Neonatal invasive fungal infections (IFIs) remain an increasing problem associated with high rates of morbidity and mortality, as well as late-onset neurodevelopmental implications. Invasive candidiasis remains the leading neonatal IFI. Candida albicans is the fungal species most often affecting this population, although a changing epidemiologic incidence to non-albicans Candida species is reported in some neonatal intensive care units. Many treatment recommendations are extrapolated from adult populations, emphasizing the need to establish the optimal antifungal agent, dosage, and duration of therapy in neonates. Historically, conventional amphotericin B has been considered an efficient and safe treatment approach for most neonatal IFIs. More recently, lipid formulations of amphotericin B have been studied, used alone or in combination with other antifungal agents such as azoles or echinocandins. The aim of this article is to review the published experience in the use of amphotericin B formulations to treat neonatal IFIs.
This is a preview of subscription content,to check access.
Access this article
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Richardson DK, Gray JE, Gortmaker SL, et al. Declining severity adjusted mortality: evidence of improving neonatal intensive care. Pediatrics. 1998;102:893–9.
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;110:285–91.
Moran C, Benjamin D. Treatment of neonatal fungal infections. Adv Exp Med Biol. 2010;659:129–38.
• Steinbach WJ. Epidemiology of invasive fungal infections in neonates and children. Clin Microbiol Infect. 2010;16(9):1321–1327. This article is one of the most up-to-date expert reviews focusing on the problem of the increasing incidence of invasive fungal infections in children and neonates, their epidemiologic factors and outcome, outlining the differences in diagnosis and therapy between adult and pediatric populations. Further information about the scope and mission of the Multicentre International Pediatric Fungal Network (PFN) is provided.
•• Blyth CC, Chen SC, Slavin MA, et al. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients; Australian Candidemia Study. Pediatrics. 2009;123(5):1360–1368. This prospective study by the Australian Candidemia Study Group analyzed and identified significant differences in the incidence of Candida infections, risk factors, treatment, and clinical outcome of candidemia in three subgroups (neonates, children and adults), emphasizing the need to develop different age-specific preventive and management guidelines.
Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003;37(5):634–43.
Horn DL, Neofytos D, Anaissie EJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2009;48(12):1695–703.
Kaufman D. Fungal infections in the very low birthweight infant. Curr Opin Infect Dis. 2004;17:253–9.
Almirante B, Rodríguez D. Antifungal agents in neonates: issues and recommendations. Paediatr Drugs. 2007;9(5):311–21.
•• Roilides E. Invasive candidiasis in neonates and children. Early Hum Dev. 2011;87:75–76. This up-to-date review includes epidemiologic data, risk factors, clinical spectrum, and diagnostic procedures for invasive candidiasis in children and neonates.
Makhoul IR, Sujov P, Smolkin T, et al. Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics. 2002;109(1):34–9.
Long SS, Stevenson DK. Reducing Candida infections during neonatal intensive care: management choices, infection control, and fluconazole prophylaxis. J Pediatr. 2005;147(2):135–41.
•• Turkova A, Roilides E, Sharland M. Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy—Is there a ‘right’ choice? Curr Opin Infect Dis. 2011;24(2):163–171. This up-to-date review summarizes the data about the differences in efficacy and safety of the amphotericin B formulations, deoxycholate and lipid amphotericin B, in the management of neonatal invasive fungal disease. The authors conclude that deoxycholate amphotericin B remains a safe and effective choice of therapy provided that potassium levels are monitored and renal function is not impaired.
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(5):1680–7.
Benjamin Jr DK, Stoll BJ, Fanaroff AA, et al. National Institute of Child Health and Human Development Neonatal Research Network. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics. 2006;117(1):84–92.
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(4):319–24.
Bayley JE, Kliegman RM, Fanaroff AA. Disseminated fungal infections in very low birth weight infants: clinical manifestations and epidemiology. Pediatrics. 1984;73:144–52.
Faix RG, Kovarik SM, Shaw TR, et al. Mucocutaneous and invasive candidiasis among very low birth weight infants in intensive care nurseries: a prospective study. Pediatrics. 1989;83:101–7.
• Kaufman DA. Challenging issues in neonatal candidiasis. Current Med Res Opin. 2010;26(7):1769–1778. This review begins with the presentation of two cases involving neonates, providing the impetus for a discussion of issues concerning management (combination treatment, screening) and prevention guidelines (antifungal prophylaxis) in neonatal candidiasis. Five well-designed tables provide a summary and overview.
Zaoutis TE, Heydon K, Localio R, et al. Outcomes attributable to neonatal candidiasis. Clin Infect Dis. 2007;44(9):1187–93.
Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292(19):2357–65.
Kaufman DA, Gurka MJ, Hazen KC, et al. Patterns of fungal colonization in preterm infants weighing less than 1000 grams at birth. Pediatr Infect Dis J. 2006;25:733–7.
Saiman L, Ludington E, Dawson JD, et al. Risk factors for Candida species colonization of neonatal intensive care unit patients. Pediatr Infect Dis J. 2001;20:1119–24.
Noyola DE, Fernandez M, Moylett EH, Baker CJ. Ophthalmologic, visceral, and cardiac involvement in neonates with candidemia. Clin Infect Dis. 2001;32:1018–23.
Benjamin Jr DK, Poole C, Steinbach WJ, et al. Neonatal candidemia and end organ damage: a critical appraisal of the literature using meta-analytic techniques. Pediatrics. 2003;112:634–40.
Smith PB, Steinbach WJ, Benjamin Jr DK. Neonatal candidiasis. Infect Dis Clin North Am. 2005;19:603–15.
Faix RG, Chapman RL. Central nervous system candidiasis in the high-risk neonate. Semin Perinatol. 2003;27(5):384–92.
Friedman S, Richardson SE, et al. Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome. Pediatr Infect Dis J. 2000;19(6):499–504.
Fernandez M, Moylett EH, Noyola DE, Baker CJ. Candida meningitis in neonates: a 10-year review. Clin Infect Dis. 2000;31:458–63.
Benjamin Jr DK, Stoll BJ, Gantz MG, et al. Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics. 2010;126:865–73.
• Zaoutis T. Candidemia in children. Curr Med Res Opin. 2010 26(7):1761–1768. This review weighs risk factors, epidemiologic features, and management of pediatric candidemia. Treatment guidelines are subcategorized according to the child’s immunosuppression status (neutropenic vs non-neutropenic). It also provides the updated IDSA guidelines for the removal of intravenous catheters.
Baradkar VP, Mathur M, Kumar S. Neonatal septicaemia in a premature infant due to Candida dubliniensis. Indian J Med Microbiol. 2008;26(4):382–5.
Benjamin Jr DK, Garges H, Steinbach WJ. Candida bloodstream infection in neonates. Semin Perinatol. 2003;27(5):375–83.
Huang Y-C, Lin T-Y, Leu H-S, et al. Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis. Infection. 1999;27:97–102.
Hernández-Castro R, Arroyo-Escalante S, Carrillo-Casas EM, et al. Outbreak of Candida parapsilosis in a neonatal intensive care unit: a health care workers source. Eur J Pediatr. 2010;169:783–7.
Lupetti A, Tavanti A, Davini P, et al. Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit. J Clin Microbiol. 2002;40:2363–9.
van Asbeck EC, Huang YC, Markham AN, et al. Candida parapsilosis fungemia in neonates: genotyping results suggest healthcare workers hands as source, and review of published studies. Mycopathologia. 2007;164:287–93.
Dizbay M, Kalkanci A, Sezer BE, et al. Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit. Braz J Infect Dis. 2008;12:395–9.
•• Montagna MT, Lovero G, De Giglio O, et al. Invasive fungal infections in neonatal intensive care units of Southern Italy: a multicentre regional active surveillance (AURORA project). J Prev Med Hyg. 2010;51(3):125–130. This prospective multicenter surveillance study evaluated the epidemiology of invasive fungal infections among infants admitted to NICUs, revealing the predominance of non-Candida spp. as well as the usefulness of (1,3)-beta-D glucan as a supplemental diagnostic test.
Faix RG. Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection. Pediatr Infect Dis J. 1992;11(2):88–93.
Levy I, Rubin LG, Vasishtha S, et al. Emergence of Candida parapsilosis as the predominant species causing candidemia in children. Clin Infect Dis. 1998;26(5):1086–8.
Benjamin Jr DK, Ross K, McKinney Jr RE, et al. When to suspect fungal infection in neonates: a clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia. Pediatrics. 2000;106(4):712–8.
Roilides E, Farmaki E, Evdoridou J, et al. Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates. Eur J Clin Microbiol Infect Dis. 2004;23(10):745–50.
Fairchild KD, Tomkoria S. Neonatal Candida glabrata sepsis: clinical and laboratory features compared with other Candida species. Pediatr Infect Dis J. 2002;21(1):39–43.
Marodi L, Johnston Jr RB. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr. 2007;19:693–7.
Zaoutis TE, Argon J, Chu J, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41:1232–9.
Farmaki E, Evdoridou J, Pouliou T, et al. Fungal colonization in the neonatal intensive care unit: risk factors, drug susceptibility, and association with invasive fungal infections. Am J Perinatol. 2007;24:127–35.
Clerihew L, Lamagni TL, Brocklehurst P, McGuire W. Invasive fungal infection in very low birthweight infants: national prospective surveillance study. Arch Dis Child Fetal Neonatal Ed. 2006;91(3):188–92.
Waggoner-Fountain LA, Whit Walker M, Hollis RJ, et al. Vertical and horizontal transmission of unique Candida species to premature newborns. Clin Infect Dis. 1996;22:803–8.
Reef SE, Lasker BA, Butcher DA, et al. Non perinatal nosocomial transmission of Candida albicans in a neonatal intensive care unit: prospective study. J Clin Microbiol. 1998;36:1255–9.
Benjamin DKJ, DeLong ER, Steinbach WJ, et al. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics. 2003;112:543–7.
• Robinson JL, Davies HD, Barton M, et al. Characteristics and outcome of infants with candiduria in neonatal intensive care—A Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study. BMC Infect Dis. 2009;23:183–193. This is a prospective, multicenter Canadian study evaluating the characteristics, treatment, and outcome of candidal urinary tract infection in infants in the NICU.
Zaoutis TE, Coffin SE, Chu JH, et al. Risk factors for mortality in children with candidemia. Pediatr Infect Dis J. 2005;24:736–9.
Pasqualotto AC, de Moraes AB, Zanini RR, et al. Analysis of independent risk factors for death among pediatric patients with candidemia and a central venous catheter in place. Infect Control Hosp Epidemiol. 2007;28:799–804.
Weese-Mayer DE, Fondriest DW, Brouillette RT, et al. Risk factors associated with candidemia in the neonatal intensive care unit: a case control study. Pediatr Infect Dis J. 1987;6:190–6.
Cotton CM, McDonald S, Stoll B, et al. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics. 2006;118:717–22.
Benjamin Jr DK, Ross K, McKinney Jr RE. When to suspect fungal infection in neonates: a clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia. Pediatrics. 2000;106:712–8.
Guillet R, Stoll BJ, Cotten CM, Gantz M, McDonald S, Poole WK, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117:137–42.
Botas CM, Kurlat I, Young SM, et al. Disseminated candidal infections and intravenous hydrocortisone in preterm infants. Pediatrics. 1995;95:883–7.
Pera A, Byun A, Gribar S, et al. Dexamethasone therapy and Candida sepsis in neonates less than 1250 grams. J Perinatol. 2002;22:204–8.
Campbell JR, Zaccaria E, Baker CJ. Systemic candidiasis in extremely low birth weight infants receiving topical petrolatum ointment for skin care: a case–control study. Pediatrics. 2000;105:1041–5.
Shetty SS, Harrison LH, Hajjeh RA, et al. Determining risk factors for candidemia among newborn infants from population-based surveillance: Baltimore, Maryland, 1998–2000. Pediatr Infect Dis J. 2005;24:601–4.
Zaoutis TE, Roilides E, Chiou CC, et al. Zygomycosis in children: a systematic review and analysis of reported cases. Pediatr Infect Dis J. 2007;26:723–7.
Roilides E, Zaoutis TE, Katragkou A, Benjamin Jr DK, Walsh TJ. Zygomycosis in neonates: an uncommon but life-threatening infection. Am J Perinatol. 2009;26(8):565–73.
Stock C, Veyrier M, Magnin-Verschelde S, et al. Primary cutaneous aspergillosis complicated with invasive aspergillosis in an extremely preterm infant: case report and literature review. Arch Pediatr. 2010;17(10):1455–9.
Erişir-Oygucu S, Akcan AB, Oygür N. Primary cutaneous aspergillosis in an extremely low birth weight preterm. Turk J Pediatr. 2009;51(6):621–3.
Galimberti R, Kowalczuk A, Hidalgo Parra I, Gonzalez Ramos M, Flores V. Cutaneous aspergillosis: a report of six cases. Br J Dermatol. 1998;139:522–6.
Woodruff CA, Hebert AA. Neonatal primary cutaneous aspergillosis: case report and review of the literature. Pediatr Dermatol. 2002;19:439–44.
Groll AH, Jaeger G, Allendorf A, Herrmann G, Schloesser R, von Loewenich V. Invasive pulmonary aspergillosis in a critically ill neonate: case report and review of invasive aspergillosis during the first 3 months of life. Clin Infect Dis. 1998;27:437–52.
Singer S, Singer D, Ruchel R, Mergeryan H, Schmidt U, Harms K. Outbreak of systemic aspergillosis in a neonatal intensive care unit. Mycoses. 1998;41:223–7.
Schwartz DA, Jacquette M, Chawla HS. Disseminated neonatal aspergillosis: report of a fatal case and analysis of risk factors. Pediatr Infect Dis J. 1998;7:349–53.
Fuchs H, von Baum H, Meth M, et al. CNS-manifestation of aspergillosis in an extremely low-birth-weight infant. Eur J Pediatr. 2006;165(7):476–80.
Herron MD, Vanderhooft SL, Byington C, King JD. Aspergillosis in a 24-week newborn: a case report. J Perinatol. 2003;23(3):256–9.
Powell DA, Hayes J, Durell DE, Miller M, Marcon MJ. Malassezia furfur skin colonization of infants hospitalized in intensive care units. J Pediatr. 1987;111:217–20.
Long JG, Keyserling HL. Catheter-related infection in infants due to an unusual lipophilic yeast Malassezia furfur. Pediatrics. 1985;76:896–900.
Koseki S, Takahashi S. Serial observation on the colonization of Pityrosporum orbiculare (ovale) on the facial skin surface of newborn infants. Jpn J Med Mycol. 1988;29:209–15.
Rapelanoro R, Mortureux P, Couprie B, Maleville J, Taıeb A. Neonatal Malassezia furfur pustulosis. Arch Dermatol. 1996;132:190–3.
Patrizi A, Bardazzi F, Neri I, Varotti E. La pustolosi neonatale da Malassezia furfur. Giorn Int Derm Ped. 1996;8:3.
Rowen JL, Tate JM. Management of neonatal candidiasis. Neonatal Candidiasis Study Group. Pediatr Infect Dis J. 1998;17:1007–11.
Baley JE, Meyers C, Kliegman RM, Jacobs MR, Blumer JL. Pharmacokinetics, outcome of treatment, and toxic effects of Amphotericin B and 5-fluorocytosine in neonates. J Pediatr. 1990;116:791–7.
Fanos V, Cataldi L. Amphotericin B-induced nephrotoxicity: a review. J Chemother. 2000;12:463–70.
Zaoutis TH, Walsh T. Antifungal therapy for neonatal candidiasis. Curr Opin Infect Dis. 2007;20:592–7.
Carter JE, Laurini JA, Evans TN, Estrada B. Neonatal Candida parapsilosis meningitis and empyema related to epidural migration of a central venous catheter. Clin Neurol Neurosurg. 2008;110(6):614–8.
Kingo AR, Smyth JA, Waisman D. Lack of evidence of amphotericin B toxicity in very low birth weight infants treated for systemic candidiasis. Pediatr Inf Dis J. 1997;16:1002–3.
Groll AH, Piscitelli SC, Walsh TJ. Antifungal pharmacodynamics: concentration-effect relationships in vitro and in vivo. Pharmacotherapy. 2001;21:133–48.
Ellis M, Amphotericin B. preparations: a maximum tolerated dose in severe invasive fungal infections? Transpl Infect Dis. 2000;2:51–61.
Jeon GW, Koo SH, Lee JH, et al. A comparison of Am Bisome to amphotericin B for treatment of systemic candidiasis in very low birth weight infants. Yonsei Med J. 2007;48(4):619–26.
Holler B, Omar SA, Maged DF, Patterson JM. Effects of fluid and electrolyte management on Amphotericin B-induced nephrotoxicity among extremely low birth weight infants. Pediatrics. 2004;113:608–16.
•• Turcu R, Patterson MJ, Omar S. Influence of sodium intake on Amphotericin B-induced nephrotoxicity among extremely premature infants. Pediatr Nephrol. 2009;24:497–505. The aim of this study was to evaluate the effect of high sodium intake (> 4 mEq/kg per day) on the incidence of AMB-induced nephrotoxicity among extremely premature infants with birth weight <1250 g. According to the authors’ observations, high sodium intake was associated with a reduced incidence of AMB-induced nephrotoxicity.
Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemother. 2002;49(1):37–41.
Bayley 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;116:791–7.
Starke JR, Mason Jr EO, Kramer WG, et al. Pharmacokinetics of amphotericin B in infants and children. J Infect Dis. 1995;155:766–74.
Kingo AR, Smyth JA, Waisman D. Lack of evidence of amphotericin B toxicity in very low birth weight infants treated for systemic candidiasis. Pediatr Infect Dis J. 1997;16:1002–3.
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;9:51–6.
Linder N, Klinger G, Shalit I, et al. Treatment of candidaemia in premature infants: comparison of three amphotericin B preparations. J Antimicrob Chemother. 2003;52:663–7.
Rowen JL, Tate JM. For the neonatal candidasis study group. Management of neonatal candidiasis. Pediatr Infect Dis J. 1998;17:1007–11.
Benjamin Jr DK, Fisher RG, McKinney Jr RE, Benjamin DK. Candidal mycetoma in the neonatal kidney. Pediatrics. 1999;104:1126–9.
Berman LH, Stringer DA, St. Onge AD, et al. An assessment of sonography in the diagnosis and management of neonatal renal candidiasis. Clin Radiol. 1989;40:577–81.
Stein RS, Alexander JA. Sodium protects against nephrotoxicity in patients receiving amphotericin B. Am J Med Sci. 1989;298:299–304.
Heideman H. Prevention of amphotericin B nephrotoxicity: the effect of salt loading and flucytosine. Mycoses. 1988;31 Suppl 2:39–44.
Gardner ML, Godley PJ, Wasan SM. Sodium loading treatment for amphotericin B-induced nephrotoxicity. DICP Ann Pharmacother. 1990;24:940–46.
Sabra R, Branch RA. Mechanisms of amphotericin B induced decrease in glomerular filtration rate in rats. Antimicrob Agents Chemother. 1991;35:2509–14.
Llanos A, Cieza J, Bernado J, et al. Effect of salt supplementation on amphotericin B nephrotoxicity. Kidney Int. 1991;40:302–8.
Adler-Moore J, Proffitt RT. Am Bisome: liposomal formulation, structure, mechanism of action and preclinical experience. J Antimicrob Chemother. 2002;49:21–30.
Würthwein G, Groll AH, Hempel G, et al. Population Pharmacokinetics of Amphotericin B Lipid Complex in Neonates. Antimicrob Agents Chemother. 2005;49:5092–8.
Janknegt R, de Marie S, Bakker-Woudenberg IA, Crommelin DJ. Liposomal and lipid formulations of amphotericin B. Clin Pharmacokinet. 1992;23:279–91.
Walsh TJ, Hiemenz JW, Seibel NL, Perfect JR, Horwith G, Lee L, et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis. 1998;26:1383–96.
Walsh TJ, Seibel NL, Arndt C, Harris RE, Dinubile MJ, Reboli A, et al. Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J. 1999;18:702–8.
Lackner H, Schwinger W, Urban C, et al. Liposomal amphotericin-B (AmBisome) for treatment of disseminated fungal infections in two infants of very low birth weight. Pediatrics. 1992;89:1259–61.
Scarcella A, Pasquariello M, Giuliano B, Vendemmia M, De Lucia A. Liposomal amphotericin B treatment for neonatal fungal infections. Pediatr Infect Dis J. 1998;17:146–8.
Bekersky I, Fielding RM, Dressler DE, et al. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother. 2002;46(3):828–33.
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;22:603–7.
Weitkamp JH, Poets CF, Sievers R, Musswessels E, Groneck P, Thomas P, et al. Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome®). Infection. 1998;26:11–5.
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;28:223–6.
Cetin H, Yalaz M, Akisu M, et al. The efficacy of two different lipid-based amphotericin B in neonatal Candida septicemia. Pediatr Int. 2005;47(6):676–80.
• Le J, Adler-Shohet FC, Nguyen C, Lieberman JM. Nephrotoxicity associated with amphotericin B deoxycholate in neonates. Pediatr Infect Dis J. 2009;28:1061–1063. This retrospective study analyzed the prevalence of nephrotoxicity in neonates receiving DAMB. Demographic, therapeutic, microbiologic, and laboratory data revealed that DAMB administration in this study population caused a transient impairment of renal function that should be closely monitored.
Carrasco Sánchez P, Castillo Montero ML, Bejarano Palma A, et al. Neonatal candidiasis and liposomal amphotericin B treatment: our experience. An Esp Pediatr. 1999;51(3):273–80.
•• Auron A, Auron-Gomez M, Raina R, Viswanathan S, Mhanna MJ. Effect of amphotericin B lipid complex (ABLC) in very low birth weight infants. Pediatr Nephrol. 2009;24:295–299. This retrospective case control study evaluated the possible nephrotoxic effect of amphotericin B lipid complex in VLBW infants by measuring serum creatinine, blood urea nitrogen, and sodium and potassium levels during treatment lasting at least 2 weeks. No substantial changes in these laboratory data were observed.
Adler-Shohet F, Waskin H, Lieberman JM. Amphotericin B lipid complex for neonatal invasive candidiasis. Arch Dis Child Fetal Neonatal Ed. 2001;84:131–3.
Queiroz-Telles F, Berezin E, Leverger G, et al. Micafungin invasive candidiasis study group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008;27(9):820–6.
López Sastre JB, Coto Cotallo GD, Fernández Colomer B. Grupo de Hospitales Castrillo. Neonatal invasive candidiasis: a prospective multicenter study of 118 cases. Am J Perinatol. 2003;20:153–63.
Hope WW, Warn PA, Sharp A, et al. Optimization of the dosage of flucytosine in combination with amphotericin B for disseminated candidiasis: a pharmacodynamic rationale for reduced dosing. Antimicrob Agents Chemother. 2007;51:3760–2.
Karatza AA, Dimitriou G, Marangos M, et al. Successful resolution of cardiac mycetomas by combined liposomal amphotericin B with fluconazole treatment in premature neonates. Eur J Pediatr. 2008;167:1021–3.
Levy I, Shalit I, Birk E, et al. Candida endocarditis in neonates: report of five cases and review of the literature. Mycoses. 2006;49:43–8.
Stocker M, Caduff JH, Spalinger J, Berger TM. Successful treatment of bilateral renal fungal balls with liposomal amphotericin B and fluconazole in an extremely low birth weight infant. Eur J Pediatr. 2000;159(9):676–8.
Wald M, Lawrenz K, Kretzer V, et al. A very low birth weight infant with Candida nephritis with fungus balls. Full recovery after pyelotomy and antifungal combination therapy. Eur J Pediatr. 2003;162(9):642–3.
Turan O, Ergenekon E, Hirfanoğlu IM, et al. Combination antifungal therapy with voriconazole for persistent candidemia in very low birth weight neonates. Turk J Pediatr. 2011;53:19–26.
Odio CM, Araya R, Pinto LE, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J. 2004;23:1093–7.
Natarajan G, Lulic-Botica M, Rongkavilit C, et al. Experience with caspofungin in the treatment of persistent fungemia in neonates. J Perinatol. 2005;25:770–7.
Haase R, Kreft B, Foell J, et al. Successful treatment of Candida albicans septicemia in a preterm infant with severe congenital ichthyosis (Harlequin baby). Pediatr Dermatol. 2009;26:575–8.
Belet N, Ciftçi E, Ince E, et al. Caspofungin treatment in two infants with persistent fungaemia due to Candida lipolytica. Scand J Infect Dis. 2006;38:559–62.
• Natarajan G, Lulic-Botica M, Aranda JV. Refractory neonatal candidemia and high-dose micafungin pharmacotherapy. J Perinatol. 2009;29:738–743. This study compared the clinical features and prognosis of two subgroups of preterm neonates with candidemia: good responders to conventional antifungals versus those with refractory candidemia. It also evaluated the clinical efficacy of high-dose micafungin pharmacotherapy in refractory neonatal candidemia. Refractory candidemia has been associated with poor outcome despite high-dose micafungin pharmacotherapy in combination with conventional antifungals.
Varisco BM, Benner KW, Prabhakaran P. Neonatal peritoneal candidiasis successfully treated with anidulafungin add-on therapy. Ann Pharmacother. 2009;43:1907–10.
Groll AH, Jaeger G, Allendorf A, et al. Invasive pulmonary aspergillosis in a critically ill neonate: Case report and review of invasive aspergillosis during the first three months of life. Clin Infect Dis. 1998;27:437–52.
Herron MD, Vanderhooft SL, Byington C, et al. Aspergillosis in a 24-week newborn: a case report. J Perinatol. 2003;23(3):256–9.
Burgos A, Zaoutis TE, Dvorak CC, et al. Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics. 2008;121(5):1286–94.
Fuchs H, von Baum H, Meth M, et al. CNS-manifestation of aspergillosis in an extremely low-birth-weight infant. Eur J Pediatr. 2006;165(7):476–80.
•• Pappas PG, Kaufmann 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(5):503–535. These updated guidelines have replaced the previous guidelines of 2004 concerning the therapeutic management of candidiasis. These guidelines include therapeutic recommendations as well as prospective data on the prevention of neonatal candidiasis.
Conflicts of Interest: Z-D. Pana: none; M. Ioannidou: none; E. Roilides: Payment for speaking and development of educational presentations from Gilead, Cephalon, Pfizer, Schering, Merck, and Astellas.
About this article
Cite this article
Pana, ZD., Ioannidou, M. & Roilides, E. Is There Still a Place for Conventional Amphotericin B in the Treatment of Neonatal Fungal Infections?. Curr Fungal Infect Rep 6, 81–94 (2012). https://doi.org/10.1007/s12281-011-0074-6