Nosocomial infections with unusual microorganisms are amajor problem in the neonatal intensive care unit1 inMalaysia,2 and accounts for the majority of the morbidity andmortality in very low and extremely low birthweight babies.2

Fungal infections are being seen with increasing frequencybecause of the use of multiple antibiotics, the higher number ofadmissions of premature neonates, and the use of long-termtotal parenteral nutrition (TPN) in the neonatal intensive careunit of Hospital University Sains Malaysia. We report on acase of an unusual fungal pathogen, Hansenula anomala (H. anomala), in a premature neonates.

CASE REPORT

A premature female infant born at 32 weeks gestation, with abirthweight of 1.07 kg was admitted to our neonatal intensivecare unit. Her mother was a 20-year-old primigravida who hadpregnancy-induced hypertension. The child was delivered byemergency caesarean section because of fetal bradycardia.Antenatal steroids were not given. The Apgar scores were 5 at1 min, 8 at 5 min and 9 at 10 min. At birth, the child was notedto have the presence of major exomphalos with liver andintestines visible within the peritoneal sac. No other grossabnormalities were detected, and the child was ventilated forperinatal asphyxia and respiratory distress syndrome. Primaryclosure was performed on the first day of life. Postoperatively,she developed lower limb swelling, was kept nil orally, andstarted on TPN and i.v. cefuroxime and metronidazole (Flagyl).On day 8 of life, the child was lethargic and off colour. Intra-venous piperacillin and amikacin were started, while awaitingblood culture. Fever was noted 2 days later, and i.v. amphotericinB commenced when yeast cells were grown from the bloodculture. The following day, the child’s condition worsened withabdominal distention, a platelet count of 35 × 109/L, pulmon-ary haemorrhage requiring higher ventilatory settings and a

haematoma on the wound site. The next few days witnessed animprovement – the platelet count rose to 80 × 109/L, and therewas resolution of the abdominal distention and of the pulmonaryhaemorrhage. An ultrasound showed no abnormalities apartfrom the haematoma overlying the liver.

The child was started on minimal oral feeds (1 mL of breastmilk given 6 hourly) in the second week of life, but developedclinical evidence of necrotizing enterocolitis (NEC) with atense abdomen, coffee ground aspirates and radiological evi-dence of dilated loops of bowel. She was then kept nil orallyfor 7 days before feeds were resumed, with the institution ofi.v. piperacillin and metronidazole. On day 28 of life, surgicalremoval of the haematoma was performed and a lyodermapatch inserted. Despite all the measures instituted, the childnever fully recovered, and continued to have thrombocy-topenia. Blood cultures repeated on days 10, 14, 19, 21 stillgrew yeast cells, initially thought to be Candida, but later iden-tified as H. anomala, by special staining techniques. Theamphotericin B dose was increased from 1–1.5 mg to 2 mg/kgper day. On day 29, after completing 30 mg/kg of amphotericinB, oral ketoconazole was substituted. No long lines wereinserted during these times, but TPN was continued throughperipheral lines. A repeat blood culture, 4 days after startingketoconazole grew no fungi. However, on day 37 of life, thechild became severely unwell. Intravenous piperacillin andamikacin were started, with imipenem substituted for piper-acillin when the child’s condition worsened 2 days later. Unfor-tunately, the child died 39 days after admission while beingcontinually ventilated during this period. The repeat culture ofblood and endotracheal secretions taken on days 37 and 39 grewPseudomonas aeroginosa. An autopsy was not performed.

We were unable to culture H. anomala from other babies orfrom environmental sources, such as hyper-alimentationsolutions, disinfectant soaps and solutions.

DISCUSSION

The yeast H. anomala was first discovered in 1891 by Hansen,and is an ascosporogenous yeast of the class ascomycetes.3,4

It is a free-living organism which thrives on high sugarenvironments, and has been isolated in soft drinks, syrups,3

fruits4 and as a contaminant in the brewing industry.1 This is anew emerging pathogen, first ascribed to humans via reports ofyeast causing interstitial pneumonia by Csillag et al. in the

J. Paediatr. Child Health (2000) 36, 609–610

Hansenula anomala infection in a neonate

AR WONG,1 H IBRAHIM,3 H VAN ROSTENBERGHE,1 Z ISHAK1 and MJ RADZI2

Departments of 1Paediatrics, 2Microbiology, and 3Surgery, School of Medical Sciences,University Sains Malaysia, Kelantan, Malaysia

Abstract: We present an unusual neonatal fungal infection, Hansenula anomala in a very low birthweight infant whounderwent abdominal surgery for an omphalocele. Despite treatment with adequate doses of amphotericin B, the yeastcontinued to grow from the blood culture, and was only eradicated with the use of oral ketoconazole.

Key words: Hansenula anomala; neonate resistance; yeast infection.

Correspondence: Dr AR Wong, Department of Paediatrics, School ofMedical Sciences, University Sains Malaysia, 16150 Kubang Kerian,Kelantan, Malaysia. Fax: (609) 765 3370; email: rahim@kck.usm.my

AR Wong, MRCP (Paeds), Lecturer. H Ibrahim, MS, AssociateProfessor. H Van Rostenberghe, Paediatric Specialist. Z Ishak, MBBS,Senior Medical Officer. MJ Radzi, MBBS, MSc (Microbiol.), Lecturer.

Accepted for publication 30 April 2000.

1950s;5 the yeast remained unidentified for 5 years and laterdiscovered to be Hansenula. However, it is now believed thatthese infections were more likely to be Pneumocytis carinii.1

There have been increasing reports of Hansenula attackingthose with decreased immunity, from chemotherapy for cancerin adults and older children,3,4,6–8 or in premature neonates as in Liverpool in 1986.1 In the latter series, reported byMurphy et al,1 52 babies (10% colonization of all admittedbabies) were colonized over a period of a year, with only eightdeveloping invasive disease. These were treated with a combin-ation of amphotericin B and flucytosine. The yeast was notedto colonize mainly the rectum and oropharynx, and was elim-inated using oral nystatin and a topical iodophore to vene-puncture sites.

Susceptibility to infection in human hosts, seems to beincreased in drug addicts, AIDS, carcinoma, multiple sclerosis,myeloproliferative disorders (e.g. leukaemia), neutropenia,steroid use, chemotherapy, broad-spectrum antibiotic usage, andfollowing motor vehicle accidents requiring intensive care.3,4,7,8

In children, additional factors seem to be low birthweight inneonates,1 abdominal sepsis (with necrotizing enterocolitis),haemolytic-uraemic syndrome, and chronic renal failure under-going peritoneal dialysis.6,8 It is also interesting to note thatinsertion of catheters and cannulation sites,1,3,4,6–8 or abdominalsurgery3,6 were reported in most cases of H. anomala infection.

In this case, H. anomala was cultured in only one neonate(over a period of a year) who had several risk factors: very lowbirthweight, abdominal surgery to close an omphalocele (witha post-surgical haematoma intraperitoneally), the use of broadspectrum antibiotics, and total parenteral nutrition. Because of the difficulty in identifying this organism, the incidence ofinfection may be under-reported.

In our patient, the organism persisted despite adequate tohigh doses of amphotericin B. Only with the substitution ofketoconazole, were we able to eradicate it from this child, whounfortunately died because of a new infection, P. aeroginosa.

Because susceptibility testing of yeasts is not standardized,7

antifungal sensitivity tests are not performed in our hospital. H. anomala is reported in the literature as being usuallysensitive to amphotericin B, but not to fluconazole.2,7,8

Therefore, it was with interest that in this patient an apparentresponse was noted only to ketoconazole. This was similar toone of the cases reported by Moses et al.6 in 1991, when a 5-month-old female infant was admitted following severe

watery diarrhoea, vomiting and abdominal distention. She wasinitially investigated and treated for septicaemia with intus-susception. Because of a normal barium enema and worsen-ing condition, she was operated on for suspected necrotizingenterocolitis. Thirty centimetres of ileum showing patchygangrenous areas was resected and purulent fluid was aspiratedfrom the abdomen. Fungal elements found in the histologicalspecimen, blood, and peritoneal fluid were identified as H. anomala. The child responded to ketoconazole,6 with failureof clearance on amphotericin B (1 mg/kg per day for 31 days).

ACKNOWLEDGEMENTS

The authors are grateful to Professor DR Lines (School ofMedicine, Flinders University of South Australia) and Pro-fessor LM Noh (School of Medical Sciences, University SainsMalaysia) for their assistance and helpful suggestions.

REFERENCES

1 Murphy N, Damjanovic V, Hart CA, Buchanan CR, Whitaker R,Cooke RWI. Infection and colonisation of neonates by Hansenulaanomala. Lancet 1986; 1: 291–3.

2 Malaysian Very Low Birth Weight Study Group. A national studyof risk factors associated with mortality in very low birthweightinfants in the Malaysian neonatal intensive care units. J. Paediatr.Child Health 1997; 33: 18–25.

3 Klein AS, Tortora GT, Malowitz R, Greene WH. Hansenulaanomala: A new fungal pathogen. Arch. Intern. Med. 1988; 148:1210–3.

4 Kwon-Chung KJ, Bennett JE, eds. Infections due to miscellaneousfungi. In Medical Mycology. Lea Febiger, Malvern, PA, 1992; 778–9.

5 Csillag A, Brandstein L. The role of blastomyces in the aetiologyof intersitital plasmocytic pneumonia of the premature infant. ActaMicrobiol. Hung. 1954; 2: 179–90.

6 Moses A, Shlomo M, Shvil Y et al. Hansenula anomala infectionsin children: From asymptomatic colonization to tissue invasion.Pediatr. Infect. Dis. J. 1991; 10: 400–2.

7 Hazen KC. New and emerging yeast pathogens. Clin. Microbiol.Rev. 1995; 8: 462–78.

8 Alter SJ, Farley J. Development of Hansenula anomala infectionin a child receiving fluconazole therapy. Pediatr. Infect. Dis. J.1994; 13: 158–9.

610 AR Wong et al.