved with debridement and antifungals, so HBOT was not discussed.

Due to the rarity of this infection, a randomized trial in humans would not be possible. Aspergillus surgical site infections are rare in general surgery but can have fatal outcomes, especially when deep organ spaces are involved. This patient’s wound was packed daily with moist saline gauze and monitored on daily rounds by the surgical team. No sign of infection was noted prior to her developing the extensive infection seen in Figure 1. Since there was no sign of infection, there was no indication to treat the wound differently at that time. In the future, the authors plan to monitor wounds in immunocompromised patients meticulously and have the surgical team complete all dressing changes.

This case highlights the importance of early and accurate identification, debridement, and systemic antifungals to prevent widespread infection.

Affiliation: Department of Surgery, Swedish Medical Center, Seattle, WA

Correspondence: Bryce French, MD, General Surgery Resident, Swedish Medical Center, Department of Surgery, 747 Broadway, Heath Tenth, Seattle, WA 98122-4307; Bryce.french@swedish.org

Disclosure: The authors disclose no financial or other conflicts of interest.