key: cord-0862500-epofdkd4
authors: Ranjbar‐Mobarake, Maryam; Nowroozi, Jamileh; Badiee, Parisa; Mostafavi, Sayed Nassereddin; Mohammadi, Rasoul
title: Fatal disseminated infection due to Sarocladium kiliense in a diabetic patient with COVID‐19
date: 2021-09-27
journal: Clin Case Rep
DOI: 10.1002/ccr3.4596
sha: 7111b58cfde7d8a805e55af22b9ee8c727dad601
doc_id: 862500
cord_uid: epofdkd4

Sarocladium kiliense is a soil saprophytic mold with worldwide distribution, which can infect humans and other mammals, sporadically. The clinical manifestations include mycetoma, onychomycosis, keratomycosis, pneumonia, and arthritis. Here, we present a disseminated infection due to S. kiliense in a diabetic patient infected to coronavirus disease 2019 (COVID‐19) from Isfahan, Iran.

due to a lesion on her toe ( Figure 1A) . Because of diabetes, she went blind when she was 59 years old. She used medicinal plants for 14 days to treat her wound; however, it got worse ( Figure 1B) . On August 7, 2020, she was referred to the Gharazi Hospital, Isfahan, Iran, with fever (38°C) and a progressive lesion (grade 3, stage D; Figure 1C ). She was admitted to the Internal Medicine Department. Her medical checkup findings were as follows: respiratory rate (RR): 32 breaths per minute, heart rate (HR): 120 beats per minute, blood pressure (BP): 120/80 mmHg, and oxygen saturation (SpO2): 95% in room air. She was relatively conscious; however, she suffered from shortness of breath. Hematological and biochemical tests were summarized in Table 1 . Regular insulin was started to decrease blood sugar, and Targocid (6 mg/kg/12 h) with Tazocin (4.5 g/8 h) was also applied for her. On August 9, 2020, septate hyaline fungal hyphae were observed in histopathological findings (Figure 2 ). At this stage, aspergillosis and fusariosis were differential diagnosis. On August 10, 2020, her toe was amputated ( Figure 3A ) and liposomal amphotericin B (AmBisome; 5 mg/kg/day) was added to her regimen. Six days later, because of necrosis, her foot was amputated from the upper part ( Figure 3B ). Due to the dyspnea and oxygen saturation of 80% in room air, chest computed tomography (CT) scan was done and demonstrated COVID-19 pneumonia (Figure 4 ). Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) confirmed SARS-CoV-2 infection. Oxygen therapy with nasal cannula (4 L/min), methylprednisolone 130 mg for 4 days, and treatment with interferon Beta-1b 0.25 mg SQ every 48 h for four dosages were started for her. On August 17, 2020, she transferred to the intensive care units (ICUs) of Chamran University Hospital, Isfahan, Iran, for better management of COVID-19 infection. She had fever (39.5°C), and one blood sample was taken for probable systemic infection. Due to the severe dyspnea and SpO2 60%, she was intubated on August 19, 2020; however, she died the same day. Four days after death, Sarocladium spp. recovered from blood culture ( Figure 5 ) and PCR-sequencing was applied for identification. ITS1-5.8SrDNA-ITS2 region was amplified using ITS1 (5′-TCC GTA GGT GAA CCT GCG G-3′) and ITS4 (5′-TCC TCC GCT TAT TGA TAT GC-3′) primers and was subjected to sequence analysis in a forward direction (Bioneer). The sequence product was analyzed with Chromas 2.4 (https://chrom as.softw are.infor mer.com/2.4/) and then evaluated using the NCBI BLAST searches against fungal sequences existing in DNA databases (https://blast.ncbi.nlm. nih.gov/Blast.cgi). The ITS gene sequence was deposited in the GenBank under the accession number MW679681. This research was approved by the Ethics Committee of Isfahan University of Medical Science (no. IR.MUI.MED. REC.1399.912), and written informed consent was obtained from the patient.

The emergence of uncommon human and animal opportunistic fungi, such as Sarocladium, definitely impresses severely immunosuppressed patients and needs a high level of clinical attention. Sarocladium genus contains several of morphologically and genetically mold fungi that are commonly found in the environment. The most of species of this genus are opportunistic pathogens of plants and soil saprobes. 5 Within the genus, S. kiliense is the most prevalent pathogen in human clinical reports, producing predominantly mycetomas 9 ; however, other critical cases affecting lungs, nails, joints, or catheter-related bloodstream infections are available. 10, 11 The most fungemia related to S. kiliense have been reported from Colombia and Chile. 12 Fever, maculopapular rash, tachycardia, and hematuria are popular symptoms of bloodstream infections in a great number of patients, 13,14 but our patient only had fever. Hematological malignancies, solid organ transplants, solid tumors, renal transplantation, and Crohn's disease are main predisposing factors for disseminated infection with Sarocladium spp. 14-16; nevertheless, the present case was diabetic with no abovementioned risk factors. Blood culture is essential for diagnosis of Sarocladium blood infections, because in almost all studies, 7 has been isolated from blood culture, similar to the present case. Bloodstream infections due to Sarocladium are usually treated with various medications such as amphotericin B (AMB) and voriconazole. 15, 18 Many patients recover after changing regimen to voriconazole following AMB failure. Unfortunately, voriconazole did not use for the present patient, and she died 9 days after taking AmBisome. In this connection, we highlight the need for antifungal susceptibility testing (AFST) of clinical isolates caused fungemia for selecting the best treatment, since empirical therapy with AMB failed in great number of patients. 14 One of the major limitations of the present investigation was the lack of AFST for current strain. Timely treatment and removal of catheter as the source of infection, if possible, were also substantial steps to overcome the infection. Sarocladium cutaneous infections have been reported in the literature [19] [20] [21] ; however, the fungus has been molecularly identified only in one case (S. strictum). 19 Reports of Sarocladium superficial and subcutaneous infections were recorded from India, 19 Turkey, 20 Russia, 22 Taiwan, 23 France, 24 Brazil, 25 and Korea. 26 To our knowledge, this is the first report of systemic Sarocladium infection from Iran that has disseminated to the skin. The clinical features of cutaneous infections include painless swelling, pustules and nodules, scaly plaque, redness, ulceration, necrotic areas, and purulent exudate. 23, 27 The cutaneous lesion of the current case was necrotic and revealed a lot of purulent exudate with no pustules, nodules, or scaly plaques. Diagnosis is based predominantly on skin biopsy, which presents a typical granulomatous reaction with giant cells in histopathological examination, and the presence of hyaline fungal hyphae. 16 Since the skin sample was taken from necrotic lesions; so, we could not see activated macrophages and giant cells in histopathological reaction ( Figure 2 ). Similar to the current case, Khan et al 28 presented a case of Sarocladium infection in a patient with long history of diabetes. They isolated S. kiliense from the peritoneal fluid, and E-test was performed to determine drug susceptibility. The isolate was susceptible to posaconazole and voriconazole but resistant to caspofungin and amphotericin B. Although, voriconazole therapy was 

We highlight the early diagnosis, accurate fungal identification, precise and adequate treatment of hyalohyphomycosis to avoid serious effects of this infection especially in COVID-19 patients who are taking corticosteroids. Since empirical therapy with amphotericin B failed in the most patients, antifungal susceptibility testing of the clinical isolates is strongly recommended for better management of this fatal infection.

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Acremonium kiliense infection in a child with chronic granulomatous disease

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Fatal disseminated infection due to Sarocladium kiliense in a diabetic patient with COVID-19

This study was financially supported by North branch Islamic Azad University, Tehran, Iran, and Isfahan University of Medical Sciences, Isfahan, Iran (no. 199519), which we gratefully acknowledge.

None declared.

MRM and SNM contributed to data acquisition and providing the clinical figures. MRM, JN, PB, and RM contributed to identifying Sarocladium kiliense using phenotypic and molecular methods, and providing the mycological illustrations. RM served as the corresponding author and designed and supervised all the aspects and contributed to manuscript editing.

Published with written consent of the patient. 

The ITS gene sequence of Sarocladium kiliense was deposited in the GenBank under the accession number MW679681.

Rasoul Mohammadi https://orcid. org/0000-0002-8220-4511