This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Web of Science (41) Citing Articles via Google Scholar Google Scholar Articles by Benjamin, D. K. Articles by Walsh, T. J. Search for Related Content PubMed PubMed Citation Articles by Benjamin, D. K., Jr Articles by Walsh, T. J. Related Collections Infectious Disease & Immunity Social Bookmarking                         What's this?

PEDIATRICS Vol. 112 No. 3 September 2003, pp. 634-640

REVIEW ARTICLE

Neonatal Candidemia and End-Organ Damage: A Critical Appraisal of the Literature Using Meta-analytic Techniques

Daniel K. Benjamin, Jr, MD, MPH, PhD^*,,, Charles Poole, MPH, ScD, William J. Steinbach, MD^*,||, Judith L. Rowen, MD^¶ and Thomas J. Walsh, MD^#

^* Department of Pediatrics, Duke University, Durham, North Carolina
Duke University Clinical Research Institute, Durham, North Carolina
University of North Carolina School of Public Health, Chapel Hill, North Carolina
^|| Duke University Mycology Research Unit, Durham, North Carolina
^¶ University of Texas Medical Branch, Galveston, Texas
^# Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland

Objective. Neonatal candidemia is an increasing cause of infant morbidity and mortality. We evaluated the current medical literature in an effort to critique the literature and to document the reported prevalences of end-organ damage after neonatal candidemia.

Methods. We analyzed all peer-reviewed articles of neonatal candidemia published in the English language; inclusion criteria included a cohort limited to all neonatal intensive care unit admissions or all episodes of candidemia in neonates. Articles that also incorporated older patients, did not define a numerator and a denominator for at least 1 form of end-organ damage, included patients from other reports, or did not include all episodes of candidemia in the source population were excluded from the analysis.

Results. Thirty-four articles reported episodes of candidemia and mortality; 21 articles reported prevalence for at least 1 form of end-organ damage. Only 4 (19%) of 21 articles reported prevalence for >4 forms of end-organ damage from the following list: endophthalmitis, meningitis, brain parenchyma invasion, endocarditis, renal abscesses, positive cultures from other normally sterile body fluids, or hepatosplenic abscesses. The median reported prevalence of endophthalmitis was 3% (interquartile range [IQR]: 0%–17%), of meningitis was 15% (IQR: 3%–23%), of brain abscess or ventriculitis was 4% (IQR: 3%–21%), of endocarditis was 5% (IQR: 0%–13%), of positive renal ultrasound was 5% (IQR: 0%–14%), and of positive urine culture was 61% (IQR: 40%–76%). The medical literature concerning end-organ evaluation after episodes of neonatal candidemia is heterogeneous and consists largely of single-center retrospective studies. Year that the data were collected and prevalence of neonates infected with Candida albicans were associated with observed heterogeneity.

Conclusions. Given the heterogeneity of the medical literature, precise estimates of the frequencies of end-organ damage are not possible and a prospective multicenter trial is warranted, but the data from the published literature suggest that the prevalence of neonates with end-organ damage not only is greater than 0 but also is high enough that until such a prospective trial is completed, end-organ studies should be considered before the conclusion of antifungal therapy.

---

Key Words: invasive candidiasis • deep tissue

Abbreviations: NICU, neonatal intensive care unit • CSF, cerebrospinal fluid • CI, confidence interval • POR, prevalence odds ratio

---

Received for publication Sep 25, 2002; Accepted Feb 27, 2003.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M Brecht, L Clerihew, and W McGuire Prevention and treatment of invasive fungal infection in very low birthweight infants Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2009; 94(1): F65 - F69. [Abstract] [Full Text] [PDF]

				R. Petraitiene, V. Petraitis, W. W. Hope, D. Mickiene, A. M. Kelaher, H. A. Murray, C. Mya-San, J. E. Hughes, M. P. Cotton, J. Bacher, et al. Cerebrospinal Fluid and Plasma (1->3)-{beta}-D-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis Antimicrob. Agents Chemother., November 1, 2008; 52(11): 4121 - 4129. [Abstract] [Full Text] [PDF]

				K. C. Wade, D. Wu, D. A. Kaufman, R. M. Ward, D. K. Benjamin Jr., J. E. Sullivan, N. Ramey, B. Jayaraman, K. Hoppu, P. C. Adamson, et al. Population Pharmacokinetics of Fluconazole in Young Infants Antimicrob. Agents Chemother., November 1, 2008; 52(11): 4043 - 4049. [Abstract] [Full Text] [PDF]

				W. W. Hope, N. L. Seibel, C. L. Schwartz, A. Arrieta, P. Flynn, A. Shad, E. Albano, J. J. Keirns, D. N. Buell, T. Gumbo, et al. Population Pharmacokinetics of Micafungin in Pediatric Patients and Implications for Antifungal Dosing Antimicrob. Agents Chemother., October 1, 2007; 51(10): 3714 - 3719. [Abstract] [Full Text] [PDF]

				P. B. Smith, D. K. Benjamin Jr., B. D. Alexander, M. D. Johnson, M. A. Finkelman, and W. J. Steinbach Quantification of 1,3-{beta}-D-Glucan Levels in Children: Preliminary Data for Diagnostic Use of the {beta}-Glucan Assay in a Pediatric Setting Clin. Vaccine Immunol., July 1, 2007; 14(7): 924 - 925. [Abstract] [Full Text] [PDF]

				L Clerihew, T L Lamagni, P Brocklehurst, and W McGuire Candida parapsilosis infection in very low birthweight infants Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2007; 92(2): F127 - F129. [Abstract] [Full Text] [PDF]

				L Clerihew, T L Lamagni, P Brocklehurst, and W McGuire Invasive fungal infection in very low birthweight infants: national prospective surveillance study Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2006; 91(3): F188 - F192. [Abstract] [Full Text] [PDF]

				S. Uko, L. M. Soghier, M. Vega, J. Marsh, G. T. Reinersman, L. Herring, V. A. Dave, S. Nafday, and L. P. Brion Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants Pediatrics, April 1, 2006; 117(4): 1243 - 1252. [Abstract] [Full Text] [PDF]

				M. Kasai, A. Francesconi, R. Petraitiene, V. Petraitis, A. M. Kelaher, H.-s. Kim, J. Meletiadis, T. Sein, J. Bacher, and T. J. Walsh Use of Quantitative Real-Time PCR To Study the Kinetics of Extracellular DNA Released from Candida albicans, with Implications for Diagnosis of Invasive Candidiasis J. Clin. Microbiol., January 1, 2006; 44(1): 143 - 150. [Abstract] [Full Text] [PDF]

				D. K. Benjamin Jr, B. J. Stoll, A. A. Fanaroff, S. A. McDonald, W. Oh, R. D. Higgins, S. Duara, K. Poole, A. Laptook, R. Goldberg, et al. Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months Pediatrics, January 1, 2006; 117(1): 84 - 92. [Abstract] [Full Text] [PDF]

				T. J. Walsh, P. C. Adamson, N. L. Seibel, P. M. Flynn, M. N. Neely, C. Schwartz, A. Shad, S. L. Kaplan, M. M. Roden, J. A. Stone, et al. Pharmacokinetics, Safety, and Tolerability of Caspofungin in Children and Adolescents Antimicrob. Agents Chemother., November 1, 2005; 49(11): 4536 - 4545. [Abstract] [Full Text] [PDF]

				D. Kaufman and K. D. Fairchild Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants Clin. Microbiol. Rev., July 1, 2004; 17(3): 638 - 680. [Abstract] [Full Text] [PDF]