Aspergillus tubingensis in Maxillary Bone Osteomyelitis
Aspergillus tubingensis in Maxillary Bone Osteomyelitis
A 19-year-old male patient born in the Netherlands (Moroccan parents) presented with fever, rhinitis and progressive pain behind the left eye. His recent medical record included a second non-myeloablative stem cell transplantation for graft failure resulting in relapse of paroxysmal nocturnal haemoglobinuria 3 weeks prior to presentation. He had undergone a maxillary tooth extraction 47 days prior to presentation. The alveolar wound did not heal due to osteomyelitis, for which he had a biopsy of the maxillary bone 23 days prior to presentation. Histological examination of the biopsy samples showed necrotic bone tissue. The surrounding connective tissue was infiltrated by leukocytes. Yeast cells, and focal bacterial colonies were noted. He was treated empirically with amoxicillin/clavulanic acid orally, which had been started 3 days prior to presentation, and the immunosuppressive drugs cyclosporine, mycophenolic acid, and prednisone. With this treatment, the patient was clinically deteriorating.
Physical examination revealed a body temperature of 37.9°C and normal vital signs. A purulent wound in the mouth resulting from the biopsy, left pre-orbital swelling, and painful cervical lymphadenopathy were observed. Laboratory tests showed increased C-reactive protein at 346 mg/L, leucopenia (leukocytes < 0.1 × 10/L), thrombopenia (thrombocytes 32 × 10/L) and normocytic anaemia (haemoglobin 5.51 × 10/L). Computed tomography of the head showed pre-orbital swelling with induration of the subcutis, swollen mucosa of the sphenoid, and maxillary sinus, and total opacification of the left ethmoid sinus (Figure 1). Since a direct surgical approach was impossible due to extensive bleeding of the swollen mucosa, an antrostomy was performed and sinus secretions were thoroughly aspirated. Cultures of purulent fluid from the biopsy wound in the mouth on Sabouraud dextrose agar at 37.0°C grew a black Aspergillus, morphologically resembling A. niger. Cultures of the aspirated secretion from sinus cavities were negative for bacteria and fungi. Results of the histological examination of mucosal lining samples of the nasal sinus were consistent with chronic sinusitis. The result of molecular identification of the black Aspergillus by sequencing of the β-tubilin gene was A. tubingensis Mosseray (CBS-KNAW, Fungal Biodiversity Centre, Utrecht, The Netherlands, strain CBS 133792; GenBank accession number KC163802). Figure 2 shows the phylogenetic relationships among Aspergillus section Nigri species, including our isolated strain (Table 1). Antifungal susceptibility testing by microdilution showed that the strain had MIC values to voriconazole of 1 μg/mL, to posaconazole of 0.25 μg/mL, to itraconazole of 0.25 μg/mL, to fluconazole of > 24 μg/mL, to anidulafungin of 0.125 μg/mL, to amphothericin B of 0.5 μg/mL, and to flucytosine of 2 μg/mL.
(Enlarge Image)
Figure 1.
Computed tomography of the head showing A: total opacification of the ethmoid sinus; B: swollen mucosa of the maxillary sinus; C: pre-orbital swelling.
(Enlarge Image)
Figure 2.
Maximum Parsimony tree based on β-tubulin sequence data of type strains ofAspergillussectionNigri,including theAspergillus tubingensis(CBS 133792) strain isolated from the presented patient. Numbers above branches represent bootstrap values.
The patient was treated with liposomal amphothericin B 5 mg/kg for 6 weeks and imipinem 500 mg/qid for 2 weeks intravenously, followed by prolonged treatment with voriconazole 300 mg/tid oral for 4 months. With this treatment the patient recovered from the sinusitis, but passed away later on that year due to BK virus encephalitis.
In summary, we describe an immunocompromised patient suffering from osteomyelitis of the maxillary bone with a probable invasive A. tubingensis infection of the surrounding connective tissue after tooth extraction. This probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis.
Case Presentation
A 19-year-old male patient born in the Netherlands (Moroccan parents) presented with fever, rhinitis and progressive pain behind the left eye. His recent medical record included a second non-myeloablative stem cell transplantation for graft failure resulting in relapse of paroxysmal nocturnal haemoglobinuria 3 weeks prior to presentation. He had undergone a maxillary tooth extraction 47 days prior to presentation. The alveolar wound did not heal due to osteomyelitis, for which he had a biopsy of the maxillary bone 23 days prior to presentation. Histological examination of the biopsy samples showed necrotic bone tissue. The surrounding connective tissue was infiltrated by leukocytes. Yeast cells, and focal bacterial colonies were noted. He was treated empirically with amoxicillin/clavulanic acid orally, which had been started 3 days prior to presentation, and the immunosuppressive drugs cyclosporine, mycophenolic acid, and prednisone. With this treatment, the patient was clinically deteriorating.
Physical examination revealed a body temperature of 37.9°C and normal vital signs. A purulent wound in the mouth resulting from the biopsy, left pre-orbital swelling, and painful cervical lymphadenopathy were observed. Laboratory tests showed increased C-reactive protein at 346 mg/L, leucopenia (leukocytes < 0.1 × 10/L), thrombopenia (thrombocytes 32 × 10/L) and normocytic anaemia (haemoglobin 5.51 × 10/L). Computed tomography of the head showed pre-orbital swelling with induration of the subcutis, swollen mucosa of the sphenoid, and maxillary sinus, and total opacification of the left ethmoid sinus (Figure 1). Since a direct surgical approach was impossible due to extensive bleeding of the swollen mucosa, an antrostomy was performed and sinus secretions were thoroughly aspirated. Cultures of purulent fluid from the biopsy wound in the mouth on Sabouraud dextrose agar at 37.0°C grew a black Aspergillus, morphologically resembling A. niger. Cultures of the aspirated secretion from sinus cavities were negative for bacteria and fungi. Results of the histological examination of mucosal lining samples of the nasal sinus were consistent with chronic sinusitis. The result of molecular identification of the black Aspergillus by sequencing of the β-tubilin gene was A. tubingensis Mosseray (CBS-KNAW, Fungal Biodiversity Centre, Utrecht, The Netherlands, strain CBS 133792; GenBank accession number KC163802). Figure 2 shows the phylogenetic relationships among Aspergillus section Nigri species, including our isolated strain (Table 1). Antifungal susceptibility testing by microdilution showed that the strain had MIC values to voriconazole of 1 μg/mL, to posaconazole of 0.25 μg/mL, to itraconazole of 0.25 μg/mL, to fluconazole of > 24 μg/mL, to anidulafungin of 0.125 μg/mL, to amphothericin B of 0.5 μg/mL, and to flucytosine of 2 μg/mL.
(Enlarge Image)
Figure 1.
Computed tomography of the head showing A: total opacification of the ethmoid sinus; B: swollen mucosa of the maxillary sinus; C: pre-orbital swelling.
(Enlarge Image)
Figure 2.
Maximum Parsimony tree based on β-tubulin sequence data of type strains ofAspergillussectionNigri,including theAspergillus tubingensis(CBS 133792) strain isolated from the presented patient. Numbers above branches represent bootstrap values.
The patient was treated with liposomal amphothericin B 5 mg/kg for 6 weeks and imipinem 500 mg/qid for 2 weeks intravenously, followed by prolonged treatment with voriconazole 300 mg/tid oral for 4 months. With this treatment the patient recovered from the sinusitis, but passed away later on that year due to BK virus encephalitis.
In summary, we describe an immunocompromised patient suffering from osteomyelitis of the maxillary bone with a probable invasive A. tubingensis infection of the surrounding connective tissue after tooth extraction. This probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis.
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