Therapy and prophylaxis in newborn patients

Authors

  • Paolo Manzoni Presidente, Academy of pediatric and neonatal fungal infections. SC Neonatologia e TIN, Ospedale S. Anna, Torino

DOI:

https://doi.org/10.7175/rhc.v4i1S.858

Keywords:

Fungal infections, Prophylaxis, Fluconazole, Micafungin, Neonatal use, Probiotics

Abstract

Fluconazole is the most used drug for antifungal prophylaxis in neonatal population. Despite its effectiveness, sometimes fungal infections occur also in newborn patients undergoing fluconazole prophylaxis: this is mainly due both to biofilm formation in patients who carry a central venous catheter (CVC), a common condi­tion among premature babies, and to the occurrence of an infection by a Candida subspecies with intrinsic resistance to fluconazole (e.g.: C. glabrata and C. krusei). A number of antifungal agents are approved for pediatric use, and their limits and advantages are analyzed in this article, but only micafungin is authorized for use in neonatal patients. Further trials are required in order to assess whether additional drugs could have a similar indication for neonatal use. A big issue is the correct identification of the most effective dosing regimen, because the drug pharmacokinetics is peculiar and somewhat unpredictable in newborn patients. In addition to fluconazole prophylaxis, other measures could be taken to prevent fungal infections in at-risk neonates, such as increasing hygienic measures, encouraging breast-feeding, removing CVCs, using probiotics, and decreasing or avoiding the use of drugs promoting the development of systemic mycoses.

References

Borghesi A, Stronati M. Strategies for the prevention of hospital-acquired infections in the neonatal intensive care unit. J Hosp Infect 2008; 68: 293-300; http://dx.doi.org/10.1016/j.jhin.2008.01.011

Karlowicz MG, Hashimoto LN, Kelly RE Jr, et al. Should central venous catheters be removed as soon as candidemia is detected in neonates? Pediatrics 2000; 106: E63; http://dx.doi.org/10.1542/peds.106.5.e63

Rowen JL, Tate JM. Management of neonatal candidiasis. Neonatal Candidiasis Study Group. Pediatr Infect Dis J 1998; 17: 1007-11; http://dx.doi.org/10.1097/00006454-199811000-00008

Wade KC, Wu D, Kaufman DA, et al; National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother 2008; 52: 4043-9; http://dx.doi.org/10.1128/AAC.00569-08

Watt K, Benjamin DK Jr, Cohen-Wolkowiez M. Pharmacokinetics of antifungal agents in children. Early Hum Dev 2011; 87 Suppl 1: S61-S65; http://dx.doi.org/10.1016/j.earlhumdev.2011.01.014

Hong Y, Shaw PJ, Nath CE, et al. Population pharmacokinetics of liposomal amphotericin B in pediatric patients with malignant diseases. Antimicrob Agents Chemother 2006; 50: 935-42; http://dx.doi.org/10.1128/AAC.50.3.935-942.2006

Kotwani RN, Gokhale PC, Bodhe PV, et al. A comparative study of plasma concentrations of liposomal amphotericin B (L-AMP-LRC-1) in adults, children and neonates. Int J Pharm 2002; 238: 11-5; http://dx.doi.org/10.1016/S0378-5173(02)00066-2

Mehta P, Vinks A, Filipovich A, et al. High-dose weekly AmBisome antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study. Biol Blood Marrow Transplant 2006; 12: 235-40; http://dx.doi.org/10.1016/j.bbmt.2005.10.010

Groll AH, Stergiopoulou T, Roilides E, et al. Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs 2005; 14: 489-509; http://dx.doi.org/10.1517/13543784.14.4.489

Kurtz MB, Douglas CM. Lipopeptide inhibitors of fungal glucan synthase. Med Vet Mycol 1997; 35: 79-86; http://dx.doi.org/10.1080/02681219780000961

Ghannoum MA, Rice LB. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 1999; 12: 501-17

Walsh TJ, Adamson PC, Seibel NL, et al. Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents. Antimicrob Agents Chemother 2005; 49: 4536-45; http://dx.doi.org/10.1128/AAC.49.11.4536-4545.2005

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: 869-75; http://dx.doi.org/10.1128/AAC.00868-08

Neely M, Jafri HS, Seibel N, et al. Pharmacokinetics and safety of caspofungin in older infants and toddlers. Antimicrob Agents Chemother 2009; 53: 1450-6; http://dx.doi.org/10.1128/AAC.01027-08

Castagnola E, Cappelli B, Faraci M, et al. Maintenance of therapeutic concentrations of caspofungin after temporary treatment interruption (48 hours) in a child with invasive aspergillosis. Antimicrob Agents Chemother 2007; 51: 3775; http://dx.doi.org/10.1128/AAC.00890-07

Benjamin DK Jr, Smith PB, Arrieta A, et al. Safety and pharmacokinetics of repeat-dose micafungin in young infants. Clin Pharmacol Ther 2010; 87: 93-9; http://dx.doi.org/10.1038/clpt.2009.200

Mehta PA, Vinks AA, Filipovich A, et al. Alternate-day micafungin antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study. Biol Blood Marrow Transplant 2010; 16: 1458-62; http://dx.doi.org/10.1016/j.bbmt.2010.05.002; http://dx.doi.org/10.1016/j.bbmt.2009.12.319

Tabata K, Katashima M, Kawamura A, et al. Linear pharmacokinetics of micafungin and its active metabolites in Japanese pediatric patients with fungal infections. Biol Pharm Bull 2006; 29: 1706-11; http://dx.doi.org/10.1248/bpb.29.1706

Hope WW, Smith PB, Arrieta A, et al. Population pharmacokinetics of micafungin in neonates and young infants. Antimicrob Agents Chemother 2010; 54: 2633-7; http://dx.doi.org/10.1128/AAC.01679-09

Cohen NR, Tatituri RV, Rivera A, et al. Innate recognition of cell wall β-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe 2011; 10: 437-50; http://dx.doi.org/10.1016/j.chom.2011.09.011

Benjamin DK Jr, Driscoll T, Seibel NL, et al. Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections. Antimicrob Agents Chemother 2006; 50: 632-8; http://dx.doi.org/10.1128/AAC.50.2.632-638.2006

Pfaller MA, Boyken L, Hollis RJ, et al. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J Clin Microbiol 2008; 46: 150-6; http://dx.doi.org/10.1128/JCM.01901-07; http://dx.doi.org/10.1128/JCM.01107-08

Odio CM, Araya R, Pinto LE, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J 2004; 23: 1093-7

Mrówczyński W, Wojtalik M. Caspofungin for Candida endocarditis. Pediatr Infect Dis J 2004; 23: 376; http://dx.doi.org/10.1097/00006454-200404000-00029

Castagnola E, Franceschi A, Natalizia AR, et al. Combined antifungal therapy for persistent central venous catheter-related candidemia in extremely low birth weight neonates. J Chemother 2009; 21: 234-5

Manzoni P, Esposito S, Gallo E, et al. Switch therapy in full-term neonates with presumed or proven bacterial infection. J Chemother 2009; 21: 68-73

Natale F, Castronovo A, Regoli D, et al. Successful treatment with caspofungin of refractory Candida krusei candidemia in a very low birth weight preterm infant. Pediatr Infect Dis J 2009; 28: 452; http://dx.doi.org/10.1097/INF.0b013e31819d1cf1

Mondello I, Rossi A, Serrao G, et al. Preterm neonates in NICU treated with Caspofungin: our experience. Early Hum Dev 2009; 85: S93-S98

Wertz KK, Pretzlaff RK. Caspofungin in a pediatric patient with persistent candidemia. Pediatr Crit Care Med 2004; 5: 181-3; http://dx.doi.org/10.1097/01.PCC.0000113264.00053.AF

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; http://dx.doi.org/10.1038/sj.jp.7211380

Pappas PG, Rotstein CM, Betts RF, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 2007; 45: 883-93; http://dx.doi.org/10.1086/520980

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: 820-6; http://dx.doi.org/10.1097/INF.0b013e31817275e6

Cateau E, Berjeaud JM, Imbert C. Possible role of azole and echinocandin lock solutions in the control of Candida biofilms associated with silicone. Int J Antimicrob Agents 2011; 37: 380-4; http://dx.doi.org/10.1016/j.ijantimicag.2010.12.016

Cateau E, Rodier MH, Imbert C. In vitro efficacies of caspofungin or micafungin catheter lock solutions on Candida albicans biofilm growth. J Antimicrob Chemother 2008; 62: 153-5; http://dx.doi.org/10.1093/jac/dkn160

Manzoni P, Benjamin DK, Hope W, et al. The management of Candida infections in preterm neonates and the role of micafungin. J Matern Fetal Neonatal Med 2011; 24: 24-7; http://dx.doi.org/10.3109/14767058.2011.604929

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: 1110-5; http://dx.doi.org/10.1097/01.inf.0000245103.07614.e1

Smith PB, Walsh TJ, Hope W, et al. Pharmacokinetics of an elevated dosage of micafungin in premature neonates. Pediatr Infect Dis J 2009; 28: 412-5; http://dx.doi.org/10.1097/INF.0b013e3181910e2d

Wynn JL, Tan S, Gantz MG, et al. Outcomes following candiduria in extremely low birth weight infants. Clin Infect Dis 2012; 54: 331-9; http://dx.doi.org/10.1093/cid/cir800

Manzoni P, Mostert M, Leonessa ML, et al. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clin Infect Dis 2006; 42: 1735-42; http://dx.doi.org/10.1086/504324

Romeo MG, Romeo DM, Trovato L, et al. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. J Perinatol 2011; 31: 63-9; http://dx.doi.org/10.1038/jp.2010.57

Manzoni P, Rinaldi M, Cattani S, et al; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, Italian Society of Neonatology. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009; 302: 1421-8; http://dx.doi.org/10.1001/jama.2009.1403

Kaufman D, Boyle R, Hazen KC, et al. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med 2001; 345: 1660-6; http://dx.doi.org/10.1056/NEJMoa010494

Manzoni P, Stolfi I, Pugni L, et al; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections; Italian Society of Neonatology. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med 2007; 356: 2483-95; http://dx.doi.org/10.1056/NEJMoa065733

Kaufman DA, Manzoni P. Strategies to prevent invasive candidal infection in extremely preterm infants. Clin Perinatol 2010; 37: 611-28; http://dx.doi.org/10.1016/j.clp.2010.06.003

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2013-07-10

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