Phaeohyphomycosis is a heterogeneous group of infections induced in human by opportunistic dematiaceous fungi. More than 50 genus and 100 species of pathogenic fungi are able to cause phaeohyphomycosis. Most of the pathogenic fungi are saprotropic fungi living in the soil or plants, but they may invade human with traumatic origin. Their infections in human could be in skin, cornea, and subcutaneous tissues and even be systemic [4]. However, phaeohyphomycoses are usually unrecognized or misidentified because the pathogens lack morphological specificity and present polymorphic appearance.
Corynespora cassiicola is a common plant pathogen, which has a broad host range worldwide. It can infect many plants in tropical and subtropical climate zones, including cucumber, tomato, rubber plant and cotton [5]. Human infections by Corynespora cassiicola are rare and thus far only four cases have been reported in the literature. The first case was reported in 1969 [6], in which Corynespora cassiicola was isolated from a patient with Madura foot in the Sudan. Huang and his colleague described a farmer with subcutaneous infection in both hands caused by Corynespora cassiicola [7]. Another subcutaneous infection caused by Corynespora cassiicola was also reported afterwards [4]. Moreover, Corynespora cassiicola has also been isolated and identified in a corneal infection [8].
The management of phaeohyphomycosis with itraconazole or voriconazole is recommended strongly but only based on lower level evidence [9]. For the treatment of Corynespora cassiicola infection, terbinafine [4] and amphotericin B [7] have also shown success. More specifically, the patient with corneal infection healed after receiving the treatment with topical voriconazole, micafungin and pimaricin for 3 months and intravenous voriconazole for 1 month [8]. Subcutaneous infections in both hands were treated successfully with amphotericin B after ineffective oral itraconazole therapy [7]. And subcutaneous infections in the legs were cured with oral terbinafine and topical povidone iodine for 6 weeks [4].
The patient in the current report was referred to our hospital mainly because of acute heart failure rather than the ulcer on the right leg. According to the description of the patient, it had been nearly two months since the ulcer occurred, which was not taken seriously. Corynespora cassiicola infection is generally found in immunocompromised patients. It is worth to note that the patient in current report is 76 years old with COPD and poor nutritional status, which may contribute to the right leg infection.
As the several Gram stains from the ulcer showed Gram-negative bacteria and large amount of leukocytes, cefoperazone/sulbactam was applied as an empiric antibacterial therapy. Meanwhile, the use of cefoperazone/sulbactam also aims at the control of pulmonary infection because cefoperazone/sulbactam is effective for the treatment of lower respiratory tract infections as well as skin and soft tissue infections. While the antibacterial therapy was successful for pulmonary infection, no obvious relief was observed on the ulcer on the right leg. Considering the unsatisfactory result might be associated with the pathogens out of the cefoperazone/sulbactam antibacterial spectrum, proofs for fungal infection had been investigated and antifungal therapy was employed afterwards.
Although the pathogenic fungus was not identified until the discharge, fortunately the voriconazole treatment was successful. Voriconazole was chosen for initial antifungal therapy based on several factors. Firstly, the antifungal spectrum of voriconazole is important. The smear examination and fungal culture revealed filamentous fungi, and voriconazole is the first-line therapy of most filamentous fungi according to the guideline [10]. Secondly, the pharmacokinetic features should be taken into account. Voriconazole is supposed to be well distributed in the skin and soft tissue, and it is a weaker inhibitor of P450 enzymes among all the azole antifungals, suggesting less potential drug interactions. Coincidently, the patient was receiving the treatment with multiple drugs but no specific drug interaction was found. Another fact need to be paid attention to is that sulfobutylether-betacyclodextrin (SBECD) was used as the solvent for intravenous administration of voriconazole. Lipophilic voriconazole was contained in the center of SBECD to enhance its solubility and stability [11, 12]. Ninety five percent of SBECD are renally excreted, and SBECD will accumulate in patients with moderate to severe renal impairment [13]. At the meantime, oral bioavailability of voriconazole is up to 96%. Consequently, oral instead of intravenous voriconazole is recommended when the GFR is < 50 mL/min [10, 14]. In this case, renal impairment occurred after acute heart failure. GFR of the patient was 51 mL/min when voriconazole treatment started. Based on renal function test, oral voriconazole had been timely started as the substitute to avoiding further renal impairment.
In summary, our patient was referred to the hospital due to acute heart failure and fortunately took the chance to deal with the ulcer on his right leg. During hospitalization, infection on right leg gradually became the major problem. Corynespora cassiicola was finally identified as the causative pathogen, which is rare to be seen in humans. This case also reminds us that monitoring of renal function and proper transition to oral formulation will be crucial for patients with reduced GFR when receiving intravenous administration of voriconazole.
