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• W2065462337 abstract "Invasive fungal infections represent the third-leading cause of late-onset sepsis in very-low-birth-weight infants (VLBWI) and have a high rate of infection-associated mortality. The infants at high risk for fungal sepsis are VLBWI with presence of additional risk factors that contribute to increased colonization and concentration of fungal organisms. Colonization with Candida spp. in neonates is secondary to either maternal vertical transmission or nosocomial acquisition in the nursery. Multiple sites may become colonized and a direct correlation between fungal colonization and subsequent progression to invasive candidemia was determined. Randomized, single and multiple-center, placebo-controlled trials found intravenous fluconazole prophylaxis to be effective in decreasing fungal colonization and sepsis for at-risk preterm infants <1500 g birth weight. The prophylactic use of fluconazole was found to be safe with no significant development of fungal resistance. Fluconazole prophylaxis administered to preterm neonates with birth weight <1000 g and/or 27 weeks’ gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality. Invasive fungal infections represent the third-leading cause of late-onset sepsis in very-low-birth-weight infants (VLBWI) and have a high rate of infection-associated mortality. The infants at high risk for fungal sepsis are VLBWI with presence of additional risk factors that contribute to increased colonization and concentration of fungal organisms. Colonization with Candida spp. in neonates is secondary to either maternal vertical transmission or nosocomial acquisition in the nursery. Multiple sites may become colonized and a direct correlation between fungal colonization and subsequent progression to invasive candidemia was determined. Randomized, single and multiple-center, placebo-controlled trials found intravenous fluconazole prophylaxis to be effective in decreasing fungal colonization and sepsis for at-risk preterm infants <1500 g birth weight. The prophylactic use of fluconazole was found to be safe with no significant development of fungal resistance. Fluconazole prophylaxis administered to preterm neonates with birth weight <1000 g and/or 27 weeks’ gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality. 1. IntroductionInvasive fungal infections (IFI) represent a leading cause of sepsis in very-low-birth-weight (VLBW) infants and result in high rates of morbidity and mortality.1Stoll B.J. Hansen N. Fanaroff A.A. et al.Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network.Pediatrics. 2002; 110: 285-291Crossref PubMed Scopus (1724) Google Scholar, 2Makhoul I.R. Sujov P. Smolkin T. Lusky A. Reichman B. Epidemiological, clinical and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survery.Pediatrics. 2002; 109: 34-39Crossref PubMed Scopus (223) Google Scholar, 3Levy I. Rubin L.G. Vasishta S. Emergence of Candida parapsilosis as the predominant species causing candidemia in children.Clin Infect Dis. 1998; 26: 1086-1088Crossref PubMed Scopus (191) Google Scholar, 4Kossoff 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 J. 1998; 17: 504-508Crossref PubMed Scopus (261) Google Scholar Among many risk factors responsible for development of IFI, previous mucosal and skin colonization are of primary importance. Colonization with Candida in neonates is secondary to either maternal transmission or to nosocomial acquisition in the neonatal intensive care unit (NICU).5Baley J.E. Kliegman R.M. Boxerbaum B. et al.Fungal colonization in the very low birth weight infant.Pediatrics. 1986; 78: 225-232PubMed Google Scholar, 6Bendel C.M. Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis.Semin Perinatol. 2007; 27: 357-364Abstract Full Text Full Text PDF Scopus (70) Google Scholar, 7Chapman R.L. Prevention and treatment of Candida infections in neonates.Semin Perinatol. 2007; 31: 39-46Abstract Full Text Full Text PDF PubMed Scopus (42) Google ScholarBecause current therapies for systemic fungal diseases are not universally successful and morbidity remains high, efforts may be better focused on preventing invasive disease by interrupting the process of colonization and subsequently preventing the development of serious fungal infections. In-depth knowledge of the Candida spp. colonization patterns, timing, anatomic sites involved and specific species distribution is important for both the clinician and scientist. The preventive strategy using fluconazole for the prevention of colonization and systemic infections with Candida spp. in both extremely low-birth-weight (ELBW) and VLBW infants was found to be effective in several studies.8Kaufman D. Strategies for prevention of neonatal invasive candidiasis.Semin Perinatol. 2003; 27: 414-424Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 9Kaufman D.A. Fluconazole prophylaxis: can we eliminate invasive Candida infections in the neonatal ICU?.Curr Opin Pediatr. 2008; 20: 332-340Crossref PubMed Scopus (28) Google Scholar, 10Kaufman D.A. Challenging issues in neonatal candidiasis.Curr Med Res Opin. 2010; 26: 1769-1778Crossref PubMed Scopus (48) Google Scholar, 11Kaufman D. Fairchild K.D. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants.Clin Microbiol Rev. 2004; 17: 638-680Crossref PubMed Scopus (316) Google ScholarWe present in this review an up-to-date summary of the information accumulated during recent years regarding the epidemiology and risk factors for IFI in the neonatal population, concentrating on the presently available strategies for decreasing fungal colonization, IFI and mortality in at-risk preterm infants.2. Neonatal Invasive Fungal InfectionsInvasive fungal infections (IFI) represent the third-leading (12.2%) cause of late-onset sepsis in VLBW (birth weight <1500 g) infants. Their estimated incidence is 1.6–3% in VLBW infants and up to 15–20% in ELBW neonates with a Candida-attributable mortality of 25–55% and presence of associated neurodevelopmental impairment at 18 years old in 57% of survivors.1Stoll B.J. Hansen N. Fanaroff A.A. et al.Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network.Pediatrics. 2002; 110: 285-291Crossref PubMed Scopus (1724) Google Scholar, 2Makhoul I.R. Sujov P. Smolkin T. Lusky A. Reichman B. Epidemiological, clinical and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survery.Pediatrics. 2002; 109: 34-39Crossref PubMed Scopus (223) Google Scholar, 11Kaufman D. Fairchild K.D. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants.Clin Microbiol Rev. 2004; 17: 638-680Crossref PubMed Scopus (316) Google Scholar, 12Benjamin D.K. Stoll B.J. Fanaroff A.A. et al.Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months.Pediatrics. 2006; 117: 84-92Crossref PubMed Scopus (498) Google Scholar The incidence of IFI varies considerably between reporting NICUs, being related, mainly, to the number of ELBW infants <24–25 weeks of age taken care at a specific NICU.1Stoll B.J. Hansen N. Fanaroff A.A. et al.Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network.Pediatrics. 2002; 110: 285-291Crossref PubMed Scopus (1724) Google Scholar, 2Makhoul I.R. Sujov P. Smolkin T. Lusky A. Reichman B. Epidemiological, clinical and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survery.Pediatrics. 2002; 109: 34-39Crossref PubMed Scopus (223) Google ScholarCandida albicans is the most prevalent fungal pathogen in neonatal disease, but the incidence of infection caused by other Candida species, particularly Candida parapsilosis and Candida glabrata has also increased dramatically during the past two decades.3Levy I. Rubin L.G. Vasishta S. Emergence of Candida parapsilosis as the predominant species causing candidemia in children.Clin Infect Dis. 1998; 26: 1086-1088Crossref PubMed Scopus (191) Google Scholar, 4Kossoff 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 J. 1998; 17: 504-508Crossref PubMed Scopus (261) Google Scholar, 13Benjamin D.K. Ross K. McKinney Jr., R.E. 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; 105: 712-718Crossref Scopus (172) Google Scholar, 14Clerihew L. Lamagni T.L. Brocklehurst P. et al.Candida parapsilosis infection in very low birth weight infants.Arch Dis Child Fetal Neonatal Ed. 2007; 92: F127-F129Crossref PubMed Scopus (57) Google Scholar Furthermore, C. glabrata and Candida krusei, another increasingly recovered representative of Candida spp., harbor innate resistance to the azole class of antifungal agents and may represent therapeutic challenges in IFI.The highest incidence of IFI in VLBW infants is recorded between the second and sixth weeks after birth. Neonatal IFI are not confined to hematogenous sepsis, but may involve the central nervous system (meningitis and brain abscesses), urinary tract, soft and deep tissues, endocarditis, endophtalmitis, hepatitis and pneumonitis.15Noyola D.E. Fernandez M. Moylett E.H. Baker C.J. Ophthalmologic, visceral and cardiac involvement in neonates with candidemia.Clin Infect Dis. 2001; 32: 1018-1023Crossref PubMed Scopus (109) Google Scholar, 16Benjamin Jr., D.K. Poole C. Steibach W.J. et al.Neonatal candidemia and end-organ damage: a critical appraisal of the literature using meta-analytic techniques.Pediatrics. 2003; 112: 634-640Crossref PubMed Scopus (191) Google Scholar While the clinical picture is similar to that of late-onset Gram-negative bacterial infections, the blood cultures of Candida spp. may be negative even in cases of deep-organ involvement and confirmed Candida meningitis.12Benjamin D.K. Stoll B.J. Fanaroff A.A. et al.Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months.Pediatrics. 2006; 117: 84-92Crossref PubMed Scopus (498) Google ScholarRisk factors for IFI include prematurity, VLBW, use of central venous lines, intubation, parenteral nutrition, broad-spectrum antibiotics administration (in particular third-generation cephalosporins), prolonged hospitalization, abdominal surgery, exposure to an H2 blocker, and colonization with Candida spp.12Benjamin D.K. Stoll B.J. Fanaroff A.A. et al.Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months.Pediatrics. 2006; 117: 84-92Crossref PubMed Scopus (498) Google Scholar, 17Saiman 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: 319-324Crossref PubMed Scopus (460) Google Scholar, 18Saiman L. Ludington E. Dawson J.D. et al.Risk factors for Candida species colonization of neonatal intensive care units patients.Pediatr Infect Dis J. 2001; 20: 1119-1124Crossref PubMed Scopus (274) Google Scholar, 19Manzoni P. Farina D. Leonessa M.L. et al.Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization.Pediatrics. 2006; 118: 2359-2364Crossref PubMed Scopus (128) Google Scholar Of these many factors, mucosal and skin colonization are of primary importance. In a single-center study enrolling 146 VLBW infants, fungal colonization occurred in 26.7% and one-third of those colonized developed IFI.5Baley J.E. Kliegman R.M. Boxerbaum B. et al.Fungal colonization in the very low birth weight infant.Pediatrics. 1986; 78: 225-232PubMed Google Scholar In 1991–1992, El-Mohandes20El-Mohandes A.E. Johnson-Robbins L. Keiser J.F. et al.Incidence of Candida parapsilosis in an intensive care nursery population and its association with invasive fungal disease.Pediatr Infect Dis J. 1994; 13: 520-524Crossref PubMed Scopus (69) Google Scholar studied 82 (61 infants <1500 g) consecutive NICU admissions and found a colonization rate with Candida spp. of 19% with stools more frequently culture-positive than skin or gastric aspirates. Five of the study patients developed fungal sepsis; the authors found that gastrointestinal colonization was strongly associated with development of C. parapsilosis sepsis. Rowen21Rowen J.L. Rench M.A. Kozinetz C.A. et al.Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates.J Pediatr. 1994; 124: 789-794Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar reported that endotracheal colonization with Candida enhances risk of systemic candidiasis in VLBW infants. Huang22Huang Y.C. Li C.C. Lin T.Y. Association of fungal colonization and invasive disease in very low birth weight infants.Pediatr Infect Dis J. 1998; 17: 819-822Crossref PubMed Scopus (106) Google Scholar found a colonization rate of 22% among 116 2-week-old VLBW infants (rectal colonization present in 76% of colonized infants) with fungemia developing in three infants; however, in only one-third of infants could an association between colonization and fungemia be found). Manzoni19Manzoni P. Farina D. Leonessa M.L. et al.Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization.Pediatrics. 2006; 118: 2359-2364Crossref PubMed Scopus (128) Google Scholar found colonization and IFI rates of 32.1% and 8.1%, respectively, among the 689 VLBW infants admitted during 1998–2005 at an NICU in Torino, Italy. After logistic regression, colonization of central venous catheters and colonization in multiple sites were found to be independent risk factors and predictors of progression to fungal sepsis.Regarding the antifungal treatment of IFI, amphotericin B deoxycholate, amphotericin B lipid preparations and fluconazole are the most commonly used antifungal in neonates with invasive infections, as well as in older pediatric patients; however, the development of newer generation azoles (voriconazole, posaconazole) and echinocandins (mainly caspofungin), still undergoing extensive study on dosing and safety, may ultimately expand the therapeutic options for single-agent and combination therapy for neonatal candidiasis.7Chapman R.L. Prevention and treatment of Candida infections in neonates.Semin Perinatol. 2007; 31: 39-46Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 23Brecht M. Clerihew L. McGuire W. Prevention and treatment of invasive fungal infection in very low birthweight infants.Arch Dis Child Fetal Neonatol Ed. 2009; 94: F65-F69Crossref PubMed Scopus (38) Google Scholar, 24Odio C.M. Araya R. Pinto L.E. et al.Caspofungin therapy of neonates with invasive candidiasis.Pediatr Infect Dis J. 2004; 23: 1093-1097PubMed Google Scholar, 25Natarajan G. Lulic-Botica M. Rongkavilit C. Pappas A. Bedard M. Experience with caspofungin in the treatment of persistent fungemia in neonates.J Perinatol. 2005; 25: 770-777Crossref PubMed Scopus (75) Google Scholar, 26Smith P.R. Steinbach W.J. Cotton C.M. et al.Caspofungin for the treatment of azole resistant candidemia in a premature infant.J Perinatol. 2007; 27: 127-129Crossref PubMed Scopus (26) Google Scholar, 27Natarajan G. Lulic-Botica M. Aranda J.V. Refractory neonatal candidemia and high-dose micafungin pharmacotherapy.J Perinatol. 2009; 29: 738-743Crossref PubMed Scopus (26) Google Scholar, 28Varisco B.M. Benner K.W. Prabhakaran P. Neonatal peritoneal candidiasis successfully treated with anidulafungin add-on therapy.Ann Pharmacother. 2009; 43: 1907-1910Crossref PubMed Scopus (16) Google Scholar3. Neonatal Colonization with Candida spp.Colonization with Candida spp. in neonates may be secondary to either vertical transmission from the mother or horizontal (nosocomial acquisition) transmission in the nursery or NICU. Studies evaluating gastrointestinal colonization have shown that 4.8–10% of neonates will harbor a strain of Candida on admission to the nursery.26Smith P.R. Steinbach W.J. Cotton C.M. et al.Caspofungin for the treatment of azole resistant candidemia in a premature infant.J Perinatol. 2007; 27: 127-129Crossref PubMed Scopus (26) Google Scholar At NICUs, around 50% of the admitted infants may be colonized by the end of the first week of life and up to 64% could be colonized by 4 weeks old.5Baley J.E. Kliegman R.M. Boxerbaum B. et al.Fungal colonization in the very low birth weight infant.Pediatrics. 1986; 78: 225-232PubMed Google Scholar, 29Waggoner-Fountain L.A. Walker M.W. Hollis R.J. et al.Vertical and horizontal transmission of unique Candida species to premature newborns.Clin Infect Dis. 1996; 22: 803-808Crossref PubMed Scopus (138) Google Scholar The majority of infants are colonized with C. albicans, but a large percentage carry C. parapsilosis6Bendel C.M. Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis.Semin Perinatol. 2007; 27: 357-364Abstract Full Text Full Text PDF Scopus (70) Google Scholar, 29Waggoner-Fountain L.A. Walker M.W. Hollis R.J. et al.Vertical and horizontal transmission of unique Candida species to premature newborns.Clin Infect Dis. 1996; 22: 803-808Crossref PubMed Scopus (138) Google Scholar (a pattern different from that encountered in adults). An increase in the incidence of C. parapsilosis neonatal infections has been reported during the past two decades in parallel to a decrease in the representation of C. albicans strains among the fungal isolates recovered at various NICUs.3Levy I. Rubin L.G. Vasishta S. Emergence of Candida parapsilosis as the predominant species causing candidemia in children.Clin Infect Dis. 1998; 26: 1086-1088Crossref PubMed Scopus (191) Google Scholar, 4Kossoff 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 J. 1998; 17: 504-508Crossref PubMed Scopus (261) Google Scholar, 20El-Mohandes A.E. Johnson-Robbins L. Keiser J.F. et al.Incidence of Candida parapsilosis in an intensive care nursery population and its association with invasive fungal disease.Pediatr Infect Dis J. 1994; 13: 520-524Crossref PubMed Scopus (69) Google ScholarThe Candida strains colonizing the infant are most frequently acquired by transmission from the maternal genitourinary or gastrointestinal tract during the perinatal period. Using molecular typing techniques, vertical transmission of C. albicans was documented in 33% of a group of premature infants.29Waggoner-Fountain L.A. Walker M.W. Hollis R.J. et al.Vertical and horizontal transmission of unique Candida species to premature newborns.Clin Infect Dis. 1996; 22: 803-808Crossref PubMed Scopus (138) Google Scholar While vertical transmission is common, horizontal acquisition of Candida (from care providers or contaminated infusions) does occur in the NICU and is probably the most common mode of transmission for C. parapsilosis.6Bendel C.M. Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis.Semin Perinatol. 2007; 27: 357-364Abstract Full Text Full Text PDF Scopus (70) Google Scholar, 29Waggoner-Fountain L.A. Walker M.W. Hollis R.J. et al.Vertical and horizontal transmission of unique Candida species to premature newborns.Clin Infect Dis. 1996; 22: 803-808Crossref PubMed Scopus (138) Google Scholar Candida spp. were isolated from the hands of 29% (859 of 2989 sampled) of health workers in a multicenter study.6Bendel C.M. Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis.Semin Perinatol. 2007; 27: 357-364Abstract Full Text Full Text PDF Scopus (70) Google Scholar, 18Saiman L. Ludington E. Dawson J.D. et al.Risk factors for Candida species colonization of neonatal intensive care units patients.Pediatr Infect Dis J. 2001; 20: 1119-1124Crossref PubMed Scopus (274) Google Scholar Candida parapsilosis was isolated from 19% and C. albicans from 5% of the hand cultures of the healthcare personnel sampled.In a multicenter study of neonatal bloodstream infections with Candida spp., molecular typing demonstrated that the same fungal strains were present in the bloodstream and the gastrointestinal tract of the sick infant, illustrating the relationship between gastrointestinal tract colonization and development of IFI.17Saiman 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: 319-324Crossref PubMed Scopus (460) Google Scholar In this study, infants >1000 g were more likely to be colonized with C. albicans than C. parapsilosis, while infants <1000 g showed no differences between the rate of colonization of C. albicans versus C. parapsilosis. The same study found by univariate analysis that rectal colonization by fungi was a risk factor for candidemia. Recently, in a single-center study from Virginia, USA, in which 50 high-risk VLBW infants were enrolled, Candida was isolated from surveillance cultures in 31 (62%) infants and the colonization was inversely proportional with the gestational age. Fungal colonization of the skin and gastrointestinal tract was reported to occur before that of the respiratory tract and C. albicans was found more likely than C. parapsilosis to colonize multiple sites.30Kaufman D.A. Gurka M.J. Hazen K.C. et al.Patterns of fungal colonization in preterm infants weighting less than 1000 grams at birth.Pediatr Infect Dis J. 2006; 25: 733-737Crossref PubMed Scopus (62) Google Scholar Vendetuolli et al31Vendetuolli 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: 1114-1116Crossref PubMed Scopus (17) Google Scholar obtained Candida surveillance cultures from 51 NICU patients during 2005–2007 and found that 16 infants (15 of them <27 weeks gestational age) with positive cultures developed subsequent IFI compared with the 34 others who did not have fungal colonization and did not develop IFI. The positive surveillance cultures led to an early initiation of antifungal treatment and only one infant died of Candida infection.31Vendetuolli 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: 1114-1116Crossref PubMed Scopus (17) Google Scholar4. Prevention of Neonatal Fungal Colonization and Invasive Disease4.1 Fluconazole prophylaxisFluconazole is an azole with a long half-life, very good cerebrospinal penetration, low protein binding and good tissue, body fluids and mucocutaneous areas levels (higher than plasma ones), characteristics that allow long dosing intervals, excellent tissue penetration and easy elimination.32Vaden S.L. Heit M. Hawkins E.C. et al.Fluconazole in cats: pharmacokinetics following intravenous and oral administration and penetration into cerebropsinal fluid, aqueous humour and pulmonary epitheliaal lining fluid.J Vet Pharmacol Ther. 1997; 20: 181-186Crossref PubMed Scopus (39) Google Scholar, 33Koks C.H. Crommentuyn K.M. Hoetelmans R.M. Mathot R.A. Beijnen J.H. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?.Ther Drug Monit. 2001; 23: 449-453Crossref PubMed Scopus (18) Google Scholar At the present time, fluconazole is considered to be the main alternative to amphotericin B in the treatment of neonatal candidiasis and has been fairly well characterized in this population.34Driessen M. Ellis J.B. Cooper P.A. et al.Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a propspective randomized trial.Pediatr Infect Dis J. 1996; 15: 1107-1112Crossref PubMed Scopus (139) Google Scholar, 35Huttova M. Hartmanova I. Kralinsky K. et al.Candida fungemia in neonates treated with fluconazole: report of forty cases, including eight with meningitis.Pediatr Infect Dis J. 1998; 17: 1012-1015Crossref PubMed Scopus (96) Google ScholarIn VLBW infants, prevention of fungal colonization and IFI by fluconazole prophylaxis has been shown to be effective in 13 studies (nine retrospective and four prospective randomized) during the past decade.36Kicklighter S.D. Springer S.C. Cox T. et al.Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infants.Pediatrics. 2001; 107: 293-298Crossref PubMed Scopus (210) Google Scholar, 37Kaufman D. Boyle R. Hazen K.C. et al.Fluconazole prophylaxis against fungal colonization and infection in preterm infants.N Engl J Med. 2001; 345: 1660-1666Crossref PubMed Scopus (424) Google Scholar, 38Kaufmann D. Boyle R. Hazen K.C. et al.Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.J Pediatr. 2005; 147: 172-179Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar, 39Bertini G. Perugi S. Dani C. et al.Fluconazole prophylaxis prevents invasive fungal infection in high-risk, very low birth weight infants.J Pediatr. 2005; 147: 162-165Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 40Healy C.M. Baker C.J. Zaccaria E. et al.Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit.J Pediatr. 2005; 147: 166-171Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 41Manzoni P. Arisio R. Mostert M. et al.Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year retrospective cohort study.Pediatrics. 2006; 117: e22-e32Crossref PubMed Scopus (123) Google Scholar, 42Ukko S. Soghier L.M. Vega M. et al.Targeted short-term prophylaxis among very low birth weight and extremely low birth weight infants.Pediatrics. 2006; 117: 1243-1252Crossref PubMed Scopus (98) Google Scholar, 43Aghai Z.H. Mudduluru M. Nakhla T.A. et al.Fluconazole prophylaxis in extremely low birth weight infants; association with cholestasis.J Perinatol. 2006; 26: 550-555Crossref PubMed Scopus (76) Google Scholar, 44Manzoni P. Stolfi I. Pugni L. et al.A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.N Engl J Med. 2007; 24: 2483-2495Crossref Scopus (287) Google Scholar, 45McCrossan B.A. McHenry E. O’Neill F. Ong G. Sweet D.G. Selective fluconazole prophylaxis in high-risk babies to reduce invasive fungal infection.Arch Dis Child Fetal Neonatal Ed. 2007; 92: F454-F458Crossref PubMed Scopus (55) Google Scholar, 46Healy C.M. Campbell J.R. Zaccaria E. Baker C.J. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole-resistant Candida species.Pediatrics. 2008; 121: 703-710Crossref PubMed Scopus (117) Google Scholar, 47Weitkamp J.H. Ozdas A. LaFleur B. Potts A.L. Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure.J Perinatol. 2008; : 405-411Crossref PubMed Scopus (53) Google Scholar, 48Aziz M. Patel A.L. Losavio J. et al.Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants.Pediatr Infect Dis J. 2010; 29: 352-356PubMed Google Scholar The four randomized, placebo-controlled studies completed during 2000–2007 are presented in detail in Table 1.36Kicklighter S.D. Springer S.C. Cox T. et al.Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infants.Pediatrics. 2001; 107: 293-298Crossref PubMed Scopus (210) Google Scholar, 37Kaufman D. Boyle R. Hazen K.C. et al.Fluconazole prophylaxis against fungal colonization and infection in preterm infants.N Engl J Med. 2001; 345: 1660-1666Crossref PubMed Scopus (424) Google Scholar, 38Kaufmann D. Boyle R. Hazen K.C. et al.Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.J Pediatr. 2005; 147: 172-179Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar, 44Manzoni P. Stolfi I. Pugni L. et al.A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.N Engl J Med. 2007; 24: 2483-2495Crossref Scopus (287) Google Scholar In 2001, Kicklighter et al and Kaufman et al reported the first two randomized, double-blind, placebo-controlled trials of administration of fluconazole prophylaxis in extremely VLBW infants in order to prevent Candida colonization and IFI.36Kicklighter S.D. Springer S.C. Cox T. et al.Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infants.Pediatrics. 2001; 107: 293-298Crossref PubMed Scopus (210) Google Scholar, 37Kaufman D. Boyle R. Hazen K.C. et al.Fluconazole prophylaxis against fungal colonization and infection in preterm infants.N Engl J Med. 2001; 345: 1660-1666Crossref PubMed Scopus (424) Google Scholar They used protocols which treated (starting in the first 72 hours of life) VLBW infants with a birth weight of <1500 g and 1000 g, respectively, with an intravenous/oral or intravenous-on" @default.
• W2065462337 created "2016-06-24" @default.
• W2065462337 creator A5069909118 @default.
• W2065462337 date "2012-04-01" @default.
• W2065462337 modified "2023-10-06" @default.
• W2065462337 title "Strategies for the Prevention of Neonatal Candidiasis" @default.
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