Original Article
Fluconazole Prophylaxis against Fungal Colonization and Infection in Preterm Infants
N Engl J Med 2001; 345:1660-1666December 6, 2001
- Abstract
Background
Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants.
Methods
We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients.
Results
The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented.
Conclusions
Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.
Media in This Article
Table 1
Demographic and Clinical Characteristics of the Study Group.Table 2
Effects of Fluconazole Prophylaxis on Fungal Colonization.Article Activity
- Article
Despite aggressive antifungal treatment of invasive candida infection, systemic fungal disease is increasing in prevalence and leads to high rates of illness and death among preterm infants.1,2 Candida species rapidly colonize the skin and mucous membranes of about 60 percent of critically ill neonates and can progress to invasive infection.2,3 Fungal infection accounts for 9 percent of cases of late-onset sepsis in infants who weigh less than 1500 g and is associated with a mortality rate of 28 percent, as compared with 7 percent among infants in whom no infection develops.1 Critically ill neonates are at an increased risk for infection because of their developmentally immature immune systems, the increased permeability of their skin and mucosal barriers, and the long-term need for central vascular access, parenteral nutrition, broad-spectrum antibiotics, postnatal steroids, and mechanical ventilation.2,4,5 This high-risk population could benefit greatly from effective prophylactic measures.
Reducing fungal colonization may prevent the development of invasive fungal infection in preterm infants.6 Antifungal prophylaxis with fluconazole has been successful in reducing fungal colonization and infection in patients who are undergoing bone marrow or solid-organ transplantation, those with leukemia or human immunodeficiency virus infection, and those who are receiving radiation and chemotherapy.7-12 The efficacy of prophylaxis in these immunocompromised groups suggests that fluconazole may also be effective in preventing invasive fungal disease in preterm infants. However, a major concern regarding the prophylactic use of antifungal agents is the emergence of resistance. In the United States, national surveillance of bloodstream infections attributable to candida species demonstrated a relatively constant level of susceptibility of all candida species to fluconazole during a seven-year period from 1992 through 1998,13 but several other studies have demonstrated some resistance to fluconazole.14-18 Our goal in this study was to evaluate the safety and effectiveness of fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants, while maintaining surveillance for fluconazole resistance.
Methods
Study Design
We conducted a prospective, randomized, double-blind clinical trial to evaluate the efficacy of fluconazole prophylaxis in 100 preterm infants. All infants admitted to our neonatal intensive care unit were eligible for the study, whether they had been born at our institution or transferred from another facility, if they had a birth weight of less than 1000 g and were less than five days old. The presence of liver failure was the only criterion for exclusion. Before enrollment, written informed consent was obtained from each infant's parent or guardian. The protocol was approved by the human investigations committee of the University of Virginia. Pfizer, which supported the study with a grant, was not involved in the study design; the collection, analysis, or interpretation of the data; or the preparation of the manuscript. The company had no control over the decision to publish this report.
Using a computer-generated randomization table, the pharmacy randomly assigned infants, in a 1:1 ratio, to receive either fluconazole or placebo for six weeks. Six weeks was chosen as the duration of therapy on the basis of unpublished data from our neonatal intensive care unit demonstrating that approximately 85 percent of invasive fungal infections in preterm infants weighing less than 1000 g occurred during the first six weeks of life.
Data on the demographic and clinical characteristics of the infants were prospectively collected during their hospitalization and through review of their medical records. Microbiologic-culture results were collected during all episodes of fungal and bacterial infection of blood, urine, and cerebrospinal fluid during and after the six-week treatment period.
Drug Administration
Fluconazole was administered intravenously for six weeks at a dose of 3 mg per kilogram of body weight every third day for the first two weeks, every other day during the third and fourth weeks, and daily during the fifth and sixth weeks. Infants in the placebo group were given an equal volume of normal saline on the same schedule. This schedule of fluconazole dosing was based on data from pharmacokinetic studies involving preterm infants.19,20 The administration of the study drug (fluconazole or placebo) and the obtaining of surveillance cultures were discontinued before the end of the six-week treatment period if intravenous access was discontinued, if antifungal therapy was initiated for the treatment of a documented or presumed systemic fungal infection, if the infant was discharged from the hospital or transferred to another facility, or if the infant died.
Fungal Isolation and Identification
Fungal surveillance cultures of the nasopharynx (tracheal secretions if the infant was intubated and nasopharyngeal sample if the infant was not intubated), skin (groin), and stool or rectum were obtained, by two clinical nurses associated with the study, at base line and then weekly during the six-week study period on the day of the week of the patient's enrollment. Cultures of the umbilicus were also performed at base line and at one week.
Cultures were also obtained when they were considered by neonatal care physicians to be clinically indicated. Invasive fungal infection was defined by a positive culture of blood, urine, or cerebrospinal fluid. Stool and tracheal secretions were submitted in sterile containers, and skin specimens were obtained on swabs (Culturette, Becton Dickinson Microbiology Systems, Sparks, Md.). Each specimen was inoculated onto Inhibitory Mold Agar (Remel, Lenexa, Kans.), and the plates were incubated and examined for four weeks at 30°C unless yeast growth occurred within two weeks.
Speciation of fungal isolates was performed according to standard methods, including an initial screening for germ-tube formation and exoenzyme production (Candida albicans screen, Carr–Scarborough Microbiologicals, Decatur, Ga.) and a commercial auxanographic method (API 20 C AUX, BioMérieux, Hazelwood, Mo.).21,22
Fluconazole-Susceptibility Testing
Each yeast isolate was tested for susceptibility to fluconazole by means of a standardized microbroth dilution assay, as described by the National Committee of Clinical Laboratory Standards.23 We report the minimal inhibitory concentration (MIC) — the lowest concentration of drug resulting in a prominent decrease in growth at 48 hours as compared with the control.
Statistical Analysis
The primary efficacy end point was the incidence of invasive fungal infection during the administration of the study drug. The secondary outcomes were fungal colonization; bacterial infection of blood, urine, or cerebrospinal fluid; isolated intestinal perforation in the absence of pneumatosis; necrotizing enterocolitis; ligation of patent ductus arteriosus; threshold retinopathy of prematurity requiring laser ablation; and abnormal findings on cranial ultrasonography, defined as grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia during hospitalization. Liver-function tests measuring aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and alkaline phosphatase were performed at base line and at the end of the administration of the study drug.
The sample size of 100 infants was based on the assumption that the study would have a two-sided type I error rate of 0.05 or less and at least 90 percent power to detect an absolute difference of 75 percent in the cumulative incidence of invasive fungal infection between the placebo group and the fluconazole group after six weeks of treatment, given a pretrial incidence of invasive fungal infection of 30 percent.24
The contingency data pertaining to the cumulative incidence of the primary and secondary outcomes during the administration of the study drug in the placebo group and the fluconazole group were analyzed by exact tests for nonparametric variables. The hypothesis tests were based on the nonparametric unconditional exact test described by Mehta and Patel,25 and all tests were two-sided. The corresponding two-sided 95 percent confidence intervals for the differences in risk were constructed according to the Berger–Boos26 modification of the exact method described by Santner and Snell.27
The weekly incidence of infection in the placebo group was analyzed by the generalized-estimating-equation approach.28 The covariates used in the model included the presence or absence of fungal colonization each week, the week of the screening, the number of sites that were colonized, and the presence or absence of fungal colonization at base line.
The presence or absence of invasive infection each week was modeled by means of a generalized linear model with a logit-link function. The parameters of the model were estimated on the basis of maximum-likelihood criteria, and an exchangeable correlation structure was used to model the correlations between the findings for the same infant at different times. Hypothesis tests and 95 percent confidence intervals were all two-sided and were based on the Wald normal approximation.
All the statistical computations were performed with the use of SAS software (version 8.1, SAS Institute, Cary, N.C.). Proc-StatXact for SAS users, a version of the StatXact-4 software package (Cytel, Cambridge, Mass.), was used to compute the nonparametric exact tests and the nonparametric exact 95 percent confidence intervals, and the SAS Proc Genmod procedure was used to perform the generalized estimating-equation analysis.
Results
Study Participants
Fifty infants were randomly assigned to the placebo group and 50 infants to the fluconazole group during the 30-month period between May 5, 1998, and October 10, 2000. A total of 114 infants met the criteria for enrollment during the study period. Seven infants died before consent had been obtained; for four infants, consent was not obtained during the first five days of life; for one infant, consent was obtained but randomization did not occur; for one, an interpreter was not available to obtain informed consent; and one infant did not have an intravenous catheter or an endotracheal tube.
There were no significant differences between the placebo and fluconazole groups in the base-line demographic characteristics or risk factors for fungal infection (Table 1Table 1
Demographic and Clinical Characteristics of the Study Group.). At base line, eight infants in the placebo group and two in the fluconazole group were colonized (difference in risk, 0.12; 95 percent confidence interval, –0.05 to 0.29; P=0.18). There was no significant difference in the age at enrollment between the infants with base-line fungal colonization and those with no colonization at base line (mean [±SD] age, 2.1±1.5 vs. 1.7±1.1 days; P=0.39). All the infants were placed in a humidified incubator and treated with Aquaphor ointment (Beiersdorf, Norwalk, Conn.) for skin care during the first 7 to 14 days of life. One infant in the placebo group without a positive fungal culture was treated with amphotericin B and a systemic fungal infection later developed, and one patient in the fluconazole group without a positive fungal culture was treated with amphotericin B and later died from respiratory failure. Both patients were included in the analysis.The mean (±SD) duration of the administration of the study drug and the obtaining of the surveillance cultures for all study participants was 5.2±1.4 weeks, and patients were followed for a mean of 13.7±8.0 weeks. On three occasions, a dose of placebo was incorrectly administered in place of fluconazole to infants in the fluconazole group, and protocol surveillance cultures were not obtained from an infant three times in the placebo group and six times in the fluconazole group.
Fungal Colonization
During the six-week treatment period, fungal colonization was present at one or more sites in 30 of the infants in the placebo group (60 percent) and 11 of those in the fluconazole group (22 percent, P=0.002) (Table 2Table 2
Effects of Fluconazole Prophylaxis on Fungal Colonization.). Fungal colonization at two or more sites occurred in 26 of the infants in the placebo group (52 percent), as compared with 9 of those in the fluconazole group (18 percent, P=0.003). Fluconazole prophylaxis led to a significantly lower incidence of colonization at three of the culture sites (skin, stool, and nasopharynx) than that found in the placebo group during the six-week treatment period (Table 2).The distribution of fungal species and the sites of colonization are shown in Table 3Table 3
Distribution of Fungal Species and Sites of Colonization.. There were 177 fungal isolates documented in 769 surveillance cultures (23.0 percent) obtained from infants in the placebo group and 42 isolates among 861 surveillance cultures (4.9 percent) obtained from infants in the fluconazole group during the treatment period (difference in risk, 0.18; 95 percent confidence interval, 0.15 to 0.22; P<0.001). The skin and stools were the most common sites of evidence of fungal colonization in both groups, whereas fungal colonization of the nasopharynx occurred only once in one infant in the fluconazole group, as compared with 37 times in 17 infants in the placebo group (P=0.002).Fluconazole prophylaxis significantly reduced the incidence of C. albicans colonization overall, as well as in the skin, stools, and nasopharynx (Table 2). After the second week, no infants in the fluconazole group had colonization with C. albicans, as compared with 10 infants in the placebo group (P=0.008). There was no significant difference between the groups in the number of patients colonized with C. parapsilosis (Table 2), but overall, there were fewer isolates of C. parapsilosis in the fluconazole group (35 of 861 cultures) than in the placebo group (79 of 769 cultures) (Table 3). The total number of infants colonized with C. parapsilosis increased from 2 at base line to 16 by week 2 of the study.
Invasive Fungal Infection
Fungal infection, as documented by growth of fungi in cultures of blood, urine, or cerebrospinal fluid, developed in 10 of the infants in the placebo group (20 percent) and none of those in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). Four of the infants with systemic fungal infection died. The 10 invasive infections were caused by C. albicans (5), C. parapsilosis (3), C. glabrata (1), and C. dubliniensis (1). The lowest concentration of fluconazole that inhibited the growth of 90 percent of these isolates (MIC90) was not different from the MIC90 of the isolates from the surveillance cultures obtained from the infants in the placebo group in whom invasive infection did not develop. There were eight episodes of sepsis (one with meningitis, one with necrotizing enterocolitis, and one with a urinary tract infection) and two isolated episodes of urinary tract infection. In one infant with a systemic fungal infection, an antecubital skin abscess developed; in another infant, endocarditis developed; and an appendiceal abscess and peritonitis developed in a third infant. Systemic fungal infection was treated in all cases with intravenous amphotericin B, with the addition of fluconazole in two cases. After the six-week treatment period, invasive fungal infection occurred in three infants in the placebo group and one infant in the fluconazole group (P=0.30). No clusters of invasive fungal infections occurred at any time during the study period.
There was no association between fungal colonization, as defined by a positive surveillance culture at any time during the study period or at base line, and the incidence of invasive fungal infection. Systemic fungal infection was preceded by colonization with the same fungal species at some time point in 8 of the 10 infants with invasive infections (80 percent). By comparison, 21 of the 40 control infants without systemic fungal infection (52 percent) also had colonization. All eight patients who had colonization before invasive fungal infection developed had positive surveillance cultures during the week before the infection appeared. In one case, C. dubliniensis fungemia with endocarditis developed in an infant who had had colonization with C. albicans. In another case, C. glabrata sepsis developed in an infant who had been colonized with C. parapsilosis. In the placebo group, colonization with a specific fungal species or at a specific site was not associated with an increased risk of invasive fungal infection.
There was an association between the occurrence of invasive fungal infection and the number of sites that had been colonized at the time of the last screening. For each additional site colonized, the odds of invasive fungal infection increased by a factor of three (odds ratio, 3.0; 95 percent confidence interval, 1.4 to 6.8).
Minimal Inhibitory Concentration
Sensitivity to fluconazole as measured by the MIC did not change significantly for infants in either group. One isolate of C. parapsilosis in one fluconazole-treated patient had an increase in MIC from 0.25 μg per milliliter at base line to 1.00 μg per milliliter at the end of the treatment period, but invasive fungal infection did not occur in this patient. In addition, patterns of sensitivity to fluconazole did not change over the 30-month study period (Table 4Table 4
Minimal Inhibitory Concentration of Fluconazole for Fungal Isolates during the 30-Month Study Period.).Secondary Outcomes
There was no significant difference in mortality between the two groups (4 infants in the fluconazole group died, as compared with 10 in the placebo group; P=0.22). The frequencies of the secondary outcomes were also similar in the two groups. The incidence of bacterial infections (73 percent of which were due to gram-positive organisms) was similar in the two groups during and after the treatment period. Bacterial infection developed in 17 infants in the placebo group (34 percent) and 19 infants in the fluconazole group (38 percent). Necrotizing enterocolitis occurred in six infants in the placebo group (12 percent) and two infants in the fluconazole group (4 percent). There were also no significant differences between the placebo and fluconazole groups in the incidence of isolated intestinal perforation (5 infants and 2 infants, respectively), ligation of patent ductus arteriosus (5 infants and 2 infants, respectively), threshold retinopathy of prematurity (11 infants and 15 infants, respectively), or abnormal findings on cranial ultrasonography (9 infants and 8 infants, respectively). No adverse effects of the fluconazole therapy were documented. Specifically, there was no appreciable adverse effect of therapy on levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, or alkaline phosphatase. No infant was withdrawn from the study because of changes in liver-function results, and the results returned to normal after treatment in all infants who survived to discharge. Aminotransferases were elevated (more than 2 SD above the mean) in three infants in each group (6 percent) during the treatment period.
Discussion
The results of this study demonstrate that fluconazole is effective in preventing invasive fungal infection in extremely-low-birth-weight preterm infants. In the past 10 years, several studies have investigated the use of fluconazole prophylaxis in immunocompromised adults.7-12,29-32 In patients receiving bone marrow transplants, 75 days of prophylactic treatment with fluconazole reduced the incidence of fungal colonization, superficial infection, systemic infection, and candidiasis-related death, despite colonization with azole-resistant fungal species.7,9,30 Fluconazole resistance did not occur. The extremely-low-birth-weight infant is an unusual host in whom the risk of fungal infection decreases with the maturation of the immune system, extubation, the discontinuation of parenteral nutrition, and the removal of central vascular access as postnatal age increases. For these reasons, the preterm infants in this study required a shorter course of medication and a lower total dose of fluconazole than adults have required in previous studies. Since azole resistance has been reported to be dependent on the total dose received, this difference in exposure may partially explain why fluconazole resistance did not develop in this cohort.14 In addition, the use of amphotericin B for primary therapy for invasive fungal disease limits the total dose of fluconazole to which fungi are exposed and may help prevent the development of resistant fungi.15,33
The elimination, as a result of fluconazole prophylaxis, of fungal colonization at multiple sites or, in some cases, of colonization altogether appeared to contribute to the prevention of invasive fungal infection. In addition, in patients who had fungal colonization, it is possible that fluconazole prophylaxis may have rendered the fungi more susceptible to the innate defenses of the host.34-39
Fluconazole prophylaxis appeared to have its most dramatic effects on C. albicans — a finding that is consistent with other data suggesting that C. albicans is more susceptible to fluconazole than other fungal species.40 The marked effect of fluconazole on nasopharyngeal colonization suggests that effective tissue drug concentrations are achieved in the nasopharyngeal mucosa.41 By the third week of life in the infants in our study, fluconazole prophylaxis eliminated colonization by C. albicans that was most likely acquired by means of vertical transmission from the mother.42 The majority of colonizations with C. parapsilosis occurred during the second week of the study, implying that C. parapsilosis has a different mechanism of colonization, which most commonly occurs by means of horizontal transmission, through the nosocomial spread of fungi from health care workers or colonized infusates.43
The fluconazole dosing used in this study was based on published data regarding the pharmacokinetics of fluconazole in preterm infants.19,20 Our study demonstrated no adverse effects of fluconazole, and the lower dose and the intermittent dosing may be responsible for this favorable side-effect profile. Because of concern about the development of azole resistance, we limited our study to preterm infants who required vascular access or endotracheal intubation during the first six weeks of life. Therefore, this study does not address the effectiveness of fluconazole in infants who continue to require vascular access or endotracheal intubation beyond six weeks of age. The prophylactic administration of fluconazole prevented fungal colonization and invasive fungal disease in extremely-low-birth-weight preterm infants without adverse effects or development of fluconazole resistance.
Supported in part by a grant from Pfizer.
Source Information
From the Departments of Pediatrics (D.K., R.B., M.R., L.G.D.), Pathology and Microbiology (K.C.H.), and Health Evaluation Sciences (J.T.P.), University of Virginia School of Medicine, Charlottesville.
Address reprint requests to Dr. Kaufman at the Division of Neonatology, Department of Pediatrics, Box 800386, University of Virginia Health System, Charlottesville, VA 22908, or at dak4r@virginia.edu.
- References
References
1
Stoll BJ ,Gordon T ,Korones SB , et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 1996;129:63-71
CrossRef | Web of Science | Medline2
Baley JE . Neonatal candidiasis: the current challenge. Clin Perinatol 1991;18:263-280
Web of Science | Medline3
Baley JE ,Kliegman RM ,Boxerbaum B ,Fanaroff AA . Fungal colonization in the very low birth weight infant. Pediatrics 1986;78:225-232
Web of Science | Medline4
Stoll BJ ,Temprosa M ,Tyson JE , et al. Dexamethasone therapy increases infection in very low birth weight infants. Pediatrics 1999;104:1121-1121 abstract.
CrossRef | Web of Science5
Kicklighter SD ,Springer SC ,Cox T ,Hulsey TC ,Turner RB . Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant. Pediatrics 2001;107:293-298
CrossRef | Web of Science | Medline6
Xanthou M ,Valassi-Adam E ,Kintsonidou E ,Matsaniotis N . Phagocytosis and killing ability of Candida albicans by blood leukocytes of healthy term and preterm babies. Arch Dis Child 1975;50:72-75
CrossRef | Web of Science | Medline7
Goodman JL ,Winston DJ ,Greenfield RA , et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992;326:845-851
Full Text | Web of Science | Medline8
Winston DJ ,Chandrasekar PH ,Lazarus HM , et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia: results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med 1993;118:495-503
Web of Science | Medline9
Slavin MA ,Osborne B ,Adams R , et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation -- a prospective, randomized, double-blind study. J Infect Dis 1995;171:1545-1552
CrossRef | Web of Science | Medline10
Powderly WG ,Finkelstein D ,Feinberg J , et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995;332:700-705
Full Text | Web of Science | Medline11
Lumbreras C ,Cuervas-Mons V ,Jara P , et al. Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation. J Infect Dis 1996;174:583-588
CrossRef | Web of Science | Medline12
Mucke R ,Kaben U ,Libera T , et al. Fluconazole prophylaxis in patients with head and neck tumours undergoing radiation and radiochemotherapy. Mycoses 1998;41:421-423
CrossRef | Web of Science | Medline13
Marr KA ,Seidel K ,White TC ,Bowden RA . Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 2000;181:309-316
CrossRef | Web of Science | Medline14
Millon L ,Manteaux A ,Reboux G , et al. Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype. J Clin Microbiol 1994;32:1115-1118
Web of Science | Medline15
Lewis RE ,Klepser ME . The changing face of nosocomial candidemia: epidemiology, resistance, and drug therapy. Am J Health Syst Pharm 1999;56:525-533
Web of Science | Medline16
Pfaller MA ,Messer SA ,Hollis RJ , et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis 1999;33:217-222
CrossRef | Web of Science | Medline17
Rex JH ,Rinaldi MG ,Pfaller MA . Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995;39:1-8
Web of Science | Medline18
Nguyen MH ,Peacock JE Jr ,Morris AJ , et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617-623
CrossRef | Web of Science | Medline19
Saxen 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;54:269-277
CrossRef | Web of Science | Medline20
Brammer KW ,Coates PE . Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis 1994;13:325-329
CrossRef | Web of Science | Medline21
Spicer AD ,Hazen KC . Rapid confirmation of Candida albicans identification by combination of two presumptive tests. Med Microbiol Lett 1992;1:284-28922
Murray PR, ed. Manual of clinical microbiology. 7th ed. Washington, D.C.: ASM Press, 1999:1191-7.
23
Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard. Wayne, Pa.: National Committee of Clinical Laboratory Standards, 1997. (NCCLS document no. M27-A.)
24
Hennekens CH, Buring JE. Epidemiology in medicine. 2nd ed. Boston: Little, Brown, 1994:87-8.
25
Mehta C, Patel N. Proc-StatXact 4 for SAS users. Cambridge, Mass.: Cytel Software, 1999:257-92.
26
Berger RL ,Boos DD . P values maximized over a confidence set for the nuisance parameter. J Am Stat Assoc 1994;89:1012-1016
CrossRef | Web of Science27
Santner TJ ,Snell MK . Small-sample confidence intervals for p1-p2 and p1 /p2 in 2×2 contingency tables. J Am Stat Assoc 1980;75:386-394
CrossRef | Web of Science28
Diggle PJ, Liang K-Y, Zeger SL. Analysis of longitudinal data. Oxford, England: Clarendon Press, 1994:143-5.
29
Kern W ,Behre G ,Rudolf T , et al. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia: results of a prospective randomized phase III study. Cancer 1998;83:291-301
CrossRef | Web of Science | Medline30
Marr KA ,Seidel K ,Slavin MA , et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood 2000;96:2055-2061
Web of Science | Medline31
Gotzsche PC ,Johansen HK . Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia. BMJ 1997;314:1238-1244
CrossRef | Web of Science | Medline32
Kanda Y ,Yamamoto R ,Chizuka A , et al. Prophylactic action of oral fluconazole against fungal infection in neutropenic patients: a meta-analysis of 16 randomized, controlled trials. Cancer 2000;89:1611-1625
CrossRef | Web of Science | Medline33
Gleason TG ,May AK ,Caparelli D ,Farr BM ,Sawyer RG . Emerging evidence of selection of fluconazole-tolerant fungi in surgical intensive care units. Arch Surg 1997;132:1197-1202
Web of Science | Medline34
Abu-el Teen K ,Ghannoum M ,Stretton RJ . Effects of sub-inhibitory concentrations of antifungal agents on adherence of Candida spp. to buccal epithelial cells in vitro. Mycoses 1989;32:551-562
CrossRef | Web of Science | Medline35
Hazen KC ,Mandell G ,Coleman E ,Wu G . Influence of fluconazole at subinhibitory concentrations on cell surface hydrophobicity and phagocytosis of Candida albicans. FEMS Microbiol Lett 2000;183:89-94
CrossRef | Web of Science | Medline36
Ghannoum MA ,Filler SG ,Ibrahim AS ,Fu Y ,Edwards JE Jr . Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B. Antimicrob Agents Chemother 1992;36:2239-2244
Web of Science | Medline37
Van 't Wout JW ,Meynaar I ,Linde I ,Poell R ,Mattie H ,Van Furth R . Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages. J Antimicrob Chemother 1990;25:803-811
CrossRef | Web of Science | Medline38
Garcha UK ,Brummer E ,Stevens DA . Synergy of fluconazole with human monocytes or monocyte-derived macrophages for killing of Candida species. J Infect Dis 1995;172:1620-1623
CrossRef | Web of Science | Medline39
Minguez Minguez F ,Lima JE ,Garcia MT ,Prieto J . Effects of antifungal pretreatment on the susceptibility of Candida albicans to human leukocytes. Chemotherapy 1997;43:346-351
CrossRef | Web of Science | Medline40
Pfaller MA ,Messer SA ,Hollis RJ , et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole. Antimicrob Agents Chemother 1998;42:3242-3244
Web of Science | Medline41
Vaden SL ,Heit MC ,Hawkins EC ,Manaugh C ,Riviere JE . Fluconazole in cats: pharmacokinetics following intravenous and oral administration and penetration into cerebrospinal fluid, aqueous humour andpulmonary epithelial lining fluid. J Vet Pharmacol Ther 1997;20:181-186
CrossRef | Web of Science | Medline42
Waggoner-Fountain LA ,Walker MW ,Hollis RJ , et al. Vertical and horizontal transmission of unique Candida species to premature newborns. Clin Infect Dis 1996;22:803-808
CrossRef | Web of Science | Medline43
Huang YC ,Lin TY ,Leu HS ,Peng HL ,Wu JH ,Chang HY . Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis. Infection 1999;27:97-102
CrossRef | Web of Science | Medline
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Daniela Testoni, P. Brian Smith, Daniel K. Benjamin. (2012) The Use of Antifungal Therapy in Neonatal Intensive Care. Clinics in Perinatology
CrossRef7
J. L. Wynn, S. Tan, M. G. Gantz, A. Das, R. N. Goldberg, I. Adams-Chapman, B. J. Stoll, S. Shankaran, M. C. Walsh, K. J. Auten, N. A. Miller, P. J. Sanchez, R. D. Higgins, C. M. Cotten, P. B. Smith, D. K. Benjamin, . (2011) Outcomes Following Candiduria in Extremely Low Birth Weight Infants. Clinical Infectious Diseases
CrossRef8
Mohan Pammi, Oya Eddama, Leonard E Weisman, Mohan Pammi. 2011. Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units. .
CrossRef9
Veena Bisht, Judith VanDer Voort. (2011) Clinical practice. European Journal of Pediatrics 170:10, 1227-1235
CrossRef10
Florentia Kaguelidou, Chiara Pandolfini, Paolo Manzoni, Imti Choonara, Maurizio Bonati, Evelyne Jacqz-Aigrain. (2011) European survey on the use of prophylactic fluconazole in neonatal intensive care units. European Journal of Pediatrics
CrossRef11
David Trofa, Lamia Soghier, Christina Long, Joshua D. Nosanchuk, Attila Gacser, David L. Goldman. (2011) A Rat Model of Neonatal Candidiasis Demonstrates the Importance of Lipases as Virulence Factors for Candida albicans and Candida parapsilosis. Mycopathologia 172:3, 169-178
CrossRef12
Vishwanath Bhat, Milliecor Fojas, Judy G. Saslow, Sahil Shah, Sulaiman Sannoh, Barbara Amendolia, Kee Pyon, Nicole Kemble, Gary Stahl, Zubair H. Aghai. (2011) Twice-weekly fluconazole prophylaxis in premature infants: Association with cholestasis. Pediatrics International 53:4, 475-479
CrossRef13
A Martin, A Pappas, M Lulic-Botica, G Natarajan. (2011) Impact of ‘targeted’ fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?. Journal of Perinatology
CrossRef14
D. A. Kaufman. (2011) Aiming for Zero: Preventing Invasive Candida Infections in Extremely Preterm Infants. NeoReviews 12:7, e381-e392
CrossRef15
Thomas Lehrnbecher, Konrad Bochennek, Dominik Schrey, Andreas H. Groll. (2011) Antifungal Therapy in Pediatric Patients. Current Fungal Infection Reports 5:2, 103-110
CrossRef16
Paolo Manzoni, Michael Mostert, Mauro Stronati. (2011) Lactoferrin for prevention of neonatal infections. Current Opinion in Infectious Diseases 24:3, 177-182
CrossRef17
David A. Kaufman, Amy L. Cuff, Julia B. Wamstad, Robert Boyle, Matthew J. Gurka, Leigh B. Grossman, Peter Patrick. (2011) Fluconazole Prophylaxis in Extremely Low Birth Weight Infants and Neurodevelopmental Outcomes and Quality of Life at 8 to 10 Years of Age. The Journal of Pediatrics 158:5, 759-765.e1
CrossRef18
Huei Hsin Shieh, Silvia Maria Ibidi, Alfredo Elias Gilio. (2011) Number Needed to Treat in Fluconazole Prophylaxis in the Neonatal Intensive Care Unit. The Pediatric Infectious Disease Journal 30:5, 449
CrossRef19
Anna Turkova, Emmanuel Roilides, Mike Sharland. (2011) Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy – is there a ‘right’ choice?. Current Opinion in Infectious Diseases 24:2, 163-171
CrossRef20
Andreas H. Groll. (2011) Efficacy and safety of antifungals in pediatric patients. Early Human Development 87, S71-S74
CrossRef21
Paolo Manzoni, Evelyne Jacqz-Aigrain, Stefano Rizzollo, Caterina Franco, Mauro Stronati, Michael Mostert, Daniele Farina. (2011) Antifungal prophylaxis in neonates. Early Human Development 87, S59-S60
CrossRef22
Kelly C. Wade, Daniel K. Benjamin. 2011. Clinical Pharmacology of Anti-Infective Drugs. , 1160-1211.
CrossRef23
Susan E. Coffin, Theoklis E. Zaoutis. 2011. HealthCare–Associated Infections in the Nursery. , 1126-1143.
CrossRef24
Catherine M. Bendel. 2011. Candidiasis. , 1055-1077.
CrossRef25
Jinlin Wu, Dezhi Mu. (2011) Vascular catheter-related complications in newborns. Journal of Paediatrics and Child Healthno-no
CrossRef26
Katalin Kristóf, L. Janik, Kinga Komka, Ágnes Harmath, Júlia Hajdú, A. Nobilis, F. Rozgonyi, K. Nagy, J. Rigó, Dóra Szabó. (2010) Clinical microbiology of neonatal candidiasis in Hungary. Acta Microbiologica et Immunologica Hungarica 57:4, 407-417
CrossRef27
Nancy Y. Tsai, Sonia S. Laforce-Nesbitt, Richard Tucker, Joseph M. Bliss. (2010) A Murine Model for Disseminated Candidiasis in Neonates. Pediatric Research1
CrossRef28
A. H. Groll, A. Tragiannidis. (2010) Update on antifungal agents for paediatric patients. Clinical Microbiology and Infection 16:9, 1343-1353
CrossRef29
David A. Kaufman, Paolo Manzoni. (2010) Strategies to Prevent Invasive Candidal Infection in Extremely Preterm Infants. Clinics in Perinatology 37:3, 611-628
CrossRef30
Sameer J. Patel, Lisa Saiman. (2010) Antibiotic Resistance in Neonatal Intensive Care Unit Pathogens: Mechanisms, Clinical Impact, and Prevention Including Antibiotic Stewardship. Clinics in Perinatology 37:3, 547-563
CrossRef31
Jamie Wilkerson, Christopher McPherson, Ann Donze. (2010) Fluconazole to Prevent Systemic Fungal Infections in Infants: Reviewing the Evidence. Neonatal Network: The Journal of Neonatal Nursing 29:5, 323-333
CrossRef32
Ruža Grizelj, Jurica Vuković, Dalibor Šarić, Tomislav Luetić. (2010) Giant Mycotic Right Atrial Thrombus Due to Candida dubliniensis Septicemia in a Premature Infant. The Pediatric Infectious Disease Journal 29:8, 785-786
CrossRef33
David A. Kaufman. (2010) Challenging issues in neonatal candidiasis. Current Medical Research and Opinion 26:7, 1769-1778
CrossRef34
L. Corbin Downey, P. Brian Smith, Daniel K. Benjamin. (2010) Risk factors and prevention of late-onset sepsis in premature infants. Early Human Development 86:1, 7-12
CrossRef35
Kathia Rueda, Maria Teresa Moreno, Manuel Espinosa, Xavier Sáez-Llorens. (2010) IMPACT OF ROUTINE FLUCONAZOLE PROPHYLAXIS FOR PREMATURE INFANTS WITH BIRTH WEIGHTS OF LESS THAN 1250 G IN A DEVELOPING COUNTRY. The Pediatric Infectious Disease Journal1
CrossRef36
Bin Xia, Jun Tang, Ying Xiong, Xi-Hong Li, De-Zhi Mu. (2010) Peripherally inserted central catheters and the incidence of candidal sepsis in VLBW and ELBW infants: is sepsis increased?. World Journal of Pediatrics 6:2, 154-157
CrossRef37
Philip Toltzis, Michele Walsh. (2010) Recently tested strategies to reduce nosocomial infections in the neonatal intensive care unit. Expert Review of Anti-infective Therapy 8:2, 235-242
CrossRef38
Antonio C. Arrieta, Kathy Shea, Vijay Dhar, John P. Cleary, Sudeep Kukreja, Mindy Morris, Ofelia M. Vargas-Shiraishi, Negar Ashouri, Jasjit Singh. (2010) Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: A prospective, randomized, open-label, placebo-controlled pilot study. Clinical Therapeutics 32:2, 265-271
CrossRef39
D K Benjamin, P B Smith, A Arrieta, L Castro, P J Sánchez, D Kaufman, L J Arnold, L L Kovanda, T Sawamoto, D N Buell, W W Hope, T J Walsh. (2010) Safety and Pharmacokinetics of Repeat-Dose Micafungin in Young Infants. Clinical Pharmacology & Therapeutics 87:1, 93-99
CrossRef40
P. Eggimann, D. Pittet. (2010) Candidemia e candidosi generalizzata. EMC - Anestesia-Rianimazione 15:2, 1-24
CrossRef41
C Moran, P B Smith, M Cohen-Wolkowiez, D K Benjamin. (2009) Clinical Trial Design in Neonatal Pharmacology: Effect of Center Differences, With Lessons From the Pediatric Oncology Cooperative Research Experience. Clinical Pharmacology & Therapeutics 86:6, 589-591
CrossRef42
L James, S Ito. (2009) Neonatal Pharmacology: Rational Therapeutics for the Most Vulnerable. Clinical Pharmacology & Therapeutics 86:6, 573-577
CrossRef43
Michael Cohen-Wolkowiez, Cassandra Moran, Daniel K Benjamin, Phillip B Smith. (2009) Pediatric antifungal agents. Current Opinion in Infectious Diseases 22:6, 553-558
CrossRef44
Mariam Aziz, Aloka L. Patel, Jennifer Losavio, Anjali Iyengar, Michael Berven, Nathan Schloemer, Andrew Jakubowicz, Tina Mathai, James B. McAuley. (2009) Efficacy of Fluconazole Prophylaxis for Prevention of Invasive Fungal Infection in Extremely Low Birth Weight Infants. The Pediatric Infectious Disease Journal1
CrossRef45
Eveline C. van Asbeck, Karl V. Clemons, David A. Stevens. (2009) Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Critical Reviews in Microbiology 35:4, 283-309
CrossRef46
M A Bhat, J I Bhat, M S Kawoosa, S M Ahmad, S W Ali. (2009) Organism-specific platelet response and factors affecting survival in thrombocytopenic very low birth weight babies with sepsis. Journal of Perinatology 29:10, 702-708
CrossRef47
Mayumi Kawada, Noriyasu Fukuoka, Masatoshi Kondo, Kaoru Okazaki, Takashi Kusaka, Kou Kawada, Susumu Itoh. (2009) PHARMACOKINETICS OF PROPHYLACTIC MICAFUNGIN IN VERY-LOW-BIRTH-WEIGHT INFANTS. The Pediatric Infectious Disease Journal 28:9, 840-842
CrossRef48
Kelly C. Wade, Daniel K. Benjamin, David A. Kaufman, Robert M. Ward, Phillip B. Smith, Bhuvana Jayaraman, Peter C. Adamson, Marc R. Gastonguay, Jeffrey S. Barrett. (2009) Fluconazole Dosing for the Prevention or Treatment of Invasive Candidiasis in Young Infants. The Pediatric Infectious Disease Journal 28:8, 717-723
CrossRef49
Hans Jürgen Dornbusch, Paolo Manzoni, Emmanuel Roilides, Thomas J. Walsh, Andreas H. Groll. (2009) Invasive Fungal Infections in Children. The Pediatric Infectious Disease Journal 28:8, 734-737
CrossRef50
Robin B. McFee. (2009) Nosocomial or Hospital-acquired Infections: An Overview. Disease-a-Month 55:7, 422-438
CrossRef51
M. C. Arendrup, B. T. Fisher, T. E. Zaoutis. (2009) Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues. Clinical Microbiology and Infection 15:7, 613-624
CrossRef52
Chiharu Kawaguchi, Ikuyo Arai, Hajime Yasuhara, Reiko Sano, Toshiya Nishikubo, Yukihiro Takahashi. (2009) Efficacy of micafungin in treating four premature infants with candidiasis. Pediatrics International 51:2, 220-224
CrossRef53
Jeffery S. Garland, Michael R. Uhing. (2009) Strategies to Prevent Bacterial and Fungal Infection in the Neonatal Intensive Care Unit. Clinics in Perinatology 36:1, 1-13
CrossRef54
C Mary Healy, Carol J. Baker. (2009) Fluconazole Prophylaxis in the Neonatal Intensive Care Unit. The Pediatric Infectious Disease Journal 28:1, 49-52
CrossRef55
Daijiro Takahashi, Tomohiko Nakamura, Reiko Shigematsu, Miyu Matsui, Shunsuke Araki, Kazuyasu Kubo, Hiroshi Sato, Akira Shirahata. (2009) Fosfluconazole for Antifungal Prophylaxis in Very Low Birth Weight Infants. International Journal of Pediatrics 2009, 1-3
CrossRef56
Valentina Vendettuoli, Milena Tana, Chiara Tirone, Brunella Posteraro, Marilena La Sorda, Giovanni Fadda, Costantino Romagnoli, Giovanni Vento. (2008) THE ROLE OF CANDIDA SURVEILLANCE CULTURES FOR IDENTIFICATION OF A PRETERM SUBPOPULATION AT HIGHEST RISK FOR INVASIVE FUNGAL INFECTION. The Pediatric Infectious Disease Journal 27:12, 1114-1116
CrossRef57
C. M. Healy. (2008) Fungal Prophylaxis in the Neonatal Intensive Care Unit. NeoReviews 9:12, e562-e570
CrossRef58
Priya A. Prasad, Susan E. Coffin, Kateri H. Leckerman, Thomas J. Walsh, Theoklis E. Zaoutis. (2008) Pediatric Antifungal Utilization. The Pediatric Infectious Disease Journal 27:12, 1083-1088
CrossRef59
David A Kaufman. (2008) Prevention of invasive Candida infections in preterm infants: the time is now. Expert Review of Anti-infective Therapy 6:4, 393-399
CrossRef60
Paolo Manzoni, MariaLisa Leonessa, Paolo Galletto, Maria Agnese Latino, Riccardo Arisio, Milena Maule, Giovanni Agriesti, Luca Gastaldo, Elena Gallo, Michael Mostert, Daniele Farina. (2008) Routine Use of Fluconazole Prophylaxis in a Neonatal Intensive Care Unit Does Not Select Natively Fluconazole-Resistant Candida Subspecies. The Pediatric Infectious Disease Journal 27:8, 731-737
CrossRef61
Amy Chang, Dionissios Neofytos, David Horn. (2008) Candidemia in the 21st century. Future Microbiology 3:4, 463-472
CrossRef62
David A Kaufman. (2008) Fluconazole prophylaxis: can we eliminate invasive Candida infections in the neonatal ICU?. Current Opinion in Pediatrics 20:3, 332-340
CrossRef63
J-H Weitkamp, A Ozdas, B LaFleur, A L Potts. (2008) Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure. Journal of Perinatology 28:6, 405-411
CrossRef64
David Isaacs. (2008) Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing?. Current Opinion in Infectious Diseases 21:3, 246-250
CrossRef65
D A Kaufman. (2008) Why prevent Invasive Candida Infections?. Journal of Perinatology 28:6, 385-388
CrossRef66
A. Borghesi, M. Stronati. (2008) Strategies for the prevention of hospital-acquired infections in the neonatal intensive care unit. Journal of Hospital Infection 68:4, 293-300
CrossRef67
Michael J O'Grady, Eugene M Dempsey. (2008) Antifungal prophylaxis for the prevention of neonatal candidiasis?. Acta Paediatrica 97:4, 430-433
CrossRef68
Mario Cruciani, Giovanni Serpelloni. (2008) Management of Candida infections in the adult intensive care unit. Expert Opinion on Pharmacotherapy 9:2, 175-191
CrossRef69
Paolo Manzoni, David A Kaufman, Michael Mostert, Daniele Farina. (2008) Neonatal Candida spp. infections: an update. Pediatric Health 2:1, 79-88
CrossRef70
S K Bharwani, R Dhanireddy. (2008) Systemic fungal infection is associated with the development of retinopathy of prematurity in very low birth weight infants: a meta-review. Journal of Perinatology 28:1, 61-66
CrossRef71
László Maródi, Richard B Johnston. (2007) Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Current Opinion in Pediatrics 19:6, 693-697
CrossRef72
Paolo Manzoni. (2007) Use of Lactobacillus casei Subspecies Rhamnosus GG and Gastrointestinal Colonization by Candida Species in Preterm Neonates. Journal of Pediatric Gastroenterology and Nutrition 45:Suppl 3, S190-S194
CrossRef73
Theoklis Zaoutis, Thomas J Walsh. (2007) Antifungal therapy for neonatal candidiasis. Current Opinion in Infectious Diseases 20:6, 592-597
CrossRef74
Linda Clerihew, Nicola Austin, William McGuire, William McGuire. 2007. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. .
CrossRef75
Christine C Chiou, Thomas J Walsh, Andreas H Groll. (2007) Clinical pharmacology of antifungal agents in pediatric patients. Expert Opinion on Pharmacotherapy 8:15, 2465-2489
CrossRef76
(2007) Empfehlung zur Prävention nosokomialer Infektionen bei neonatologischen Intensivpflegepatienten mit einem Geburtsgewicht unter 1500 g. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 50:10, 1265-1303
CrossRef77
(2007) Prophylactic Fluconazole in Preterm Neonates. New England Journal of Medicine 357:13, 1348-1349
Full Text78
Mohan Pammi, Oya Eddama, Leonard E Weisman, Mohan Pammi. 2007. Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units. .
CrossRef79
Sobel, Jack D., Revankar, Sanjay G., . (2007) Echinocandins — First-Choice or First-Line Therapy for Invasive Candidiasis?. New England Journal of Medicine 356:24, 2525-2526
Full Text80
Manzoni, Paolo, Stolfi, Ilaria, Pugni, Lorenza, Decembrino, Lidia, Magnani, Cristiana, Vetrano, Gennaro, Tridapalli, Elisabetta, Corona, Giuseppina, Giovannozzi, Chiara, Farina, Daniele, Arisio, Riccardo, Merletti, Franco, Maule, Milena, Mosca, Fabio, Pedicino, Roberto, Stronati, Mauro, Mostert, Michael, Gomirato, Giovanna, . (2007) A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates. New England Journal of Medicine 356:24, 2483-2495
Full Text81
Paolo Manzoni, Daniele Farina, Paolo Galletto, Marialisa Leonessa, Claudio Priolo, Riccardo Arisio, Giovanna Gomirato. (2007) Type and number of sites colonized by fungi and risk of progression to invasive fungal infection in preterm neonates in neonatal intensive care unit. Journal of Perinatal Medicine 35:3, 220-226
CrossRef82
Luc P. Brion, Smart E. Uko, David L. Goldman. (2007) Risk of resistance associated with fluconazole prophylaxis: Systematic review. Journal of Infection 54:6, 521-529
CrossRef83
T. E. Zaoutis, K. Heydon, R. Localio, T. J. Walsh, C. Feudtner. (2007) Outcomes Attributable to Neonatal Candidiasis. Clinical Infectious Diseases 44:9, 1187-1193
CrossRef84
Imad R. Makhoul, Yoram Bental, Meir Weisbrod, Polo Sujov, Ayala Lusky, Brian Reichman. (2007) Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey. Journal of Hospital Infection 65:3, 237-243
CrossRef85
Rachel L. Chapman. (2007) Prevention and Treatment of Candida Infections in Neonates. Seminars in Perinatology 31:1, 39-46
CrossRef86
Soo Young Kim, Soon Joo Lee, Mi Jeong Kim, Eun Song Song, Young Youn Choi. (2007) Fluconazole prophylaxis in high-risk, very low birth weight infants. Korean Journal of Pediatrics 50:7, 636
CrossRef87
Paolo Manzoni, Daniele Farina, Cesare Monetti, Claudio Priolo, MariaLisa Leonessa, Chiara Giovannozzi, Giovanna Gomirato. (2007) Early-onset neutropenia is a risk factor for Candida colonization in very low-birth-weight neonates. Diagnostic Microbiology and Infectious Disease 57:1, 77-83
CrossRef88
Benito Almirante, Dolors Rodríguez. (2007) Antifungal Agents in Neonates. Pediatric Drugs 9:5, 311-321
CrossRef89
Ralf Bialek, Andreas Groll, Ulrich Heininger, Volker Schuster. 2007. Infektionserkrankungen. , 439-533.
CrossRef90
J. M. Cisneros Herreros, E. Cordero Matía. (2006) Therapeutic armamentarium against systemic fungal infections. Clinical Microbiology and Infection 12:s7, 53-64
CrossRef91
Paolo Manzoni, Daniele Farina, Elisa Antonielli d'Oulx, Maria Luisa Leonessa, Giovanna Gomirato, Ricardo Arisio. (2006) An association between anatomic site of Candida colonization and risk of invasive candidiasis exists also in preterm neonates in neonatal intensive care unit. Diagnostic Microbiology and Infectious Disease 56:4, 459-460
CrossRef92
Gloria P. Heresi, Dale R. Gerstmann, Michael D. Reed, John N. van den Anker, Jeffrey L. Blumer, Laura Kovanda, James J. Keirns, Donald N. Buell, Gregory L. Kearns. (2006) The Pharmacokinetics and Safety of Micafungin, a Novel Echinocandin, in Premature Infants. The Pediatric Infectious Disease Journal 25:12, 1110-1115
CrossRef93
Mehmet Adnan Ozturk, Tamer Gunes, Esad Koklu, Neside Cetin, Nedret Koc. (2006) Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit. Mycoses 49:6, 484-492
CrossRef94
Jacob Gilad, Abraham Borer. (2006) Prevention of catheter-related bloodstream infections in the neonatal intensive care setting. Expert Review of Anti-infective Therapy 4:5, 861-873
CrossRef95
Miguel Salavert Lletí, Isidro Jarque Ramos, Javier Pemán García. (2006) Los aspectos epidemiológicos cambiantes de la candidemia y sus implicaciones clinicoterapéuticas. Enfermedades Infecciosas y Microbiología Clínica 24, 36-45
CrossRef96
William J. Steinbach, Thomas J. Walsh. (2006) Mycoses in Pediatric Patients. Infectious Disease Clinics of North America 20:3, 663-678
CrossRef97
Z H Aghai, M Mudduluru, T A Nakhla, B Amendolia, D Longo, N Kemble, S Kaki, R Sutsko, J G Saslow, G E Stahl. (2006) Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis. Journal of Perinatology 26:9, 550-555
CrossRef98
David A. Kaufman, Matthew J. Gurka, Kevin C. Hazen, Robert Boyle, Melinda Robinson, Leigh B. Grossman. (2006) Patterns of Fungal Colonization in Preterm Infants Weighing Less Than 1000 Grams at Birth. The Pediatric Infectious Disease Journal 25:8, 733-737
CrossRef99
Shelley S. Magill, Sandra M. Swoboda, Elizabeth A. Johnson, William G. Merz, Robert K. Pelz, Pamela A. Lipsett, Craig W. Hendrix. (2006) The association between anatomic site of Candida colonization, invasive candidiasis, and mortality in critically ill surgical patients. Diagnostic Microbiology and Infectious Disease 55:4, 293-301
CrossRef100
P Mohan, O Asim, LE Weisman, Pammi Mohan. 2006. Effect of patient isolation measures for infants with candida colonization or infection on the transmission of candida. .
CrossRef101
P. Manzoni, M. Mostert, M. L. Leonessa, C. Priolo, D. Farina, C. Monetti, M. A. Latino, G. Gomirato. (2006) Oral Supplementation with Lactobacillus casei Subspecies rhamnosus Prevents Enteric Colonization by Candida Species in Preterm Neonates: A Randomized Study. Clinical Infectious Diseases 42:12, 1735-1742
CrossRef102
Renato S. Procianoy, Mariluce V. Enéas, Rita C. Silveira. (2006) Empiric guidelines for treatment of Candida infection in high-risk neonates. European Journal of Pediatrics 165:6, 422-423
CrossRef103
Lisa Saiman. (2006) Strategies for prevention of nosocomial sepsis in the neonatal intensive care unit. Current Opinion in Pediatrics 18:2, 101-106
CrossRef104
Konstantinos Z. Vardakas, George Samonis, Argyris Michalopoulos, Elpidoforos S. Soteriades, Matthew E. Falagas. (2006) Antifungal prophylaxis with azoles in high-risk, surgical intensive care unit patients: A meta-analysis of randomized, placebo-controlled trials*. Critical Care Medicine 34:4, 1216-1224
CrossRef105
R. Perniola, M. L. Faneschi, E. Manso, M. Pizzolante, A. Rizzo, A. Sticchi Damiani, R. Longo. (2006) Rhodotorula mucilaginosa outbreak in neonatal intensive care unit: microbiological features, clinical presentation, and analysis of related variables. European Journal of Clinical Microbiology & Infectious Diseases 25:3, 193-196
CrossRef106
Josef Ben-Ari, Zmira Samra, Elhanan Nahum, Izhak Levy, Shai Ashkenazi, Tommy M. Schonfeld. (2006) Oral amphotericin B for the prevention of Candida bloodstream infection in critically ill children*. Pediatric Critical Care Medicine 7:2, 115-118
CrossRef107
Dolors Rodriguez, Benito Almirante, Benjamin J. Park, Manuel Cuenca-Estrella, Ana M. Planes, Ferran Sanchez, Amadeu Gene, Mariona Xercavins, Dionisia Fontanals, Juan L. Rodriguez-Tudela, David W. Warnock, Albert Pahissa. (2006) Candidemia in Neonatal Intensive Care Units. The Pediatric Infectious Disease Journal 25:3, 224-229
CrossRef108
Catherine M. Bendel. 2006. Candidiasis. , 1107-1128.
CrossRef109
José Manuel Martínez Sesmero, Francisco José Farfán Sedano, Teresa Molina García, Marta Muro Brussi, Javier Sánchez-Rubio Ferrández, Raúl Díez Fernández, Cristóbal Montojo Guillén. (2005) Fungal Chemoprophylaxis with Fluconazole in Preterm Infants. Pharmacy World & Science 27:6, 475-477
CrossRef110
T. E. Zaoutis, J. Argon, J. Chu, J. A. Berlin, T. J. Walsh, C. Feudtner. (2005) The Epidemiology and Attributable Outcomes of Candidemia in Adults and Children Hospitalized in the United States: A Propensity Analysis. Clinical Infectious Diseases 41:9, 1232-1239
CrossRef111
P. Brian Smith, William J. Steinbach, Daniel K. Benjamin. (2005) Neonatal Candidiasis. Infectious Disease Clinics of North America 19:3, 603-615
CrossRef112
Kenneth F Tiffany, Phillip B Smith, Daniel K Benjamin Jr. (2005) Neonatal candidiasis: prophylaxis and treatment. Expert Opinion on Pharmacotherapy 6:10, 1647-1655
CrossRef113
Sharmila S. Shetty, Lee H. Harrison, Rana A. Hajjeh, Tom Taylor, Sara A. Mirza, Alicia Bustamante Schmidt, Laurie Thomson Sanza, Kathleen A. Shutt, Scott K. Fridkin. (2005) Determining Risk Factors for Candidemia Among Newborn Infants From Population-Based Surveillance. The Pediatric Infectious Disease Journal 24:7, 601-604
CrossRef114
Kenneth F Ilett, Judith H Kristensen. (2005) Drug use and breastfeeding. Expert Opinion on Drug Safety 4:4, 745-768
CrossRef115
P. Brian Smith, William J. Steinbach, Daniel K. Benjamin. (2005) Invasive Candida infections in the neonate. Drug Resistance Updates 8:3, 147-162
CrossRef116
Eric C. Eichenwald. 2005. Care of the Extremely Low-Birth-Weight Infant. , 410-426.
CrossRef117
Margaret K. Hostetter. 2005. Fungal Infections in the Neonatal Intensive Care Unit. , 595-600.
CrossRef118
N. E. Edi-Osagie, A. J. B. Emmerson. (2005) Seasonality of invasive Candida infection in neonates. Acta Paediatrica 94:1, 72-74
CrossRef119
N. Edi-Osagie, A. Emmerson. (2005) Seasonality of invasive Candida infection in neonates. Acta Paediatrica 94:1, 72
CrossRef120
J.J. Bafeltowska, E. Buszman. (2005) Pharmacokinetics of Fluconazole in the Cerebrospinal Fluid of Children with Hydrocephalus. Chemotherapy 51:6, 370-376
CrossRef121
Y.-C. Huang, L.-H. Su, T.-L. Wu, T.-Y. Lin. (2004) Genotyping analysis of colonizing candidal isolates from very-low-birthweight infants in a neonatal intensive care unit. Journal of Hospital Infection 58:3, 200-203
CrossRef122
E. Roilides, E. Farmaki, J. Evdoridou, J. Dotis, E. Hatziioannidis, M. Tsivitanidou, E. Bibashi, I. Filioti, D. Sofianou, C. Gil-Lamaignere, F.-M. Mueller, G. Kremenopoulos. (2004) Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates. European Journal of Clinical Microbiology & Infectious Diseases 23:10, 745-750
CrossRef123
Anucha Apisarnthanarak, Galit Holzmann‐Pazgal, Aaron Hamvas, Margaret A. Olsen, Victoria J. Fraser. (2004) Antimicrobial Use and the Influence of Inadequate Empiric Antimicrobial Therapy on the Outcomes of Nosocomial Bloodstream Infections in a Neonatal Intensive Care Unit • . Infection Control and Hospital Epidemiology 25:9, 735-741
CrossRef124
N. Linder, O. Levit, G. Klinger, I. Kogan, I. Levy, I. Shalit, S. Ashkenazi, L. Sirota. (2004) Risk factors associated with candidaemia in the neonatal intensive care unit: a case–control study. Journal of Hospital Infection 57:4, 321-324
CrossRef125
H Johnsson, U Ewald. (2004) The rate of candidaemia in preterm infants born at a gestational age of 23-28 weeks is inversely correlated to gestational age. Acta Paediatrica 93:7, 954-958
CrossRef126
Bradley A. Yoder, Deanna A. Sutton, Vicki Winter, Jacqueline J. Coalson. (2004) RESISTANT CANDIDA PARAPSILOSIS ASSOCIATED WITH LONG TERM FLUCONAZOLE PROPHYLAXIS IN AN ANIMAL MODEL. The Pediatric Infectious Disease Journal 23:7, 687-688
CrossRef127
David Kaufman. (2004) Fungal infection in the very low birthweight infant. Current Opinion in Infectious Diseases 17:3, 253-259
CrossRef128
Luis Ostrosky-Zeichner. (2004) Novel approaches to antifungal prophylaxis. Expert Opinion on Investigational Drugs 13:6, 665-672
CrossRef129
OFER LEVY. (2004) Genetic Screening for Susceptibility to Infection in the NICU Setting. Pediatric Research 55:4, 546-548
CrossRef130
E. Castagnola, M. Machetti, B. Bucci, C. Viscoli. (2004) Antifungal prophylaxis with azole derivatives. Clinical Microbiology and Infection 10:s1, 86-95
CrossRef131
W McGuire, L Clerihew, N Austin, William McGuire. 2004. Prophylactic intravenous antifungal agents to prevent mortality and morbidity in very low birth weight infants. .
CrossRef132
Peter G. Pappas, John H. Rex, Jack D. Sobel, Scott G. Filler, William E. Dismukes, Thomas J. Walsh, John E. Edwards. (2004) Guidelines for Treatment of Candidiasis. Clinical Infectious Diseases 38:2, 161-189
CrossRef133
Philippe Eggimann, Jorge Garbino, Didier Pittet. (2003) Management of candidiasis Management of Candida species infections in critically ill patients. The Lancet Infectious Diseases 3:12, 772-785
CrossRef134
R.P Hobson. (2003) The global epidemiology of invasive Candida infections—is the tide turning?. Journal of Hospital Infection 55:3, 159-168
CrossRef135
Nicola Austin, Brian A Darlow, Nicola Austin. 2003. Prophylactic oral antifungal agents to prevent systemic candida infection in preterm infants. .
CrossRef136
Catherine M Bendel. (2003) Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis. Seminars in Perinatology 27:5, 357-364
CrossRef137
Daniel K Benjamin, Harmony Garges, William J Steinbach. (2003) Candida bloodstream infection in neonates. Seminars in Perinatology 27:5, 375-383
CrossRef138
David Kaufman. (2003) Strategies for prevention of neonatal invasive candidiasis. Seminars in Perinatology 27:5, 414-424
CrossRef139
Joseph M Bliss, Melanie Wellington, Francis Gigliotti. (2003) Antifungal pharmacotherapy for neonatal candidiasis. Seminars in Perinatology 27:5, 365-374
CrossRef140
Rachel L. Chapman. (2003) Candida infections in the neonate. Current Opinion in Pediatrics 15:1, 97-102
CrossRef141
&NA;. (2002) FEATURED ARTICLE. Obstetric Anesthesia Digest 22:4, 165-166
CrossRef142
Helen L. Leather, John R. Wingard. (2002) Prophylaxis, empirical therapy, or pre-emptive therapy of fungal infections in immunocompromised patients: which is better for whom?. Current Opinion in Infectious Diseases 15:4, 369-375
CrossRef143
(2002) Fluconazole Prophylaxis against Fungal Infection in Preterm Infants. New England Journal of Medicine 346:24, 1913-1914
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