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Refractory Arthrographis kalrae native knee joint infection
Medical Mycology Case Reports 1 (2012) 112–114
Contents lists available at SciVerse ScienceDirect
Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr
Refractory Arthrographis kalrae native knee joint infection Peter Boan a,n, Ian Arthur a, Clay Golledge a, David Ellis b a b
Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine, QEII medical centre, Hospital Avenue, Nedlands, Perth 6009, Australia Mycology Unit, SA Pathology at the Women’s and Children’s Hospital, Adelaide 5005, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 10 October 2012 Received in revised form 11 October 2012 Accepted 26 October 2012
Rare reports of infection with Arthrographis kalrae have often demonstrated a protracted clinical course. We describe refractory infection of the native knee with Arthrographis kalrae after a penetrating injury and Yttrium synovectomy, finally controlled with two stage joint revision and combination antifungal therapy. The paucity of worldwide data about such uncommon invasive fungal infections contributes to the diagnostic and therapeutic challenges of these cases. & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. All rights reserved.
Keywords: Arthrographis Arthrographis kalrae
1. Introduction Arthrographis kalrae is a slow growing hyaline mould with initially yeast-like colonies, and typical microscopic features are the development of dendritic conidiophores bearing lateral branches and arthroconidia. The small number of case reports of Arthrographis kalrae infection are predominately cornea, sinus, soft tissue and nail infections, though rarely more invasive infection has been described. This case contributes to this worldwide literature demonstrating a clinical course refractory to azoles, terbinafine and amphotericin therapy, resolving only with very aggressive surgical debridement.
2. Case A 33 year old previously well man sustained a penetrating injury to his native knee by sheet metal in May 2009 (day 0), complicated by haemarthrosis requiring washout. He had progressive pain and swelling in the knee and joint aspirate on day þ30 was culture negative (this was not cultured specifically for fungi). He was thought to have traumatic synovitis, treated at day þ180 with oral prednisolone and methotrexate, intra-articular corticosteroids and Yttrium synovectomy (radioactive Yttrium is injected into the knee leading to sclerosis of the synovial membrane with associated alleviation of pain and inflammation). Ten days following Yttrium synovectomy (day þ190) the knee n Corresponding author. Present address: Department of Microbiology, PathWest, Princess Margaret Hospital, Roberts Road, Subiaco, Perth 6008, Australia. Tel.: þ61 8 9340 8222; fax: þ61 8 9380 4474. E-mail address: [email protected] (P. Boan).
was acutely swollen and therefore washed out, culturing a yeastlike organism that was referred to our laboratory for identification. The culture plate received from the referring laboratory demonstrated a cream coloured yeast-like organism which on microscopy demonstrated oval shaped budding yeast-like cells. The isolate was sub-cultured onto Sabouraud agar supplemented with chloramphenicol (SABþC) at 36 1C (Fig. 1a culture, Fig. 1b microscopy). According to our routine examination for yeasts, initial testing of the organism proved it to be germ-tube negative, Dalmau plate (using Rice Tween agar) demonstrated ‘‘atypical’’ yeast-like cells as above, and testing with the ID32C test gave a profile of 2000200003, E neg at 48 h (BioMerieux, Marcy-l’Etoile, France). This profile does not provide an identification with the manufacturer’s database, although the time of incubation may also be critical. The isolate was therefore sent for sequencing of the internal transcribed spacer (ITS) region and further morphological studies were performed including sub-culturing on SABþC both at 26 1C and 36 1C and Potato dextrose agar (PDA) at 26 1C. Within 7 days the culture appearance altered, producing a flat, dry, granular colony on SABþ C at 26 1C (Fig. 2) and 36 1C. Microscopy revealed early hyphal growth with arthroconidia production. The ITS1 sequence of the ribosomal DNA gene using universal primers ITS1 and ITS2 showed 100% similarity with GenBank accession number EU513380, from a previous clinical case of A. kalrae [1], as well as 499% homology with other A. kalrae strains recorded in GenBank. Further examination of the culture by tease mount and slide culture on SABþC and PDA at 26 1C demonstrated hyaline septate hyphae with conidophores branched in a dendritic pattern and producing chains of one-celled arthrospores without disjunctor cells (Fig. 3a). With time the isolate also produced single conidia, often on a short pedicle (Fig. 3b). Based on
2211-7539/$ - see front matter & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.mmcr.2012.10.005
P. Boan et al. / Medical Mycology Case Reports 1 (2012) 112–114
Fig. 1. (a) Culture appearance of the knee isolate at 48 h incubation in 36 1C on Sabouraud agar supplemented with chloramphenicol. (b) Microscopy (with lactophenol cotton blue stain) from a 48 h-old colony of organism isolated from the knee, demonstrating oval shaped budding yeast-like cells.
Fig. 2. Culture appearance of the knee isolate at 7 days incubation on Sabouraud agar supplemented with chloramphenicol.
the morphological features previously described [2,3] and the molecular studies, the isolate was reported as A. kalrae. Mould susceptibility testing by the CLSI microbroth dilution method [4] was performed 4 times from December 2009 (dayþ210) to January 2011 (day þ1000). Results were quite reproducible: mean inhibitory concentration (MIC) ranges for fluconazole 8–16 mg/L, itraconazole 0.25–0.5 mg/L, voriconazole 0.06–0.5 mg/L, posaconazole 0.25–0.5 mg/L, amphotericin 0.25–0.5 mg/L and flucytosine
113
Fig. 3. (a) Microscopy from slide culture of the knee isolate demonstrating hyaline septate hyphae with conidiophores branched in a dendritic pattern and producing chains of one-celled arthrospores without disjunctor cells. (b) Microscopy from slide culture of the knee isolate demonstrating formation of single conidia, often on a short pedicle.
464 mg/L. Disc testing of terbinafine suggested the fungus was sensitive to this agent. MICs did not increase over time following extensive exposure to antifungal agents. Despite in vitro testing sensitive to fluconazole at day þ190, after one month treatment at a dosage of 400 mg daily, there was ongoing pyoarthrosis and cultures remained positive. Fluconazole was substituted with oral voriconazole 250 mg bd at day þ210 however knee aspirate culture remained positive despite six weeks therapy with this agent. Open synovectomy was performed in April 2010 (day þ330) followed by one month of intravenous (IV) liposomal amphotericin 200 mg thrice weekly followed by combination posaconazole 200 mg tds and terbinafine 250 mg daily. Despite this at day þ420 magnetic resonance imaging (MRI) of the knee demonstrated large intra-articular abscesses and oedema of the medial condyle of the femur consistent with osteomyelitis. This lead to extensive debridement at day þ450 where there was invasion around the tibial nerve sheath and the popliteal vessels akin to the behaviour of a tumour, and A. kalrae was again cultured from the synovial fluid. Intravenous liposomal amphotericin 300 mg daily was administered for 6 weeks followed by posaconazole (400 mg bd) and terbinafine (500 mg daily). The knee continued to be inflamed with C-reactive protein (CRP) levels of 30–50 mg/L (normal o5 mg/L) and ongoing intraarticular collections evident on imaging. First stage revision total
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P. Boan et al. / Medical Mycology Case Reports 1 (2012) 112–114
knee replacement (an aggressive debridement of bone and implantation of an amphotericin-impregnated spacer) was performed in November 2010 (day þ 580) with posaconazole and terbinafine continued for one month post procedure. Significant seborrhoeic dermatitis deemed secondary to one of the antifungals was a factor in the decision to discontinue antifungal treatment. The second stage revision total knee replacement was performed in January 2011 (day þ640). Of great concern operative knee samples again cultured A. kalrae, and he was treated with another month of IV liposomal amphotericin followed by combination oral posaconazole and terbinafine. At last review in August 2012 (over 3 years since initial presentation and 18 months since 2nd stage of the knee joint revision) there was no sign of active inflammation in the knee clinically or by MRI, and CRP was 1.4 mg/L. Antifungal therapy was ceased at this time and the patient has ongoing close follow up.
3. Discussion At the U.S. national library of medicine (PubMed; /http:// www.ncbi.nlm.nih.gov/S) there are 11 reports of infection with A. kalrae: 3 cases of keratitis, 2 cases of sinusitis, 2 cases of onychomycosis, 1 case of endocarditis, 1 case of cerebral fungal vasculitis, 1 case of pulmonary infection and 1 case of mycetoma. The case of endocarditis involved A. kalrae infection of a bovine pericardial patch put in 9 years earlier to fix an atrial septal defect. They debrided the infected tissue and a mechanical aortic valve and Gore-Tex patch of the proximal aorta were placed, followed by 4 months of antifungal therapy (utilising amphotericin, voriconazole and posaconazole). The infection recurred one year later in the aortic patch which was replaced followed by 6 months of posaconazole 400 mg daily. Despite this the infection recurred again and the patient died in the operating room [5]. The cerebral vasculitis case was a 39 year old immunocompetent cattle breeder who presented with sinusitis and lymphocytic meningitis who died shortly after admission with a stroke-like syndrome. Fungal infiltrates with necrotising arteritis was found on post-mortem histopathology of the brain and A. kalrae grew from the cerebrospinal fluid [1]. The three reported cases of A. kalrae keratitis were all associated with contact lenses. The clinical presentations were similar to Acanthamoeba keratitis. One case in particular was refractory to therapy requiring 4 keratoplasties despite prolonged systemic and topical voriconazole [6,7,8]. Pan-ophthlamitis and sinusitis were described following injury to the eye with yellow oil containing steel chips, treated with conventional amphotericin B and prolonged itraconazole [9]. At our own laboratory we have found A. kalrae in a patient with a keratitis [10] and in a case of presumed onychomycosis in 2011. Arthrographis kalrae is a known inhabitant of soil [11], so most likely gained entry to the knee at the time of injury, though potentially was introduced with a subsequent procedure to the knee such as corticosteroid injection or Yttrium synovectomy, a
procedure which has been used in a variety of inflammatory and degenerative joint diseases. One large study documented an infection rate of 5 per 93 patients post Yttrium synovectomy. The microorganisms were Staphylococci or Streptococci [12]. In our case unfortunately the first knee fluid sample 1 month after penetrating injury before other interventions did not have prolonged or specific culture for fungi so it will remain uncertain whether A. kalrae was present in this first sample. Infection with A. kalrae is extremely rare, though it is likely under-recognised as the organism initially has a yeast-like appearance and may be considered an atypical ‘‘Candida species’’ without the use of specialist mycology resources. While some case reports suggest quite prompt improvement with surgery and antifungal therapy, several cases including our own have been refractory to aggressive debridement and antifungal agents of differing classes. Such uncommon invasive fungal infections with a limited body of worldwide data are a significant diagnostic and therapeutic challenge.
Conflict of interest There are none.
References [1] Pichon N, Ajzenberg D, Desnos-Ollivier M, Clavel M, Gantier JC, Labrousse F. Fatal-stroke syndrome revealing fungal cerebral vasculitis due to Arthrographis kalrae in an immunocompetent patient. J Clin Microbiol 2008;46(9): 3152–3155. [2] Chin-Hong PV, Sutton DA, Roemer M, Jacobson MA, Aberg JA. Invasive fungal sinusitis and meningitis due to Arthrographis kalrae in a patient with AIDS. J Clin Microbiol 2001;39(2):804–807. [3] Malloch D, Sigler L. The Eremomycetaceae (Ascomycotina). Can J Bot 1988;66:1929–1932. [4] Clinical Laboratory and Standards Institute. Reference method for broth microdilution antifungal susceptibility testing of filamentous fungi; approved standard. CLSI document M38-A [ISBN 1-56238-470-8]. Pennsylvania, USA: CLSI; 2002. [5] de Diego Candela J, Forteza A, Garcia D, Prieto G, Bellot R, Villar S, et al. Endocarditis caused by Arthrographis kalrae. Ann Thorac Surg 2010;90(1): e4–e5. [6] Perlman EM, Binns L. Intense photophobia caused by Arthrographis kalrae in a contact lens-wearing patient. Am J Ophthalmol 1997;123(4):547–549. [7] Biser SA, Perry HD, Donnenfeld ED, Doshi SJ, Chatuvedi V. Arthrographis keratitis mimicking Acanthamoeba keratitis. Cornea 2004;23(3):314–317. [8] Thomas BC, Zimmerman S, Vockler HE, Auffarth GU, Dithmar S. Severe Arthrographis kalrae keratomycosis in an immunocompetent patient. Cornea 2011;30(3):364–366. [9] Xi L, Fukushima K, Takizawa K, Liao R, Nishimura K. First case of Arthrographis kalrae ethmoid sinusitis and ophthalmitis in the People’s Republic of China. J Clin Microbiol 2004;42(10):4828–4831. [10] McAleer R, Froudist JH, Cherian G. Xth International Society for Human and Animal Mycology Congress 1988; abstract 172. [11] Sugiura Y, Hironaga M. Arthrogaphis kalrae, a rare causal agent of onychomycosis and its occurrence in the natural and commercially available soils. Med Mycol 2010;48:384–389. [12] Kisielinski K, Bremer D, Knutsen A, Rottger P, Fitzek JG. Complications following radiosynoviorthesis in osteoarthritis and arthroplasty: osteonecrosis and intra-articular infection. Joint Bone Spine 2010;77(3):252–257.
Contents lists available at SciVerse ScienceDirect
Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr
Refractory Arthrographis kalrae native knee joint infection Peter Boan a,n, Ian Arthur a, Clay Golledge a, David Ellis b a b
Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine, QEII medical centre, Hospital Avenue, Nedlands, Perth 6009, Australia Mycology Unit, SA Pathology at the Women’s and Children’s Hospital, Adelaide 5005, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 10 October 2012 Received in revised form 11 October 2012 Accepted 26 October 2012
Rare reports of infection with Arthrographis kalrae have often demonstrated a protracted clinical course. We describe refractory infection of the native knee with Arthrographis kalrae after a penetrating injury and Yttrium synovectomy, finally controlled with two stage joint revision and combination antifungal therapy. The paucity of worldwide data about such uncommon invasive fungal infections contributes to the diagnostic and therapeutic challenges of these cases. & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. All rights reserved.
Keywords: Arthrographis Arthrographis kalrae
1. Introduction Arthrographis kalrae is a slow growing hyaline mould with initially yeast-like colonies, and typical microscopic features are the development of dendritic conidiophores bearing lateral branches and arthroconidia. The small number of case reports of Arthrographis kalrae infection are predominately cornea, sinus, soft tissue and nail infections, though rarely more invasive infection has been described. This case contributes to this worldwide literature demonstrating a clinical course refractory to azoles, terbinafine and amphotericin therapy, resolving only with very aggressive surgical debridement.
2. Case A 33 year old previously well man sustained a penetrating injury to his native knee by sheet metal in May 2009 (day 0), complicated by haemarthrosis requiring washout. He had progressive pain and swelling in the knee and joint aspirate on day þ30 was culture negative (this was not cultured specifically for fungi). He was thought to have traumatic synovitis, treated at day þ180 with oral prednisolone and methotrexate, intra-articular corticosteroids and Yttrium synovectomy (radioactive Yttrium is injected into the knee leading to sclerosis of the synovial membrane with associated alleviation of pain and inflammation). Ten days following Yttrium synovectomy (day þ190) the knee n Corresponding author. Present address: Department of Microbiology, PathWest, Princess Margaret Hospital, Roberts Road, Subiaco, Perth 6008, Australia. Tel.: þ61 8 9340 8222; fax: þ61 8 9380 4474. E-mail address: [email protected] (P. Boan).
was acutely swollen and therefore washed out, culturing a yeastlike organism that was referred to our laboratory for identification. The culture plate received from the referring laboratory demonstrated a cream coloured yeast-like organism which on microscopy demonstrated oval shaped budding yeast-like cells. The isolate was sub-cultured onto Sabouraud agar supplemented with chloramphenicol (SABþC) at 36 1C (Fig. 1a culture, Fig. 1b microscopy). According to our routine examination for yeasts, initial testing of the organism proved it to be germ-tube negative, Dalmau plate (using Rice Tween agar) demonstrated ‘‘atypical’’ yeast-like cells as above, and testing with the ID32C test gave a profile of 2000200003, E neg at 48 h (BioMerieux, Marcy-l’Etoile, France). This profile does not provide an identification with the manufacturer’s database, although the time of incubation may also be critical. The isolate was therefore sent for sequencing of the internal transcribed spacer (ITS) region and further morphological studies were performed including sub-culturing on SABþC both at 26 1C and 36 1C and Potato dextrose agar (PDA) at 26 1C. Within 7 days the culture appearance altered, producing a flat, dry, granular colony on SABþ C at 26 1C (Fig. 2) and 36 1C. Microscopy revealed early hyphal growth with arthroconidia production. The ITS1 sequence of the ribosomal DNA gene using universal primers ITS1 and ITS2 showed 100% similarity with GenBank accession number EU513380, from a previous clinical case of A. kalrae [1], as well as 499% homology with other A. kalrae strains recorded in GenBank. Further examination of the culture by tease mount and slide culture on SABþC and PDA at 26 1C demonstrated hyaline septate hyphae with conidophores branched in a dendritic pattern and producing chains of one-celled arthrospores without disjunctor cells (Fig. 3a). With time the isolate also produced single conidia, often on a short pedicle (Fig. 3b). Based on
2211-7539/$ - see front matter & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.mmcr.2012.10.005
P. Boan et al. / Medical Mycology Case Reports 1 (2012) 112–114
Fig. 1. (a) Culture appearance of the knee isolate at 48 h incubation in 36 1C on Sabouraud agar supplemented with chloramphenicol. (b) Microscopy (with lactophenol cotton blue stain) from a 48 h-old colony of organism isolated from the knee, demonstrating oval shaped budding yeast-like cells.
Fig. 2. Culture appearance of the knee isolate at 7 days incubation on Sabouraud agar supplemented with chloramphenicol.
the morphological features previously described [2,3] and the molecular studies, the isolate was reported as A. kalrae. Mould susceptibility testing by the CLSI microbroth dilution method [4] was performed 4 times from December 2009 (dayþ210) to January 2011 (day þ1000). Results were quite reproducible: mean inhibitory concentration (MIC) ranges for fluconazole 8–16 mg/L, itraconazole 0.25–0.5 mg/L, voriconazole 0.06–0.5 mg/L, posaconazole 0.25–0.5 mg/L, amphotericin 0.25–0.5 mg/L and flucytosine
113
Fig. 3. (a) Microscopy from slide culture of the knee isolate demonstrating hyaline septate hyphae with conidiophores branched in a dendritic pattern and producing chains of one-celled arthrospores without disjunctor cells. (b) Microscopy from slide culture of the knee isolate demonstrating formation of single conidia, often on a short pedicle.
464 mg/L. Disc testing of terbinafine suggested the fungus was sensitive to this agent. MICs did not increase over time following extensive exposure to antifungal agents. Despite in vitro testing sensitive to fluconazole at day þ190, after one month treatment at a dosage of 400 mg daily, there was ongoing pyoarthrosis and cultures remained positive. Fluconazole was substituted with oral voriconazole 250 mg bd at day þ210 however knee aspirate culture remained positive despite six weeks therapy with this agent. Open synovectomy was performed in April 2010 (day þ330) followed by one month of intravenous (IV) liposomal amphotericin 200 mg thrice weekly followed by combination posaconazole 200 mg tds and terbinafine 250 mg daily. Despite this at day þ420 magnetic resonance imaging (MRI) of the knee demonstrated large intra-articular abscesses and oedema of the medial condyle of the femur consistent with osteomyelitis. This lead to extensive debridement at day þ450 where there was invasion around the tibial nerve sheath and the popliteal vessels akin to the behaviour of a tumour, and A. kalrae was again cultured from the synovial fluid. Intravenous liposomal amphotericin 300 mg daily was administered for 6 weeks followed by posaconazole (400 mg bd) and terbinafine (500 mg daily). The knee continued to be inflamed with C-reactive protein (CRP) levels of 30–50 mg/L (normal o5 mg/L) and ongoing intraarticular collections evident on imaging. First stage revision total
114
P. Boan et al. / Medical Mycology Case Reports 1 (2012) 112–114
knee replacement (an aggressive debridement of bone and implantation of an amphotericin-impregnated spacer) was performed in November 2010 (day þ 580) with posaconazole and terbinafine continued for one month post procedure. Significant seborrhoeic dermatitis deemed secondary to one of the antifungals was a factor in the decision to discontinue antifungal treatment. The second stage revision total knee replacement was performed in January 2011 (day þ640). Of great concern operative knee samples again cultured A. kalrae, and he was treated with another month of IV liposomal amphotericin followed by combination oral posaconazole and terbinafine. At last review in August 2012 (over 3 years since initial presentation and 18 months since 2nd stage of the knee joint revision) there was no sign of active inflammation in the knee clinically or by MRI, and CRP was 1.4 mg/L. Antifungal therapy was ceased at this time and the patient has ongoing close follow up.
3. Discussion At the U.S. national library of medicine (PubMed; /http:// www.ncbi.nlm.nih.gov/S) there are 11 reports of infection with A. kalrae: 3 cases of keratitis, 2 cases of sinusitis, 2 cases of onychomycosis, 1 case of endocarditis, 1 case of cerebral fungal vasculitis, 1 case of pulmonary infection and 1 case of mycetoma. The case of endocarditis involved A. kalrae infection of a bovine pericardial patch put in 9 years earlier to fix an atrial septal defect. They debrided the infected tissue and a mechanical aortic valve and Gore-Tex patch of the proximal aorta were placed, followed by 4 months of antifungal therapy (utilising amphotericin, voriconazole and posaconazole). The infection recurred one year later in the aortic patch which was replaced followed by 6 months of posaconazole 400 mg daily. Despite this the infection recurred again and the patient died in the operating room [5]. The cerebral vasculitis case was a 39 year old immunocompetent cattle breeder who presented with sinusitis and lymphocytic meningitis who died shortly after admission with a stroke-like syndrome. Fungal infiltrates with necrotising arteritis was found on post-mortem histopathology of the brain and A. kalrae grew from the cerebrospinal fluid [1]. The three reported cases of A. kalrae keratitis were all associated with contact lenses. The clinical presentations were similar to Acanthamoeba keratitis. One case in particular was refractory to therapy requiring 4 keratoplasties despite prolonged systemic and topical voriconazole [6,7,8]. Pan-ophthlamitis and sinusitis were described following injury to the eye with yellow oil containing steel chips, treated with conventional amphotericin B and prolonged itraconazole [9]. At our own laboratory we have found A. kalrae in a patient with a keratitis [10] and in a case of presumed onychomycosis in 2011. Arthrographis kalrae is a known inhabitant of soil [11], so most likely gained entry to the knee at the time of injury, though potentially was introduced with a subsequent procedure to the knee such as corticosteroid injection or Yttrium synovectomy, a
procedure which has been used in a variety of inflammatory and degenerative joint diseases. One large study documented an infection rate of 5 per 93 patients post Yttrium synovectomy. The microorganisms were Staphylococci or Streptococci [12]. In our case unfortunately the first knee fluid sample 1 month after penetrating injury before other interventions did not have prolonged or specific culture for fungi so it will remain uncertain whether A. kalrae was present in this first sample. Infection with A. kalrae is extremely rare, though it is likely under-recognised as the organism initially has a yeast-like appearance and may be considered an atypical ‘‘Candida species’’ without the use of specialist mycology resources. While some case reports suggest quite prompt improvement with surgery and antifungal therapy, several cases including our own have been refractory to aggressive debridement and antifungal agents of differing classes. Such uncommon invasive fungal infections with a limited body of worldwide data are a significant diagnostic and therapeutic challenge.
Conflict of interest There are none.
References [1] Pichon N, Ajzenberg D, Desnos-Ollivier M, Clavel M, Gantier JC, Labrousse F. Fatal-stroke syndrome revealing fungal cerebral vasculitis due to Arthrographis kalrae in an immunocompetent patient. J Clin Microbiol 2008;46(9): 3152–3155. [2] Chin-Hong PV, Sutton DA, Roemer M, Jacobson MA, Aberg JA. Invasive fungal sinusitis and meningitis due to Arthrographis kalrae in a patient with AIDS. J Clin Microbiol 2001;39(2):804–807. [3] Malloch D, Sigler L. The Eremomycetaceae (Ascomycotina). Can J Bot 1988;66:1929–1932. [4] Clinical Laboratory and Standards Institute. Reference method for broth microdilution antifungal susceptibility testing of filamentous fungi; approved standard. CLSI document M38-A [ISBN 1-56238-470-8]. Pennsylvania, USA: CLSI; 2002. [5] de Diego Candela J, Forteza A, Garcia D, Prieto G, Bellot R, Villar S, et al. Endocarditis caused by Arthrographis kalrae. Ann Thorac Surg 2010;90(1): e4–e5. [6] Perlman EM, Binns L. Intense photophobia caused by Arthrographis kalrae in a contact lens-wearing patient. Am J Ophthalmol 1997;123(4):547–549. [7] Biser SA, Perry HD, Donnenfeld ED, Doshi SJ, Chatuvedi V. Arthrographis keratitis mimicking Acanthamoeba keratitis. Cornea 2004;23(3):314–317. [8] Thomas BC, Zimmerman S, Vockler HE, Auffarth GU, Dithmar S. Severe Arthrographis kalrae keratomycosis in an immunocompetent patient. Cornea 2011;30(3):364–366. [9] Xi L, Fukushima K, Takizawa K, Liao R, Nishimura K. First case of Arthrographis kalrae ethmoid sinusitis and ophthalmitis in the People’s Republic of China. J Clin Microbiol 2004;42(10):4828–4831. [10] McAleer R, Froudist JH, Cherian G. Xth International Society for Human and Animal Mycology Congress 1988; abstract 172. [11] Sugiura Y, Hironaga M. Arthrogaphis kalrae, a rare causal agent of onychomycosis and its occurrence in the natural and commercially available soils. Med Mycol 2010;48:384–389. [12] Kisielinski K, Bremer D, Knutsen A, Rottger P, Fitzek JG. Complications following radiosynoviorthesis in osteoarthritis and arthroplasty: osteonecrosis and intra-articular infection. Joint Bone Spine 2010;77(3):252–257.