Treatment of Candida infection in neonates
- Mohan Pammi, MD, PhD
Mohan Pammi, MD, PhD
- Associate Professor
- Baylor College of Medicine
Candida has emerged as an important cause of neonatal infections with significant morbidity and mortality, especially in extremely low and very low birth weight infants, defined as birth weights below 1000 g and 1500 g, respectively [1-5]. Successful management of neonatal candidiasis requires effective treatment of candidal infection with appropriate antifungal therapy and supportive care, and preventive measures to reduce the risk of systemic candidal infections.
The treatment of Candida infections in neonates will be reviewed here. The clinical manifestations, diagnosis, etiology, risk factors, and prevention of neonatal candidal infections are discussed separately. (See "Clinical manifestations and diagnosis of Candida infection in neonates" and "Epidemiology and risk factors for Candida infection in neonates" and "Prevention of Candida infection in neonates".)
In addition, the treatment of breastfeeding mothers with candidal skin infections is also presented elsewhere. (See "Common problems of breastfeeding and weaning", section on 'Candidal infection'.)
Management of Candida infections is dependent upon the clinical presentation of candidal infection. (See "Clinical manifestations and diagnosis of Candida infection in neonates".)
●Candidemia and invasive focal infection – Treatment consists of systemic antifungal agents and the removal of any potentially contaminated medical hardware, such as a central venous catheter or bladder catheter.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Kossoff EH, Buescher ES, Karlowicz MG. Candidemia in a neonatal intensive care unit: trends during fifteen years and clinical features of 111 cases. Pediatr Infect Dis J 1998; 17:504.
- Beck-Sague CM, Azimi P, Fonseca SN, et al. Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study. Pediatr Infect Dis J 1994; 13:1110.
- Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110:285.
- Fridkin SK, Kaufman D, Edwards JR, et al. Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995-2004. Pediatrics 2006; 117:1680.
- Saiman L, Ludington E, Pfaller M, et al. Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group. Pediatr Infect Dis J 2000; 19:319.
- Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503.
- Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:1.
- Manzoni P, Mostert M, Castagnola E. Update on the management of Candida infections in preterm neonates. Arch Dis Child Fetal Neonatal Ed 2015; 100:F454.
- Karlowicz MG, Hashimoto LN, Kelly RE Jr, Buescher ES. Should central venous catheters be removed as soon as candidemia is detected in neonates? Pediatrics 2000; 106:E63.
- Eckstein CW, Kass EJ. Anuria in a newborn secondary to bilateral ureteropelvic fungus balls. J Urol 1982; 127:109.
- Khan MY. Anuria from candida pyelonephritis and obstructing fungal balls. Urology 1983; 21:421.
- Johnson DE, Base JL, Thompson TR, et al. Candida septicemia and right atrial mass secondary to umbilical vein catheterization. Am J Dis Child 1981; 135:275.
- Faix RG, Feick HJ, Frommelt P, Snider AR. Successful medical treatment of Candida parapsilosis endocarditis in a premature infant. Am J Perinatol 1990; 7:272.
- Hundalani S, Pammi M. Invasive fungal infections in newborns and current management strategies. Expert Rev Anti Infect Ther 2013; 11:709.
- Rowen JL, Tate JM. Management of neonatal candidiasis. Neonatal Candidiasis Study Group. Pediatr Infect Dis J 1998; 17:1007.
- American Academy of Pediatrics. Candidiasis. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.275.
- Baley JE, Meyers C, Kliegman RM, et al. Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates. J Pediatr 1990; 116:791.
- Butler KM, Rench MA, Baker CJ. Amphotericin B as a single agent in the treatment of systemic candidiasis in neonates. Pediatr Infect Dis J 1990; 9:51.
- Starke JR, Mason EO Jr, Kramer WG, Kaplan SL. Pharmacokinetics of amphotericin B in infants and children. J Infect Dis 1987; 155:766.
- Hall JE, Cox F, Karlson K, Robertson A. Amphotericin B dosage for disseminated candidiasis in premature infants. J Perinatol 1987; 7:194.
- Bendel CM. Candidiasis. In: Infectious diseases of the fetus and newborn infant, 6th, Remington JS, Klein JO, Wilson CB, Baker CJ (Eds), Elsevier Saunders, Philadelphia 2006. p.1107.
- Le J, Adler-Shohet FC, Nguyen C, Lieberman JM. Nephrotoxicity associated with amphotericin B deoxycholate in neonates. Pediatr Infect Dis J 2009; 28:1061.
- Foker JE, Bass JL, Thompson T, et al. Management of intracardiac fungal masses in premature infants. J Thorac Cardiovasc Surg 1984; 87:244.
- Benjamin DK Jr, Fisher RG, McKinney RE Jr, Benjamin DK. Candidal mycetoma in the neonatal kidney. Pediatrics 1999; 104:1126.
- Berman LH, Stringer DA, St Onge O, et al. An assessment of sonography in the diagnosis and management of neonatal renal candidiasis. Clin Radiol 1989; 40:577.
- Walsh TJ, Seibel NL, Arndt C, et al. Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J 1999; 18:702.
- Scarcella A, Pasquariello MB, Giugliano B, et al. Liposomal amphotericin B treatment for neonatal fungal infections. Pediatr Infect Dis J 1998; 17:146.
- Juster-Reicher A, Flidel-Rimon O, Amitay M, et al. High-dose liposomal amphotericin B in the therapy of systemic candidiasis in neonates. Eur J Clin Microbiol Infect Dis 2003; 22:603.
- Juster-Reicher A, Leibovitz E, Linder N, et al. Liposomal amphotericin B (AmBisome) in the treatment of neonatal candidiasis in very low birth weight infants. Infection 2000; 28:223.
- Weitkamp JH, Poets CF, Sievers R, et al. Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome). Infection 1998; 26:11.
- Ascher SB, Smith PB, Watt K, et al. Antifungal therapy and outcomes in infants with invasive Candida infections. Pediatr Infect Dis J 2012; 31:439.
- Saxén H, Hoppu K, Pohjavuori M. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clin Pharmacol Ther 1993; 54:269.
- Wainer S, Cooper PA, Gouws H, Akierman A. Prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr Infect Dis J 1997; 16:763.
- Driessen M, Ellis JB, Cooper PA, et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J 1996; 15:1107.
- Wenzl TG, Schefels J, Hörnchen H, Skopnik H. Pharmacokinetics of oral fluconazole in premature infants. Eur J Pediatr 1998; 157:661.
- Wade KC, Benjamin DK Jr, Kaufman DA, et al. Fluconazole dosing for the prevention or treatment of invasive candidiasis in young infants. Pediatr Infect Dis J 2009; 28:717.
- Piper L, Smith PB, Hornik CP, et al. Fluconazole loading dose pharmacokinetics and safety in infants. Pediatr Infect Dis J 2011; 30:375.
- Smith PB, Steinbach WJ, Cotten CM, et al. Caspofungin for the treatment of azole resistant candidemia in a premature infant. J Perinatol 2007; 27:127.
- Natarajan G, Lulic-Botica M, Rongkavilit C, et al. Experience with caspofungin in the treatment of persistent fungemia in neonates. J Perinatol 2005; 25:770.
- Odio CM, Araya R, Pinto LE, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J 2004; 23:1093.
- Heresi GP, Gerstmann DR, Reed MD, et al. The pharmacokinetics and safety of micafungin, a novel echinocandin, in premature infants. Pediatr Infect Dis J 2006; 25:1110.
- Manzoni P, Wu C, Tweddle L, Roilides E. Micafungin in premature and non-premature infants: a systematic review of 9 clinical trials. Pediatr Infect Dis J 2014; 33:e291.
- Manzoni P, Benjamin DK Jr, Franco C, et al. Echinocandins for the nursery: an update. Curr Drug Metab 2013; 14:203.
- Sáez-Llorens X, Macias M, Maiya P, et al. Pharmacokinetics and safety of caspofungin in neonates and infants less than 3 months of age. Antimicrob Agents Chemother 2009; 53:869.
- Natarajan G, Lulic-Botica M, Aranda JV. Refractory neonatal candidemia and high-dose micafungin pharmacotherapy. J Perinatol 2009; 29:738.
- Kaufman DA. Challenging issues in neonatal candidiasis. Curr Med Res Opin 2010; 26:1769.
- Vendettuoli V, Tana M, Tirone C, et al. The role of Candida surveillance cultures for identification of a preterm subpopulation at highest risk for invasive fungal infection. Pediatr Infect Dis J 2008; 27:1114.
- Hoppe JE. Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J 1997; 16:885.
- Goins RA, Ascher D, Waecker N, et al. Comparison of fluconazole and nystatin oral suspensions for treatment of oral candidiasis in infants. Pediatr Infect Dis J 2002; 21:1165.
- National Institute for Health and Care Excellence (NICE) Guidance: Postnatal care up to 8 weeks after birth (2006). Available at: https://www.nice.org.uk/guidance/CG37/chapter/1-Recommendations (Accessed on October 27, 2016).
- Darmstadt GL, Dinulos JG, Miller Z. Congenital cutaneous candidiasis: clinical presentation, pathogenesis, and management guidelines. Pediatrics 2000; 105:438.
- Lee BE, Cheung PY, Robinson JL, et al. Comparative study of mortality and morbidity in premature infants (birth weight, < 1,250 g) with candidemia or candidal meningitis. Clin Infect Dis 1998; 27:559.
- Faix RG, Kovarik SM, Shaw TR, Johnson RV. Mucocutaneous and invasive candidiasis among very low birth weight (less than 1,500 grams) infants in intensive care nurseries: a prospective study. Pediatrics 1989; 83:101.
- Adams-Chapman I, Bann CM, Das A, et al. Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. J Pediatr 2013; 163:961.
- Friedman S, Richardson SE, Jacobs SE, O'Brien K. Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome. Pediatr Infect Dis J 2000; 19:499.
- Removal of medical hardware or fungal mass
- Overview systemic antifungal therapy
- Amphotericin B
- - Side effects
- - Duration of therapy
- - Amphotericin B lipid formulations
- Our approach to treating candidemia
- Surveillance cultures
- MUCOCUTANEOUS CANDIDIASIS
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS