Professional Documents
Culture Documents
Osteomielitis Nejm-1 PDF
Osteomielitis Nejm-1 PDF
review article
Edward W. Campion, M.D., Editor
B
From Children’s Hospital, University of acteria may reach bone through direct inoculation from trau-
Helsinki, and Helsinki University Central matic wounds, by spreading from adjacent tissue affected by cellulitis or
Hospital, Helsinki (H.P.); and the Divi
sion of Diseases of the Musculoskeletal septic arthritis, or through hematogenous seeding. In children, an acute
System, University of Turku, and Turku bone infection is most often hematogenous in origin.1
University Hospital, Turku, Finland (M.P.). In high-income countries, acute osteomyelitis occurs in about 8 of 100,000
Address reprint requests to Dr. Pääkkönen
at Turku University Hospital, Kiinamyllyn children per year,2 but it is considerably more common in low-income countries.
katu 4-8, P.O. Box 52, 20521 Turku, Finland, Boys are affected twice as often as girls.2,3 Unless acute osteomyelitis is diagnosed
or at markus.paakkonen@helsinki.fi. promptly and treated appropriately,4 it can be a devastating or even fatal disease
N Engl J Med 2014;370:352-60. with a high rate of sequelae, especially in resource-poor countries where patients
DOI: 10.1056/NEJMra1213956 present with advanced disease and survivors often have complications that are
Copyright © 2014 Massachusetts Medical Society.
serious and long-lasting.
Staphylococcus aureus is by far the most common causative agent in osteomyelitis,
followed by the respiratory pathogens Streptococcus pyogenes and S. pneumoniae.5-9 For
unknown reasons, Haemophilus influenzae type b is more likely to affect joints than
bones. Salmonella species are a common cause of osteomyelitis in developing coun-
tries and among patients with sickle cell disease.10 Infections due to Kingella kingae
are increasing and are most common in children younger than 4 years of age.11
Di agnosis
Draftaccording
3 to12/19/13
the
tails extensive radiation exposure. Magnetic reso- data in Krogstad,1 Gillespie and Mayo,4 Peltola et al.,9 and Dartnell et al.12
Author Paakkonen
nance imaging (MRI) is often considered the are shown. Darker shades of red denote a higher burden
Fig # of
1 infection.
Evaluation
Symptoms suggestive
of acute osteomyelitis
Yes
Repeat examinations
Consider other diagnosis
or discharge
Abscess or complicated
disease? Yes
No
Clinical
improvement
and decrease in No Evaluate need for surgery
CRP in 2–4
days?
Yes
Prolonged intravenous antibiotic
Intravenous antibiotic Consider repeat imaging to rule
treatment tailored out complications
Yes MRSA?
to individual patient
Total antibiotic treat-
ment, usually 4–6 wk No
* When relevant, the same dose may be used parenterally and orally. MRSA denotes methicillin-resistant Staphylococcus aureus, and MSSA
methicillin-susceptible S. aureus.
† The maximal daily dose is not always well defined, but the maximal adult dose should not be exceeded.
‡ Bone penetration is the ratio of the bone concentration to the serum concentration.
§ Data on antistaphylococcal penicillins, first-generation cephalosporins, and clindamycin21,22 are from in vivo studies involving children; the
remaining data were derived from studies involving adults or from experimental models.
¶ Cephalothin and cefazolin are administered intravenously, cephalexin and cefadroxil are administered orally, and cephradine is administered
by either route. If no parenteral first-generation agent is available, cefuroxime can be used for parenteral administration.
‖ Chloramphenicol at a dose of 100 mg per kilogram of body weight per day in four equal doses is generally used in bacterial meningitis.
Current clinical-practice guidelines of the In- mortality decreased and there were more sequel-
fectious Diseases Society of America recommend ae.40 Since it is conceivable that extensive inter-
individualized therapy and typically a minimum vention in the initial, critical moments of treat-
of 4 to 6 weeks of medication for children with ment produces more harm than benefit, perhaps
acute osteomyelitis due to MRSA.14 Since data only trepanation or drainage should be performed.
on short-term treatment for cases due to MRSA Once the patient’s condition is stable, or if there
or the virulent Panton–Valentine leukocidin is no response to medication within days, an in-
gene-expressing S. aureus are lacking,43 this recom- tervention such as draining an abscess might
mendation is justified. It may also apply to pa- speed up the healing process.9,42,48 Data from
tients who present with advanced disease and prospective trials are required to explore these
those in areas where osteomyelitis due to salmo- issues further. Aggressive débridement has been
nella is common. Pathologic fractures are asso- suggested in difficult-to-treat cases of MRSA, but
ciated with a type of MRSA that is characterized again, data from relevant trials are lacking.49 In-
by a single pulsed-field pattern (strain USA300- traosseous abscesses in cases of subacute or
0114),44 but even a fracture does not necessarily chronic osteomyelitis (Brodie’s abscesses) are of-
warrant surgical intervention. As compared with ten thought to require surgery.50
MSSA, MRSA is more frequently associated with
deep-vein thrombosis, septic pulmonary emboli, C a se R ep or t
or both.36 Whereas resistance to methicillin is
associated with an increased risk of complica- Fever, focal redness (Fig. 3A), and pain in the left
tions in staphylococcal disease, pneumococcal biceps region developed in an 8-year-old boy who
resistance to penicillin has not been associated had not had prior trauma. A radiograph obtained
with an increased risk of complications in pneu- 2 days later was normal (July 10 in Fig. 3B), the
mococcal osteoarticular disease.45 leukocyte count was 10,000 per cubic millimeter,
There are some other caveats in relation to and the serum CRP level was clearly increased, at
shorter treatments as well. Although data are 106 mg per liter (normal level, <20).16 The child
lacking on the use of shorter treatments in neo- was hospitalized. Three days later, the leukocyte
nates, immunocompromised or malnourished count was only 4100 per cubic millimeter, where-
patients, and patients with sickle cell disease, as the CRP level had increased to 384 mg per liter,
these patients are likely to need a longer course and the erythrocyte sedimentation rate was 66 mm
of medication.46 When acute osteomyelitis is com- per hour (normal level, <20).16 MRI showed mas-
plicated by septic arthritis, the disease is chron- sive edema around the proximal humerus. A spec-
ic, and the CRP level normalizes slowly, a longer imen for bacteriology was drilled from the bone,
course probably also makes sense. Figure 2 sum- and a blood culture was obtained; acute osteomy-
marizes the treatment of acute osteomyelitis. elitis was diagnosed. Intravenous clindamycin
was administered, with cefuroxime for concomi-
Rol e of Surger y tant pneumonia. The child’s condition deterio-
rated for 2 days, and then he began to recover.
Since data are lacking from randomized trials of MSSA grew from the bone and blood cultures.
surgery for osteomyelitis in children, questions Treatment with clindamycin was switched to oral
about the timing and extent of surgery and the administration on day 2, and cefuroxime was
overall need for surgical intervention other than discontinued on day 7. The boy was discharged
biopsy remain unanswered. Conservative treat- on day 11, when the CRP level was 113 mg per
ment is effective in up to 90% of cases of acute liter and the erythrocyte sedimentation rate was
osteomyelitis if it is diagnosed early in the course 117 mm per hour. On day 20, recovery was well
of the illness.38,42 In a series of 68 patients who advanced, and because the CRP level had normal-
underwent aggressive primary surgery, 17% of ized, clindamycin was discontinued. The patient
the patients had chronic osteomyelitis after the was afebrile, but the erythrocyte sedimentation
procedure.47 An important observation made in rate was still elevated, at 100 mm per hour.
the pre-antibiotic era was that immediate surgery At follow-up 1 month later, the boy’s parents
for osteomyelitis was associated with increased reported that he was doing well, except that climb-
mortality, whereas sequelae were rather rare, and ing a ladder caused pain in the upper arm. A plain
vice versa: if surgery was delayed by a week or so, radiograph (Sept. 2 in Fig. 3B) revealed a patho-
References
1. Krogstad P. Osteomyelitis. In: Feigin tious Diseases Society of America for the 27. Tetzlaff TR, McCracken GH Jr, Nelson
RD, Cherry JD, Demmler-Harrison GJ, treatment of methicillin-resistant Staphy- JD. Oral antibiotic therapy for skeletal infec-
Kaplan SL, eds. Pediatric infectious dis- lococcus aureus infections in adults and tions of children. II. Therapy of osteomy-
eases. 6th ed. Philadelphia: Saunders, children. Clin Infect Dis 2011;52(3):e18- elitis and suppurative arthritis. J Pediatr
2009:725-42. e55. [Erratum, Clin Infect Dis 2011;53:319.] 1978;92:485-90.
2. Riise ØR, Kirkhus E, Handeland KS, 15. Butbul-Aviel Y, Koren A, Halevy R, 28. Green JH. Cloxacillin in treatment of
et al. Childhood osteomyelitis-incidence Sakran W. Procalcitonin as a diagnostic acute osteomyelitis. Br Med J 1967;2:414-6.
and differentiation from other acute on- aid in osteomyelitis and septic arthritis. 29. Kaplan SL, Mason EO Jr, Feigin RD.
set musculoskeletal features in a popula- Pediatr Emerg Care 2005;21:828-32. Clindamycin versus nafcillin or methicil-
tion-based study. BMC Pediatr 2008;8:45. 16. Pääkkönen M, Kallio MJ, Kallio PE, lin in the treatment of Staphylococcus aureus
3. Grammatico-Guillon L, Maakaroun Peltola H. Sensitivity of erythrocyte sedi- osteomyelitis in children. South Med J
Vermesse Z, Baron S, Gettner S, Rusch E, mentation rate and C-reactive protein in 1982;75:138-42.
Bernard L. Paediatric bone and joint in- childhood bone and joint infections. Clin 30. Martínez-Aguilar G, Hammerman
fections are more common in boys and Orthop Relat Res 2010;468:861-6. WA, Mason EO Jr, Kaplan SL. Clindamy-
toddlers: a national epidemiology study. 17. Arnold JC, Cannavino CR, Ross MK, cin treatment of invasive infections
Acta Paediatr 2013;102(3):e120-e125. et al. Acute bacterial osteoarticular infec- caused by community-acquired, methicil-
4. Gillespie WJ, Mayo KM. The manage- tions: eight-year analysis of C-reactive lin-resistant and methicillin-susceptible
ment of acute haematogenous osteomy- protein for oral step-down therapy. Pedi- Staphylococcus aureus in children. Pediatr
elitis in the antibiotic era: a study of the atrics 2012;130(4):e821-e828. Infect Dis J 2003;22:593-8.
outcome. J Bone Joint Surg Br 1981;63- 18. Ceroni D, Regusci M, Pazos J, Dayer 31. Dubnov-Raz G, Scheuerman O,
B:126-31. R, Kaelin A. Acute bone and joint infec- Chodick G, Finkelstein Y, Samra Z, Garty
5. Syrogiannopoulos GA, Nelson JD. tions in children: how much attention BZ. Invasive Kingella kingae infections in
Duration of antimicrobial therapy for should be paid to persistent fever during children: clinical and laboratory charac-
acute suppurative osteoarticular infec- intravenous antibiotic therapy? Rev Chir teristics. Pediatrics 2008;122:1305-9.
tions. Lancet 1988;1:37-40. Orthop Reparatrice Appar Mot 2003;89: 32. Messina AF, Namtu K, Guild M, Du-
6. Jaberi FM, Shahcheraghi GH, Ahadza- 250-6. (In French.) mois JA, Berman DM. Trimethoprim-sul-
deh M. Short-term intravenous antibiotic 19. Connolly LP, Connolly SA, Drubach famethoxazole therapy for children with
treatment of acute hematogenous bone LA, Jaramillo D, Treves ST. Acute hema- acute osteomyelitis. Pediatr Infect Dis J
and joint infection in children: a prospec- togenous osteomyelitis of children: assess- 2011;30:1019-21.
tive randomized trial. J Pediatr Orthop ment of skeletal scintigraphy-based diag- 33. Sherman JW, Conte JE Jr. Ceftriaxone
2002;22:317-20. nosis in the era of MRI. J Nucl Med 2002; treatment of multidrug-resistant Salmo-
7. Prado SMA, Lizama CM, Peña DA, 43:1310-6. nella osteomyelitis. Am J Med 1987;83:
Valenzuela MC, Viviani ST. Short duration 20. Peltola H, Pääkkönen M, Kallio P, 137-8.
of initial intravenous treatment in 70 pe- Kallio MJT. Clindamycin vs. first-genera- 34. Bradley JS, Jackson MA, Committee
diatric patients with osteoarticular infec- tion cephalosporins for acute osteoarticu- on Infectious Diseases, American Acade-
tions. Rev Chilena Infectol 2008;25:30-6. lar infections of childhood — a prospec- my of Pediatrics. The use of systemic and
(In Spanish.) tive quasi-randomized controlled trial. topical fluoroquinolones. Pediatrics 2011;
8. Jagodzinski NA, Kanwar R, Graham K, Clin Microbiol Infect 2012;18:582-9. 128(4):e1034-e1045.
Bache CE. Prospective evaluation of a 21. Tetzlaff TR, Howard JB, McCraken 35. Ebong WW. Acute osteomyelitis in
shortened regimen of treatment for acute GH, Calderon E, Larrondo J. Antibiotic Nigerians with sickle cell disease. Ann
osteomyelitis and septic arthritis in chil- concentrations in pus and bone of chil- Rheum Dis 1986;45:911-5.
dren. J Pediatr Orthop 2009;29:518-25. dren with osteomyelitis. J Pediatr 1978;92: 36. Mantadakis E, Plessa E, Voulouma-
9. Peltola H, Pääkkönen M, Kallio P, Kal- 135-40. nou EK, Michailidis L, Chatzimichael A,
lio MJ. Short- versus long-term antimicro- 22. Feigin RD, Pickering LK, Anderson D, Falagas ME. Deep venous thrombosis in
bial treatment for acute hematogenous Keeney RE, Shackleford PG. Clindamycin children with musculoskeletal infections:
osteomyelitis of childhood: prospective, treatment of osteomyelitis and septic arthri- the clinical evidence. Int J Infect Dis 2012;
randomized trial on 131 culture-positive tis in children. Pediatrics 1975;55:213-23. 16(4):e236-e243.
cases. Pediatr Infect Dis J 2010;29:1123-8. 23. Landersdorfer CB, Bulitta JB, Kinzig 37. Dich VQ, Nelson JD, Haltalin KC.
10. Atkins BL, Price EH, Tillyer L, Novelli M, Holzgrabe U, Sörgel F. Penetration of Osteomyelitis in infants and children:
V, Evans J. Salmonella osteomyelitis in antibacterials into bone: pharmacokinetic, a review of 163 cases. Am J Dis Child 1975;
sickle cell disease children in the east end pharmacodynamic and bioanalytical con- 129:1273-8.
of London. J Infect 1997;34:133-8. siderations. Clin Pharmacokinet 2009;48: 38. Vaughan PA, Newman NM, Rosman
11. Yagupsky P, Porsch E, St Geme JW III. 89-124. MA. Acute hematogenous osteomyelitis
Kingella kingae: an emerging pathogen in 24. Kaplan SL, Afghani B, Lopez P, et al. in children. J Pediatr Orthop 1987;7:652-5.
young children. Pediatrics 2011;127:557- Linezolid for the treatment of methicillin- 39. Penberthy GC, Weller CN. Chemo-
65. resistant Staphylococcus aureus infection in therapy as an aid in the management of
12. Dartnell J, Ramachandran M, Katch- children. Pediatr Infect Dis J 2003;22: acute osteomyelitis. Ann Surg 1941;114:
burian M. Haematogenous acute and sub- Suppl:S178-S185. 129-46.
acute paediatric osteomyelitis: a system- 25. Chen CJ, Chiu CH, Lin TY, Lee ZL, 40. Kenney WE. The prognosis in acute
atic review of the literature. J Bone Joint Yang WE, Huang YC. Experience with lin haematogenous osteomyelitis with and
Surg Br 2012;94:584-95. ezolid therapy in children with osteoar- without chemotherapy. Surgery 1944;16:
13. Ju KL, Zurakowski D, Kocher MS. Dif- ticular infections. Pediatr Infect Dis J 477-84.
ferentiating between methicillin-resistant 2007;26:985-8. 41. Harris NH. Some problems in the diag-
and methicillin-sensitive Staphylococcus au- 26. Summersgill JT, Schupp LG, Raff MJ. nosis and treatment of acute osteomyelitis.
reus osteomyelitis in children: an evidence- Comparative penetration of metronida- J Bone Joint Surg Br 1960;42-B:535-41.
based clinical prediction algorithm. J Bone zole, clindamycin, chloramphenicol, 42. Cole WG, Dalziel RE, Leitl S. Treat-
Joint Surg Am 2011;93:1693-701. cefoxitin, ticarcillin, and moxalactam ment of acute osteomyelitis in childhood.
14. Liu C, Bayer A, Cosgrove SE, et al. into bone. Antimicrob Agents Chemother J Bone Joint Surg Br 1982;64:218-23.
Clinical practice guidelines by the Infec- 1982;21:601-3. 43. Bocchini CE, Hulten KG, Mason EO
Jr, Gonzalez BE, Hammerman WA, Kaplan Pediatric pneumococcal bone and joint tis of the pelvis in children. AJR Am J
SL. Panton-Valentine leukocidin genes are infections. Pediatrics 1998;102:1376-82. Roentgenol 2007;189:867-72.
associated with enhanced inflammatory 46. Martí-Carvajal AJ, Agreda-Pérez LH. 49. Vander Have KL, Karmazyn B, Verma
response and local disease in acute hema- Antibiotics for treating osteomyelitis in M, et al. Community-associated methicil-
togenous Staphylococcus aureus osteomyeli- people with sickle cell disease. Cochrane lin-resistant Staphylococcus aureus in acute
tis in children. Pediatrics 2006;117:433- Database Syst Rev 2012;12:CD007175. musculoskeletal infection in children:
40. 47. Meller I, Manor Y, Bar-Ziv J, Torok G. a game changer. J Pediatr Orthop 2009;29:
44. Belthur MV, Birchansky SB, Verdugo Acute hematogenous osteomyelitis in chil- 927-31.
AA, et al. Pathologic fractures in children dren: long-term results of surgical treat- 50. Stephens MM, MacAuley P. Brodie’s
with acute Staphylococcus aureus osteomy- ment. Orthop Rev 1989;18:824-31. abscess: a long-term review. Clin Orthop
elitis. J Bone Joint Surg Am 2012;94:34- 48. Connolly SA, Connolly LP, Drubach Relat Res 1988;234:211-6.
42. LA, Zurakowski D, Jaramillo D. MRI for Copyright © 2014 Massachusetts Medical Society.
45. Bradley JS, Kaplan SL, Tan TQ, et al. detection of abscess in acute osteomyeli-