Clinical and epidemiological features and organ dysfunction in newborns with neonatal sepsis

Purpose. To evaluate clinical and epidemiological features of neonatal sepsis and assess the impact of organ dysfunction on its outcome.

Characteristics of children and research methods. The authors carried out a retrospective analysis of 66 patients with neonatal sepsis hospitalized to the neonatal intensive care unit of the Kazan City Children’s Hospital No. 1 from 2013 to 2017. The diagnosis was based on the development of a systemic inflammatory response syndrome, an increase in C-reactive protein concentration in the blood more than 1 mg/dl, the presence of one or more foci of infection, the development of organ dysfunction and the isolation of the microorganism from venous blood. Bacteremia was a mandatory inclusion criterion.

Results. In the most cases (54.5%) neonatal sepsis was caused by gram-negative bacteria. 41 and 4.5% of cases were caused by gram-positive bacteria and fungi, respectively. Among the gram-negative bacteria, the main causative agents of sepsis were Klebsiella pneumoniae (27 cases, 41%), among the gram-positive bacteria –staphylococci (24 cases, 36.5%). Fungal sepsis was caused by Candida kruzei (2 cases) and Candida albicans (1 case). In 11 (17%) cases there was a dysfunction of a single organ, in 31 (47%) cases – dysfunction of 2 organs and in 24 (36%) cases – dysfunction of more than 2 organs. The most common impairments were respiratory dysfunction (86%) and hemostatic disorders in the form of thrombocytopenia (58%). Neonatal sepsis was fatal in 11 (17%) cases. It was found that the multiple organ dysfunction was associated with a risk of death (odds ratio – OR = 29.3; 95% CI 3.4–249.7). Among the signs of organ dysfunction, coma (OR = 30.8; 95% CI 3.0–316.6), elevated blood lactate level of more than 5 mmol/l (OR = 22.1; 95% CI 3.5–139,6) and a low platelet count of less than 50 · 109/l (OR = 5; 95% CI 1.2–21.3) had the prognostic significance.

Conclusion. Modern neonatal sepsis has a diverse etiology with gram-negative bacteria as causative agents in half of the cases. Despite modern treatment methods, neonatal sepsis remains a formidable infectious pathology. The risk of fatal outcome is associated with organ dysfunction. Coma, elevated blood lactate level and severe thrombocytopenia are the most significant predictors of fatal outcome in neonatal sepsis.

1. Verma P., Berwal P.K., Nagaraj N. Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Int J Contemp Pediatr 2015; 2 (3): 176–180. DOI: 10.18203/2349-3291.ijcp20150523

2. Camacho-Gonzales A., Spearman P.W., Stoll B.J. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013; 60: 367–389. DOI: 10.1016/j.pcl.2012.12.003

3. Vergano S., Menson E., Kennea N., Embleton N., Russell A.B., Watts, T. et al. Neonatal Infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011; 96: F9–14. DOI: 10.1136/adc.2009.178798

4. Stoll B.J., Hansen N.I., Sanchez P.J., Faix R.G., Poindexter B.B., Van Meurs K.P. et al. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics 2011; 127: 817–826. DOI: 10.1542/peds.2010–2217

5. Самсыгина Г.А. Неонатальный сепсис. М., 2014; 173. [Samsygina G.A. Neonatal sepsis. Moscow, 2014; 173 (in Russ.)]

6. Островский А.Д., Воробьев А.С. Сепсис у детей раннего возраста. Л., 1979; 125. [Ostrovskij A.D., Vorob’ev A.S. Sepsis in young children. Leningrad, 1979; 125 (in Russ.)]

7. Borghesi A., Stronati M. Superbugs and antibiotics in the newborn. J Pediatr Neonat Indiv Med 2015; 4(2): e040253. DOI: 10.7363/040253

8. Shane A., Sanchez P., Stoll B. Neonatal sepsis. Lancet 2017; www.the lancet.com. DOI: dx.doi.org/10.1016/S010-6736(17)31002-4

9. Wynn J.L. Defining neonatal sepsis. Curr Opin Pediatr 2016; 28: 135–140. DOI: 10.1097/MOP.0000000000000315

10. Singer M., Deuschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M. et al. The Third International Consensus definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801–810. DOI: 10.1001/jama.2016.0287

11. Cuenca A.G., Wynn J.L., Moldawer L.L., Levy O. Role of Innate Immunity in Neonatal Infection. Am J Perinatol 2013; 30(2): 105–112. DOI: 10.1055/s-0032-1333412

12. Cortese F., Scicchitano P., Gesualdo M., Filaninno A., De Giorgi E. Early and Late Infections in Newborns: Where Do We Stand? Pediatr Neonatol 2016; 57: 265–273. DOI: 10.1016/j.pedneo.2015.09.007

13. Tsai M.H., Hsu J.F., Chu S.M., Lien R., Huang H.R., Chiang M.C. et al. Incidence, clinical characteristics, and risk factors for adverse outcome in neonates with late onset sepsis. Pediatr Infect Dis J 2014; 33: 7–13. DOI: 10.1097/INF.0b013e3182a72ee0

14. Paolucci M., Landini M.P., Sambri V. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis? Int J Pediatr 2012; 2012: 120139. DOI: 10.1155/2012/120139

15. Stoll B.J., Hansen N.I., Fanaroff A.A., Wright L.L., Carlo W.A., Ehrenkranz R.A. et al. Late onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110: 285–291.

16. Dong Y., Speer C.P. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed 2014; 0: F1–F7. DOI: 10.1136/archdischild-2014-306213

17. Gelband H., Miller-Petrie M., Pant S., Gandra S., Levinson J., Barter D. et al. The state of the world’s antibiotics. 2015; Washington: Center for Disease Dynamics, Economics, Policy. https://cddep.org/sites/default/files/swa_2015_final.pdf

18. Haller S., Eller C., Hermes J., Kaase M., Steglich M., Radonic A. et al. What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstucting transmission with epidemiological analysis and whole-genome sequencing. BMJ 2015; 5: e007397. DOI: 10.1136/bmjopen-2014-007397

19. Хаертынов Х.С., Анохин В.А, Николаева И.В., Семенова Д.Р., Любин С.А., Агапова И.В. и др. Клебсиеллезный неонатальный сепсис. Медицинский Вестник Северного Кавказа 2016; 1: 82–86. [Khaertynov Kh.S., Anohin V.A., Nikolaeva I.V., Semenova D.R., Lyubin S.A., Agapova I.V. et al. Neonatal sepsis caused by Klebsiella. Meditsinskii vestnik Severnogo Kavkaza 2016; 11: 82–86. DOI: 10.14300/mnnc.2016. 11004 (in Russ.)]

20. Podschun R., Ullmann U. Klebsiella spp. As Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors. Clin Microbiol Rev 1998; 4: 589–603.

21. Perlroth J., Choif., Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 2007; 45: 321–346. DOI: 10.1080/13693780701218689

22. Cohen-Wolkowiez M., Moran C., Benjamin D.K., Cotten C.M., Clark R.H., Benjamin D.K et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009; 28: 1052–1056.

23. Wong H.R., Salisbury S., Xiao Q., Cvijanovich N.Z., Hall M., Allen G.L. et al. The pediatric sepsis biomarker risk model. Crit Care 2012; 16(5): R174. DOI: 10.1186/cc11652

24. Wong H.R., Weiss S.L., Giuliano J.S., Wainwright M.S., Cvijanovich N.Z., Thomas N.J. et al. Testing the prognostic accuracy of the updated pediatric sepsis biomarker risk model. PLoS One 2014; 9(1): e86242. DOI: 10.1371/journal.pone.0086242

25. Aufieri R., Picone S., Paolillo P. Multiple organ failure in the newborn. J Pediatr Neonat Individ Med 2014; 3(2): e030254. DOI: 10.7363/030254

26. Matics T.J., L. Sanchez-Pinto N. Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children. JAMA Pediatr 2017; 171(10): e172352. DOI: 10.1001/jamapediatrics.2017.2352

27. Лекманов А.У., Миронов П.И., Руднов В.А., Кулабухов В.В. Современные дефиниции и принципы интенсивной терапии сепсиса у детей. Вестник анестезиологии и реаниматологии 2018; 15(4): 61–69. [Lekmanov А.U., Mironov P.I., Rudnov V.А., Kulabukhov V.V. Modern definitions and principles of intensive care for sepsis in children. Vestnik anesteziologii i reanimatologii ( Bulletin of Anesthesiology and Intensive Care) 2018; 15(4): 61–69 (in Russ.)] DOI: 10.21292/2078-5658-2018-15-4-61-69