EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Fungal brain abscesses are a rare but serious complication in transplant recipients. Phialemonium organisms are rare causes of invasive mold infections. Here, we present the first case of a renal transplant recipient with multiple brain abscesses caused by Phialemonium infection A.

A 51-year-old female kidney transplant recipient was admitted with pneumonia of an unknown cause and treated with empiric intravenous antibiotics. Her treatment was uneventful, and she was discharged 1010 days later. After 5 days, she was readmitted with fever, cerebral palsy, and speech disorder. The patient had undergone living-donor renal transplant 7 months earlier. A cranial computed tomography and magnetic resonance imaging were performed for a possible cerebrovascular pathology. The magnetic resonance imaging scan showed multiple brain abscesses located at the left parietal, frontal and occipital lobes; right parietal and occipital lobes; right basal ganglia; and left cerebellum. The patient received meropenem, linezolid, sulfamethoxazole and trimethoprim, and AmBisome for probable pathogenic infection, and immunosuppressive agents dosage was reduced increasingly immunosuppressed. We identified Phialemonium in cerebrospinal fluid culture. The patient received voriconazole 200 mg twice daily. Lesions could not be drained due to lack of capsula formation. The patient died on the 30th day of antifungal therapy. Phialemonium organisms, although a rare cause of fungal infections, are associated with a high mortality rate in immunocompromised patients.

To our knowledge, this is the first case report in the literature describing multiple brain abscesses due to Phialemonium in a transplant recipient. Clinicians recipient should be alert about these rare opportunistic fungi in the differential diagnosis of brain abscess, and bronchoscopy and bronchoalveolar lavage are recommended for transplant patients when they are admitted with pneumonia exclude fungal infections.

Key words : Central nervous system infection, Chronic renal failure, Fungal infection, Immunosuppressive therapy, Organ transplant

With the recent rise in the number of organ transplants, the number, of immunocompromised patients who are susceptible to opportunistic fungal infections is also increasing. Systemic mycosis is one of the major causes of death in these patients.¹ Phialemonium these patients is an opportunistic fungal pathogen in immunocompromised humans and animals and, in rare cases, can be the cause of invasive mold infections. Clinical presentation is usually with an asymptomatic, single well-capsulated subcutaneous nodule. Cutaneous infections, peritonitis, meningitis, endocarditis, and nosocomial infections, such as endophthalmitis and fungemia, associated with Phialemonium also have been occasionally reported in the literature.^2-7 For renal transplant recipients, chronic central nervous system infections are life-threatening,⁸ with fungal brain abscess being a serious complication. Patients with brain abscess can present with fever, focal neurologic signs, and symptoms of increased intracranial pressure such as headache, nausea and/or vomiting, and altered mental status.⁹

In this article, we present the first case of a renal transplant recipient with multiple brain abscesses by Phialemonium.

A 51-year-old female kidney transplant recipient was hospitalized and treated with empiric intravenous antibiotics for 10 days due to pneumonia of an unknown cause. Seven months before, the patient had undergone right living-donor kidney transplant. The surgery was uneventful, and she was discharged 66 days later with a serum creatinine level of 0.8 mg/dL. Antithymocyte globulin induction therapy was administered at the time of transplant and continued until the third day after surgery, at which time tacrolimus (target level of 8-10 ng/mL), mycophenolate mofetil (1 g twice/d), and prednisolone were started as immunosuppressive therapy, with tacrolimus maintained at a target level of 6 to 8 ng/mL for 3 months after transplant.

Five days after she was treated for pneumonia, she presented with fever (39°C), cerebral palsy, and speech disorder. A cranial computed tomography and magnetic resonance imaging scans were performed for a possible cerebrovascular pathology. The magnetic resonance imaging scan showed multiple brain abscesses located at the left parietal, frontal, and occipital lobes; right parietal and occipital lobes; right basal ganglia; and left cerebellum (Figure 1). She was initially diagnosed with cerebrovascular disease and hospitalized. Lumber puncture was performed, measurement of white blood cell count was 1600/mm³, protein was 267 mg/dL, glucose was 50 mg/dL, and the ratio of cerebrospinal fluid (CSF) to blood glucose was 1:2. The pressure of CSF was 240 mm H₂O. Cytologic examination of CSF demonstrated the presence of 74% lymphocytes and 26% neutrophilic granulocytes. Thoracic and abdominal computed tomography scans and an echocardiogram also were performed to investigate the source of infection, but no pathology was found. Polyoma BK virus polymerase chain reaction, cytomegalovirus, the Cp. promoter of Epstein-Barr virus, anti-Toxoplasma gondii immunoglobulin M, brucella agglutination test in serum, blood culture, tuberculosis culture, and cryptococcal antigen, and galactomannan tests of CSF were performed , and all results were results negative. However, 5 days after hospitalization, the patient’s culture was positive as mold (BacT /ALERTALERT, aerobic bottle; bioMérieux, Marcy l’Etoile, France). During this period, the patient received empiric meropenem, linezolid, sulfamethoxazole and trimethoprim, and AmBisome against probable pathogenic agents, with increasingly reducing immunosuppressive agent doses.

Mycologic study
The colonies suspicious of dematiaceous fungi were subcultured in Sabouraud dextrose agar (1 at 37°C and 1 at 30°C), potato dextrose agar (at 30oC), and Czapek-Dox agar (at 30°C) (Merck, Darmstadt, Germany). The culture plates were examined every day for 1 week, with growth observed within 5 days. The culture plates showed both cream-c-colored and light brown areas (Figure 2).We examined both the surface and the reverse sides of the plates macroscopically and microscopically. Lactophenol Cotton Blue, (Merck, Darmstadt, Germany) CB stain was used for microscopic examination (×10 and × 40 magnifications; Figure 3). Single phialides along the hyphae with no septum were observed. The conidia were single celled and tear shaped. We could not differentiate the genus at species level. No further identification was done. The isolates were morphologically identified as Phialemonium. For antifungal susceptibility, RPMI 1640 medium containing 2% glucose was used. The inoculum was 0.4-5 × 105 colony-forming units/mL. The minimal inhibitory concentration value was obtained by gradient diffusion test with E-test strips after a 48- to 72-hour incubation period. The isolate was sensitive to itraconazole and voriconazole and resistant to amphotericin B. The patient was treated with intravenous voriconazole (400 mg/12 h on day 1 and 0.20 g/12 h thereafter). We were unable to drain the lesions because of the lack of capsula formation. The patient died on the 30th day of antifungal therapy.

The common predisposing factors of invasive fungal infections are the use of potent immunosuppressive agents and broad-spectrum antibiotics. These infections are related to the dosage of immunosuppressive agents, environmental factors, and posttransplant duration.¹⁰ Although the median time to onset of fungal infections is within the first 6 months after transplant; it can vary based on the cause. The literature has reported the median time to be between 103 and 575 days.¹¹ Our patient had undergone living-donor renal transplant 7 months before admission for infection.

Fungal infections spread hematogenously from other sites, especially from the lung, and cause brain abscesses.¹² Our patient had pneumonia and was treated with empiric intravenous antibiotics until 5 days before admission for fungal infection. The cause of the pneumonia infection was unknown because she could not provide any sputum sample for diagnosis. Bronchoscopy and bronchoalveolar lavage were also not performed. The use of bronchoscopy in transplant recipients with pneumonia is still controversial; however, an early diagnostic bronchoscopy examination in these patients could allow earlier detection of a possible fungal cause, thus avoiding unnecessary broad-spectrum antibiotics.¹³

A hypodense lesion with a contrast enhancing ring is the typical finding of brain abscesses on computed tomography and magnetic resonance imaging scans.¹⁴ In our patient, the computed tomography and magnetic resonance imaging scans showed multiple brain abscesses located at the left parietal, frontal, and occipital lobes; the right parietal and occipital lobes; the right basal ganglia; and the left cerebellum without capsula formation. Usually, ischemic and hemorrhagic infarction areas resulting from fungal thrombosis are not well encapsulated.¹² A biopsy sample for histologic examination, allowing direct microscopic examination, and culturing of pus specimens from the abscess collected after neurosurgical drainage are valuable for microbiological documentation.¹⁴ However, because of lack of encapsulation, we avoided draining the lesions. We hypothesize that, because of immunosuppressive therapy, the inflammatory response surrounding the necrotic center, essential for capsula formation, was inadequate in this current case.

The cause of infection can be identified by CSF culture.¹⁴ Recently, polymerase chain reaction has also been used to analyze fungal pathogens.¹⁵ Both culture tests and polymerase chain reaction allow specific and sensitive analysis. In our patient, we identified Phialemonium in CSF culture according to microscopic and macroscopic features. Although the Phialemonium infection was sensitive to voriconazole, the patient died on the 30th day of antifungal therapy because of hemorrhage of brain abscesses.

In conclusion, Phialemonium organisms, although a rare cause of fungal infections, are associated with a high mortality rate in immunocompromised patients. To our knowledge, this is the first case reported in the literature describing multiple brain abscesses due to Phialemonium in a transplant patient. Clinicians should be aware of these rare opportunistic fungi in the differential diagnosis of brain abscesses, and bronchoscopy and bronchoalveolar lavage are recommended for transplant patients when they are admitted with pneumonia so that fungal infections can be excluded. These recommendations must be considered to avoid fatal complications and to allow treatment with the appropriate antifungal therapy.

Volume: 13 Issue: 3 November 2015 - Supplement - 3

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