Comparison of serum procalcitonin and interleukin-6 levels with CRP levels in the follow-up of antimicrobial treatment of patients with pyogenic and granulomatous vertebral osteomyelitis

Abstract

Background/Aim: Infection of the intervertebral disc and adjacent vertebrae is called vertebral osteomyelitis (VO). This study aims to determine whether procalcitonin (PCT) and interleukin (IL)-6 markers are more valuable than white blood cells (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the follow-up in patients with VO who were administered antibiotherapy. Methods: All adult patients with a diagnosis of VO were included in this prospective cohort study. The patients were divided into two groups as those with pyogenic and granulomatous VO. Serum WBC, CRP, ESH, PCT and IL-6 levels were measured at baseline, and the 2nd, 4th, 8th and 12th weeks of antibiotherapy. The changes in the laboratory parameters of the patients during follow-up were evaluated. Results: Of the 30 patients included in the study, there were 22 and 8 patients in the PVO and GVO groups, respectively. Baseline IL-6 measurement was above the reference in all patients, CRP was elevated in 96.6%, and PCT was increased in only one patient. Although there was a paradoxical increase in PCT values in the PVO group in the 2nd week compared to the pre-treatment values, a rapid decrease was observed in the 4th and 8th weeks. In the GVO group, the gradual decrease in PCT in parallel with the treatment response was considered to predict clinical improvement. IL-6 values decreased by 43.2% and 50% compared to baseline at the 4th and 8th weeks of treatment, respectively, in the PVO group. In the GVO group, a 50% reduction was detected in the 4th week of treatment compared to baseline. Conclusion: PCT and IL-6 biomarkers are valuable indicators in treatment follow-up. Although not statistically significant, the most stable decrease was observed in IL-6. Using IL-6 for the follow-up of the patients with VO may prevent long-term antibiotherapy.

Keywords

• Vertebral osteomyelitis
• Interleukin-6
• Procalcitonin
• C-reactive protein

References

1. 1. Berbari EF, Steckelberg JM, Osmon DR. Osteomyelitis In: Mandell GL Bennett JE, Dolin R, Blaser MJ. Principles and practice of infectious diseases, vol 2, 8th edn. Churchill Livingstone, Philadelphia, 2015:1318-27.
2. 2. Sevgi DY, Gunduz A, Oncul A, et al. Retrospective evaluation of spontaneous pyogenic sponydylodiscitis cases hospitalized in our clinic. Med Bull Sisli Etfal Hosp. 2016;50(1):20-5.
3. 3. Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, et al. Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61(6):e26-e46.
4. 4. Grammatico L, Baron S, Rusch E, Lepage B, Surer N, Desenclos JC, et al. Epidemiology of vertebral osteomyelitis (VO) in France: analysis of hospital-discharge data 2002–2003. Epidemiol Infect. 2008; 136(5):653–60.
5. 5. Tali ET. Spinal infections. Eur J Radiol. 2004;50(2):120-33.
6. 6. Enercan M, Ozturk C, Karaca S, Hamzaoglu A. Infections of the spinal column. TOTBID J. 2011;10(3):245-57.
7. 7. Gouliouris T, Aliyu SH, Brown NM. Spondylodiscitis: update on diagnosis and management. J Antimicrob Chemother. 2010;65(3):11-24.
8. 8. Uckaya I, Garzoni C, Ferry T, Harbarth S, Sterna R, Assala M, et al. Postoperative serum pro-calcitonin and C-reactive protein levels in patients with orthopaedic infections. Swiss Med Wkly. 2010;140:w13124.

9. 9. Yu Z, Liu J, Sun Q, Qiu Y, Han S, Guo X. The accuracy of the procalcitonin test for the diagnosis of neonatal sepsis: a meta-analysis. Scand J Infect Dis. 2010;42(10):723-33.
10. 10. Sonmezer MC, Tulek N. Biomarkers in bacterial infections and sepsis. Klimik J. 2015;28(3):96-102.
11. 11. Gentile LF, Cuenca AG, Vanzant EL, Efron PA, McKinley B, Moore F, et al. Is there value in plasma cytokine measurements in patients with severe trauma and sepsis? Methods. 2013;61(1):3-9.
12. 12. Sahbudak Bal Z, Karadas Ozdemir N, Sen S, Yılmaz Karapınar D, Zararsiz E, Aydemir S, et al. Diagnostic accuracy of interleukin-6, interleukin-8, and interleukin-10 for predicting bacteremia in children with febrile neutropenia. Turk J Haematol. 2017:34(3);254-57.
13. 13. Carragee EJ, Kim D, van der Vlugt T, Vittum D. The clinical use of erythrocyte sedimentation rate in pyogenic vertebral osteomyelitis. Spine. 1997;22(18):2089-93.
14. 14. Maharajan K, Patro DK, Menon J, Hariharan AP, Parija SC, Poduval M, et al. Serum procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis. J Orthop Surg Res. 2013;8:19.
15. 15. Paosong S, Narongroeknawin P, Pakchotanon R, Asavatanabodee P, Chaiamnuay S. Serum procalcitonin as a diagnostic aid in patients with acute bacterial septic arthritis. Int J Rheum Dis. 2015;18(3):352-9.
16. 16. Shen CJ, Wu MS, Lin KH, Lin WL, Chen HC, Wu JY, et al. The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2013; 32(6):807-14.
17. 17. Drago L, Vassena C, Dozio E, Corsi MM, De Vecchi E, Mattina R, et al. Procalcitonin, C-reactive protein, interleukin-6, and soluble intercellular adhesion molecule-1 as markers of postoperative orthopaedic joint prosthesis infections. Int J Immunopathol Pharmacol. 2011;24(2):433-40.
18. 18. Mete B, Kurt C, Yilmaz MH, Ertan G, Ozaras R, Mert A, et al. Vertebral osteomyelitis: eight years’ experience of 100 cases. Rheumatol Int. 2012;32(11):3591–7.
19. 19. Kaya S, Ercan S, Kaya S, Aktas U, Kamasak K, Ozalp H, et al. Spondylodiscitis: evaluation of patients in a tertiary hospital. J Infect Dev Ctries. 2014;8(10):1272-6.
20. 20. Chang WS, Ho MW, Lin PC, Ho CM, Chou CH, Lu MC, et al. Clinical characteristics, treatments, and outcomes of hematogenous pyogenic vertebral osteomyelitis, 12-year experience from a tertiary hospital in central Taiwan. J Microbiol Immunol Infect. 2018;51(2):235-42.
21. 21. Eren Gok S, Kaptanoglu E, Celikbas A, et al. Vertebral osteomyelitis: clinical features and diagnosis. Clin Microbiol Infect. 2014;20(10):1055–60.
22. 22. Lora-Tamayo J, Euba G, Narváez JA, Murillo O, Verdaguer R, Sobrino B, et al. Changing trends in the epidemiology of pyogenic vertebral osteomyelitis: the impact of cases with no microbiologic diagnosis. Semin Arthritis Rheum. 2011;41(2):247-55.
23. 23. Yoon YK, Jo YM, Kwon HH, Yoon HJ, Lee EJ, Park SY, et al. Differential diagnosis between tuberculous spondylodiscitis and pyogenic spontaneous spondylodiscitis: a multicenter descriptive and comparative study. Spine J. 2015;15(8):1764-71.
24. 24. Yoon SH, Chung SK, Kim KJ, Kim HJ, Jin YJ, Kim HB. Pyogenic vertebral osteomyelitis: identification of microorganism and laboratory markers used to predict clinical outcome. Eur Spine J. 2010;19:575–82.
25. 25. Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med. 2011;37(5):747-62.
26. 26. Jeong K, Lee HW, Kwon YM. Clinical value of procalcitonin in patients with spinal infection. J Korean Neurosurg Soc. 2015;58(3):271-5.
27. 27. Maus U, Andereya S, Gravius S, Ohnsorge JA, Miltner O, Niedhart C. Procalcitonin (PCT) as diagnostic tool for the monitoring of spondylodiscitis. Z Orthop Unfall. 2009;147(1):59-64.
28. 28. Randau TM, Friedrich MJ, Wimmer MD, Reichert B, Kuberra D, Stoffel-Wagner B, et al. Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening. PLoS One. 2014:9(2);e89045.
29. 29. Van Asten SA, Nichols A, La Fontaine J, Bhavan K, Peters EJ, Lavery LA. The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis. Int Wound J. 2017;14(1):40-5.
30. 30. Jiang N, Ma YF, Jiang Y, Zhao XQ, Xie GP, Hu YJ, et al. Clinical characteristics and treatment of extremity chronic osteomyelitis in Southern China: a retrospective analysis of 394 consecutive patients. Medicine. 2015;94(42):e1874.
31. 31. Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br. 2007;89(1):94-9.
32. 32. Glehr M, Friesenbichler J, Hofmann G, Bernhardt GA, Zacherl M, Avianet A, et al. Novel biomarkers to detect infection in revision hip and knee arthroplasties. Clin Orthop Relat Res. 2013;471(8):2621-8.