Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2024

Open Access 01-12-2024 | Neonatal Sepsis | Research

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study

Authors: Paraskevi Stylianou-Riga, Theodora Boutsikou, Panayiotis Kouis, Kyriaki Michailidou, Paraskevi Kinni, Rozeta Sokou, Zoi Iliodromiti, Constantinos Pitsios, Panayiotis K. Yiallouros, Nicoletta Iacovidou

Published in: BMC Pediatrics | Issue 1/2024

Login to get access

Abstract

Background

Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition.

Methods

The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as “Confirmed LOS”: positive blood culture - microorganism isolated and LOS symptoms, “Unconfirmed LOS”: negative blood culture and LOS symptoms, and “Controls” group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression.

Results

A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as “Confirmed LOS”, and “unconfirmed LOS” cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01–1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07–1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13–10.25).

Conclusions

The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.
Appendix
Available only for authorised users
Literature
1.
Shuai X, Li X, Wu Y. Prediction for late-onset sepsis in preterm infants based on data from East China. Front Pead 2022, 10.
2.
Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):257.CrossRef
3.
Tsai M, Chu S, Lee C, Hsu J, Huang H, Chiang M, Fu R, Lien R, Huang Y. Recurrent late-onset sepsis in the neonatal intensive care unit: incidence, clinical characteristics and risk factors. Clin Microbiol Infect. 2014;20(11):O928–35.PubMedCrossRef
4.
Rand KM, Austin NC, Inder TE, Bora S, Woodward LJ. Neonatal Infection and later neurodevelopmental risk in the very preterm infant. J Pediatr. 2016;170:97–104.PubMedCrossRef
5.
Shah J, Jefferies AL, Yoon EW, Lee SK, Shah PS. Canadian neonatal network: risk factors and outcomes of late-onset bacterial sepsis in preterm neonates born at < 32 weeks’ gestation. Am J Perinatol. 2015;32(07):675–82.PubMed
6.
Dal-Bó K, Silva RMd, Sakae TM. Nosocomial Infections in a neonatal intensive care unit in South Brazil. Revista Brasileira De Terapia Intensiva. 2012;24:381–5.PubMedPubMedCentralCrossRef
7.
Wu I, Tsai M, Lai M, Hsu L, Chiang M, Lien R, Fu R, Huang H, Chu S, Hsu J. Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus. BMC Infect Dis. 2017;17(1):465.PubMedPubMedCentralCrossRef
8.
Hassani EME, Berkhout S, Niemarkt DJC, Mann HJ, de Boode S, Cossey WP, Hulzebos V, van Kaam CV, Kramer AH, van Lingen BW, van Goudoever RA, Vijlbrief JB, van Weissenbruch DC, Benninga MM, de Boer MA, de Meij NKH. Risk factors for late-onset Sepsis in Preterm infants: a Multicenter Case-Control Study. Neonatology. 2019;116(1):42–51.CrossRef
9.
Resende DS, Peppe ALG, Reis Hd, Abdallah VOS, Ribas RM, Gontijo PP. Late onset sepsis in newborn babies: epidemiology and effect of a bundle to prevent central line associated bloodstream Infections in the neonatal intensive care unit. Brazilian J Infect Dis. 2015;19:52–7.CrossRef
10.
Legeay C, Bourigault C, Lepelletier D, Zahar JR. Prevention of healthcare-associated Infections in neonates: room for improvement. J Hosp Infect. 2015;89(4):319–23.PubMedPubMedCentralCrossRef
11.
Zhang X, Zhivaki D, Lo-Man R. Unique aspects of the perinatal immune system. Nat Rev Immunol. 2017;17(8):495–507.PubMedCrossRef
12.
Dardas M, Gill SR, Grier A, Pryhuber GS, Gill AL, Lee Y, Guillet R. The impact of postnatal antibiotics on the preterm intestinal microbiome. Pediatr Res. 2014;76(2):150–8.PubMedCrossRef
13.
Greenwood C, Morrow AL, Lagomarcino AJ, Altaye M, Taft DH, Yu Z, Newburg DS, Ward DV, Schibler KR. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr. 2014;165(1):23–9.PubMedPubMedCentralCrossRef
14.
McDonnell L, Gilkes A, Ashworth M, Rowland V, Harries TH, Armstrong D, White P. Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis. Gut Microbes. 2021;13(1):1870402.PubMedPubMedCentralCrossRef
15.
Kullberg RF, Wiersinga WJ, Haak BW. Gut microbiota and sepsis: from pathogenesis to novel treatments. Curr Opin Gastroenterol. 2021;37(6):578–85.PubMedCrossRef
16.
Tapiainen T, Koivusaari P, Brinkac L, Lorenzi HA, Salo J, Renko M, Pruikkonen H, Pokka T, Li W, Nelson K. Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci Rep. 2019;9(1):1–11.CrossRef
17.
Zhang X, Borbet TC, Fallegger A, Wipperman MF, Blaser MJ, Müller A. An antibiotic-impacted microbiota compromises the development of colonic regulatory T cells and predisposes to dysregulated immune responses. Mbio. 2021;12(1):3335.CrossRef
18.
Wójkowska-Mach J, Chmielarczyk A, Strus M, Lauterbach R, Heczko P. Neonate bloodstream Infections in organization for economic cooperation and development countries: an update on epidemiology and prevention. J Clin Med. 2019;8(10):1750.PubMedPubMedCentralCrossRef
19.
Cortese F, Scicchitano P, Gesualdo M, Filaninno A, De Giorgi E, Schettini F, Laforgia N, Ciccone MM. Early and late Infections in newborns: where do we stand? A review. Pediatr Neonatology. 2016;57(4):265–73.CrossRef
20.
Shehab El-Din EMR, El-Sokkary MMA, Bassiouny MR, Hassan R. Epidemiology of neonatal sepsis and implicated pathogens: a study from Egypt. BioMed research international 2015, 2015.
21.
Vergnano S, Menson E, Kennea N, Embleton N, Russell AB, Watts T, Robinson MJ, Collinson A, Heath PT. Neonatal Infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed. 2011;96(1):F9–F14.PubMedCrossRef
22.
Daley AJ, Isaacs D, Australasian Study Group for Neonatal Infections. Ten-year study on the effect of intrapartum antibiotic prophylaxis on early onset group B streptococcal and Escherichia coli neonatal sepsis in Australasia. Pediatr Infect Dis J. 2004;23(7):630–4.PubMedCrossRef
23.
Colomer BF, Badia MC, Cotallo DC, Sastre JL, Network GC. The Spanish National Network Grupo Castrillo: 22 years of nationwide neonatal Infection surveillance. Am J Perinatol. 2020;37(S 02):71–S75.
24.
Kyprianou T. Perinatal health indicators, Cyprus public and private maternity units 2014–2016. 2018.
25.
Coggins SA, Glaser K. Updates in Late-Onset Sepsis: Risk Assessment, Therapy, and Outcomes. NeoReviews 2022, 23(11):738–755.
26.
El Hassani SEM, Berkhout DJ, Niemarkt HJ, Mann S, De Boode WP, Cossey V, Hulzebos CV, Van Kaam AH, Kramer BW, van Lingen RA. Risk factors for late-onset sepsis in preterm infants: a multicenter case-control study. Neonatology. 2019;116(1):42–51.CrossRef
27.
Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2):285–91.PubMedCrossRef
28.
29.
Wagstaff JS, Durrant RJ, Newman MG, Eason R, Ward RM, Sherwin CM, Enioutina EY. Antibiotic treatment of suspected and confirmed neonatal sepsis within 28 days of birth: a retrospective analysis. Frontiers in pharmacology 2019,:1191.
30.
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6(1):2–8.PubMedCrossRef
31.
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care–associated Infection and criteria for specific types of Infections in the acute care setting. Am J Infect Control. 2008;36(5):309–32.PubMedCrossRef
32.
Berardi A, Sforza F, Baroni L, Spada C, Ambretti S, Biasucci G, Bolognesi S, Capretti M, Carretto E, Ciccia M. Epidemiology and Complications of late-onset sepsis: an Italian area-based study. PLoS ONE. 2019;14(11):e0225407.PubMedPubMedCentralCrossRef
33.
Team RC. R: A language and environment for statistical computing. 2013.
34.
Tsai M, Hsu J, Chu S, Lien R, Huang H, Chiang M, Fu R, Lee C, Huang Y. Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J. 2014;33(1):e7–e13.PubMedCrossRef
35.
Różańska A, Wójkowska-Mach J, Adamski P, Borszewska-Kornacka M, Gulczyńska E, Nowiczewski M, Helwich E, Kordek A, Pawlik D, Bulanda M. Infections and risk-adjusted length of stay and hospital mortality in Polish neonatology Intensive Care Units. Int J Infect Dis. 2015;35:87–92.PubMedCrossRef
36.
Michael Cotten C, Oh W, McDonald S, Carlo W, Fanaroff AA, Duara S, Stoll B, Laptook A, Poole K, Wright LL. Prolonged hospital stay for extremely premature infants: risk factors, center differences, and the impact of mortality on selecting a best-performing center. J Perinatol. 2005;25(10):650–5.PubMedCrossRef
37.
Stevens W, Shih T, Incerti D, Ton TG, Lee HC, Peneva D, Macones GA, Sibai BM, Jena AB. Short-term costs of preeclampsia to the United States health care system. Obstet Gynecol. 2017;217(3):237–48. e16.
38.
Fenny AP, Otieku E, Labi KA, Asante FA, Enemark U. Costs and extra length of stay because of neonatal bloodstream Infection at a teaching hospital in Ghana. PharmacoEconomics-Open. 2021;5(1):111–20.PubMedCrossRef
39.
Sahiledengle B, Tekalegn Y, Zenbaba D, Woldeyohannes D, Teferu Z. Which factors predict hospital length-of-stay for children admitted to the neonatal intensive care unit and pediatric ward? A hospital-based prospective study. Global Pediatr Health. 2020;7:2333794X20968715.CrossRef
40.
Kawanishi F, Yoshinaga M, Morita M, Shibata Y, Yamada T, Ooi Y, Ukimura A. Risk factors for ventilator-associated Pneumonia in neonatal intensive care unit patients. J Infect Chemother. 2014;20(10):627–30.PubMedCrossRef
41.
Choi Y, Lee J, Park J, Jun YH. Impact of prolonged mechanical ventilation in very low birth weight infants: results from a national cohort study. J Pediatr. 2018;194:34–9. e3.PubMedCrossRef
42.
Rangelova VR, Raycheva RD, Kevorkyan AK, Krasteva MB, Kalchev YI. Ventilator-Associated Pneumonia in neonates admitted to a Tertiary Care NICU in Bulgaria. Front Pediatr. 2022;10:909217.PubMedPubMedCentralCrossRef
43.
Iqbal Q, Younus MM, Ahmed A, Ahmad I, Iqbal J, Charoo BA, Ali SW. Neonatal mechanical ventilation: indications and outcome. Indian J Crit care Medicine: peer-reviewed Official Publication Indian Soc Crit Care Med. 2015;19(9):523.CrossRef
44.
Ramirez P, Bassi GL, Torres A. Measures to prevent nosocomial Infections during mechanical ventilation. Curr Opin Crit Care. 2012;18(1):86–92.PubMedCrossRef
45.
Makhoul IR, Sujov P, Smolkin T, Lusky A, Reichman B. Israel Neonatal Network: Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics. 2002;109(1):34–9.PubMedCrossRef
46.
Bech CM, Stensgaard CN, Lund S, Holm-Hansen C, Brok JS, Nygaard U, Poulsen A. Risk factors for neonatal sepsis in Sub-saharan Africa: a systematic review with meta-analysis. BMJ open. 2022;12(9):e054491.PubMedPubMedCentralCrossRef
47.
48.
Andegiorgish AK, Andemariam M, Temesghen S, Ogbai L, Ogbe Z, Zeng L. Neonatal mortality and associated factors in the specialized neonatal care unit Asmara, Eritrea. BMC Public Health. 2020;20(1):1–9.CrossRef
49.
Tewabe T, Mehariw Y, Negatie E, Yibeltal B. Neonatal mortality in the case of Felege Hiwot referral hospital, Bahir Dar, Amhara Regional State, North West Ethiopia 2016: a one year retrospective chart review. Ital J Pediatr. 2018;44(1):1–5.CrossRef
50.
Falciglia HS, Merkel RC, Glover V, Hasselfeld KA, Brady WK. The mortality of periviable and extremely premature infants and their impact on the overall neonatal mortality rate. Sci Rep. 2020;10(1):1–7.CrossRef
51.
52.
Stylianou-Riga P, Kouis P, Kinni P, Rigas A, Papadouri T, Yiallouros PK, Theodorou M. Maternal socioeconomic factors and the risk of premature birth and low birth weight in Cyprus: a case–control study. Reproductive Health. 2018;15(1):1–8.CrossRef
53.
Howarth C, Banerjee J, Aladangady N. Red blood cell transfusion in Preterm infants: current evidence and controversies. Neonatology. 2018;114(1):7–16.PubMedCrossRef
54.
Meyer MP, O’Connor KL, Meyer JH. Thresholds for blood transfusion in extremely preterm infants: a review of the latest evidence from two large clinical trials. Front Pead. 2022;10:957585.CrossRef
55.
dos Santos AMN, Guinsburg R, de Almeida MFB, Procianoy RS, Marba STM, Ferri WAG, Rugolo LMS, Lopes JMA, Moreira MEL, Luz JH. Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units. BMC Pediatr. 2015;15(1):1–8.
56.
57.
Resch E, Hinkas O, Urlesberger B, Resch B. Neonatal thrombocytopenia—causes and outcomes following platelet transfusions. Eur J Pediatr. 2018;177(7):1045–52.PubMedPubMedCentralCrossRef
58.
Amrutiya RJ, Mungala BM, Patel VT, Ganjiwale JD, Nimbalkar SM. Blood component transfusion in Tertiary Care neonatal intensive care unit and neonatal Intermediate Care Unit: an audit. Cureus 2020, 12(8).
59.
Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, LaGamma EF. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. 2006;23(08):451–8.PubMedCrossRef
60.
Slidsborg C, Jensen A, Forman JL, Rasmussen S, Bangsgaard R, Fledelius HC, Greisen G, la Cour M. Neonatal risk factors for treatment-demanding retinopathy of prematurity: a Danish national study. Ophthalmology. 2016;123(4):796–803.PubMedCrossRef
61.
Baer VL, Lambert DK, Henry E, Snow GL, Butler A, Christensen RD. Among very-low‐birth‐weight neonates is red blood cell transfusion an Independent risk factor for subsequently developing a severe intraventricular Hemorrhage? Transfusion 2011, 51(6):1170–8.
62.
Ghirardello S, Dusi E, Cortinovis I, Villa S, Fumagalli M, Agosti M, Milani S, Mosca F. Effects of red blood cell transfusions on the risk of developing Complications or death: an observational study of a cohort of very low birth weight infants. Am J Perinatol. 2017;34(01):88–95.PubMed
63.
dos Santos AMN, Guinsburg R, de Almeida MFB, Procianoy RS, Leone CR, Marba STM, de Souza Rugolo LMS, Fiori HH, de Andrade Lopes JM, Martinez FE. Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants. J Pediatr. 2011;159(3):371–6. e3.PubMedCrossRef
64.
Heeger LE, Counsilman CE, Bekker V, Bergman KA, Zwaginga JJ, Te Pas AB, Lopriore E. Restrictive guideline for red blood cell transfusions in preterm neonates: effect of a protocol change. Vox Sang. 2019;114(1):57–62.PubMedCrossRef
65.
Knee D, Knoop S, Davis AT, Rawson B, DiCarlo A, Olivero R. Outcomes after implementing restrictive blood transfusion criteria in extremely premature infants. J Perinatol. 2019;39(8):1089–97.PubMedCrossRef
66.
Wang P, Wang X, Deng H, Li L, Chong W, Hai Y, Zhang Y. Restrictive versus Liberal transfusion thresholds in very low birth weight infants: a systematic review with meta-analysis. PLoS ONE. 2021;16(8):e0256810.PubMedPubMedCentralCrossRef
67.
68.
69.
Samuels N, van de Graaf RA, de Jonge RC, Reiss IK, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17(1):1–9.CrossRef
70.
71.
Unger S, Stintzi A, Shah P, Mack D, O’Connor DL. Gut microbiota of the very-low-birth-weight infant. Pediatr Res. 2015;77(1):205–13.PubMedCrossRef
72.
AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evidence-Based Child Health: A Cochrane Review Journal. 2014;9(3):584–671.PubMedCrossRef
73.
Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi SN, Pirotta M, Morley CJ, Garland SM, ProPrems Study Group. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics. 2013;132(6):1055–62.PubMedCrossRef
74.
Zhang G, Hu H, Liu C, Shakya S, Li Z. Probiotics for preventing late-onset sepsis in preterm neonates: a PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine 2016, 95(8).
75.
Craighead AF, Caughey AB, Chaudhuri A, Yieh L, Hersh AR, Dukhovny D. Cost-effectiveness of probiotics for necrotizing enterocolitis prevention in very low birth weight infants. J Perinatol. 2020;40(11):1652–61.PubMedCrossRef
76.
Beghetti I, Panizza D, Lenzi J, Gori D, Martini S, Corvaglia L, Aceti A. Probiotics for preventing necrotizing enterocolitis in preterm infants: a network meta-analysis. Nutrients. 2021;13(1):192.PubMedPubMedCentralCrossRef
77.
Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2015;100(3):F257–63.PubMedCrossRef
78.
Dillenseger L, Langlet C, Iacobelli S, Lavaux T, Ratomponirina C, Labenne M, Astruc D, Severac F, Gouyon JB, Kuhn P. Early inflammatory markers for the diagnosis of late-onset sepsis in neonates: the nosodiag study. Front Pead. 2018;6:346.CrossRef
79.
Bury G, Leroux S, Leon Borrego C, Gras Leguen C, Mitanchez D, Gascoin G, Thollot A, Roué JM, Carrault G, Pladys P. Diagnosis of neonatal late-onset Infection in very preterm infant: inter-observer agreement and international classifications. Int J Environ Res Public Health. 2021;18(3):882.PubMedPubMedCentralCrossRef
Metadata
Title
Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study
Authors
Paraskevi Stylianou-Riga
Theodora Boutsikou
Panayiotis Kouis
Kyriaki Michailidou
Paraskevi Kinni
Rozeta Sokou
Zoi Iliodromiti
Constantinos Pitsios
Panayiotis K. Yiallouros
Nicoletta Iacovidou
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Neonatal Sepsis
Published in
BMC Pediatrics / Issue 1/2024
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-023-04359-6

Other articles of this Issue 1/2024

BMC Pediatrics 1/2024 Go to the issue

Research

Ultrasound assessment of malnutrition in infancy: a pilot case-control study

Research

Population-based cross-sectional study of factors influencing full vaccination status of children aged 12- 23 months in a rural district of the Upper East Region, Ghana

Research

Risk factor analysis and nomogram prediction model construction for NEC complicated by intestinal perforation

Research

Vacuum bell therapy for pectus excavatum: a retrospective study

Research

Identifying factors associated with substantially reduced adult height in patients with juvenile idiopathic arthritis: a retrospective cohort study

Research

Values of serum intestinal fatty acid-binding protein, fecal calprotectin, and fecal human β-defensin 2 for predicting necrotizing enterocolitis