Peculiarities of therapeutic tactics in neonatal sepsis depending on the body's inflammatory response

Authors

DOI:

https://doi.org/10.15574/SP.2023.134.77

Keywords:

newborns, neonatal sepsis, antibacterial therapy

Abstract

Purpose - to conduct a comparative analysis of the effectiveness of etiotropic treatment and supporting therapy of infants with neonatal sepsis with an alternative content of C-reactive protein in the blood serum to improve individualized therapy of generalized infectious and inflammatory diseases in the newborn period.

Materials and methods. A comprehensive examination of 56 newborns suffering from neonatal sepsis the 1st, 3rd and 7th days of the disease. The Group I included 25 patients with neonatal sepsis with a serum C-reactive protein level <20 mg/l, and the Group II included 31 newborns with sepsis with a serum C-reactive protein level >20 mg/l.

Determination of the content of C-reactive protein in blood serum (mg/l) was carried out by the method of immunoenzymatic analysis on the «StatFax 303 / Plus» device.

The obtained results were analyzed by methods of descriptive statistics, biostatistics and clinical epidemiology. Fisher’s exact test (Pφ) and Student’s test were used for statistical processing; the results were significant at p<0.05 with a tendency to significance - at p=0.05-0.1.

Results. It was established that in 20.0% of newborns of the Group I and in 11.4% of patients of the Group II (Рφ>0.05), etiotropic treatment was changed due to insufficient effectiveness of the previous two courses. Patients of the Group I had a higher risk of needing to re-review the composition of antibiotic therapy: odds ratio (OR) = 1.9 (95% confidence interval (95% CI): 0.8-4.3), attributive risk (AR) = 16.0%. Practically all patients of the Group I were on oxygen support, the risk of this event was significantly higher for them compared to children of the Group II: OR=2.7 (95% CI: 1.2-6.6).

Newborns of the Group II compared to babies of the Group I received inpatient treatment for less time, their chances of being discharged from the hospital before the 20th day were probably higher: OR=5.7 (95% CI: 1.85-17.32). The better effectiveness of the standard treatment of sepsis of newborns in the Group II in terms of the frequency of discharge from the hospital up to 20 days is demonstrated by a decrease in the AR of event realization, which is 15.4%.

Conclusions. Patients of the Group I twice as often received the third course of antibiotic therapy. Infants of the Group II more often needed combined antibacterial therapy with a slightly shorter course and also recovered faster with discharge of every fifth baby by the 20th day. Against the background of a relatively higher content of C-reactive protein in blood serum, the standard treatment of newborns is more effective and allows for a 79.3% increase in the relative risk of rapid recovery at the same time, the minimum number of treated patients - 1.3.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the work. The informed consent of the children's parents was obtained for the conducting the studies.

No conflict of interests was declared by the authors.

References

Bruns N, Dohna-Schwake C. (2022). Antibiotics in critically ill children-a narrative review on different aspects of a rational approach. Pediatr. Res. 91 (2): 440-446. https://doi.org/10.1038/s41390-021-01878-9; PMid:34873285 PMCid:PMC8816725

Cohen-Bacrie S, Ninove L, Nougairède A, Charrel R, Richet H, Minodier P et al. (2011). Revolutionizing clinical microbiology laboratory organization in hospitals with in situ point-of-care. PLoS One. 6 (7): e22403. https://doi.org/10.1371/journal.pone.0022403; PMid:21811599 PMCid:PMC3139639

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM et al. (2013). Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 41 (2): 580-637. https://doi.org/10.1097/CCM.0b013e31827e83af; PMid:23353941

Flannery DD, Chiotos K, Gerber JS, Puopolo KM. (2022). Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr. Res. 91 (2): 380-391. https://doi.org/10.1038/s41390-021-01745-7; PMid:34599280 PMCid:PMC8819496

Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. (2018). The global burden of paediatric and neonatal sepsis: a systematic review. The Lancet Respiratory Medicine. 6 (3): 223-230. https://doi.org/10.1016/S2213-2600(18)30063-8; PMid:29508706

Giannoni E, Dimopoulou V, Klingenberg C, Navér L, Nordberg V, Berardi A et al. (2022). Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia. JAMA Netw Open. 5 (11): e2243691. https://doi.org/10.1001/jamanetworkopen.2022.43691; PMid:36416819 PMCid:PMC9685486

Glaser MA, Hughes LM, Jnah A, Newberry D. (2021). Neonatal Sepsis: A Review of Pathophysiology and Current Management Strategies. Adv Neonatal Care. 21 (1): 49-60. https://doi.org/10.1097/ANC.0000000000000769; PMid:32956076

Gyllensvärd J, Ingemansson F, Hentz E, Studahl M, Elfvin A. (2020). C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative. BMC Pediatr. 20 (1): 531. https://doi.org/10.1186/s12887-020-02426-w; PMid:33218324 PMCid:PMC7678045

Humberg A, Fortmann I, Siller B, Kopp MV, Herting E, Göpel W et al. (2020). Preterm Birth and Sustained Inflammation: Consequences for the Neonate. Semin. Immunopathol. 42: 451-468. https://doi.org/10.1007/s00281-020-00803-2; PMid:32661735 PMCid:PMC7508934

Janković B, Pasić S, Marković M, Veljković D, Milicić M. (2001). Koncentracije C-reaktivnog proteina tokom pocetnog lecenja sepse kod novorodjenceta [C-reactive protein concentrations during initial (empiric) treatment of neonatal sepsis]. Srp Arh Celok Lek. 129 (1): 17-22. Serbian. PMID: 15637985.

Korang SK, Safi S, Nava C, Greisen G, Gupta M, Lausten-Thomsen U et al. (2021). Antibiotic regimens for late‐onset neonatal sepsis. Cochrane Database of Systematic Reviews: 5. https://doi.org/10.1002/14651858.CD013836.pub2; PMid:33998665 PMCid:PMC8127057

Lanziotti VS, Póvoa P, Prata-Barbosa A, Pulcheri LB, Rabello LSCF, Lapa E Silva JR et al. (2018). Patterns of C-reactive protein ratio response to antibiotics in pediatric sepsis: A prospective cohort study. J Crit Care. 44: 217-222. https://doi.org/10.1016/j.jcrc.2017.11.018; PMid:29161668

Molloy EJ, Bearer CF. (2022). Paediatric and neonatal sepsis and inflammation. PediatrRes. 91 (2): 267-269. https://doi.org/10.1038/s41390-021-01918-4; PMid:35046541 PMCid:PMC8766624

Procianoy RS, Silveira RC. (2020). The challenges of neonatal sepsis management. J Pediatr (Rio J). 96 (1): 80-86. https://doi.org/10.1016/j.jped.2019.10.004; PMid:31747556 PMCid:PMC9432313

Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. (2017). Recognizing sepsis as a global health priority - a WHO resolution. N Engl J Med. 377 (5): 414-417. https://doi.org/10.1056/NEJMp1707170; PMid:28658587

Sarlangue J, Castella C, Lehours P. (2009). Modalités de l'antibiothérapie (initiale et ultérieure) chez l'enfant d'un à trois mois et de plus de trois mois (examen direct positif et examen direct négatif) [First and second line antibiotic therapy for bacterial meningitis in infants and children]. Med Mal Infect. 39 (7-8): 521-530. French. https://doi.org/10.1016/j.medmal.2009.02.031; PMid:19409744

Shunko YeYe, editor. (2015). Neonatology. National textbook. Kyiv: 93-138.

Songer CN, Calip GS, Srinivasan N, Barbosa VM, Pham JT. (2021). Factors influencing antibiotic duration in culture-negative neonatal early-onset sepsis. Pharmacotherapy. 41 (2): 148-161. https://doi.org/10.1002/phar.2507; PMid:33527426

Speer CP. (2009). Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology. 95 (4): 353-361. https://doi.org/10.1159/000209301; PMid:19494557

Stocker M, Klingenberg C, Navér L, Nordberg V, Berardi A, El Helou S et al. (2023). Less is more: Antibiotics at the beginning of life. Nat Commun. 14 (1): 2423. https://doi.org/10.1038/s41467-023-38156-7; PMid:37105958 PMCid:PMC10134707

Swigart LR, Sanchez-Pinto LN, Nolan BE, Seed PC, Coates BM. (2022). A specialized multi-disciplinary care program for children with sepsis and multiple organ dysfunction-associated immune dysregulation. Pediatr. Res. 91 (2): 464-469. https://doi.org/10.1038/s41390-021-01891-y; PMid:35022559 PMCid:PMC8754067

Weimer KE, Smith PB, Puia-Dumitrescu M, Aleem S. (2022). Invasive fungal infections in neonates: a review. Pediatr. Res. 91 (2): 404-412. https://doi.org/10.1038/s41390-021-01842-7; PMid:34880444

Wong HR. (2022). Pediatric sepsis biomarkers for prognostic and predictive enrichment. Pediatric Research. 91 (2): 283-288. https://doi.org/10.1038/s41390-021-01620-5; PMid:34127800 PMCid:PMC8202042

Published

2023-10-28

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Original articles