Neonatal Invasive Candidiasis: A Prospective Multicenter Study of 118 Cases

 

 Buy Article Permissions and Reprints

ABSTRACT

A prospective multicenter study was conducted to assess the epidemiology of neonatal invasive candidiasis in Spain. In a total of 20,565 admissions to the 27 participating neonatal units over an 18-month period, systemic candidiasis was diagnosed in 118 (0.57%) neonates. Candida species were isolated from the blood in 79 infants, from the urine in 33, and from the cerebrospinal fluid in 4; in 2 cases, histologic evidence of deep tissue candidiasis was found at autopsy. Very-low-birth-weight (VLBW) infants (≤ 1500 g) showed a significantly higher incidence of systemic candidiasis (4.8%) than infants weighing > 1500 g (0.2%) (p < 0.001). Candida albicans was the most frequent species (52.5%) followed by C. parapsilosis (23.7%), and C. tropicalis (7.6%). Only seven infants were treated with amphotericin B (initial dose 0.18 ± 0.3 mg/kg, maximal daily dose 1.7 ± 0.9 mg/kg) but treatment was stopped in three of them (43%) due to nephrotoxicity. Liposomal amphotericin B was given to 81 neonates and amphotericin B lipid complex to 29. There were no differences in mortality rate and in the incidence of adverse effects in relation to treatment with liposomal amphotericin B or amphotericin B lipid complex. The mortality rate was 10.2% and all deaths occurred in the VLBW cohort with candidemia.

REFERENCES

• 1 Butler K M, Baker C J. Candida: an increasingly important pathogen in the nursery.  Pediatr Clin North Am . 1988;  35 543-563
  PubMedGoogle Scholar
• 2 Ng P C. Systemic fungal infections in neonates.  Arch Dis Child . 1994;  71 F130-F135
  PubMedGoogle Scholar
• 3 Miller M J. Fungal infections. In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant 4th ed. Philadelphia: WB Saunders 1995: 703-744
  Google Scholar
• 4 Faix R G, Kovarik S M, Shaw T R, Johnson R V. Mucocutaneous and invasive candidiasis among very low birth weight (<1,500 grams) infants in intensive care nurseries: a prospective study.  Pediatrics . 1989;  83 101-107
  PubMedGoogle Scholar
• 5 Baley J E, Kliegman R M, Fanaroff A A. Disseminated fungal infections in very low-birth-weight infants: clinical manifestations and epidemiology.  Pediatrics . 1984;  73 144-152
  PubMedGoogle Scholar
• 6 Faix R G. Systemic candida infections in infants in intensive care nurseries: high incidence of central nervous system involvement.  J Pediatr . 1984;  105 616-622
  PubMedGoogle Scholar
• 7 Johnson D E, Thompson T R, Green T P, Ferrieri P. Systemic candidiasis in very low-birth-weight infants (<1,500 grams).  Pediatrics . 1984;  73 138-143
  PubMedGoogle Scholar
• 8 Smith H, Congdon P. Neonatal systemic candidiasis.  Arch Dis Child . 1985;  60 365-369
  PubMedGoogle Scholar
• 9 López  Sastre JB, Coto Collado GD, Ramos Aparicio A, Crespo Hernández M. Infecciones del recién nacido. Libro del Año de Pediatría Madrid: Editorial Saned 1994: 123-169
• 10 Pourcyrous M, Bada H S, Korones S B, Baselski V, Wong S P. Significance of serial C-reactive protein responses in neonatal infection and other disorders.  Pediatrics . 1993;  92 431-435
  Google Scholar
• 11 Manroe B L, Weinberg A G, Rosenfeld C R, Browne R. The neonatal blood count in health and disease I: reference values for neutrophilic cells.  J Pediatr . 1979;  95 89-98
  CrossrefPubMedGoogle Scholar
• 12 Sarff L D, Platt L H, McCracken Jr H G. Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis.  J Pediatr . 1976;  88 473-477
  PubMedGoogle Scholar
• 13 Bonadio W A, Stanco L, Bruce R, Barry D, Smith D. Reference values of normal cerebrospinal fluid composition in infants ages 0 to 8 weeks.  Pediatr Infect Dis J . 1992;  11 589-591
  PubMedGoogle Scholar
• 14 Stoll B J, Gordon T, Korones S B. et al . Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human and Development Neonatal Research Network.  J Pediatr . 1996;  129 72-80
  CrossrefPubMedGoogle Scholar
• 15 Stoll B J, Gordon T, Korones S B. et al . Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human and Development Neonatal Research Network.  J Pediatr . 1996;  129 63-71
  PubMedGoogle Scholar
• 16 Freedman R M, Ingram D L, Gross I, Enrenkranz R A, Warshaw J B, Baltimore R S. A half century of neonatal sepsis at Yale: 1928 to 1978.  Am J Dis Child . 1981;  135 140-144
  CrossrefPubMedGoogle Scholar
• 17 Freij B H, McCracken Jr H G. Acute infections. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: Pathophysiology and Management of the Newborn 5th ed. Philadelphia: Lippincott Williams & Wilkins 1999: 1189-1230
  Google Scholar
• 18 McGowan K L, Hodinka R L. Laboratory diagnosis of fetal infections.  Clin Lab Med . 1992;  12 523-552
  PubMedGoogle Scholar
• 19 Kossoff E H, Buescher E S, Karlowicz M G. Candidemia in a neonatal intensive care unit: trends during fifteen years and clinical features of 111 cases.  Pediatr Infect Dis . 1998;  17 504-508
  CrossrefPubMedGoogle Scholar
• 20 Rowen J L, Atkins J T, Levy M L, Baer S C, Baker C J. Invasive fungal dermatitis in the < or = 1000-gram neonate.  Pediatrics . 1995;  95 682-687
  PubMedGoogle Scholar
• 21 Shareef M J, Myers T F, Mathews H L, Witek-Janusek L. Reduced capacity of neonatal lymphocytes to inhibit growth of Candida albicans Biol Neonate .  1999;  75 31-39
  PubMedGoogle Scholar
• 22 Goldman D A, Leclair J, Macone A. Bacterial colonization of neonates admitted to an intensive care environment.  J Pediatr . 1978;  93 288-293
  CrossrefPubMedGoogle Scholar
• 23 Danker W M, Spector S A, Fierer J, Davis C E. Malassezia fungemia in neonates and adults:complication of hyperalimentation.  Rev Infect Dis . 1987;  9 743-753
  PubMedGoogle Scholar
• 24 MacDonald L, Baker C, Chenoweth C. Risk factors for candidemia in a children's hospital.  Clin Infect Dis . 1998;  26 642-645
  PubMedGoogle Scholar
• 25 Mullett M D, Cook E F, Gallager R. Nosocomial sepsis in the neonatal intensive care unit.  J Perinatol . 1998;  18 112-115
  PubMedGoogle Scholar
• 26 Weese-Mayer D E, Fondriest D W, Brouillette R T, Shulman S T. Risk factors associated with candidemia in the neonatal intensive care unit: a case-control study.  Pediatr Infect Dis . 1987;  6 190-196
  PubMedGoogle Scholar
• 27 Nicholls J M, Yuen K Y, Tam A Y. Systemic fungal infections in neonates.  Br J Hosp Med . 1993;  49 420-424
  PubMedGoogle Scholar
• 28 Baley J E. Neonatal candidiasis: the current challenge.  Clin Perinatol . 1991;  18 263-280
  PubMedGoogle Scholar
• 29 Botas C M, Kurlat I, Young S M, Sola A. Disseminated candidal infections and intravenous hydrocortisone in preterm infants.  Pediatrics . 1995;  95 883-887
  PubMedGoogle Scholar
• 30 Sánchez P J, Cooper B H. Candida lusitaniae: sepsis and meningitis in a neonate.  Pediatr Infect Dis . 1987;  6 758-759
  PubMedGoogle Scholar
• 31 Coto Cotallo D G, López Sastre B J, Fernández Colomer B, Concha Torre A J, González González M. Neonatal invasive candidiasis: study of 44 cases in 22 years.  Prenat Neonat Med . 1996;  1 (suppl 1) 213
  PubMedGoogle Scholar
• 32 Waggoner-Fountain L A, Walker M W, Hollis R J. et al . Vertical and horisontal transmission of unique Candida species to premature newborns.  Clin Infect Dis . 1996;  22 803-808
  PubMedGoogle Scholar
• 33 Baley J E, Kliegman R M, Boxerbaum B, Fanaroff A A. Fungal colonization in the very low birth weight infant.  Pediatrics . 1986;  78 225-232
  PubMedGoogle Scholar
• 34 Reef S E, Lasker B A, Butcher D S. et al . Nonperinatal nosocomial transmission of Candida albicans in a neonatal intensive care unit: prospective study.  J Clin Microbiol . 1998;  36 1255-1256
  PubMedGoogle Scholar
• 35 Strausbaugh L J, Sewell D L, Ward T T, Pfaller M A, Heitzman T, Tjoelker R. High frequency of yeast carriage on hands of hospital personnel.  J Clin Microbiol . 1994;  32 2299-2300
  PubMedGoogle Scholar
• 36 Huang Y C, Lin T Y, Leu H S, Peng H L, Wu J H, Chang H Y. Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis.  Infection . 1999;  27 97-102
  PubMedGoogle Scholar
• 37 Brown J, Froese-Fretz A, Luckey D, Todd J K. High rate of hand contamination and low rate of hand-washing before infant contact in a neonatal intensive care unit.  Pediatr Infect Dis . 1996;  15 908-910
  CrossrefPubMedGoogle Scholar
• 38 Ehl S, Gering B, Bartmann P, Högel J, Pohlandt F. C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection.  Pediatrics . 1997;  99 216-221
  CrossrefPubMedGoogle Scholar
• 39 Coto G D, López Sastre J, Concheso C. et al . Proteína C reactiva y orosomucoide como parámetros de control evolutivo y eficacia terapúetica an la sepsis neonatal.  An Esp Pediatr . 1982;  17 204-210
  PubMedGoogle Scholar
• 40 Rønnestad A, Abrahamsen T G, Gaustad P, Finne P H. C-reactive protein (CRP) response patterns in neonatal septicaemia.  APMIS . 1999;  107 593-600
  CrossrefPubMedGoogle Scholar
• 41 Rowen J L, Tate J M, for the Neonatal Candidiasis Study Group. Management of neonatal candidiasis.  Pediatr Infect Dis . 1998;  17 1007-1011
  CrossrefPubMedGoogle Scholar
• 42 Baley J E, Meyers C, Kliegman R M, Jacobs M R, Blumer J L. Pharmacokinetics and outcome of treatment toxic effects of amphotericin B 5-fluorocytosine in neonates.  J Pediatr . 1990;  116 791-797
  PubMedGoogle Scholar
• 43 Kingo A RM, Smyth J A, Waisman D. Lack of evidence of amphotericin B toxicity in very low birth weight infants treated for systemic candidiasis.  Pediatr Infect Dis J . 1997;  16 1002-1003
  CrossrefPubMedGoogle Scholar
• 44 Robinson R F, Nahata M C. A comparative review of conventional and lipid formulations of amphotericin B.  J Clin Pharm Ther . 1999;  24 249-257
  CrossrefPubMedGoogle Scholar
• 45 Koren G, Lau A, Klein J. et al . Pharmacokinetics and adverse effects of amphotericin B in infants children.  J Pediatr . 1988;  113 559-563
  PubMedGoogle Scholar
• 46 Lackner H, Schwinger W, Urban C. et al . Liposomal amphotericin B (AmBisome) for treatment of disseminated fungal infections in two infants with very low-birth-weight.  Pediatrics . 1992;  89 1259-1261
  PubMedGoogle Scholar
• 47 Da Silva P L, Amaral J M, Ferreira N C. Which is the most appropriate dosage of liposomal amphotericin B (AmBisome) for the treatment of fungal infections in infants or very low birth weight?.  Pediatrics . 1993;  91 1217-1218
  PubMedGoogle Scholar
• 48 Baquero Artigao F, Salas Hernández S, Quero Jiménez J. La anfotericina B liposomal (AmBisome) en el tratamiento de las infecciones fúngicas sistémicas en el neonato: a propósito de un caso.  An Esp Pediatr . 1996;  45 209-212
  PubMedGoogle Scholar
• 49 Weitkamp J H, Poets C F, Sievers R. et al . Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with amphotericin B (AmBisome).  Infection . 1998;  26 11-15
  PubMedGoogle Scholar
• 50 Scarcella A, Pasquariello M B, Giugliano B, Vendemmia M, De Lucia A. Liposomal amphotericin B treatment for neonatal fungal infections.  Pediatr Infect Dis . 1998;  17 146-148
  CrossrefPubMedGoogle Scholar
• 51 López Sastre J, Coto Cotallo D G, Fernández Colomer B, Santos Rodríguez P, Crespo Hernández M. A retrospective clinical comparison between antifungal treatment with liposomal amphotericin B (Ambisome®)and conventional amphotericin B in very low birth weight infants.  Prenat Neonat Med . 1996;  1 (suppl 1) 214
  PubMedGoogle Scholar
• 52 Hiemenz J W, Walsh T J. Lipid formulations of amphotericin B: recent progress and future directions.  Clin Infect Dis . 1996;  22 (suppl 2) S133-S255
  PubMedGoogle Scholar
• 53 Walsh T J, Seibel N L, Arndt C. et al . Amphotericin B lipid complex in pediatric patients with invasive fungal infections.  Pediatr Infect Dis . 1999;  18 702-708
  CrossrefPubMedGoogle Scholar
• 54 Faix R G. Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection.  Pediatr Infect Dis . 1992;  11 88-93
  PubMedGoogle Scholar
• 55 Levy I, Rubin L G, Vasishtha S, Tucci V, Sood S K. Emergence of Candida parapsilosis as the predominant species causing candidemia in children.  Clin Infect Dis . 1998;  26 1086-1088
  PubMedGoogle Scholar
• 56 Pacheco-Ríos A, Avila-Figueroa C, Nobigrot-Kleinman D, Santos J I. Mortality associated with systemic candidiasis in children.  Arch Med Res . 1997;  28 229-232
  PubMedGoogle Scholar
• 57 Stamos J K, Rowley A H. Candidemia in a pediatric population.  Clin Infect Dis . 1995;  20 571-575
  CrossrefPubMedGoogle Scholar
• 58 Nucci M, Colombo A L, Silveira F. et al . Risk factors for death in patients with candidemia.  Infect Control Hosp Epidemiol . 1998;  19 846-850
  PubMedGoogle Scholar
• 59 Weems Jr J J. Candida parapsilosis: epidemiology, pathogenicity, clinical manifestations, antimicrobial susceptibility.  Clin Infect Dis . 1992;  14 756-766
  PubMedGoogle Scholar
• 60 Saxen H, Virtanen M, Carlson P. et al . Neonatal Candida parapsilosis outbreak with a high case fatality rate.  Pediatr Infect Dis . 1995;  14 776-781
  PubMedGoogle Scholar