Prompt diagnosis of Scedosporium apiospermum soft tissue infection: Life-saving in a renal transplant recipient.

Scedosporium apiospermum, an ubiquitous filamentous fungus, a known cause of mycetoma, is emerging as an opportunistic pathogen in immunocompromised individuals. We report a case of painful foot abscess in a renal allograft recipient on immunosuppressive therapy, which was clinically diagnosed as a suppurative bacterial abscess. Pus was aspirated, which showed septate, branching hyphal elements and culture on Sabouraud's dextrose agar yielded S. apiospermum, which was identified based on its macroscopic and microscopic features. There are very few reports of scedosporiasis from India. High index of suspicion for unusual fungal infection helps in prompt etiological diagnosis in a transplant recipient and rapid management prevents further dissemination.

Introduction

The incidence of severe systemic fungal infections has been increased significantly, mainly because of the marked increase in the number of patients with compromised immune system. Invasive fungal infections (IFIs) are among the most important causes of morbidity and mortality among solid organ transplant recipients who are on long-term graft-preserving immunosuppressive therapy. Immunosuppressive treatment with calcineurin inhibitors, such as cyclosporine, pimecrolimus and tacrolimus impairs interleukin-2 (IL-2) expression, resulting in increased susceptibility to various invasive fungal diseases. Indiscriminate use of antibiotics also contributes to the worsening of this picture, leading to the installation of fungal infections. High mortality rate (25%–80%) due to IFIs within the first 6 months after organ transplantation has been documented.[1] Commonly reported IFIs among transplant recipients are invasive candidiasis, cryptococcosis, and invasive mold infections, such as aspergillosis and zygomycosis.[1] Among nonAspergillus molds, Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections after transplantation and can present with broad spectrum clinical diseases.

Case Report

A 27-year-old girl presented with a very painful, gradually increasing swelling in the left sole which appeared following a trauma sustained 3 months ago. She underwent renal allograft transplantation 18 months back due to chronic kidney disease Stage 5D. The patient was on tacrolimus (1 mg BD), azathioprine (50 mg OD), and prednisolone (10 mg OD) when she presented. She was also suffering from diabetes with a fasting sugar 92 mg/dl and was on glipizide and pioglitazone. Her history sheet revealed that induction immunosuppressive therapy was carried out before transplantation with 20 mg single dose basiliximab on the day of transplant. There was no episode of graft rejection during posttransplant period. On clinical examination, it was tender, soft, fluctuant abscess over the left sole measuring about 4 cm × 3 cm, there was local increase of temperature and pus oozing from small breach of overlying skin [Figure 1].

Figure 1

Soft, fluctuant abscess over left sole (4 cm × 3 cm in size) with oozing pus

Abscess was surgically drained and a pus swab and biopsy was taken from abscess bed. Histopathological examination revealed irregular epidermal acanthosis, dermal fibrosis, vascular proliferation, and dense infiltration of inflammatory cells. Pus swab was cultured on routine media and showed the growth of coagulase negative Staphylococcus. With the view of immunosupressed condition of the patient, she was treated with amoxicillin-clavulanic acid and levofloxacin but pus filled swelling reappeared within 7 days. Then, the aspirated pus sample was collected in the Microbiology Laboratory which was examined by Gram-staining, Ziehl–Neelsen staining, and potassium hydroxide (KOH) preparation. KOH mount showed the plenty of branching, septate hyaline hyphae. The sample was inoculated on blood agar, Sabouraud's dextrose chloramphenicol agar and incubated at 25°C and 37°C. Growth of white mycelial fungus was seen after the 3rd day of incubation. Fast growing, grayish-white colony, with suede like surface and grayish-black reverse was examined with lactophenol-cotton blue preparation on the 5th day and it showed hyaline, branching, septate hyphae with single, oval conidia present on the tip of erect conidiophores [Figure 2]. Slide culture was done on distilled water agar and potato dextrose agar showed the presence of cleistothecia after 3 weeks of incubation. With the help of suggestive microscopic features isolate was phenotypically identified as Scedosporium spp.[2] The isolate was deposited (Deposition no.: ILK997) in the reference laboratory at Postgraduate Institute of Medical Education and Research, Chandigarh, India for and it was confirmed as Scedosporium apiospermum.

Figure 2

(a) Sabouraud dextrose agar with growth of greyish-white colony and greyish-black reverse. (b) Lactophenol-cotton blue preparation showing hyaline branching septate hyphae with single conidia present on the tip of erect conidiophores (×400)

The patient was promptly started on oral voriconazole 250 mg BD and continued for 6 weeks. Dose of tacrolimus was reduced from 2 to 1 mg/day. Her infection started to improve. However, 6 weeks later, she reported nausea, difficulty in concentration and visual hallucinations. The complaints were consistent with known voriconazole side effects. Hence, the dose of voriconazole was reduced to 200 mg twice/day. In this regimen, her adverse symptoms improved in 2 weeks. The patient ultimately completed a total of 3 months of oral voriconazole and remained free of any signs of recurrence 8 months after the completion of therapy.

Discussion

S. apiospermum complex, the asexual form or anamorph state of Pseudallescheria boydii, has been recognized to encompass several distinct, medically important species[3]. It is a hyaline, filamentous, ascomycetous fungus, ubiquitously present in soil, sewage, and polluted waters. The asexual form produces brown colored, round, or elliptical single celled conidia borne singly from the tips of long or short erect, slender conidiophores. The sexual form (teleomorph) exhibits cleistothecia, which are sac like structures that contain asci and ascospores. Unlike S. apiospermum, Scedosporium prolificans produces conidiophores with distinctly swollen bases, and the conidial mass forms apical aggregates of conidia. The teleomorph state is also not produced by S. prolificans.[2]

It was described more than a century ago as a cause of Madura foot and subsequently white grain mycetoma, otitis externa and disseminated mycosis in lungs with cystic fibrosis. Four types of infection caused by either Pseudallescheria or Scedosporium spp. have been described in literature: (i) Mycetoma, (ii) opportunistic infections among transplantation recipients and those receiving antineoplasic or immunosuppressive therapy, (iii) nonopportunistic infections commonly following penetrating trauma, (iv) sino-pulmonary and central nervous system infections in immunocompetent individuals following near drowning in polluted waters.[3] Although, previously the organism with low inherent virulence was considered exceedingly rare, an increasing number of invasive infections are being reported in recent times mainly in patients with hematological malignancies or in those who have undergone solid organ transplantation.[3] High rate of dissemination following deep seated Scedosporium infections commonly seen in transplant recipients due to their immune-suppressed status. There are very few subcutaneous and invasive Scedosporium infections have been reported from India except mycetoma.[456]

In histopathological examination, Scedosporium could not be distinguished from other septate, hyaline molds, such as Aspergillus, Fusarium, Paecilomyces, which are relatively common but have different resistance profile. Fungal culture is the gold standard in establishing accurate and prompt diagnosis of S. apiospermum. It is essential, because this organism can often be misidentified as other filamentous fungus with different resistance profiles.[7] Scedosporium species are generally resistant to amphotericin B and. S. prolificans, in particular, is also resistant to most of the currently available antifungal agents.[8] Hence, empirical use of antifungals against Candida and Aspergillus in immunocompromised patients might create a selective pressure and contribute to the increased incidence of Scedosporium infections.

In our case, the early detection of fungal elements in the direct microscopy, culture isolation and speciation were all necessary to make a timely and accurate diagnosis. Treatment of Scedosporium spp. is often difficult, particularly when abscess sites are not amenable to surgical intervention, as inadequate debridement impedes the penetration of systemic antifungals. Although voriconazole, with broadened antifungal spectrum, showed promising result in S. apiospermum infections, significant side effect of vision disturbance and its pharmacokinetic interaction with IL-2 inhibitors, makes the dose titration difficult.[3] Combination therapy of voriconazole and terbinafine/micafungin, antifungal with granulocyte-macrophage colony-stimulating factor also showed efficacy in disseminated cases.[8] Fortunately, our case responded with oral voriconazole therapy without further spread.

Conclusion

This case enlightens us to consider fungal infections in the differential diagnosis, especially in immunocompromised patients and to be aware of unusual hyalohyphomycosis. It also highlights the importance of sending aspirated pus sample instead of a swab for diagnosing fungal etiology; which plays a vital role in prompt treatment and favorable outcome for the patient.

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Conflicts of interest

There are no conflicts of interest.