Utility of Routine Laboratory Tests for Predicting Gram-Negative Neonatal Sepsis in Low Resources Settings

  • Nabeeha Najatee Akram Mustansiriyah University https://orcid.org/0000-0001-8964-8943
  • Sabah Mohsen Ali Department of Pediatrics, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
  • Rasha Sulaiman Abdul Raheem Department of Pediatrics, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
  • Shaymaa Khalid Abdulqader Department of Radiology Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq
Keywords: Acinetobacter baumannii, C- reactive protein, Neonatal sepsis

Abstract


Background: Gram-negative bacteria increasingly recognized as major pathogens in early-onset neonatal sepsis (EONS). Accurate early prediction of causative agents in EONS remains challenging, particularly in resource-limited settings where specific diagnostic markers are lacking. This study evaluates the diagnostic utility of routinely performed laboratory tests in predicting gram-negative bacterial etiology in EONS.

Methods: retrospective study included neonates with culture proven EONS who admitted to tertiary hospital in Iraq over 12 months period. Based on result of blood culture, participants divided into 2 groups: (group 1): neonates diagnosed with gram negative bacterial sepsis, while (group 2) involve neonates having positive bacterial growth on blood culture. Clinical characteristics and the results of routine septic screen employed include C-reactive protein and hematologic parameters obtained from complete blood counts compared between both groups. A receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of routine laboratory tests for Gram-negative sepsis.

Results: a total of eighty neonates included in the study, Gram negative bacteria accounted for most bacterial isolates 64 (80%), from which Acinetobacter baumannii was the most frequent isolates 31 (38.8%). C-reactive protein titer was significantly higher in neonate with gram negative bacteria (P value 0.003), while each of absolute neutrophile count and N:L ratio was higher in gram positive bacteria (P value 0.03,0.04 consecutively). On multivariate analysis, CRP was significantly associated with gram negative sepsis and on ROC curve CRP titer at cutoff 19.53 demonstrated excellent prediction of gram-negative EONS with an area under the curve of 0.933 (95% CI: 0.807–1.000; p = 0.009).

Conclusion: Most EONS cases were due to gram-negative bacteria, especially Acinetobacter baumannii. High CRP with low ANC and N:L ratio pointed to gram-negative sepsis. CRP >19.5 mg/dl was a strong early predictor for gram negative bacterial growth in blood cultures.

References

Hayes R, Hartnett J, Semova G, Murray C, Murphy K, Carroll L, et al; Infection, Inflammation, Immunology and Immunisation (I4) section of the European Society for Paediatric Research (ESPR). Neonatal sepsis definitions from randomised clinical trials. Pediatr Res. 2023 Apr;93(5):1141-8. doi: 10.1038/s41390-021-01749-3. Epub 2021 Nov 6. Erratum in: Pediatr Res. 2024 Dec;96(7):1882. doi: 10.1038/s41390-024-03416-9.

Mariani M, Parodi A, Minghetti D, Ramenghi LA, Palmero C, Ugolotti E, et al. Early and late onset neonatal sepsis: epidemiology and effectiveness of empirical antibacterial therapy in a III level neonatal intensive care unit. Antibiotics (Basel). 2022 Feb 21;11(2):284. doi: 10.3390/antibiotics11020284.

Sands K, Spiller OB, Thomson K, Portal EAR, Iregbu KC, Walsh TR. Early-onset neonatal sepsis in low- and middle-income countries: current challenges and future opportunities. Infect Drug Resist. 2022 Mar 9;15:933-46. doi: 10.2147/IDR.S294156.

Raturi A, Chandran S. Neonatal sepsis: aetiology, pathophysiology, diagnostic advances and management strategies. Clin Med Insights Pediatr. 2024 Sep 25;18:11795565241281337. doi: 10.1177/11795565241281337.

Abe R, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Tateishi Y, et al. Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care. 2010;14(2):R27. doi: 10.1186/cc8898.

von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, et al. Effect of C-reactive protein-guided antibiotic treatment duration, 7-day treatment, or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated Gram-negative bacteremia: a randomized clinical trial. JAMA. 2020 Jun 2;323(21):2160-9. doi: 10.1001/jama.2020.6348.

Akram NN, Abed MY. Indications and outcome of albumin infusion in a neonatal population: a cross sectional study. J Med Chem Sci. 2022;5(1):129-36. doi: 10.26655/JMCHEMSCI.2022.1.14.

Wen SCH, Ezure Y, Rolley L, Spurling G, Lau CL, Riaz S, et al. Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis. PLoS Med. 2021 Sep 28;18(9):e1003787. doi: 10.1371/journal.pmed.1003787.

Kovacevic P. Can the terms "low resource setting" and "low-income country" be used interchangeably in the context of intensive care medicine? Intensive Care Med. 2023 Oct;49(10):1274-5. doi: 10.1007/s00134-023-07203-8.

Neal SR, Fitzgerald F, Chimhuya S, Heys M, Cortina-Borja M, Chimhini G. Diagnosing early-onset neonatal sepsis in low-resource settings: development of a multivariable prediction model. Arch Dis Child. 2023 Aug;108(8):608-15. doi: 10.1136/archdischild-2022-325158.

Khadka P, Maharjan G, Chapagain G, JanukaThapaliya, Paudyal P. Economic and diagnostic biomarker tests of neonatal sepsis: a prospective study from a tertiary care hospital in a low-income country. Biomed Res Int. 2022 Nov 25;2022:5166380. doi: 10.1155/2022/5166380.

Bunduki GK, Adu-Sarkodie Y. The usefulness of C-reactive protein as a biomarker in predicting neonatal sepsis in a sub-Saharan African region. BMC Res Notes. 2020 Apr 1;13(1):194. doi: 10.1186/s13104-020-05033-1.

Okomo U, Akpalu ENK, Le Doare K, Roca A, Cousens S, Jarde A, et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis. 2019 Nov;19(11):1219-34. doi: 10.1016/S1473-3099(19)30414-1.

Puopolo KM, Benitz WE, Zaoutis TE; Committee on Fetus and Newborn; Committee on Infectious Diseases. Management of neonates born at ≥35 0/7 weeks' gestation with suspected or proven early-onset bacterial sepsis. Pediatrics. 2018 Dec;142(6):e20182894. doi: 10.1542/peds.2018-2894.

Flannery DD, Puopolo KM. Neonatal early-onset sepsis. Neoreviews. 2022 Nov 1;23(11):756-70. doi: 10.1542/neo.23-10-e756.

Kariniotaki C, Thomou C, Gkentzi D, Panteris E, Dimitriou G, Hatzidaki E. Neonatal sepsis: a comprehensive review. Antibiotics (Basel). 2024 Dec 25;14(1):6. doi: 10.3390/antibiotics14010006.

Sgro M, Campbell DM, Mellor KL, Hollamby K, Bodani J, Shah PS. Early-onset neonatal sepsis: Organism patterns between 2009 and 2014. Paediatr Child Health. 2019 Aug 9;25(7):425-31. doi: 10.1093/pch/pxz073.

Moftian N, Rezaei-Hachesu P, Arab-Zozani M, Samad-Soltani T, Esfandiari A, Tabib MS, et al. Prevalence of Gram-negative bacteria and their antibiotic resistance in neonatal sepsis in Iran: a systematic review and meta-analysis. BMC Infect Dis. 2023 Aug 15;23(1):534. doi: 10.1186/s12879-023-08508-1.

Pillay K, Ray-Chaudhuri A, O'Brien S, Heath P, Sharland M. Acinetobacter spp. in neonatal sepsis: an urgent global threat. Front Antibiot. 2024 Sep 3;3:1448071. doi: 10.3389/frabi.2024.1448071.

Mahich S, Angurana SK, Suthar R, Sundaram V, Munda VS, Gautam V. Acinetobacter sepsis among out-born neonates admitted to neonatal unit in pediatric emergency of a tertiary care hospital in North India. Indian J Pediatr. 2021 Feb;88(2):127-33. doi: 10.1007/s12098-020-03460-3.

De AS, Rathi MR, Mathur MM. Mortality audit of neonatal sepsis secondary to acinetobacter. J Glob Infect Dis. 2013 Jan;5(1):3-7. doi: 10.4103/0974-777X.107165.

Al-Mayah QS, Chalob FA, Jawad TI. Incidence of neonatal sepsis in a sample of Iraqi newborns. Pakistan J Biotechnol 2017;14(4):797-802.

Al-Mossawi H, Hassan J, Al-bashier N, Omrani AA. Identification common cause of neonatal sepsis by analytical profile index system (API). Iraqi J Med Sci .2018;16(3):327-34. doi: 10.22578/ijms.16.3.12.

Wahaab ITA, Almaroof SQM, Yaseen ZT. Causative microorganisms and antibiotics susceptibility in neonatal sepsis at neonatal intensive care unit: a longitudinal study from Diyala Governorate in Iraq. Ind J Forensic Med Toxicol. 2021;15(1):101-10. doi: 10.37506/ijfmt.v15i1.13382.

Stocker M, Giannoni E. Game changer or gimmick: inflammatory markers to guide antibiotic treatment decisions in neonatal early-onset sepsis. Clin Microbiol Infect. 2024 Jan;30(1):22-7. doi: 10.1016/j.cmi.2023.02.021.

Kilpatrick R, Greenberg R, Hansen NI, Shankaran S, Carlo WA, Cotten CM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Use and utility of C-reactive protein (CRP) in neonatal early-onset sepsis: a secondary analysis of a prospective surveillance study. J Perinatol. 2025 Jan;45(1):139-45. doi: 10.1038/s41372-024-02064-5.

Güneş H, Yurttutan S, Çobanuşağı M, Doğaner A. CRP/albumin ratio: A promising marker of Gram-negative bacteremia in late-onset neonatal sepsis. Turk Arch Pediatr. 2021 Jan 1;56(1):32-6. doi: 10.14744/TurkPediatriArs.2020.99076.

Published
2025/12/31
Section
Original article