{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:16:43Z","timestamp":1790831803025,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Kingella kingae is now recognised as the leading cause of osteoarticular infections (OAIs) in young children. Because these infections typically produce mild symptoms and a weak inflammatory response, early diagnosis remains challenging. Complete blood count-derived immune-inflammatory biomarkers (IIBs) have recently gained interest as accessible, low-cost indicators of systemic inflammation, with potential diagnostic value in several fields, including oncology, rheumatology, cardiology, and infectious diseases. This study therefore aimed to assess whether IIBs could support the screening of K. kingae OAIs. We retrospectively reviewed the medical records of 209 children admitted to our hospital between 2007 and 2025 with confirmed or highly suspected K. kingae OAIs. Complete blood counts were analysed for each patient, including leukocyte subtypes such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils. We then calculated biomarkers (NLR, MLR, PLR, SII, SIRI, and PIV) and interpreted them using age-adjusted reference values. As expected, most children were younger than 48 months, and septic arthritis was the predominant clinical presentation. Classical acute-phase reactants (WBC, CRP, and ESR) were frequently normal or only mildly elevated. Likewise, most IIBs remained within or near reference ranges; the platelet-to-lymphocyte ratio was the most commonly abnormal marker, exceeding the threshold in only 59.3% of patients. These results indicate that, like conventional inflammatory markers, CBC-derived IIBs have limited standalone screening utility for K. kingae OAIs. Further studies are needed to determine whether systemic IIBs can help distinguish OAIs caused by K. kingae from those caused by pyogenic bacteria.<\/jats:p>","DOI":"10.3390\/pathogens15070763","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Evaluation of Novel Inflammatory Biomarkers in Children with Kingella kingae Osteoarticular Infections"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5800-4407","authenticated-orcid":false,"given":"Matteo","family":"Fortunato","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland"},{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-1048","authenticated-orcid":false,"given":"Anne","family":"Tabard-Foug\u00e8re","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"De Marco","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1325-8575","authenticated-orcid":false,"given":"Oscar","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Steiger","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Paris","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland"},{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5894-2436","authenticated-orcid":false,"given":"Ardian","family":"Ramadani","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6530-3471","authenticated-orcid":false,"given":"Andreas","family":"Tsoupras","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Dayer","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-4881","authenticated-orcid":false,"given":"Dimitri","family":"Ceroni","sequence":"additional","affiliation":[{"name":"Paediatric Orthopaedics Service, Geneva Children\u2019s Hospital, Geneva University Hospitals, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/BPO.0b013e3181d4732f","article-title":"Kingella kingae Osteoarticular Infections in Young Children: Clinical Features and Contribution of a New Specific Real-Time PCR Assay to the Diagnosis","volume":"30","author":"Ceroni","year":"2010","journal-title":"J. Pediatr. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/01.inf.0000259954.88139.f4","article-title":"Specific Real-Time Polymerase Chain Reaction Places Kingella kingae as the Most Common Cause of Osteoarticular Infections in Young Children","volume":"26","author":"Chometon","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1128\/JCM.00144-09","article-title":"New Real-Time PCR-Based Method for Kingella kingae DNA Detection: Application to Samples Collected from 89 Children with Acute Arthritis","volume":"47","author":"Ilharreborde","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mimet.2006.06.010","article-title":"Development of a Broad-Range 16S rDNA Real-Time PCR for the Diagnosis of Septic Arthritis in Children","volume":"68","author":"Rosey","year":"2007","journal-title":"J. Microbiol. Methods"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1097\/01.inf.0000172153.10569.dc","article-title":"Contribution of a Broad Range Polymerase Chain Reaction to the Diagnosis of Osteoarticular Infections Caused by Kingella kingae: Description of Twenty-Four Recent Pediatric Diagnoses","volume":"24","author":"Verdier","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1099\/jmm.0.47707-0","article-title":"Molecular Diagnosis of Kingella kingae Osteoarticular Infections by Specific Real-Time PCR Assay","volume":"58","author":"Cherkaoui","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/clinids\/27.5.1328","article-title":"Polymerase Chain Reaction Diagnosis of Kingella kingae Arthritis in a Young Child","volume":"27","author":"Goldenberger","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S1473-3099(04)01046-1","article-title":"Kingella kingae: From Medical Rarity to an Emerging Paediatric Pathogen","volume":"4","author":"Yagupsky","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/INF.0b013e31825d3419","article-title":"Small Risk of Osteoarticular Infections in Children with Asymptomatic Oropharyngeal Carriage of Kingella kingae","volume":"31","author":"Ceroni","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1097\/INF.0b013e31821c3aee","article-title":"Differentiating Osteoarticular Infections Caused By Kingella kingae From Those Due to Typical Pathogens in Young Children","volume":"30","author":"Ceroni","year":"2011","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Principi, N., and Esposito, S. (2016). Infectious Discitis and Spondylodiscitis in Children. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040539"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/01241398-200205000-00010","article-title":"Nontuberculous Spondylodiscitis in Children","volume":"22","author":"Garron","year":"2002","journal-title":"J. Pediatr. Orthop."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chargui, M., Krzysztofiak, A., Bernaschi, P., De Marco, G., Coulin, B., Steiger, C., Dayer, R., and Ceroni, D. (2022). Presumptive Bacteriological Diagnosis of Spondylodiscitis in Infants Less than 4 Years by Detecting K. Kingae DNA in Their Oropharynx: Data from a Preliminar Two Centers Study. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.1046254"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1302\/0301-620X.100B4.BJJ-2017-1080.R1","article-title":"Spinal Infections in Children: A Multicentre Retrospective Study","volume":"100-B","author":"Dayer","year":"2018","journal-title":"Bone Jt. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.2106\/JBJS.M.00791","article-title":"Primary Epiphyseal or Apophyseal Subacute Osteomyelitis in the Pediatric Population: A Report of Fourteen Cases and a Systematic Review of the Literature","volume":"96","author":"Ceroni","year":"2014","journal-title":"J. Bone Jt. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11832-016-0739-3","article-title":"Primary Subacute Hematogenous Osteomyelitis in Children: A Clearer Bacteriological Etiology","volume":"10","author":"Spyropoulou","year":"2016","journal-title":"J. Child. Orthop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1097\/INF.0000000000003410","article-title":"Primary Pyomyositis Caused by Kingella kingae in a 21-Month-Old Infant: A Case Report","volume":"41","author":"Chargui","year":"2022","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_18","first-page":"6586517","article-title":"Pediatric Infectious Prepatellar Bursitis with Kingella kingae","volume":"2020","author":"Pitts","year":"2020","journal-title":"Case Rep. Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1097\/INF.0000000000001673","article-title":"Pyogenic Tenosynovitis in Infants: A Case Series","volume":"36","author":"Lironi","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Coulin, B., DeMarco, G., Vazquez, O., Spyropoulou, V., Gavira, N., Vendeuvre, T., Tabard-Foug\u00e8re, A., Dayer, R., Steiger, C., and Ceroni, D. (2022). Osteoarticular Infections in Children: Accurately Distinguishing between MSSA and Kingella kingae. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010011"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1542\/peds.2007-3070","article-title":"Invasive Kingella kingae Infections in Children: Clinical and Laboratory Characteristics","volume":"122","author":"Scheuerman","year":"2008","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Yue, Y., Sun, Z., Li, P., Wang, X., Cheng, G., Huang, H., and Li, Z. (2025). Pan-Immune-Inflammation Value and Its Association with All-Cause and Cause-Specific Mortality in the General Population: A Nationwide Cohort Study. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1534018"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Guven, D.C., Sahin, T.K., Erul, E., Kilickap, S., Gambichler, T., and Aksoy, S. (2022). The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancers, 14.","DOI":"10.3390\/cancers14112675"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ayaz, \u00c7.M., Turhan, \u00d6., Y\u0131lmaz, V.T., Adan\u0131r, H., Sezer, B., and \u00d6\u011f\u00fcn\u00e7, D. (2024). Can the Pan-Immune-Inflammation Value Predict Gram Negative Bloodstream Infection-Related 30-Day Mortality in Solid Organ Transplant Patients?. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09413-x"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21752","DOI":"10.1038\/s41598-025-05856-7","article-title":"Diagnostic Value of Neutrophil to Lymphocyte Ratio and Serum Biomarkers in Chronic Osteomyelitis","volume":"15","author":"Zhao","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e22964","DOI":"10.1002\/jcla.22964","article-title":"Systemic Immune-inflammation Index, Neutrophil-to-lymphocyte Ratio, Platelet-to-lymphocyte Ratio Can Predict Clinical Outcomes in Patients with Metastatic Non-small-cell Lung Cancer Treated with Nivolumab","volume":"33","author":"Liu","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, Y., Fan, Y., Gao, D., and Zhang, Z. (2025). NLR (Neutrophil to Lymphocyte Ratio), PLR (Platelet to Lymphocyte Ratio), and SII (Systemic Immune-Inflammation Index) Reflect Disease Activity and Renal Remission in Patients with Lupus Nephritis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1646276"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ihj.2023.10.008","article-title":"Comparison of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII) as Marker of Adverse Prognosis in Patients with Infective Endocarditis","volume":"75","author":"Thottuvelil","year":"2023","journal-title":"Indian Heart J."},{"key":"ref_29","first-page":"40","article-title":"The Value of Inflammatory Markers to Diagnose and Monitor Diabetic Foot Osteomyelitis","volume":"14","author":"Nichols","year":"2015","journal-title":"Int. Wound J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xiu, J., Lin, X., Chen, Q., Yu, P., Lu, J., Yang, Y., Chen, W., Bao, K., Wang, J., and Zhu, J. (2023). The Aggregate Index of Systemic Inflammation (AISI): A Novel Predictor for Hypertension. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1163900"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e11138","DOI":"10.1097\/MD.0000000000011138","article-title":"Reference Values of Neutrophil-Lymphocyte Ratio, Lymphocyte-Monocyte Ratio, Platelet-Lymphocyte Ratio, and Mean Platelet Volume in Healthy Adults in South Korea","volume":"97","author":"Lee","year":"2018","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10566","DOI":"10.1038\/s41598-018-28646-w","article-title":"Reference Values for White Blood-Cell-Based Inflammatory Markers in the Rotterdam Study: A Population-Based Prospective Cohort Study","volume":"8","author":"Fest","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e22228","DOI":"10.1002\/jcla.22228","article-title":"Determinant Roles of Gender and Age on SII, PLR, NLR, LMR and MLR and Their Reference Intervals Defining in Henan, China: A Posteriori and Big-data-based","volume":"32","author":"Meng","year":"2017","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"966","DOI":"10.7754\/Clin.Lab.2022.220837","article-title":"Establishment of Reference Intervals for SII, NLR, PLR, and LMR in Healthy Adults in Jiangsu Region in Eastern China","volume":"69","author":"Liu","year":"2023","journal-title":"Clin. Lab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103281","DOI":"10.1016\/j.arcmed.2025.103281","article-title":"Establishment of High-Altitude Reference Values for the Pan-Immune-Inflammation Value in Healthy Adults Living in Mexico City","volume":"57","year":"2026","journal-title":"Arch. Med. Res."},{"key":"ref_36","first-page":"276","article-title":"Comprehensive Analysis of Novel Inflammatory Biomarkers (dNLR, NHR, MHR, SIRI): Reference Intervals in Healthy Adults and Diagnostic Value in AMI and HF","volume":"65","year":"2025","journal-title":"Haydarpasa Numune Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/ijlh.13768","article-title":"Age- and Sex-Specific Pediatric Reference Intervals for Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio","volume":"44","author":"Moosmann","year":"2022","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/ijlh.13306","article-title":"Complex Biological Patterns of Hematology Parameters in Childhood Necessitating Age- and Sex-Specific Reference Intervals for Evidence-Based Clinical Interpretation","volume":"42","author":"Bohn","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_39","unstructured":"(2026, June 15). Lecture Critique de L\u2019h\u00e9mogramme: Valeurs Seuils \u00e0 Reconna\u00eetre Comme Probablement Pathologiques et Principales Variations non Pathologiques. Available online: https:\/\/www.has-sante.fr\/jcms\/c_271914\/fr\/lecture-critique-de-l-hemogramme-valeurs-seuils-a-reconnaitre-comme-probablement-pathologiques-et-principales-variations-non-pathologiques."},{"key":"ref_40","unstructured":"(2026, June 15). Valeurs Normales de l\u2019H\u00e9mogramme Selon l\u2019\u00e2ge|HEMATOCELL. Available online: https:\/\/www.hematocell.fr\/cellules-du-sang-et-de-la-moelle-osseuse\/valeurs-normales-de-l-hemogramme-selon-l-age."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e230","DOI":"10.1542\/peds.2012-0810","article-title":"Detection of Kingella kingae Osteoarticular Infections in Children by Oropharyngeal Swab PCR","volume":"131","author":"Ceroni","year":"2013","journal-title":"Pediatrics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00631-19","DOI":"10.1128\/mBio.00631-19","article-title":"Kingella kingae Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing","volume":"10","author":"Porsch","year":"2019","journal-title":"mBio"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mib.2020.01.009","article-title":"Virulence Determinants of the Emerging Pathogen Kingella kingae","volume":"54","author":"Porsch","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hernandez, K.A., Porsch, E.A., Mu\u00f1oz, V.L., and St. Geme, J.W. (2025). Identification of a Kingella kingae Factor H Binding Protein That Is the Major Determinant of Serum Resistance. PLoS Pathog., 21.","DOI":"10.1371\/journal.ppat.1013473"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:24:39Z","timestamp":1784564679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pathogens15070763"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15070763","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}