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Peripheral thromboembolism associated with Malassezia Furfur sepsis

2002; Lippincott Williams & Wilkins; Volume: 21; Issue: 4 Linguagem: Inglês

10.1097/00006454-200204000-00022

1532-0987

Alexander T. Kessler, Athena P. Kourtis, Neal P. Simon,

Fungal Infections and Studies

Malassezia furfur fungemia can cause sepsis in low birth weight neonates receiving parenteral lipids through central intravenous catheters. Its presentation has varied from nonspecific signs and symptoms to pulmonary vasculitis and endocarditis. We report the case of a premature infant who developed peripheral thromboembolic phenomena without evidence of endocarditis associated with M. furfur fungemia, an association not previously described. Malassezia furfur (also known as Pityrosporum ovale or Pityrosporum orbiculare) is a species of lipophilic budding yeast that requires exogenous long chain fatty acids for growth. Typically it causes several dermatologic infections such as tinea versicolor or folliculitis, but it has been associated with invasive infection in association with central venous catheters and intravenous lipid administration in premature infants 1–4 and in immunocompromised or seriously ill adults. 3M. furfur fungemia causes a spectrum of presenting signs, ranging from asymptomatic infection or nonspecific symptoms of sepsis to endocarditis. 4 Typically the syndrome of M. furfur sepsis in the neonate is characterized by fever, respiratory distress or apnea/bradycardia and thrombocytopenia. 5 We describe a premature neonate with peripheral thromboembolism associated with M. furfur fungemia which resolved completely after the central venous catheter was removed and amphotericin B therapy was given. Peripheral thromboembolic phenomena in association with M. furfur fungemia have not been previously described in the literature. Case report. This is a female infant, born at 34 weeks of gestation, who developed intestinal perforation caused by midgut volvulus soon after birth. She underwent bowel resection and ileostomy with subsequent reanastomosis and formation of a closed enterocutaneous fistula. Her surgeries were complicated by an infection of the abdominal wound as well as bacteremia and sepsis caused by Escherichia coli. As a result of her bowel resection she required parenteral alimentation through a percutaneous central venous catheter. At 1 month of age she presented with fever and purple-black discoloration of several toes bilaterally with a few additional ecchymotic and purpuric lesions on the dorsum of the feet, face and upper extremities. She also exhibited leukopenia (white blood cell count, 4100/mm3 with 52% neutrophils and 38% lymphocytes), thrombocytopenia (platelets of 44 000/mm3) and elevated C-reactive protein to 10.3 mg/dl. Liver and renal function tests were normal, and the chest radiograph was unremarkable. Prothrombin time was normal with increased activated partial thromboplastin time (50.1 s) and normal fibrinogen and fibrin split product values. After blood and urine cultures were obtained, therapy was started with vancomycin, amikacin and clindamycin; amphotericin B was added a few hours later. Blood and urine cultures were negative, but a Gram-stained smear of the buffy coat of blood from the central venous catheter showed unipolar budding yeast;M. furfur subsequently grew in culture from blood obtained from the central venous catheter, when olive oil was overlaid on the culture medium. The central venous catheter was removed, lipid administration was temporarily reduced and amphotericin B was continued for 3 weeks. M. furfur grew from the catheter tip as well. The cardiac echocardiogram was normal; no vegetations or thrombi were seen in the heart or near the tip of the catheter. The purpuric lesions and toe discoloration resolved within 3 days. Discussion. Frequent (30 to 64%) skin colonization with M. furfur has been reported among premature infants 6–9; in contrast only 3% of healthy infants 2 to 8 weeks of age in outpatient settings were colonized with this fungus. 4, 8 Culture positivity is associated with younger gestational age and longer stay in the intensive care nursery. Use of antibiotics, frequent handling by different adult care providers and use of intravenous lipids and skin emollients have been hypothesized to contribute to this high skin colonization rate in premature infants. 8, 10 The first case of invasive M. furfur infection was described in 1981 in an infant receiving lipid alimentation through a central venous catheter. A number of cases of sepsis have since been reported, particularly in infants receiving intravenous lipids. 1, 3, 4, 10 Organisms may enter from the skin through the catheter site and colonize the catheter. Intralipids administered through the catheter may provide medium and long chain fatty acids necessary for the growth of M. furfur.10 Cases have also been described in immunocompromised adults with deep intravascular catheters, 3, 11 or in patients with preceding abdominal surgery or pathology. 7 Most infected adults had only fever, whereas infants had a number of symptoms and signs, ranging from low grade fever to more pronounced signs of sepsis. Diagnosis is difficult, because M. furfur grows poorly, if at all, in standard culture media. Gram stain of a buffy coat drawn from the intravenous catheter provides rapid detection of M. furfur. The organism has been seen in a peripheral blood smear. 10 Subculturing onto media overlaid with sterile olive oil provides the necessary fatty acids for it to grow. Some studies showed that the DuPont Isolator culture system is superior for the isolation of the fungus because of its ease of use and the fact that specimens can be plated directly and supplemented with sterile olive oil, 12 whereas others have shown that lipid supplementation of BACTEC Peds Plus blood culture bottles also improves its recovery. 13, 14 Culture plates are incubated for up to 7 days before being discarded as negative. Optimal growth of M. furfur occurs between 35 and 37°C. 7 Management consists of removal of the catheter with or without a short course of antifungal therapy and temporary cessation of the lipid emulsion. When removal of the catheter is not feasible, amphotericin B administered through the catheter “locked” into place for 21 days was successful in four of seven patients. 3 However, Powell and Marcon 15 reported failure to eradicate M. furfur fungemia with antifungal therapy without removal of the catheter. In some cases fungemia cleared after discontinuation of the lipid emulsion with the catheter left in place. 7M. furfur is variably susceptible to the azole antifungal agents, 16 but in vitro susceptibility may not directly translate into clinical efficacy. 15 Our patient is the first in the medical literature in whom peripheral thromboembolic-hemorrhagic phenomena occurred in association with M. furfur sepsis. The low platelet count might have contributed to this presentation; however, there was no evidence of disseminated intravascular coagulation in our case or in other cases in the medical literature. 1 In the first few weeks of life a newborn is physiologically predisposed to thrombosis because of a deficiency in various regulatory proteins. It is likely that an underlying hypercoagulable state might have contributed to thromboembolism precipitated by the fungemia and associated with focal peripheral ischemia. Hemodynamic instability leading to pronounced vasoconstriction in the periphery that subsequently resolved is an alternative explanation even though no frank hypotension developed. The rapidity and completeness of recovery after removal of the catheter and intravenous administration of amphotericin and without any anticoagulation were impressive, attesting to the causal relatedness of this phenomenon with the infection.