Acute Hematogenous Osteomyelitis
Acute Hematogenous Osteomyelitis is frequently accompanied by adjacent infections. Acute hematogenous osteomyelitis (AHO) represented approximately 47% of pediatric musculoskeletal infections with surgical data (1003/2132) in a multi-center study. Of qualifying patients with AHO, accompanying conditions included subperiosteal abscess (22.7%), septic arthritis (21.6%), pyomyositis (11.2%), cellulitis (7.3%), myositis (3.1%), superficial abscess (3.1%), necrotizing fasciitis (0.5%), septic bursitis (0.4%), and lymphadenitis (0.2%).
Osteomyelitis can cross from metaphysis to cause septic arthritis of the adjacent joint without crossing the physis in long bones with intra-articular metaphyses (proximal humerus, radial head, proximal femur, distal fibula). Hamilton et al. found that septic arthritis accompanied by contiguous osteomyelitis has a markedly worse outlook than septic arthritis alone, with longer hospitalizations (median 8 vs 4 days), a higher rate of intensive care hospitalization (21% vs. 1.5%), higher readmission rate (17.1% vs. 5.2%) and a higher complication rate (38.1% vs. 0.7%). These differences may reflect the ongoing seeding of the joint with bacteria in contiguous disease.
In children with Staphylococcal osteomyelitis, Ju and colleagues identified clinical predictors to differentiate MRSA from MRSSA: temperature >38°C, hematocrit <34%, WBC of >12,000 cells/µL, and CRP > 13 mg/L. Based on the number of predictors present from zero to four, they reported the probability of MRSA osteomyelitis as 0%, 1%, 10%, 45%, and 92%, respectively.
Acute complication risk correlates with A-SCORE criteria including (1) bone abscess (Odds Ratio for complications: 2.3), (2) temperature ≥38°C more than 48 hours from the start of antibiotics (OR 2.7), (3) suppurative arthritis (OR 3.2), (4) presence of disseminated disease consisting of deep venous thrombosis, septic pulmonary emboli, or endocarditis (OR 4.6), and (5) delayed source control consisting of surgical intervention past day 3 (OR 5.1). One point is assigned for each of criterion met (range 0-5). Acute complications correlating with these criteria include “treatment failure within 6 weeks of initiation of antibiotic therapy, ≥ 2 bone debridements, or hospitalization > 14 days.”
Long-term complications occur in approximately 7.9% of patients with osteomyelitis and are most common in children with MRSA and under 3 years of age. Chronic complication risk correlates with C-SCORE criteria including (1) CRP≥ 10 mg/dL at 2 to 4 days after starting antibiotics (OR 2.7), (2) presence of disseminated disease (OR 3.3), and (3) occurrence of a bone debridement (OR 6.7). One point is assigned for each C-score criterion met (range 0-3). Chronic morbidity indicators include “growth arrest or limb length discrepancy, pathologic fracture, avascular necrosis, frozen joint, chronic dislocation, or chronic osteomyelitis defined as persistence or recurrence of attributable symptoms and signs associated with a sequestrum, involucrum, or osteosclerosis on a plain radiograph, requiring antibiotics for at least 12 weeks.” Vij and colleagues found that an A-SCORE of 4 or more factors had >85% sensitivity and >92% sensitivity for acute complications, whereas a C-SCORE of 3 had >70% sensitivity and >93% specificity for chronic morbidity.
Surgical practices for osteomyelitis vary widely. A study conducted at 18 US pediatric medical centers found that “variation in the surgical management of AHO [acute hematogenous osteomyelitis] appears to be driven primarily based on institutional practice.” Twelve institutions operated on 72% of patients “regardless of clinical factors,” whereas six facilities operated on only 26% of patients without multifocal infection . However, 74% went to surgery if there was multifocal surgery and ESR >37.5 mm/h across all institutions. Clinical risk factors for surgery were secondary and included “inability to ambulate, presence of multifocal infection, elevated admission C-reactive protein, increased admission platelet count, and location of the osteomyelitis.” Odds ratios by clinical factors include multifocal disease (OR 3.85), long bone involvement (OR 2.11), small joint involvement (OR 1.64), and inability to ambulate (OR 1.67), whereas involvement of the spine (OR 0.26) and other sites (OR 0.34) decreased the risk for surgery. Elevated C-reactive protein (OR 1.006) and platelet count (OR 1.003) were statistically significant risk factors, although the magnitude of increase was tiny (<1%) and may not be clinically significant. Patients with surgery experienced longer hospital stays compared to those without (median 6 days vs. 4 days) and higher rates of recurrence (OR 2.3) and readmission (OR 2.1).
Institutional variability was by far the largest predictor of surgery, with patients presenting to Lurie Children’s Hospital in Chicago (OR 8.53), Cincinnati Children’s (OR 3.38), and Rady Children’s San Diego (OR 3.07) having substantially increased odds ratios for surgery attributed by the authors to “custom/dogma.” Patients presenting to Children’s Hospital Los Angeles (OR 0.13), Boston Children’s Hospital (0.15), Seattle Children’s Hospital (0.18), Nationwide (OR 0.18) , Texas Scottish Rite [Dallas] (OR 0.32) and Mott Children’s Hospital (OR 0.36) having substantially decreased odds ratios.
Clinical factors should supplant institutional affiliation as the principal predictor of surgical need as evidence-based medicine techniques become more widely adopted. Whereas surgery is believed to have an important role in facilitating the recovery of some patients, those who underwent surgery experienced longer stays and more complications. Further research is needed to delineate surgical indications, especially for patients without multifocal infection and with ESR less than 37.5 mm/h.
Septic Arthritis of the Hip
The Caird-modified Kocher criteria may be helpful in differentiating septic arthritis of the hip from other causes. These include non-weight bearing, history of fever ≥38.5° C, erythrocyte sedimentation rate ≥ 40 mm/h, serum white blood cell count ≥12×109 cells/L, and C-Reactive Protein (CRP) >2.0). Kocher and colleagues proposed the probability of septic arthritis as 0.2%, 3%, 40%, 93.1%, and 99.6% with 0 to 4 of the first four above criteria, respectively. Others have found the Kocher algorithm less predictive. Luhmann found only 59% predictive accuracy with all four factors present. Caird and colleagues found predictive value enhanced with the additional criterion of C-Reactive Protein (CRP) >2.0 mg/dL at 16.9%, 36.7%, 62.4%, 82.6%, 93.1%, and 97.5% with 0 to 5 criteria met.
Nickel and colleagues found that the Caird algorithm (Kocher criteria plus CRP) was superior to the original Kocher criteria alone in all groups, and that it was helpful for distinguishing septic arthritis from other causes of single joint pain in all joints with an AUC (area under curve) of 0.80 for non-hip joints. In contrast, Obey and colleagues reported that the Kocher criteria were poorly sensitive for septic arthritis of the knee, missing 52% of cases; adding CRP did not improve predictive power.
Septic Arthritis of the Knee
Short-motion arc pain may be predictive of septic arthritis of the knee. Baldwin et al. found predictors of septic arthritis of the knee to include pain with short-arc motion of less than 30°, CRP > 4.0 mg/dl, patient-reported history of fever, and age below 2 years as predictive factors with 2%, 18%, 45%, 84%, and 100% rate of septic arthritis with 0 to 4 factors present, respectively.  Pain with short-arc motion alone was reported as having a sensitivity of 0.78 and specificity of 0.92 for septic arthritis, but these correlations may be less reproducible in areas with lower rates of Lyme disease.
Patients with septic arthritis of the knee tend to be younger than patients with septic arthritis of the hip, but both can occur at any age. Joshy and colleagues in the United Kingdom found a mean age of 2.5 years for patients with knee septic arthritis compared to a mean of 4.3 years for patients with hip septic arthritis.
In patients with septic arthritis, a periarticular infection may be more likely in patients with 3 or more Rosenfeld criteria (age above 3.6 years, CRP>13.8 mg/L, duration of symptoms >3 d, platelets <314×10 cells/μL, and ANC>8.6×10 cells/μL). Rosenfeld and colleagues found that for patients with septic arthritis, the above five variables were found to be predictive of adjacent infection. Patients with ≥3 risk factors were classified as high risk for septic arthritis with adjacent infection (sensitivity: 90%, specificity: 67%, positive predictive value: 80%, negative predictive value: 83%). Refakis et al. found lower sensitivity (86%), specificity (54%), and a 50% false-positive rate for the Rosenfeld criteria in their patients.
Polymerase Chain Reaction (PCR) for Kingella kingae may be considered in preschool children. A substantial portion of children with septic arthritis (18-48%) and osteomyelitis have negative cultures. Kingella kingae, a common etiologic organism for septic arthritis and osteomyelitis in children between 6 months and 4 years, is difficult to culture and is best detected by PCR.
Leukocyte esterase strip test of synovial fluid aspirate has high predictive value for septic arthritis. Mortazavi and colleagues reported that a positive leukocyte esterase (LE) strip test (“++” and “+++” readings) of synovial fluid aspirate had a 100% sensitivity, 83% specificity, 95% positive predictive value, and 100% negative predictive value for septic arthritis in a series of 25 children. With near-immediate results and high predictive value, the leukocyte esterase test may assist with diagnosis during joint arthrocentesis.
 Upasani VV, Burns JD, Bastrom TP, et al. Practice Variation in the Surgical Management of Children With Acute Hematogenous Osteomyelitis. J Pediatr Orthop. 2022;42(5):e520-e525. doi:10.1097/BPO.0000000000002123. Level III retrospective study
 Schallert EK, Kan JH, Monsalve J, Zhang W, Bisset GS 3rd, Rosenfeld S. Metaphyseal osteomyelitis in children: how often does MRI-documented joint effusion or epiphyseal extension of edema indicate coexisting septic arthritis? [published correction appears in Pediatr Radiol. 2016 May;46(5):734]. Pediatr Radiol. 2015;45(8):1174-1181. doi:10.1007/s00247-015-3293-0
 Hamilton EC, Villani MC, Klosterman MM, Jo C, Liu J, Copley LAB. Children with Primary Septic Arthritis Have a Markedly Lower Risk of Adverse Outcomes Than Those with Contiguous Osteomyelitis. J Bone Joint Surg Am. 2021;103(13):1229-1237. doi:10.2106/JBJS.20.01685
 Alhinai Z, Elahi M, Park S, et al. Prediction of Adverse Outcomes in Pediatric Acute Hematogenous Osteomyelitis [published correction appears in Clin Infect Dis. 2020 Oct 23;71(7):1805] [published correction appears in Clin Infect Dis. 2022 Feb 11;74(3):565]. Clin Infect Dis. 2020;71(9):e454-e464. doi:10.1093/cid/ciaa211. Level III retrospective study*
 Alhinai et al., ibid.
 Vij N, Singleton I, Kang P, Esparza M, Burns J, Belthur MV. Clinical Scores Predict Acute and Chronic Complications in Pediatric Osteomyelitis: An External Validation. J Pediatr Orthop. 2022;42(6):341-346. doi:10.1097/BPO.0000000000002159. Level III retrospective chart review
 Upasani et al., ibid.
 Upasani et al, ibid
 Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am. 1999;81(12):1662-1670. doi:10.2106/00004623-199912000-00002. Level III retrospective study*
 Luhmann SJ, Jones A, Schootman M, Gordon JE, Schoenecker PL, Luhmann JD. Differentiation between septic arthritis and transient synovitis of the hip in children with clinical prediction algorithms. J Bone Joint Surg Am. 2004;86(5):956-962. doi:10.2106/00004623-200405000-00011. Level III or IV retrospective study*
 Caird MS, Flynn JM, Leung YL, Millman JE, D’Italia JG, Dormans JP. Factors distinguishing septic arthritis from transient synovitis of the hip in children. A prospective study. J Bone Joint Surg Am. 2006;88(6):1251-1257. doi:10.2106/JBJS.E.00216. Level II prospective cohort study*
 Nickel AJ, Bretscher BS, Truong WH, Laine JC, Kharbanda AB. Novel Uses of Traditional Algorithms for Septic Arthritis. J Pediatr Orthop. 2022;42(2):e212-e217. doi:10.1097/BPO.0000000000002024. Level III retrospective study
 Obey MR, Minaie A, Schipper JA, Hosseinzadeh P. Pediatric Septic Arthritis of the Knee: Predictors of Septic Hip Do Not Apply. J Pediatr Orthop. 2019;39(10):e769-e772. doi:10.1097/BPO.0000000000001377. Level III retrospective study
 Baldwin KD, Brusalis CM, Nduaguba AM, Sankar WN. Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children. J Bone Joint Surg Am. 2016;98(9):721-728. doi:10.2106/JBJS.14.01331. Level III diagnostic study
 Baldwin et al., ibid.
 Joshy S, Choudry Q, Akbar N, Crawford L, Zenios M. Comparison of bacteriologically proven septic arthritis of the hip and knee in children, a preliminary study. J Pediatr Orthop. 2010;30(2):208-211. doi:10.1097/BPO.0b013e3181cfcd4f. Level III retrospective study
 Rosenfeld S, Bernstein DT, Daram S, Dawson J, Zhang W. Predicting the Presence of Adjacent Infections in Septic Arthritis in Children. J Pediatr Orthop. 2016;36(1):70-74. doi:10.1097/BPO.0000000000000389. Level III retrospective comparative study.
 Refakis CA, Arkader A, Baldwin KD, Spiegel DA, Sankar WN. Predicting Periarticular Infection in Children With Septic Arthritis of the Hip: Regionally Derived Criteria May Not Apply to All Populations. J Pediatr Orthop. 2019;39(5):268-274. doi:10.1097/BPO.0000000000000934. Level IV retrospective cohort study.
 Luhmann et al., ibid.
 Khattak M, Vellathussery Chakkalakumbil S, Stevenson RA, et al. Kingella kingae septic arthritis. Bone Joint J. 2021;103-B(3):584-588. doi:10.1302/0301-620X.103B3.BJJ-2020-0800.R1. Level IV prospective case series*
 Mortazavi SMJ, Kalantar H, Baghdadi S, et al. The Utility of Leukocyte Esterase Strip Test in the Diagnosis of Pediatric Septic Arthritis. J Pediatr Orthop. 2020;40(4):e312-e316. doi:10.1097/BPO.0000000000001413. Level II diagnostic study