Systemic Candidosis Diagnostic Test with Candida Score and Monocyte Count in Premature Infants with Late-Onset Sepsis: Research in Low Resources Country

Irene Ratridewi; Ратридеви Ирэн; K. Amalia; Амалия Х.; T. E.C.J. Huwae; Хувеа Т. Э.К.Ю.; M. A. Putera; Путера М. Э.; E. Sulistijono; Сулистихоно Э.

doi:10.15789/2220-7619-SCD-2012

Systemic Candidosis Diagnostic Test with Candida Score and Monocyte Count in Premature Infants with Late-Onset Sepsis: Research in Low Resources Country

Authors: Ratridewi I.¹, Amalia K.¹, Huwae T.E.¹, Putera M.A.², Sulistijono E.¹
Affiliations:
1. Saiful Anwar Hospital
2. Melati Husada Hospital
Issue: Vol 13, No 1 (2023)
Pages: 133-140
Section: ORIGINAL ARTICLES
URL: https://journal-vniispk.ru/2220-7619/article/view/126041
DOI: https://doi.org/10.15789/2220-7619-SCD-2012
ID: 126041

Cite item

Full Text

Abstract
Full Text
About the authors
References
Supplementary files
Statistics

Abstract

Introduction. Candida is the cause of most systemic fungal infections that plays a role in the pathophysiology of sepsis in newborns, especially in premature infants with late-onset sepsis. The Candida score can be used to assess the occurrence of systemic candidosis where a Candida score > 2.5 can accurately identify patients who are at high risk for candidiasis infection. Monocytes also play an important role in preventing candida invasion. Materials and methods. This study used a cross sectional research design. Data was collected from premature infants with late-onset sepsis being suspected of systemic candidosis in neonatology inpatient ward. It was submitted from the period of November-December 2021. It takes a minimum of 31 samples to meet the criteria to process and analyze the data. The data obtained were processed and analyzed using the Receiver Operating Characteristic (ROC) method to obtain the Area Under Curve (AUC) value. Based on the AUC curve, the search for the most optimal intersection is carried out to obtain the sensitivity and specificity values. Results. Of the 31 research subjects, the number of subjects with positive PCR results was 27 (76.93%) while negative were 4 respondents (12.9%). The mean value of PCR density in the positive group of subjects was 76.93 and the range was 40.23–122.78. Meanwhile, in the group of subjects who were negative, the PCR density value was 0. The results of the Candida score diagnostic test showed that the sensitivity obtained was 81%. Higher sensitivity and specificity > 70% were found in the combined examination of Candida scores and monocyte counts according to cut-off compared with separate examinations. Conclusions. The combined examination of Candida score and monocyte count can be used as a diagnostic test for systemic candidosis in premature infants with late-onset sepsis, and could be used to consider the initiation of empirical antifungal therapy, either prophylactically or therapeutically, especially in limited laboratory facilities in Indonesia.

Keywords

Candida score, diagnostic test, late onset sepsis, monocyte count, premature infant, systemic candidosis

Full Text

Dr., SpA(K), Pediatric Department, Division of Neonatology

Indonesia, Malang, Jawa Timur

References

Avila-Aguero M.L., Canas-Coto A., Ulloa-Gutierrez R., Caro M.A., Alfaro B., Paris M.M. Risk factors for Candida infections in a neonatal intensive care unit in Costa Rica. Int. J. Infect. Dis., 2005, vol. 9, no. 2, pp. 90–95. doi: 10.1016/j.ijid.2004.05.007
Aziz M., Patel A.L., Losavio J., Iyengar A., Berven M., Schloemer N., Jakubowicz A., Mathai T., McAuley J.B. Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants. Pediatr. Infect. Dis. J., 2010, vol. 29, no. 4, pp. 352–356. doi: 10.1097/INF.0b013e3181bf8eb1
De Jong E., Strunk T., Burgner D., Lavoie P.M., Currie A. The phenotype and function of preterm infant monocytes: implications for susceptibility to infection. J. Leukoc. Biol., 2017, vol. 102, no. 3, pp. 645–656. doi: 10.1189/jlb.4RU0317-111R
El-Atawi K., Elhalik M., Kulkarni T., Abdelsamed A., Alexander L., Alexander L., Satyan A.D., Mahfouz R. Evolving invasive neonatal systemic candidiasis, a review. J. Pediatr. Neonatal Care, 2017, vol. 6, no. 6: 00271. doi: 10.15406/jpnc.2017.06.00271
Greenberg R.G., Kandefer S., Do B.T., Smith P.B., Stoll B.J., Bell E.F., Carlo W.A., Laptook A.R., Sánchez P.J., Shankaran S., Van Meurs K.P., Ball M.B., Hale E.C., Newman N.S., Das A., Higgins R.D., Cotten C.M.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Late-onset sepsis in extremely premature infants: 2000–2011. Pediatr. Infect. Dis. J., 2017, vol. 36, no. 8, pp. 774–779. doi: 10.1097/INF.0000000000001570
Hernández-Castro R., Arroyo-Escalante S., Carrillo-Casas E.M., Moncada-Barrón D., Alvarez-Verona E., Hernández-Delgado L., Torres-Narváez P., Lavalle-Villalobos A. Outbreak of Candida parapsilosis in a neonatal intensive care unit: a health care workers source. Eur. J. Pediatr., 2010, vol. 169, no. 7, pp. 783–787. doi: 10.1007/s00431-009-1109-7
Hsieh E., Smith P.B., Jacqz-Aigrain E., Kaguelidou F., Cohen-Wolkowiez M., Manzoni P., Benjamin D.K. Jr. Neonatal fungal infections: when to treat? Early Hum. Dev., 2012, vol. 88 (suppl. 2), pp. S6–S10. doi: 10.1016/S0378-3782(12)70004-X
İstanbullu K., Köksal N., Çetinkaya M., Özkan H., Yakut T., Karkucak M., Doğan H. The potential utility of real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal sepsis. Turk. J. Pediatr., 2019, vol. 61, no. 4, pp. 493–499. doi: 10.24953/turkjped.2019.04.004
Jaya I.G.A., Suryawan I.W.B., Rahayu P.P. [The relationship of prematurity with the incidence of neonatal sepsis treated in the perinatology ward and the Neonatal Intensive Care Unit (NICU) Wangaya Hospital, Denpasar city]. Intisari Sains Medis, 2019, vol. 10, no. 1, pp. 18–22. doi: 10.15562/ism.v10i1.319
Jordan J.A. PCR identification of four medically important Candida species by using a single primer pair. J. Clin. Microbiol., 1994, vol. 32, no. 12, pp. 2962–2967. doi: 10.1128/jcm.32.12.2962-2967.1994
Kang C.M., Chen X.J., Chih C.C., Hsu C.C., Chen P.H., Lee T.F., Teng L.J., Hsueh P.R. Rapid identification of bloodstream bacterial and fungal pathogens and their antibiotic resistance determinants from positively flagged blood cultures using the BioFire FilmArray blood culture identification panel. J. Microbiol. Immunol. Infect., 2020, vol. 53, no. 6, pp. 882–891. doi: 10.1016/j.jmii.2020.03.018
Kara S.S., Kahveci H., Doğan H., Laloğlu F., Cayir A. Toll-like receptor polymorphism associated with neonatal sepsis in term babies. Firat Med. J., 2020, vol. 25, no. 2, pp. 90–96.
León C., Ruiz-Santana S., Saavedra P., Almirante B., Nolla-Salas J., Alvarez-Lerma F., Garnacho-Montero J., León M.A.; EPCAN Study Group. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit. Care Med., 2006, vol. 34, no. 3, pp. 730–737. doi: 10.1097/01.CCM.0000202208.37364.7D
Lordier L., Meskaldji D.E., Grouiller F., Pittet M.P., Vollenweider A., Vasung L., Borradori-Tolsa C., Lazeyras F., Grandjean D., Van De Ville D., Hüppi P.S. Music in premature infants enhances high-level cognitive brain networks. Proc. Natl Acad. Sci. USA, 2019, vol. 116, no. 24, pp. 12103–12108. doi: 10.1073/pnas.1817536116
Lupetti A., Tavanti A., Davini P., Ghelardi E., Corsini V., Merusi I., Boldrini A., Campa M., Senesi S. Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit. J. Clin. Microbiol., 2002, vol. 40, no. 7, pp. 2363–2369. doi: 10.1128/JCM.40.7.2363-2369.2002
Manzoni P. Invasive Fungal Infections (IFI) in Neonates. URL: https://www.ema.europa.eu/en/documents/presentation/presentation-invasive-fungal-infections-ifi-neonates-state-art-paolo-manzoni_en.pdf (01.07.2022)
Manzoni P., Arisio R., Mostert M., Leonessa M., Farina D., Latino M.A., Gomirato G. 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, vol. 117, no. 1: e22-32. doi: 10.1542/peds.2004-2227
Michalski C., Kan B., Lavoie P.M. Antifungal immunological defenses in newborns. Front. Immunol., 2017, vol. 8: 281. doi: 10.3389/fimmu.2017.00281
Nicholls J.M., Yuen K.Y., Tam A.Y. Systemic fungal infections in neonates. Br. J. Hosp. Med., 1993, vol. 49, no. 6, pp. 420–424.
Ningrum N.D., Suswihardhyono A.N.R. [Maternal and infant factors that influence the incidence of early-onset neonatal sepsis in premature infants]. Jurnal Kedokteran Diponegoro, 2015, vol. 4, no. 4, pp. 1331–1341.
Pappas P.G., Lionakis M.S., Arendrup M.C., Ostrosky-Zeichner L., Kullberg B.J. Invasive candidiasis. Nat. Rev. Dis. Primers, 2018, vol. 4: 18026. doi: 10.1038/nrdp.2018.26
Pauline Voie M., Tunby J., Strømsvik N. Collaboration challenges faced by nurses when premature infants are discharged. Nurs Child Young People, 2018, vol. 30, no. 2, pp. 33–38. doi: 10.7748/ncyp.2018.e960
Puopolo K.M., Mukhopadhyay S., Hansen N.I., Cotten C.M., Stoll B.J., Sanchez P.J., Bell E.F., Das A., Hensman A.M., Van Meurs K.P., Wyckoff M.H.; NICHD Neonatal Research Network. Identification of extremely premature infants at low risk for early-onset sepsis. Pediatrics, 2017, vol. 140, no. 5: e20170925. doi: 10.1542/peds.2017-0925
Putra P.J. [Incidence and factors associated with neonatal sepsis at Sanglah Hospital, Denpasar]. Sari Pediatr., 2012, vol. 14, no. 3, pp. 205–210.
Rahmawati P., Mayetti M., Rahman S. [Relationship between neonatal sepsis and birth weight in babies at RSUP Dr. M. Djamil Padang]. Andalas J. Health., 2018, vol. 7, no. 3, pp. 405–410.
Ratridewi I., Juwita N., Putera M.A., Nugroho S. [The role of Candida score as a diagnostic method of invasive candidiasis against severe neutropenia in children with malignancy]. Sari Pediatr., 2021, vol. 22, no. 6, pp. 351–358.
Rhee C.J., Rios D.R., Kaiser J.R., Brady K. Cerebral hemodynamics in premature infants. Neonatal Med., 2018, vol. 25, no. 1, pp. 1–6. doi: 10.5385/nm.2018.25.1.1
Roilides E., Farmaki E., Evdoridou J., Francesconi A., Kasai M., Filioti J., Tsivitanidou M., Sofianou D., Kremenopoulos G., Walsh T.J. Candida tropicalis in a neonatal intensive care unit: epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen. J. Clin. Microbiol., 2003, vol. 41, no. 2, pp. 735–741. doi: 10.1128/JCM.41.2.735-741.2003
Shane A.L., Sánchez P.J., Stoll B.J. Neonatal sepsis. Lancet, 2017, vol. 390, no. 10104, pp. 1770–1780. doi: 10.1016/S0140-6736(17)31002-4
Șular F.-L., Iancu M., Cucerea M., Moldovan E., Ognean M.L., Dobreanu M. Oxidative burst of neonatal and adult peripheral blood phagocytes confronting Escherichia coli and Candida albicans. Rom. Biotechnol. Lett., 2020, vol. 25, no. 2, pp. 1340–1347. doi: 10.25083/rbl/25.2/1340.1347
Swanson J.R., Gurka M.J., Kaufman D.A. Risk Factors for invasive fungal infection in premature infants: enhancing a targeted prevention approach. J. Pediatric Infect. Dis. Soc., 2014, vol. 3, no. 1, pp. 49–56. doi: 10.1093/jpids/pit068
Tezer H., Canpolat F.E., Dilmen U. Invasive fungal infections during the neonatal period: diagnosis, treatment and prophylaxis. Expert Opin. Pharmacother., 2012, vol. 13, no. 2, pp. 193–205. doi: 10.1517/14656566.2012.647685
Tirodker U.H., Nataro J.P., Smith S., LasCasas L., Fairchild K.D. Detection of fungemia by polymerase chain reaction in critically ill neonates and children. J. Perinatol., 2003, vol. 23, no. 2, pp. 117–122. doi: 10.1038/sj.jp.7210868
Trovato L., Betta P., Romeo M.G., Oliveri S. Detection of fungal DNA in lysis-centrifugation blood culture for the diagnosis of invasive candidiasis in neonatal patients. Clin. Microbiol. Infect., 2012, vol. 18, no. 3: E63-5. doi: 10.1111/j.1469-0691.2011.03731.x
Vogel K., Pierau M., Arra A., Lampe K., Schlueter D., Arens C., Brunner-Weinzierl M.C. Developmental induction of human T-cell responses against Candida albicans and Aspergillus fumigatus. Sci. Rep., 2018, vol. 8, no. 1: 16904. doi: 10.1038/s41598-018-35161-5
White P.L., Williams D.W., Kuriyama T., Samad S.A., Lewis M.A., Barnes R.A. Detection of Candida in concentrated oral rinse cultures by real-time PCR. J. Clin. Microbiol., 2004, vol. 42, no. 5, pp. 2101–2107. doi: 10.1128/JCM.42.5.2101-2107.2004
Wynn J.L. Defining neonatal sepsis. Curr. Opin. Pediatr., 2016, vol. 28, no. 2, pp. 135–140. doi: 10.1097/MOP.0000000000000315