Prospective evaluation of c-reactive protein as a diagnostic biomarker with correlation to blood culture and antibiotic susceptibility patterns in neonatal sepsis: A cross-sectional study.

Sri Dharani Munagala; Aditi Tomer Thakur; S Ruth Ramya; Taruni; R Kondal Rao; Nagasaikaran Sade

doi:10.51168/kd82c583

Autori

Sri Dharani Munagala Post Graduate, Department of Microbiology, Government Medical College, Suryapet, Telangana, India
Aditi Tomer Thakur Assistant Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India
S Ruth Ramya Assistant Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India
Taruni Professor and Head, Department of Microbiology, Gandhi Medical College, Secunderabad, Telangana, India
R Kondal Rao Associate Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India
Nagasaikaran Sade Intern, Department of General Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana, India

DOI:

https://doi.org/10.51168/kd82c583

Cuvinte cheie:

Neonatal sepsis, C-reactive protein, Blood culture, Antibiogram, Antimicrobial resistance, Neonatal Intensive Care Unit

Rezumat

Background

Neonatal sepsis remains a major cause of neonatal morbidity and mortality. Its clinical features are often nonspecific, while blood culture, although definitive, has delayed turnaround and variable yield. C-reactive protein (CRP) is a simple acute-phase marker that supports early decision-making when correlated with microbiological findings.

Objectives

To evaluate the diagnostic utility of CRP in suspected neonatal sepsis and correlate CRP status with blood culture positivity and antimicrobial susceptibility patterns.

Methods

This prospective cross-sectional study was conducted from January 2024 to December 2024 in the Neonatal Intensive Care Unit of Government General Hospital, Suryapet, a tertiary care teaching hospital attached to Government Medical College, Suryapet, Telangana, India. A total of 302 neonates with suspected sepsis were enrolled. Blood samples were collected aseptically before antibiotic administration for CRP estimation and culture. Quantitative CRP was measured using the RHELAX-CRP latex agglutination method, with >6 mg/L considered elevated. Blood cultures and antibiotic susceptibility testing were performed using standard microbiological methods and CLSI guidance.

Results

Among 302 neonates, 178 (58.9%) were males, 186 (61.6%) had low birth weight and 164 (54.3%) were preterm. Blood culture was positive in 70 neonates (23.2%). Gram-negative bacteria predominated, comprising 48 isolates (68.6%), with Klebsiella pneumoniae as the commonest isolate. Elevated CRP was observed in 50 culture-positive neonates. CRP showed 71.4% sensitivity, 92.2% specificity, 73.5% positive predictive value and 91.5% negative predictive value. Elevated CRP was significantly associated with culture positivity (p<0.001). Gram-negative isolates showed high resistance to cefotaxime and ceftriaxone, with better sensitivity to imipenem and piperacillin-tazobactam.

Conclusion

CRP is a useful adjunctive marker for neonatal sepsis, especially due to its high specificity and strong culture correlation.

Recommendations

CRP testing should complement blood culture to guide early antibiotics and strengthen NICU antimicrobial stewardship

Biografii autori

Sri Dharani Munagala, Post Graduate, Department of Microbiology, Government Medical College, Suryapet, Telangana, India

is a Post Graduate in the Department of Microbiology, Government Medical College, Suryapet, Telangana, India. Her academic interests include neonatal sepsis, diagnostic microbiology, inflammatory biomarkers and antimicrobial resistance surveillance. ORCID iD: https://orcid.org/0009-0003-0119-2286
Aditi Tomer Thakur, Assistant Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India

contributed to study design, supervision of laboratory methods, data interpretation, manuscript preparation and critical revision of intellectual content.
S Ruth Ramya, Assistant Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India

is an Assistant Professor in the Department of Microbiology, Government Medical College, Suryapet, Telangana, India. Her professional interests include diagnostic microbiology, neonatal infections, laboratory quality assurance and antimicrobial resistance monitoring. ORCID iD https://orcid.org/0009-0007-4003-2444
Taruni, Professor and Head, Department of Microbiology, Gandhi Medical College, Secunderabad, Telangana, India

is Professor and Head, Department of Microbiology, Gandhi Medical College, Secunderabad, Telangana, India. She previously served as Professor and Head in the Department of Microbiology, Government Medical College, Suryapet, for four years, where she contributed significantly to academic leadership, departmental development, undergraduate and postgraduate teaching, and supervision of microbiological research. Her areas of academic and professional interest include clinical microbiology, infection control practices, diagnostic laboratory services, antimicrobial resistance surveillance, and mentorship of undergraduate and postgraduate students. She has actively guided students in academic activities, research methodology, laboratory-based investigations, and scientific manuscript preparation.
R Kondal Rao, Associate Professor, Department of Microbiology, Government Medical College, Suryapet, Telangana, India

is an Associate Professor in the Department of Microbiology, Government Medical College, Suryapet, Telangana, India. His professional interests include clinical microbiology, infection control practices, environmental microbiological monitoring, and teaching in medical microbiology.
Nagasaikaran Sade, Intern, Department of General Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana, India

is a medical intern in the Department of General Medicine at Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana, India. Dr Sade is actively involved in clinical training, patient care, and academic learning, with a growing interest in general medicine and evidence-based clinical practice. The current professional focus includes strengthening diagnostic skills and contributing to medical research.

Referințe

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

2. Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390(10104):1770-1780.

https://doi.org/10.1016/S0140-6736(17)31002-4

3. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60(2):367-389. https://doi.org/10.1016/j.pcl.2012.12.003

4. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21-47.

https://doi.org/10.1128/CMR.00031-13

5. Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):F257-F263.

https://doi.org/10.1136/archdischild-2014-306213

6. Celik IH, Hanna M, Canpolat FE, Pammi M. Diagnosis of neonatal sepsis: the past, present and future. Pediatr Res. 2022;91(2):337-350. https://doi.org/10.1038/s41390-021-01696-z

7. Eichberger J, Resch E, Resch B. Diagnosis of neonatal sepsis: the role of inflammatory markers. Front Pediatr. 2022;10:840288.

https://doi.org/10.3389/fped.2022.840288

8. Cantey JB, Baird SD. Biomarkers for the diagnosis of neonatal sepsis. Clin Perinatol. 2021;48(2):215-227.

https://doi.org/10.1016/j.clp.2021.03.012

9. Brown JVE, Meader N, Wright K, Cleminson J, McGuire W. Assessment of C-reactive protein diagnostic test accuracy for late-onset infection in newborn infants: a systematic review and meta-analysis. JAMA Pediatr. 2020;174(3):260-268.

https://doi.org/10.1001/jamapediatrics.2019.5669

10. Brown JVE, Meader N, Cleminson J, McGuire W. C-reactive protein for diagnosing late-onset infection in newborn infants. Cochrane Database Syst Rev. 2019;1(1):CD012126. https://doi.org/10.1002/14651858.CD012126.pub2

11. Benitz WE, Han MY, Madan A, Ramachandra P. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics. 1998;102(4):E41. https://doi.org/10.1542/peds.102.4.e41

12. Hofer N, Zacharias E, Muller W, Resch B. An update on the use of C-reactive protein in neonatal sepsis. Acta Paediatr. 2021;110(3):705-710. https://doi.org/10.1111/apa.15562

13. Investigators of the Delhi Neonatal Infection Study (DeNIS) collaboration. Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study. Lancet Glob Health. 2016;4(10):e752-e760. https://doi.org/10.1016/S2214-109X(16)30148-6

14. Chaurasia S, Sivanandan S, Agarwal R, Ellis S, Sharland M, Sankar MJ. Neonatal sepsis in South Asia: huge burden and spiralling antimicrobial resistance. BMJ. 2019;364:k5314. https://doi.org/10.1136/bmj.k5314

15. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2024. 16. Folgori L, Bielicki J, Heath PT, Sharland M. Antimicrobial-resistant Gram-negative infections in neonates: burden of disease and challenges in treatment. Curr Opin Infect Dis. 2017;30(3):281-288. https://doi.org/10.1097/QCO.0000000000000371

17. Sands K, Carvalho MJ, Portal E, Thomson K, Dyer C, Akpulu C, et al. Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Nat Microbiol. 2021;6(4):512-523.

https://doi.org/10.1038/s41564-021-00870-7

18. Klingenberg C, Kornelisse RF, Buonocore G, Maier RF, Stocker M. Culture-negative early-onset neonatal sepsis - at the crossroad between efficient sepsis care and antimicrobial stewardship. Front Pediatr. 2018;6:285.

https://doi.org/10.3389/fped.2018.00285

19. Cantey JB, Baird SD. Ending the culture of culture-negative sepsis in the neonatal ICU. Pediatrics. 2017;140(4):e20170044.

https://doi.org/10.1542/peds.2017-0044

20. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2021;76(8):1858-1870.

https://doi.org/10.1093/jac/dkab122