Acute Hematogenous Osteomyelitis in Children: Clinical Presentation and Management

Figures & data

Table 1 Relative Frequency of Organism Identification in Pediatric Acute Hematogenous Osteomyelitis

Causative Organism	Proportion of Cases (%)
Staphylococcus aureus	43–63
MRSA as a proportion of S. aureus	0–69.1
Streptococcus pyogenes	2.5–7
Salmonella spp.	1–3.8
S. agalactiae	0.5–5.1
S. pneumoniae	0–1.9
Kingella kingae	0–47.4*
Other Organisms	1–3
No Organism Identified	24–43.7

Notes: *It should be noted that most studies reporting high rates of K. kingae identification have relied on molecular assays combined with traditional culture methods. Data from references ^{1, 6, 14, 15, 22, 33–35} and ⁴⁸.

Table 2 Pathogens to Consider in Unique Populations

Patient Population	AHO Pathogens
Infants < 1 Year of Age	Group B Streptococcus Haemophilus influenzae S. aureus Neisseria gonorrheae Group A Streptococcus Enterobacteriaceae
Children 1–5 Years of Age	Kingella kingae S. aureus S. pneumoniae
School Age - Adolescence	S. aureus Group A Streptococcus
Hemoglobinopathy/Asplenia	Salmonella spp. S. aureus Plesiomonas H. influenzae S. pneumoniae
Intravenous Drug Users	S. aureus Enterobacteriaceae Pseudomonas aeruginosa
Animal Exposures	S. aureus Salmonella spp. Bartonella henselae Brucella spp.

Notes: Data from references ^{2, 3, 21, 28, 42} and ⁵⁶.

Table 3 Potential Antimicrobial Agents for the Management of AHO

Antimicrobial	Bacteriostatic/Bactericidal	Antimicrobial Spectra*	Adverse Effects	Other Considerations
Antistaphylococcal penicillins	Bactericidal	MSSA, Group A Streptococcus	Potential for drug induced neutropenia, nephritis. Oxacillin associated with hepatotoxicity. Phlebitis and/or local discomfort may develop with IV infusion, particularly with nafcillin.	One of the agents of choice for MSSA. Limited activity against K. kingae. Liquid formulations of oral flucloxacillin and dicloxacillin have poor palatability.
First-generation cephalosporins	Bactericidal	MSSA, Group A Streptococcus, K. kingae	Potential for drug induced neutropenia, nephritis.	Poor CNS penetration. Some concern exists for inactivation of these drugs in the presence of large inoculum of S. aureus (i.e., cefazolin inoculum effect), although data are limited
Vancomycin	Bactericidal	MRSA, MSSA, Group A Streptococcus, Group B Streptococcus	Potential for drug induced neutropenia, thrombocytopenia. Infusion reactions (“Red Man Syndrome”). Nephrotoxicity associated with vancomycin is well described.	Optimal monitoring parameters not established in children. Close monitoring of renal function recommended. Intravenous only administration.
Clindamycin	Bacteriostatic	Clindamycin-susceptible MRSA and MSSA, Group A Streptococcus. Some K. kingae strains are susceptible.	Gastrointestinal distress, diarrhea are common. Potential for transaminitis.	May be administered intravenously but has high oral bioavailability. Local rates of clindamycin-resistance among S. aureus should be considered prior to empiric use. Poor CNS penetration. Not recommended if endovascular disease present. Many liquid formulations have poor palatability.
Linezolid	Bacteriostatic	S. aureus, Group A Streptococcus, Pneumococcus	Potential for drug induced neutropenia, thrombocytopenia. Prolonged use has been associated with optic neuritis and peripheral neuropathy. Tyramine containing foods should be avoided.	May be administered intravenously but has high oral bioavailability. Close monitoring for adverse events, particularly myelosuppression, is advised. Cost of this agent may be prohibitive
Daptomycin	Bactericidal	S. aureus, Group A Streptococcus, Pneumococcus	Potential for transaminitis. Rhabdomyolysis is a reported but rare adverse event	In animal models, inactivated by pulmonary surfactant. Good CNS penetration. Intravenous only administration. Limited data in the setting of pediatric AHO.
Trimethoprim-Sulfamethoxazole	Bactericidal	S. aureus, K. kingae, some gram-negative enterics	Drug induced cytopenias, nephritis, rash. May rarely be associated with erythema multiforme/Stevens Johnson	Excellent in vitro activity against S. aureus in most studies. Data are limited in the setting of invasive S. aureus infection particularly AHO.
Tetracyclines	Bacteriostatic	S. aureus	Potential for transaminitis. Patients may become very photosensitive and should be advised to wear sun screen while outdoors. Dental staining in young children with prolonged use (relative contraindication in those < 8 years)	Excellent in vitro activity against S. aureus in most studies. Data are limited in setting of invasive S. aureus infection, particularly AHO.
Penicillins, Aminopenicillins	Bactericidal	Group A Streptococcus, Group B Streptococcus penicillin-susceptible pneumococci, β-lactamase negative H. influenza	Rash. Drug-induced cytopenias with prolonged use. Nephritis
Third Generation Cephalosporins	Bactericidal	Group A Streptococcus, K. kingae, pneumococci, H. influenzae, many gram-negative enterics (including Salmonella)	Diarrhea. Rash. Drug induced cytopenias, transaminitis, nephritis are possible with prolonged use.	Generally well tolerated class of drugs with agents that can be administered either intravenously or orally. Ceftriaxone with in vitro activity against MSSA, however clinical data in children with invasive MSSA are limited.

Notes: *The description of antimicrobial spectra is not intended to be comprehensive, but to briefly describe a few relevant AHO pathogens included within the antimicrobial spectra of the agent of interest.

Figure 1 Suggested Decision Tree for Empiric Therapy Selection in Acute Hematogenous Osteomyelitis. Disclaimer: This is intended as a framework for thought and is no substitute for clinical judgment, obtainment of a thorough patient history and knowledge of local microbiology/epidemiology. *Data are limited regarding the use of ceftaroline and daptomycin in the treatment of osteoarticular infections in children. **Clindamycin is not recommended if patients are critically ill or there is concern for endovascular disease or infection involving the central nervous system.

Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26(6):703–708. doi:10.1097/01.bpo.0000242431.91489.b417065930

 PubMed Web of Science ®Google Scholar

McNeil JC, Forbes AR, Vallejo JG, et al. Role of operative or interventional radiology-guided cultures for osteomyelitis. Pediatrics. 2016;137:e20154616. doi:10.1542/peds.2015-461627244827

 PubMed Web of Science ®Google Scholar

Peltola H, Paakkonen M, Kallio P, Kallio MJ. Osteomyelitis-Septic Arthritis Study G. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Pediatr Infect Dis J. 2010;29(12):1123–1128. doi:10.1097/INF.0b013e3181f55a8920842069

 PubMed Web of Science ®Google Scholar

Calvo C, Nunez E, Camacho M, et al. Epidemiology and management of acute, uncomplicated septic arthritis and Osteomyelitis: Spanish Multicenter Study. Pediatr Infect Dis J. 2016;35(12):1288–1293. doi:10.1097/INF.000000000000130927455444

 PubMed Web of Science ®Google Scholar

Section J, Gibbons SD, Barton T, Greenberg DE, Jo CH, Copley LA. Microbiological culture methods for pediatric musculoskeletal infection: a guideline for optimal use. J Bone Joint Surg Am. 2015;97(6):441–449. doi:10.2106/JBJS.N.0047725788299

 PubMed Web of Science ®Google Scholar

Bocchini CE, Hulten KG, Mason EO Jr, Gonzalez BE, Hammerman WA, Kaplan SL. Panton-valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children. Pediatrics. 2006;117(2):433–440. doi:10.1542/peds.2005-056616452363

 PubMed Web of Science ®Google Scholar

Hawkshead JJ 3rd, Patel NB, Steele RW, Heinrich SD. Comparative severity of pediatric osteomyelitis attributable to methicillin-resistant versus methicillin-sensitive Staphylococcus aureus. J Pediatr Orthop. 2009;29(1):85–90. doi:10.1097/BPO.0b013e3181901c3a19098653

 PubMed Web of Science ®Google Scholar

Juchler C, Spyropoulou V, Wagner N, et al. The contemporary bacteriologic epidemiology of osteoarticular infections in children in Switzerland. J Pediatr. 2018;194:190–196 e191. doi:10.1016/j.jpeds.2017.11.02529263015

 PubMed Web of Science ®Google Scholar

Guitierrez K. Osteomeylitis In: Long SS, Pickering LK, Prober CG, editors. Principles and Practice of Pediatric Infectious Diseases. New York: Elsevier Saunders 2012:469–477.

 Google Scholar

Krogstad P. Osteomyelitis In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, editors. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. Vol. 1 8 Philadelphia, PA: Elsevier;2019:516–529.

 Google Scholar

Saavedra-Lozano J, Falup-Pecurariu O, Faust SN, et al. Bone and joint infections. Pediatr Infect Dis J. 2017;36(8):788–799. doi:10.1097/INF.000000000000163528708801

 PubMed Web of Science ®Google Scholar

Edwards MS, Baker CJ, Wagner ML, Taber LH, Barrett FF. An etiologic shift in infantile osteomyelitis: the emergence of the group B streptococcus. J Pediatr. 1978;93(4):578–583. doi:10.1016/S0022-3476(78)80891-9359771

 PubMed Web of Science ®Google Scholar

Boguniewicz J, Rubiano Landinez A, Kaplan SL, Lamb GS. Comparison of musculoskeletal infections due to nontyphoidal salmonella species and Staphylococcus aureus in immunocompetent children. Pediatr Infect Dis J. 2019;38(10):1020–1024. doi:10.1097/INF.000000000000244031425328

 PubMed Web of Science ®Google Scholar

Rubin LG, Shin J, Kaur I, Scheuerman O, Levy I, Long SS. Frequency of multifocal disease and pyogenic arthritis of the hip in infants with osteoarticular infection in three neonatal intensive care units. J Pediatr. 2020;227:157–162. doi:10.1016/j.jpeds.2020.07.05532707046

 PubMed Web of Science ®Google Scholar