In recent decades, the incidence of ROCM in patients with hematological malignancies were increasing, which caused high mortality. ROCM requires early clinical suspicion and accurate identification, as the mucormycosis invade to the vessels advances rapidly. Early diagnosis, prompt medical drug treatment combined with active surgical treatment and improve patient's basic diseases as much as possible, such as restoring the number of white blood cells, and adjusting the use of immunosuppressants, will significantly improve the survival rate of patients with hematological diseases complicated by mucormycosis[6].
The most common symptoms for ROCM were eyeball protrusion, ophthalmoplegia, and decreased vision, which were not specific[7]. The only specific finding of ROCM described in the relevant reports is the necrotic eschar with blackened nasal mucosa. However, facial necrosis remains a late sign, with only 2% of patients presenting with this sign[7]. It is reported that the orbital involvement rate of nose brain mucormycosis ranges from 66–100%, orbital involvement leads to increased mortality, and the survival rate of patients with fungal encephalopathy is very low[8]. A combined surgical and medical management was associated with better survival. Surgical debridement of necrotic tissue may enable better penetration of antifungal agents, thereby improving outcomes. Unfortunately, surgical debridement is not feasible for patients with intracranial extension. Despite appropriate antifungal treatment, the mortality rate of patients who were unable to undergo surgery was high, indicating the need for early diagnosis and better treatment strategies[9]. Thus, surgical debridement may be considered in patients with malignant hematological disease even if they had leukopenia and thrombocytopenia[10]. Liposome amphotericin B should be used as a first-line treatment drug and given early in the course of the disease. Delayed initiation of liposome amphotericin B therapy (> 6 days after diagnosis) has been reported to be associated with a doubling mortality at 3 month[11]. Isaconazole has recently become a first-line alternative for patients who are either intolerant to amphotericin B or do not respond favorably to it[12]. Some cases of successful treatment of mucormycosis with posaconazole have been reported, thus posaconazole was considered as salvage treatment for mucormycosis[13].
Trichosporon species have emerged as important opportunistic fungal pathogens, with T. asahii being the leading cause of disseminated infections and result in significant morbidity and death among those with a hematologic malignancy. 75% T. asahii was isolated from blood in pediatric cases and invasive T.asahii was frequently observed cutaneous involvement, which is helpful for high index of suspicion, early determine the etiology and initiate appropriate treatment[14]. Clinicians should highly suspicious of trichosporonosis in pediatric patients with a hematologic malignancy
who present with persistent fever and neutropenia, especially when echinocandins are given for antifungal prophylaxis[15]. It is well known that Trichosporon is inherently resistant to echinocandins and has poor sensitivity to polyene drugs. Moreover, breakthrough trichosporosis may occur in patients receiving echinocandin as an empirical antifungal treatment[16]. In the past decade, amphotericin B and fluconazole have also been reported as antifungal drugs with high risk of breakthrough trichosporosis, including prophylactic joint use of fluconazole plus amphotericin B[16]. A number of studies have shown that the recommended first-line therapy for T. asahii is voriconazole, and likely superior to amphotericin B, fluconazole, and itraconazole for the treatment, but successful outcome depends largely on the underlying immune status of the host[17]. The mortality rate of was exceeding 80%, in patients with hematologic malignancy survival is thought to be primarily related to bone marrow recovery. Reported cured patients did not have neutropenia at the time of diagnosis or quickly recovered from neutropenia[17]. Clinicians should maintain a high level of clinical suspicion in patients with aforementioned risk factors, particularly in those with hematologic malignancies who have catheters in place. Remove central venous catheter and address the underlying immunosuppression may be possible to decrease mortality rates[17].
According to our investigation, this case is the third case of Mucormycosis and T.asahii co-infection. The clinical characterizations of Mucormycosis and T.asahii co-infection previously reported were listed in Table 1[18, 19].
Table 1
Summary of reported cases of Mucormycosis and T.asahii co-infection
Number | Year | Author | Age/sex | Presenting symptoms | Primary lesion | Underlying conditions | Treatment | Outcome |
1 | 2006 | De Decker, K et al.[18] | 12/F | Skin and muscles necrosis | Leg necrotizing fasciitis | Traffic accident | Amphotericin B, Posaconazole, surgery, Hyperbaric oxygen | Live |
2 | 2016 | Ozkaya-Parlakay, A et al.[19] | 16/M | cutaneous necrosis, nasal bone necrosis | Paranasal | Ewing sarcoma | Caspofungin, liposomal amphotericin B | Dead |
In our case, P. aeruginosa BSI occurred in this immunocompromised children further worsened his immunity, and later a rare co-infection with Rhinocerebral Mucormycosis and T. asahii Fungemia associated with mortality. A acute lymphoblastic leukemia patient presented with necrotic eschar should maintain high level of clinical suspicion Mucor and Trichosporon, reversal of risk factors, early diagnosis together with prompt and appropriate antifungal therapy and surgical debridement are essential for a favorable outcome.