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 Table of Contents  
Year : 2014  |  Volume : 16  |  Issue : 2  |  Page : 96-99

Aspergillus terreus : An emerging pathogen: A case series

Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Univeristy, Porur, Chennai, Tamil Nadu, India

Date of Web Publication14-Nov-2014

Correspondence Address:
Premamalini Thayanidhi
Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Univeristy, Porur, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-1282.144736

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Aspergillosis is one of the most common fungal infections in humans caused by Aspergillus species. However, not all Aspergillus species possess the same antifungal susceptibility patterns. Aspergillus terreus is an emerging pathogen which commonly occurs in infections of immunocompromised individuals and is associated with high mortality. It gains its importance in being mostly resistant to treatment with amphotericin B. The four cases of A. terreus reported here highlight the fact that fungal infections caused by this species are on the rise. Early diagnosis and prompt treatment are important to prevent an unfavorable outcome. The optimal therapy for infections caused by this emerging pathogen is still to be ascertained.

Keywords: Amphotericin B resistance, Aspergillosis, Aspergillus terreus

How to cite this article:
Thayanidhi P, Subramanian A, Kindo AJ. Aspergillus terreus : An emerging pathogen: A case series. J Acad Clin Microbiol 2014;16:96-9

How to cite this URL:
Thayanidhi P, Subramanian A, Kindo AJ. Aspergillus terreus : An emerging pathogen: A case series. J Acad Clin Microbiol [serial online] 2014 [cited 2021 Apr 22];16:96-9. Available from: https://www.jacmjournal.org/text.asp?2014/16/2/96/144736

  Introduction Top

Aspergillus species are the most common cause of invasive filamentous fungal infections in immunocompromised hosts. [1],[2] There are more than 200 species of Aspergillus, and as compared to Aspergillus flavus and A. fumigatus which is commonly associated with clinical infections, A. terreus occasionally infects humans. [3] It can cause localized, invasive, or disseminated disease. [4] Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. A. terreus is second to A. fumigatus as the most common cause of IA. [5]

Four cases of A. terreus infection with different clinical presentations, including two cases of A. terreus peritonitis and one each of cutaneous aspergillosis and rhinosinusitis from our institute, a tertiary care center in Chennai (South India), are being reported here. For all cases, identification and susceptibility testing was done in-house following standard methods described below.

  Case Reports Top

Case 1

A 59-year-old male, on chronic ambulatory peritoneal dialysis (CAPD) for past 3 years, came for routine follow-up, was found to have cloudy peritoneal fluid and was advised for admission for further investigations. Blood cultures were sterile. CAPD fluid analysis showed elevated cell counts. Bacterial culture of CAPD fluid was found to be negative. KOH mount of the CAPD fluid showed the presence of septate hyphae and the patient was started on Amphotericin B. In spite of the treatment, his condition did not improve and so the patient was started on hemodialysis. Since then the patient was on regular hemodialysis. Fungal culture of the CAPD fluid showed pure growth of A. terreus on 7 th day after the sample was received. The patient was started on oral Voriconazole 400 mg twice daily for 2 days followed by 200 mg twice daily for 3 weeks following which the patient's condition improved. Arteriovenous (AV) fistula was created and the patient was discharged after 20 days.

Case 2

A 73-year-old male presented with complaints of hiccups, anorexia, and abdominal pain. He was a known case of diabetes and chronic kidney disease, and was on CAPD since 2 years. He was also a diagnosed case of miliary tuberculosis and was on antituberculous treatment since 2 years. CAPD fluid was collected and sent to the laboratory. CAPD fluid showed elevated cell count and the culture showed no growth. Empirical diagnosis of CAPD peritonitis was made and the patient was started on intraperitoneal and intravenous antibiotics. The patient's condition deteriorated. The catheter was removed, and catheter tip and CAPD fluid were sent for fungal culture after 12 days. The KOH mount of the CAPD fluid showed septate hyphae. Patient was started on antifungal therapy with Amphotericin B. Fungal culture of the CAPD fluid and catheter tip showed pure growth of A. terreus 5 days after receiving sample. Patient's condition did not improve and he was put on ventilator and tracheostomy was done. In spite of the treatment, the patient succumbed to the infection.

Case 3

A 58-year-old male was admitted with complaints of nonhealing ulcer on the right leg and fever since 1 month. The patient gave past history of injury in his right leg. He was a known diabetic for 10 years. On examination, there was a verrucous growth near the right big toe. His total white blood cell count was 14,000 cells/μl with 52.5% polymorphs, 37.5% lymphocytes, and 6.3% eosinophils. Erythrocyte sedimentation rate (ESR) was elevated. Tissue biopsy samples were taken and sent to the laboratory. KOH mount of the tissue showed septate hyphae. Histopathological examination of the biopsy tissue showed chronic inflammation with ulceration. Periodic acid-Schiff (PAS) staining was positive for fungal elements [Figure 1]. After 6 days, fungal culture of the biopsy tissue showed growth of A. terreus. Bacterial cultures were negative. Since the patient could not afford Voriconazole for a prolonged period, he was started on oral Voriconazole 200 mg twice daily for 2 weeks. Wound debridement surgery was done on the 10 th day and wound dressing was done daily with povidone iodine antiseptic solution till his condition improved, and the patient was discharged.
Figure 1: Periodic acid-Schiff staining showing septate hyphae (×40 magnifi cation)

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Case 4

A 45-year-old male was admitted with complaints of swelling of the left maxillary region for the past 1 month and bleeding from the left nostril for 1 week. Patient had another swelling below the medial aspect of the eye for which excision was done 2 months back. Local examination of the face showed diffuse bony swelling involving nasolabial region and an exophytic irregular mass filling the lateral nasal cavity extending into oral cavity. Computed tomography (CT) and magnetic resonance imaging (MRI) showed an enhanced lesion in the left maxillary sinus region with bony destruction and intranasal, intraoral extension of the lesion. A biopsy was taken and sent for histopathological examination which showed tiny strips of metastatic squamous epithelium. Special fungal stain by Gomori's methenamine silver stain showed septate hyphae [Figure 2].
Figure 2: Gomori's methenamine silver stain showing septate hyphae (×20 magnification)

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KOH mount was positive for fungal elements. Fungal culture showed pure growth of A. terreus after a week.

Patient was treated by surgical debridement and antifungal therapy with oral Voriconazole 400 mg twice daily for 2 days followed by 200 mg twice daily for 3 weeks. The patient's condition improved and was discharged.

The identification of all the above isolates was based on colony characteristics on Sabouraud's dextrose agar (SDA) [Figure 3] and microscopic morphology in lactophenol cotton blue mount [Figure 4]. SDA had growth of cinnamon brown colonies with granular to velvety texture. Microscopy showed conidiophores which were smooth, hyaline, and produced dome-shaped/subspherical vesicles. Conidiogenous cells were borne on vesicles on the upper half of their surface which were biseriate (containing metulae that support phialides). Conidia were smooth-walled, spherical, and arranged in columnar fashion.
Figure 3: Growth on Sabouraud's dextrose agar

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Figure 4: The lactophenol cotton blue mount showing biseriate conidiation (×40 magnification)

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Antifungal susceptibility testing has been standardized for molds by Central Laboratory Standards Institute (CLSI). [6] Antifungal susceptibility testing and determination of minimum inhibitory concentration (MIC) for all the four isolates was performed using CLSI M38-A2 broth macrodilution method. [4]

Antifungal drugs

The antifungal agents used were Amphotericin B (range, 0.0313-16 μg/ml; HiMedia), Voriconazole (range, 0.0313-16 μg/ml; Sigma Aldrich). Stock solutions were prepared in dimethyl sulfoxide. All drugs were diluted in RPMI 1640 medium buffered to pH 7.0 with morpholine propane sulfonic acid (MOPS) buffer and dispensed into round-bottomed snap-cap sterile polystyrene tubes. Tubes containing an aliquot of appropriate working drug solutions for the range of concentrations to be tested (2 final concentration) were sealed and stored at −70°C until use.

Antifungal susceptibility testing

In brief, isolates were grown on potato dextrose agar slants at 35°C for 7 days. The slants were covered with 1 ml of sterile 0.85% saline and a suspension was made by gently probing the colonies with the tip of a transfer pipette. The resulting suspensions were transferred to separate sterile tubes. After allowing heavy particles to settle for 3-5 min, the upper homogenous suspension was transferred to a sterile tube and vortexed for 15 s. The turbidity of the conidial suspensions were measured and adjusted to an optical density (OD) at 530 nm that ranged from 0.09 to 0.1. A volume of 0.1 ml of this inoculum suspension with 0.1 ml of each concentration of the working drug solution was used for susceptibility testing. Drug-free controls were included in each test. The macrodilution tubes were incubated at 35°C for 48 h. Following incubation, MIC endpoints were determined as the lowest drug concentrations that prevented any discernible growth (optically clear) compared to that of the drug-free controls [Table 1].
Table 1: In vitro antifungal susceptibilitytesting: Macrobroth dilution method for Aspergillus terreus

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  Discussion Top

Aspergillus spores are ubiquitous in the environment and with a suitable portal of entry such as intravenous line, catheter site, wound, or burns; the spores may get lodged and proliferate. [5] A. terreus is an uncommon but an important fungal pathogen with a fairly aggressive behavior, and a higher mortality rate than infections by other Aspergillus species. [1] A. terreus infections may be resistant to Amphotericin B and is associated with a high rate of dissemination and poor outcome.

Fungal peritonitis in patients on CAPD has been associated with high mortality and CAPD discontinuation rates. [6] Two patients of A. terreus peritonitis described here were immunocompromised. The first patient responded well with the removal of CAPD catheter and antifungal therapy. The second patient showed a slow progressive course and died. The diagnosis of aspergillosis by blood culture is rare and all blood cultures of our patients were sterile. Most of the species of A. terreus is known for its refractoriness to Amphotericin B therapy. [7],[8] Previous literature supports the fact that A. terreus peritonitis can be incurred during change of CAPD catheters. [9] The reason that two CAPD patients developed fungal peritonitis due to A. terreus emphasizes the fact that utmost hygiene and care should be taken while changing or maneuvering the CAPD catheters.

The third case is primary cutaneous aspergillosis caused by A. terreus. Primary cutaneous aspergillosis usually occurs due to trauma or colonization. This is a case of primary cutaneous aspergillosis where the patient was immunocompromised and had previous history of injury which predisposed to the infection. The patient responded well to a brief course of oral Voriconazole, surgical debridement, and daily wound dressing with povidone iodine. Povidone iodine is known to have some antifungal activity. [10]

Localized infections with this organism in an immunocompromised individual requires antifungal therapy along with early surgical debridement and daily dressing of the wound.

Fourth is a case of A. terreus invasive maxillary sinusitis in an immunocompromised patient. Aspergillosis of the paranasal sinuses is infrequent and maxillary sinus is the most common sinus to be affected. [11] Our patient had invasive maxillary sinusitis and another swelling in the medial aspect of the eye for which excision was done earlier which could be probably due to the same etiology. With surgical debridement and oral dose of Voriconazole, the patient improved. Very few cases of A. terreus sinusitis with extension of growth to other sites have been reported so far. Early diagnosis is important to prevent an unfavorable outcome of this fungi causing sinusitis.

Until recently, Amphotericin B had been used as primary treatment for IA. Since A. terreus infections are relatively resistant to treatment with Amphotericin B as evidenced by the higher MICs seen in this study and as stated in previous studies, [8] those patients who received Amphotericin B as primary treatment had slow disease progression and poor clinical response than in those patients who had Voriconazole as primary treatment. [12],[13]

  Conclusion Top

A. terreus is an important emerging fungal infection which causes rapidly progressive invasive infections in the immunocompromised. It is usually resistant to Amphotericin B therapy. Identification of A. terreus infections is important because therapy is distinct. So there should be more importance given to the correct identification and susceptibility testing of mold fungi for early institution of appropriate antifungal therapy for these patients. High risk patients may be given barrier nursing in order to avoid infection with A. terreus. Treatment of choice for IA is Voriconazole, which can be given as oral therapy. Voriconazole when given as a primary antifungal therapy has a more favorable outcome when compared to primary antifungal therapy with conventional antifungal agents.

  References Top

Denning DW. Invasive aspergillosis in immunocompromised patients. Curr Opin Infect Dis 1994;7:456-62.  Back to cited text no. 1
Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in haematopoetic stem cell transplant recipients. Clin Infect Dis 2002;34:909-17.  Back to cited text no. 2
Cookie FJ, Terpos E, Boyle J, Rahemtulla A, Rogers TR. Disseminated Aspergillus terreus infection arising from cutaneous inoculation treated with caspofungin. Clin Microbiol Infect 2003;9:1238-41.  Back to cited text no. 3
CLSI (2008b) Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; Approved standard CLSI document M38-A2. Clinical and Laboratory Standards Institute, Wayne.  Back to cited text no. 4
Steinbach WJ, Perfect JR, Schell WA, Walsh TJ, Benjamin DK. In vitro analysis, animal models and 60 clinical cases of invasive Aspergillus terreus infection. Antimicrob Agents Chemother 2004;48:3217-25.  Back to cited text no. 5
Nannini EC, Paphitou NI, Ostrosky-Zeichner L. Peritonitis due to Aspergillus and zygomycetes in patients undergoing peritoneal dialysis: Report of 2 cases and review of the literature. Diagn Microbiol Infect Dis 2003;46:49-54.  Back to cited text no. 6
Steinbach WJ, Benjamin DK Jr, Kontoyiannis DP, Perfect JR, Lutsar I, Marr KA, et al. Infections due to Aspergillus terreus: A multicenter retrospective analysis of 83 cases. Clin Infect Dis 2004;39:192-8.  Back to cited text no. 7
Sutton, DA, Sanche SE, Revankar SG, Fothergill AW, Rinaldi MG. In vitro Amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Microbiol 1999;37:2343-5.  Back to cited text no. 8
Varughese S, Mathews MS, Tamilarasi V. Successful renal transplantation following treatment of Aspergillus terreus peritonitis in a continuous ambulatory peritoneal dialysis patient. Indian J Nephrol 2011;21:208-11.  Back to cited text no. 9
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Ozer B, Kalaci A, Duran N, Dogramaci Y, Yanat AN. Cutaneous infection caused by Aspergillus terreus. J Med Microbiol 2009;58:968-70.  Back to cited text no. 10
Akhaddar A, Gazzaz M, Albouzidi A, Lmimouni B, Elmostarchid B, Boucetta M. Invasive Aspergillus terreus sinusitis with orbitocranial extension: Case report. Surg Neurol 2008;69:490-5.  Back to cited text no. 11
Stevens DA, Kan VL, Judson MA, Morrison VA, Dummer SD, Denning DW, et al. Practice guidelines for disease caused by Aspergillus. Infectious Diseases Society of America. Clin Infect Dis 2000;30:696-709.  Back to cited text no. 12
Baddley JW, Pappas PG, Smith AC, Moser SA. Epidemiology of Aspergillus terreus at a University hospital. J Clin Microbial 2003;41:5525-9.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]

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