Clinical Features and Outcomes of Invasive Fusariosis: A Case Series in a Single Center with Literature Review

Fusarium species, which are commonly found in soil, water, and organic substrates, are one of the most clinically important molds in immunocompromised patients [1] and can cause life-threatening fungal infections in humans. The clinical manifestation of fusariosis relies on the patient's immunity [2]. Invasive fusariosis, such as fungemia, pneumonia, and disseminated infection, manifest in immunosuppressed hosts seldom responding to antifungals [3]. Decreased cellular immunity, solid organ transplantation, hematopoietic stem cell transplantation, and prolonged neutropenia after cytotoxic chemotherapy are known as risk factors for development of invasive fusariosis [3, 4]. Although invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients, there are limited reports describing predisposing factors and clinical characteristics of invasive fusariosis in Korea. Herein, we reported 14 years of experience of invasive fusariosis in a single institution.

We retrospectively reviewed patients with fusariosis at Samsung Medical Center, Seoul, Korea from September 2003 to January 2017. We searched data by reviewing the electronic medical records of the patients. We collected data on clinical characteristics, underlying diseases, and treatment outcomes from all patients who were categorized according to the definitions of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria [5]. Invasive fusariosis was defined as any case with at least one positive blood culture or with the concurrent involvement of two or more non-contiguous sites. We excluded colonizers, contaminated specimens, and superficial infections such as onychomycosis or keratitis. Positive sputum or nasal cultures without any infection in lung or sinonasal area were considered colonizers.

We identified 57 culture-proven cases of fusariosis, of which 20 cases of keratitis or onychomycosis were excluded. Another 13 colonizers and contamination specimens were excluded as well. Of the remaining 24 patients, 10 cases were excluded as sputum and nasal cultures were considered non-invasive infections. As a result, 14 cases were defined as invasive fusariosis according to EORTC/MSG criteria (Fig. 1).

Figure 1
Inclusion and exclusion of fusariosis cases.
PICC, peripherally inserted central catheter.

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The mean age of patients with invasive fusariosis was 47 years (range, 5 - 72 year). Table 1 shows the clinical characteristics of patients. The most common underlying diseases were hematologic malignancy (n = 7, 50.0%) such as acute myeloid leukemia and lymphoma, followed by liver transplantation (n = 2, 14.2%). Blood and skin were the most common sites of infections (n = 6, 42.8%), followed by lung (n = 3, 21.4%). Co-infections were common (n = 5, 35.7%), and Aspergillus fumigatus was the most common (n = 3, 21.4%) co-pathogen. Most of the invasive fusariosis patients were treated with liposomal amphotericin B or voriconazole.

Table 1
Characteristics of 14 patients with fusarium infection

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The diagnosis of skin fusariosis was established with skin biopsy, and most of the patients with skin fusariosis recovered with antifungal treatment unless they had fungemia. The patients with pulmonary fusariosis showed dyspnea, cough, and fever (n = 4), and most of them had co-infection with A. fumigatus. Fusarium species were isolated from bronchial washing fluid (n = 1) and tracheal aspirate cultures (n = 3). As shown in Table 1, although most patients received antifungal treatment such as liposomal amphotericin B, half of patients eventually died of pneumonia or sepsis.

The overall mortality rate of patients with invasive fusariosis was 50% (7/14). Seven of 14 patients with invasive fusariosis according to EORTC/MSG criteria died from sepsis, neutropenic fever and pneumonia. The mortality rate of disseminated fusariosis cases was 83% (5/6). Among six patients with fusarium fungemia, three received antifungal treatment, and five died of prolonged neutropenic fever or sepsis.

We have reviewed previous reports on invasive fusariosis in Korea and described in Table 2.

Table 2
Clinical characteristics in invasive fusariosis reported in Korea (previous reports)

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In the current study, we have reported clinical features and outcomes of invasive fusariosis, based on the 14-years' experience in a Korean tertiary-care hospital. Most of the cases developed in severely-immunocompromised patients and the treatment outcome was poor. Invasive fusariosis is a rare and opportunistic infectious disease that may occur in immunocompromised patients [2]. Since the first report in a patient with acute leukemia in 1973 [6], invasive fusariosis has been increasingly documented as an emerging pathogen in severely-immunosuppressed hosts [7, 8].

Management of invasive fusariosis is challenging to clinicians given the poor prognosis of invasive fusariosis [7]. Early diagnosis of invasive fusariosis may be difficult as the diagnostic yield of blood or tissue cultures is low in most cases, although molecular methods such as polymerase chain reaction (PCR)-restriction fragment length polymorphism has been introduced recently [9, 10]. Prolonged severe neutropenia, long-term use of corticosteroids, use of broad-spectrum antibiotics, and solid organ transplantation are important risk factors of invasive fusariosis [11]. In addition, fusarium spp. are relatively resistant to multiple antifungal agents which leads to unfavorable prognosis [12]. Several studies have shown that Fusarium spp. are resistant or have high minimum inhibitory concentration to old azoles and echinocandins [12]. The optimal treatment regimen for invasive fusariosis has not been yet clarified. However, recent case reports have shown the efficacy of liposomal amphotericin B and voriconazole in the treatment of invasive fusariosis [13]. In our cases, liposomal amphotericin B and voriconazole were used in most patients, although the results were dependent on the hosts' immunity.

There is a paucity of English-language reports of case series and literature reviews [14]. In Korea, fungal pneumonia with fusarium species was described in 1990 [15] and the first case with fusarium fungemia was reported in a child with acute leukemia in 1997 [16]. Since then, there have been several case reports of invasive fusariosis [7, 8, 10, 15, 17, 18, 19, 20, 21]. To our knowledge, this is the first and largest case series report describing the clinical characteristics and outcomes of invasive fusariosis in Korea.

In this case series, most cases were developed in severely-immunocompromised patients, and the treatment outcome was poor, similar to that in previous reports. However, in this study, underlying diseases of patients with invasive fusariosis were various (e.g. leukemia, solid organ transplant, Stevens-Johnson syndrome and trauma, etc.). Successful outcome of invasive fusariosis relies on the degree and persistence of immunosuppression and the extent of infection [2].

Invasive fusariosis is a newly emerging fungal infection in immunocompromised patients, and the mortality rate so far exceeds 50% despite antifungal treatments [14]. Given the high mortality rate of invasive fusariosis, healthcare professionals treating immunocompromised patients should be aware of the clinical characteristics and risk factors of invasive fusariosis, especially disseminated fusariosis.