TRICHOSPORON ASAHII: AN UNUSUAL CAUSE OF INVASIVE INFECTION IN NEONATES

Abstract

Trichosporon asahii causes white piedra, an infection of hair shafts and onychomycosis in immunocompetent patients, as well as various localized or disseminated invasive infections in immunodeficient hosts. We describe a 26-week gestation 890-g vaginally delivered female neonate who had severe respiratory distress syndrome and on the sixth day of life developed Klebsiella pneumoniae sepsis. At the same time two blood cultures were positive for T. asahii. The neonate was also colonized with T. asahii in the pharynx and perineum. The infant was successfully treated with conventional amphotericin B. Trichosporon asahii (formerly known as Trichosporon beigelii and cutaneum) is a basidiomycetous yeast. It is ubiquitous, found in soil, vegetation and water samples. T. asahii causes white piedra, a superficial infection of hair shafts mainly restricted to tropical regions and less commonly onychomycosis in immunocompetent humans. 1 In immunodeficient hosts it has been isolated from blood, skin and viscera causing various localized or disseminated deep infections. Invasive disease with high associated mortality has been described in patients with hematologic malignancies, burns and organ transplants. 2 The majority of patients with invasive disease have been difficult to treat with standard antifungal agents and have died. 3 Although ∼110 cases have been reported in adults, 81% of whom had leukemia or bone marrow transplantation, 4 few cases in neonates 5–10 and immunocompromised children 11–15 have been published. We report a case of invasive infection caused by T. asahii in a prematurely born neonate. Case report. The patient, an 890-g girl, was delivered vaginally to a para 2 healthy 26-year-old mother. She was born after a 26-week gestation and membrane rupture 20 h before labor. The Apgar score was 3 at 1 min and not recorded at 5 min. The neonate was intubated and transferred to the neonatal intensive care unit (NICU), Aristotle University of Thessaloniki, because of prematurity and respiratory distress syndrome (RDS). An umbilical vein catheter was inserted. Because of prolonged membrane rupture, empiric treatment with ampicillin and gentamicin was initiated. The chest roentgenogram was suspicious of severe RDS, and surfactant was administered three times. Intermittent positive pressure ventilation was initiated. Admission hemoglobin was 12.2 g/dl, and the white blood cell count was 8.8 × 10 9 /l with 45% polymorphonuclear leukocytes and a platelet count of 193 × 10 9 /l. On Day 3 of life and while RDS was improving, the neonate developed bradycardic episodes. On Day 6, while still receiving ampicillin and gentamicin, the infant manifested worsening of the respiratory function, signs of gastrointestinal tract dysfunction and shock. Blood studies showed glucose 171 mg/dl, white blood cell count 13 × 10 9 /l and platelet count 144 × 10 9 /l, along with a concurrent rise of C-reactive protein to a maximum value of 63.9 mg/l on Day 7. The antibiotic regimen was changed to vancomycin, imipenem and amikacin. A blood culture obtained on Day 6 was positive for Klebsiella pneumoniae and a yeast that was later identified as T. asahii. Cerebrospinal fluid and urine cultures were sterile. Deoxycholate amphotericin B (Bristol-Myers Squibb, Paris, France) was started on Day 11 in a dose of 0.25 mg/kg/day and escalated daily to 1 mg/kg. A second blood culture on Day 11 taken before the initiation of antifungal therapy grew T. asahii only. Repeat blood cultures on Days 14, 17, 31 and 34 were all negative except for the culture of the tip of the intravenous catheter that yielded T. asahii on Day 16. T. asahii also grew from pharyngeal and perineal swabs of the patient on Day 13. From a total of 20 surveillance cultures taken before or after the first positive blood culture, no other specimen was positive for this or another yeast. In addition no surveillance cultures taken from the same sites of other neonates in the NICU around the time of the episode were positive for T. asahii. Surveillance cultures taken from the hospital environment (incubators, sink and shower drains) were all negative for T. asahii. The infant’s condition and laboratory values improved gradually during the following week. After treatment with amphotericin B for 28 days, fungal cultures were all negative and treatment was discontinued. Mechanical ventilation was used for a total of 25 days followed by administration of supplemental oxygen for another 24 days because of bronchopulmonary dysplasia. She was discharged at the age of 2.5 months with no sequelae, and she is well 1 year later. The isolation and identification of T. asahii were performed at the Microbiology Laboratory of Hippokration Hospital of Thessaloniki. Blood samples were incubated in a continuous monitoring culture system (Pedi-BacT Alert; Organon Teknika, Durham, NC) at 37°C. Identification of the fungus was accomplished with the system API ID 32C (bioMérieux, Marcy l’ Etoile, France). Pharyngeal and perineal swabs were taken weekly and cultured on Sabouraud dextrose agar at the Research Laboratory of Infectious Diseases, Third Department of Pediatrics, Aristotle University. After screening of colonizers by germ tube test, the identification was also completed with the API ID 32C system. The MIC and minimum fungicidal concentrations (MFC), evaluated at the Research Laboratory of Infectious Diseases by use of the National Committee for Clinical Laboratory Standards Method M-27A, 16 were 1 and 4 μg/ml, respectively, for amphotericin B, 8 and >128 μg/ml for flucytosine, 1 and 32 μg/ml for fluconazole and 0.5 and >32 μg/ml for itraconazole. Discussion. T. asahii is usually nonpathogenic and may be part of normal skin flora. Systemic infections occur rarely in immunocompromised patients and may be either localized or disseminated. Localized infections (18 to 20% of cases with invasive disease) 1 include endocarditis, 17 acute or chronic meningitis, 18 peritoneal dialysis-associated peritonitis, 19 pneumonia, arthritis, 5 cholangitis, 5 hepatitis 5 and ocular infections. Disseminated disease has developed in patients with hematologic malignancies, burns and organ transplants with high associated mortality. Our patient was an extremely low birth weight neonate who manifested symptoms of systemic infection within the first week of life while receiving ampicillin and gentamicin. She had a concurrent infection caused by K. pneumoniae successfully treated with imipenem. The T. asahii infection was confirmed with two consecutive blood cultures (on Days 6 and 11) and by isolation of the same yeast from the catheter tip on Day 16. Antifungal treatment did not start until 5 days after the first positive blood culture was obtained. However, the response to the treatment was favorable, and she did not manifest any further septic episodes. In a study of neonates weighing <1500 g, the colonization rate with T. cutaneum (asahii) was ∼10%. 20 At our NICU, during the period when the case occurred, only 1 case of T. asahii colonization was found. Specimens from both pharynx and perineum of 593 high risk neonates were collected. Our patient was the only one who was colonized with T. asahii at both sites 1 week after the first positive blood culture. In none of the previously published neonatal cases was colonization reported. Once diagnosed invasive T. asahii infection is difficult to treat, and the outcome is generally poor. In neutropenic patients cure is strongly associated with the recovery from neutropenia, 2, 4 and in patients having indwelling catheters it is strongly associated with the removal of the catheter. 5 Treatment with amphotericin B is not often successful. The mortality rate is 65 to 75% in adults 1 and approaches 100% in patients without neutrophil recovery. 15 In vitro susceptibility data suggest that MFCs of amphotericin B for T. asahii may exceed the safely achievable concentrations in serum (≤2 μg/ml). The favorable outcome in our patient who was treated with amphotericin B may be a result of an achievable MFC (1.0 μg/ml) or the relatively high daily dose of 1 mg/kg used. In this case amphotericin B was continued as the only antifungal therapy because follow-up cultures after its initiation remained negative. Animal model studies 21, 22 and clinical data 14 have shown that antifungal triazoles, such as fluconazole, behave like fungicidal agents against invasive infection caused by T. asahii and may be preferred. Invasive infection caused by T. asahii is a serious fungal disease. Early identification of the fungus from clinical specimens and determination of species should prompt urgent communication between clinical microbiologist, infectious disease specialist and neonatologist regarding additional cultures, susceptibility testing to polyenes and azoles as well as prompt initiation of antifungal treatment. Acknowledgments. PP and JF were supported by Grant PENED99 ED14 from the Hellenic Ministry of Development. We thank Dr. Evangelia Farmaki for her contribution to the study.