Devleta H Hadzic, Fahrija Skokic, Selmira Brkic, Amina Saracevic


Introduction: Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which has increased the risk of infection and, consequently, fungal sepsis. Candida is the dominant cause, with the rise of resistant non-albicans species. The mortality rate is high and requires timely suspicion and adequate treatment to counteract fatal outcomes.

Objectives:To analyze the clinical and laboratory characteristics of Candida sepsis, compared to bacterial sepsis, in neonates treated in the neonatal intensive care unit. Methods: A retrospective cohort study conducted at the Intensive care unit of Pediatric Clinic Tuzla over a three-year period (2016-2018) analyzed the clinical and laboratory characteristics of neonates with Candida sepsis, evidenced by positive blood culture. The control group was neonates treated at the same time for proven bacterial sepsis. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution.

Results: Out of the total 921 neonates treated over a three-year period, culture-confirmed Candida sepsis was found in 48 (5.2%). Prematurity and low birth weight were the most significant risk factors and affected neonates had a more difficult clinical presentation, more receiving parenteral nutrition, mechanical ventilation, intravenous gamma globulin, and longer intensive treatment. Candida sepsis manifested mainly as late-onset. Laboratory abnormalities mainly included CRP elevation, anemia, leukocyte count deviations, and thrombocytopenia. There was no difference in mortality, 44 neonates recovered (91.7%), while 4 (8.3%) died. Antifungal therapy lasted 20.6 ± 6 days, and intensive treatment 38.2 ± 23.2 days, and was significantly longer compared to the control. All isolates were Candida species without in vitro resistance. In 8 neonates (16.7%) treatment complications were recorded.

Conclusions: Neonatal Candida sepsis endangers life, complicates treatment, increases costs and mortality rate. Recovery depends on timely suspicion, adequate treatment, and supervision. Antifungal susceptibility is also important and requires monitoring of local epidemiological dynamics.


Candida sepsis, neonates, clinical and laboratory characteristics

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Ting JY, Roberts A, Synnes A, Canning R, Bodani J, Monterossa L, et al. Invasive fungal infections in neonates in Canada: epidemiology and outcomes. Pediatr Infect Dis J. 2018;37(11):1154-9.

Klingspor L, Ullberg M, Rydberg J, Kondori N, Serrander L, Swanberg J, et al. Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey. Mycoses. 2018;61(10):777-85.

Caggiano G, Lovero G, De Giglio O, Barbuti G, Montagna O, Laforgia N,et al. Candidemia in the Neonatal Intensive Care Unit: a retrospective, observational survey, and analysis of literature data. Biomed Res Int. 2017;2017:7901763. doi:10.1155/2017/7901763.

Ozkan H, Cetinkaya M, Koksal N, Celebi S, Hacimustafaoglu M. Culture-proven neonatal sepsis in preterm infants in a neonatal intensive care unit over a 7 year period: coagulase-negative Staphylococcus as the predominant pathogen. Pediatrics International. 2014;56(1):60–6.

Kelly M S, Benjamin D K, Smith P B The epidemiology and diagnosis of invasive candidiasis among premature infants. Clin perinatol. 2015;42(1):105–17.

Ballot D E, Bosman N, Nana T, Ramdin T, Cooper PA. Background changing patterns of neonatal fungal sepsis in a developing country. J Trop Pediatr. 2013;59(6):460–4.

Autmizguine J, Tan S, Cohen-Wolkowiez M, Cotten CM, Wiederhold N, Goldberg RN, et al. Antifungal susceptibility and clinical outcome in neonatal candidiasis. Pediatr Infect Dis J. 2018;37(9):923-9.

Chapman B, Slavin M, Marriott D, Halliday C, Kidd S, Arthur I, et al. Changing epidemiology of candidaemia in Australia. J Antimicrob Chemother. 2017; 72(4):1103-8.

Leibovitz E. Strategies for the prevention of neonatal candidiasis. Pediatrics and neonatology. 2012;53(2):83–9.

Mantadakis E, Pana ZD, Zaoutis T. Candidemia in children: Epidemiology, prevention and management. Mycoses. 2018;61(9):614-22.

Tortorano AM, Prigitano A, Lazzarini C, Passera M, Deiana ML, Cavinato S, et al. A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade. Infection. 2013 ;41(3):655-62.

Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche HU, Quan SP et al. Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance) registry, 2004–2008. Diagn Microbiol Infect Dis. 2012;74(4):323–31.

Robinson J A, Pham H D, Bloom B T, Wittler RR. Risk factors for persistent candidemia infection in a neonatal intensive care unit and its effect on mortality and length of hospitalization. J Perinatol. 2012;32(8):621–5.

Hoffmann-Santos H D, Paula C R, Yamamoto ACA, Tadano T, Hahn RC. Six-year trend analysis of nosocomial candidemia and risk factors in two intensive care hospitals in Mato Grosso, midwest region of Brazil. Mycopathologia. 2013;176(5-6):409–15.

Chen IL, Chiu NC, Chi H, Hsu CH, Chang JH, Huang DT, et al. Changing of bloodstream infections in a medical center neonatal intensive care unit. Journal of Microbiology, Immunology and Infection. 2017;50(4):514-20.

Chaurasia D, Goel M, Dhruw S, Dubey D, Dwivedi R. Changing pattern of neonatal fungal sepsis: a matched case–control study. Natl J Med Allied Sci. 2015;4(1):3-7.

Wadile R, Bhate V. Study of clinical spectrum and risk factors of neonatal candidemia. Indian J Pathol Microbiol. 2015;58(4):472–4.

Dorling JS, Field DJ, Manktelow B. Neonatal disease severity scoring systems. Arch Dis Child Fetal Neonatal Ed. 2005;90(1):11–6.

Afonso EDP, Blot S. Effect of gestational age on the epidemiology of late-onset sepsis in neonatal intensive care units - a review. Expert Rev Anti Infect Ther. 2017;15(10):917-24.

Bizzarro MJ, Shabanova V, Baltimore RS, Dembry LM, Ehrenkranz RA, Gallagher PG. Neonatal sepsis 2004-2013: The rise and fall of coagulase-negative staphylococci. J Pediatr. 2015;166(5):1193–9.

Juyal D, Sharma M, Pal S, Rathaur VK, Sharma N. Emergence of non-albicans Candida species in neonatal candidemia. N Am J Med Sci. 2013;5(9):541–5.

Khan EA, Choudhry S, Fatima M, Batool Z. Clinical spectrum, management and outcome of neonatal candidiasis. J Pak Med Assoc. 2015;65(11):1206–9.

Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):e1–50.

Hammoud MS, Al-Taiar A, Fouad M, Raina A, Khan Z. Persistent candidemia in neonatal care units: Risk factors and clinical significance. Int J Infect Dis. 2013; 17(8): e624–8.

Mehara V, Yadava D, Somania P, Bhatambareb G, Mulyea S, Singh K. Neonatal sepsis in a tertiary care center in central India: microbiological profile, antimicrobial sensitivity pattern and outcome. J Neonatal-Perinatal Med. 2013;6(2):165–72.

Hornik CP, Benjamin DK, Becker KC, Benjamin DK Jr, Li J, Clark RH, et al. Use of the complete blood cell count in late-onset neonatal sepsis. Pediatr Infect Dis J. 2012; 31(8):799-802.

Sarvikivi E, Lyytikainen O, Soll DR, Pujol C, Pfaller MA, Richardson M et al. Emergence of fluconazole resistance in a Candida parapsilosis strain that caused infections in a neonatal intensive care unit. J Clin Microbiol 2005;43(6):2729–35.

Sardana V, Pandey A, Madan M, SP Goel, Ashish K Asthana. Neonatal candidemia: a changing trend. Indian J Pathol Microbiol 2012;55(1):132–3.

Rodriguez D, Almirante B, Park BJ, Cuenca-Estrella M, Planes AM, Sanchez F et al. Candidemia in neonatal intensive care units: Barcelona, Spain. Pediatr Infect Dis J. 2006;25(3):224–9.



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