Osteomyelitis:​Diagnosis and Treatment

David C. Bury, DO, MPH, Martin Army Community Hospital, Fort Benning, Georgia;​
Uniformed Services University of the Health Sciences, Bethesda, Maryland
Tyler S. Rogers, MD, and Michael M. Dickman, DO, MBA, Madigan Army Medical Center,
Joint Base Lewis-McChord, Washington;​Uniformed Services University of the Health Sciences,
Bethesda, Maryland;​University of Washington School of Medicine, Seattle, Washington

Osteomyelitis is an inflammatory condition of bone secondary to an infectious process. Osteomyelitis

is usually clinically diagnosed with support from imaging and laboratory findings. Bone biopsy and
microbial cultures offer definitive diagnosis. Plain film radiography should be performed as initial
imaging, but sensitivity is low in the early stages of disease. Magnetic resonance imaging with and
without contrast media has a higher sensitivity for identifying areas of bone necrosis in later stages.
Staging based on major and minor risk factors can help stratify patients for surgical treatment. Antibi-
otics are the primary treatment option and should be tailored based on culture results and individual
patient factors. Surgical bony debridement is often needed, and further surgical intervention may be
warranted in high-risk patients or those with extensive disease. Diabetes mellitus and cardiovascular
disease increase the overall risk of acute and chronic osteomyelitis. (Am Fam Physician. 2021;​104(4):​
395-402. Copyright © 2021 American Academy of Family Physicians.)

Osteomyelitis is an inflammatory condition of bone methicillin-resistant S. aureus. Hematogenous osteomy-

secondary to infection;​it may be acute or chronic. Symp- elitis is often monomicrobial and can occur from aerobic
toms of acute osteomyelitis include pain, fever, and edema gram-negative rods or from P. aeruginosa or Serratia mar-
of the affected site, and patients typically present without cescens in injection drug users.4 Vertebral osteomyelitis is
bone necrosis in days to weeks following initial infection. the most common type of hematogenous osteomyelitis
Chronic osteomyelitis develops after months to years of per- and is polymicrobial in 5% to 10% of cases.1 Blood cultures
sistent infection and may be characterized by the presence may be negative if osteomyelitis develops following bacte-
of necrotic bone and fistulous tracts from skin to bone.1,2 rial clearance from the bloodstream. Nonhematogenous
Osteomyelitis is further classified by mechanism of infection osteomyelitis can be polymicrobial;​S. aureus is the most
as hematogenous or nonhematogenous. With hematogenous common pathogen in addition to coagulase-negative staph-
osteomyelitis, bacteria are seeded into bone secondary to a ylococci and gram-negative aerobes and anaerobes. Poly-
bloodstream infection and the condition is most common microbial diabetic foot infections and decubitus ulcers may
in children, older adults, and immunocompromised pop- include Streptococcus species and Enterococcus species.1
ulations.1-3 Nonhematogenous osteomyelitis occurs from
direct inoculation in the setting of surgery or trauma or with
spread from contiguous soft tissue and joint infections.1,2 BEST PRACTICES IN INFECTIOUS DISEASE

Etiology Recommendations from the Choosing

Methicillin-sensitive Staphylococcus aureus is the most Wisely Campaign
frequently identified pathogen across all types of osteo- Recommendation Sponsoring organization
myelitis, followed by Pseudomonas aeruginosa and
Do not routinely use magnetic American Podiatric
resonance imaging to diagnose Medical Association
CME This clinical content conforms to AAFP criteria for bone infection (osteomyelitis) in
CME. See CME Quiz on page 338. the foot.
Author disclosure:​ No relevant financial affiliations. Source:​For more information on the Choosing Wisely Campaign,
Patient information:​ A handout on this topic, written by the see https://​w ww.choosingwisely.org. For supporting citations and
authors of this article, is available at https://​w ww.aafp.org/ to search Choosing Wisely recommendations relevant to primary
afp/2021/1000/p395-s1.html. care, see https://​w ww.aafp.org/afp/recommendations/search.htm.

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 OSTEOMYELITIS
SORT:​KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating Comments

The preferred diagnostic criterion for osteomyelitis is a positive C Consensus guideline and
bacterial culture from bone biopsy, but clinical, laboratory, and clinical review
radiographic findings can also inform a clinical diagnosis.9,12

Magnetic resonance imaging is the imaging modality of choice C Consensus guideline

for suspected osteomyelitis, although plain film radiography is
often done initially.13

In adult patients hospitalized with chronic osteomyelitis, B Systematic review of eight

parenteral followed by oral antibiotic therapy appears to be as small trials and a random-
effective as long-term parenteral therapy.37,38 ized controlled trial

A = consistent, good-quality patient-oriented evidence;​B = inconsistent or limited-quality patient-oriented evidence;​

C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the
SORT evidence rating system, go to https://​w ww.aafp.org/afpsort.

Less common pathogens can be associated with occur in the sternoclavicular, pelvic, and long
certain clinical conditions, including immuno- bones.9 When hematogenous osteomyelitis
compromise (Aspergillus species, Mycobacterium affects prepubertal children, it typically occurs in
tuberculosis, Candida species), sickle cell disease the metaphysis of long bones adjacent to growth
(Salmonella species), HIV infection (Bartonella plates, with a predilection for the tibia and femur.1
henselae), and tuberculosis (M. tuberculosis).1,5,6
Diagnosis
Clinical Features A diagnosis of osteomyelitis should be considered
The clinical presentation of nonhematogenous in any patient with acute onset or progressive
osteomyelitis varies and symptoms are often non- worsening of musculoskeletal pain accompanied
specific. Signs and symptoms common to all sub- by constitutional symptoms such as fever, malaise,
types may include pain, edema, and erythema. lethargy, and irritability. Constitutional symp-
Acute osteomyelitis may present with a more toms do not always occur in adults, especially in
rapid onset of symptoms (development over days) the setting of immunocompromise. The index of
and is more likely to be associated with fever. suspicion for osteomyelitis should be higher in
Systemic symptoms are not common in chronic patients with underlying conditions, including
osteomyelitis, and the presence of fistulous tracts poorly controlled diabetes mellitus, neuropathy,
from skin to bone is diagnostic. Long-standing, peripheral vascular disease, chronic or ulcerated
nonhealing ulcers and nonhealing fractures may wounds, history of recent trauma, sickle cell dis-
also be associated with chronic osteomyelitis. ease, history of implanted orthopedic hardware,
Patients with diabetic neuropathy are at higher or a history or suspicion of intravenous drug use.
risk of developing osteomyelitis secondary to local A dedicated physical examination can increase
spread from diabetic foot infections and unrec- the likelihood of diagnosing osteomyelitis if
ognized wounds.2 Smoking increases the risk of findings include erythema, soft tissue infection,
osteomyelitis from diabetic foot infections and bony tenderness, joint effusion, decreased range
healing fractures.7 Peripheral vascular disease and of motion, or exposed bone. The probe-to-bone
poorly healing wounds (e.g., decubitus ulcers) are test may be useful to rule out diabetic foot osteo-
more likely to lead to bone inflammation. Osteo- myelitis in low-risk patients.10,11
myelitis secondary to diabetic foot ulcers can be The differential diagnosis of osteomyeli-
difficult to diagnose given chronic changes from tis includes soft tissue infection, gout, Char-
vascular insufficiency and ischemia.8 cot arthropathy, fracture, malignancy, bursitis,
Hematogenous osteomyelitis often presents osteonecrosis, sickle cell vasoocclusive pain cri-
similarly to nonhematogenous disease. The most sis, and SAPHO syndrome (synovitis, acne, pus-
common form of hematogenous osteomyelitis is tulosis, hyperostosis, and osteitis). Uncertain
vertebral;​patients often have back or neck pain clinical diagnosis should prompt further workup
and muscle tenderness, sometimes followed by that includes laboratory evaluation and imag-
fever. Hematogenous osteomyelitis may also ing (Table 12,9,12,13). Definitive diagnosis is made

396 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 OSTEOMYELITIS

correlation.19,20 Positive blood cultures in associ-

TABLE 1 ation with radiographic evidence of osteomyelitis
may prevent the need for a more invasive bone
Clinical Findings Suggesting biopsy.21
Osteomyelitis
Imaging studies (e.g., plain film radiography, IMAGING
magnetic resonance imaging, bone scintig- Plain film radiography is the first-line evaluation
raphy) demonstrating contiguous soft tissue
infection or bony destruction
of suspected osteomyelitis. Advanced imaging is
often needed for diagnosis following plain film
Clinical signs radiography, because 50% to 75% of the bone
Chronic wound overlying surgical hardware matrix must be destroyed before lytic changes
Chronic wound overlying traumatic injury or are evident on plain radiographs.22 Findings can
fracture include soft tissue swelling, osteopenia, corti-
Exposed bone cal loss, bony destruction, and periosteal reac-
Persistent sinus tract tion12,23,24 (Figure 12). Advanced imaging can
Tissue necrosis overlying bone be guided by onset of symptoms and patient
Laboratory evaluation variables (Table 22,9,13,24-30). Magnetic resonance
Elevated C-reactive protein level
Elevated erythrocyte sedimentation rate
FIGURE 1
Leukocytosis
Positive blood cultures
Thrombocytosis

Note:​If osteomyelitis is suspected, a bone biopsy with

bacterial culture should be considered for definitive
diagnosis.
Adapted with permission from Hatzenbuehler J, Pull-
ing TJ. Diagnosis and management of osteomyelitis.
Am Fam Physician. 2011;​ 84(9):​1028, with additional
information from references 9, 12, and 13.

with a positive culture from biopsy of the affected

bony structure. Polymerase chain reaction test-
ing may help in the rapid diagnosis of organisms
or for cultures taken after antibiotic therapy.12,14
Bone biopsy remains the diagnostic standard but
is not always feasible. Some evidence suggests
that biopsy should be reserved only for select
cases because the results may not lead to treat-
ment alterations.15

LABORATORY EVALUATION
Initial laboratory evaluation should include a
complete blood count, erythrocyte sedimentation
Plain film radiograph showing osteomyeli-
rate, C-reactive protein, and blood cultures. Leu-
tis of the distal fourth metatarsal and distal
kocytosis may be present in acute osteomyelitis, third and fourth phalanges (arrows). Corti-
but it can be absent in chronic osteomyelitis.16,17 cal disruption and osteolysis are present.
There is some evidence that thrombocytosis Reprinted with permission from Hatzenbuehler J,
may positively predict osteomyelitis in patients Pulling TJ. Diagnosis and management of osteomyeli-
with chronic leg ulcers.18 If inflammatory mark- tis. Am Fam Physician. 2011;​84(9):​1030.
ers are elevated, they can be trended for clinical

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 397
 OSTEOMYELITIS

imaging (MRI) has a high sensitivity and nega- a complementary role to other modalities and
tive predictive value. Plain radiography and MRI may demonstrate inflammatory changes in the
are often both indicated and complementary 13 periosteum, particularly in children. Ultrasonog-
(Figures 2 through 4). Although contrast media is raphy can be useful for identification of soft tissue
not required for diagnosis, it may be helpful to abscess and helpful for abscess aspiration.13
distinguish between abscess and phlegmon, espe-
cially in patients with chronic osteomyelitis.25-27 Treatment
MRI is more readily available and avoids radi- Osteomyelitis treatment requires a multifaceted
ation exposure, but positron emission tomogra- approach that may include antibiotics, surgical
phy (PET) and single-photon emission computed intervention, and other modalities depending on
tomography (SPECT) can also reliably diagnose multiple clinical factors, including clinical stage.
osteomyelitis.25 In patients in whom MRI is con- Clinical staging guides decision-making when
traindicated, a tagged leukocyte scan, computed choosing specific surgical treatments and limits
tomography (CT), PET/CT, or sulfur colloid mar- the need for amputation.31 The 2015 modification
row scan can be appropriate;​however, diagnosis of the Cierny-Mader staging system (developed in
may be impeded because of false-positive results 1985) is commonly used and classifies osteomyeli-
from recent surgery or trauma, healed osteomy- tis based on the anatomic location and the physi-
elitis, arthritis, bony tumors, Paget disease of ologic condition of the patient.31,32 Anatomic types
bone, or reduced uptake secondary to necrosis include medullary (stage 1), superficial (stage 2),
and poor blood flow.13,29,30 Ultrasonography plays localized (stage 3), and diffuse (stage 4), with

TABLE 2

Diagnostic Imaging Studies and Osteomyelitis

Sensitivity Specificity
Imaging modality (%) (%) Comments

Plain film radiography 14 to 54 68 to 70 Preferred initial imaging modality;​useful to rule out other bony pathology
(anteroposterior, lateral,
and oblique views)

MRI 78 to 90 60 to 90 Intravenous contrast media preferred;​useful to distinguish between

soft tissue and bone infection, and to determine extent of infection;​less
useful in areas with surgical hardware because of image distortion

Computed tomography 67 50 Contrast media preferred to help with soft tissue evaluation;​may be
used if MRI is contraindicated

Ultrasonography NA NA Cannot be used to evaluate bone, but may be useful for identifying
surrounding soft tissue changes or guiding needle aspiration;​use for
evaluation of suspected foreign body with negative results on radiogra-
phy;​may be used if MRI is contraindicated

Technetium-99 bone 82 25 Low specificity, especially if patient has had recent trauma or surgery;​
scintigraphy useful to differentiate osteomyelitis from cellulitis;​SPECT improves sen-
sitivity;​may be used if MRI is contraindicated

Leukocyte scintigraphy 61 to 84 60 to 68 Combining with technetium-99 bone scintigraphy can increase specific-
ity;​may be used if MRI is contraindicated

Positron emission 96 91 Expensive;​limited availability;​may be used if MRI is contraindicated

tomography

MRI = magnetic resonance imaging;​NA = not applicable;​SPECT = single-photon emission computed tomography.
Adapted with permission from Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Physician. 2011;​84(9):​1028, with
additional information from references 9, 13, and 24-30.

398 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 OSTEOMYELITIS

FIGURE 2 FIGURE 4

Anteroposterior foot radiograph demon-

strating focal osteopenia and cortical dis-
ruption of the third distal phalanx with
surrounding periosteal reaction (short
thick arrow), consistent with osteomyeli-
Axial T1-weighted (T1W) foot magnetic
tis. The first digit has been amputated at
resonance imaging scan demonstrating
the level of the proximal phalanx diaphysis
confluent low T1 signal (compared to nor-
(long thin arrow) from prior osteomyelitis.
mal bone marrow) throughout the third
Copyright © Timothy G. Russell, MD distal phalanx marrow (short thick arrow),
consistent with osteomyelitis. There is also
some involvement of the head of the third
middle phalanx (long thin arrow). The first
FIGURE 3 digit has been amputated at the level of
the proximal phalanx diaphysis (long thick
arrow) from prior osteomyelitis.
Copyright © Timothy G. Russell, MD

higher stages requiring more complex surgical

intervention.32 The physiologic condition of the
patient (host) can be classified as type A (normal
immune response and healthy vascular system),
type B (local immunocompromise), or type C
(noncandidate for surgery). In those classified as
type C, treatment is expected to cause more harm
Lateral foot radiograph demonstrating focal osteo- than the disease process itself, so the focus of care
penia and cortical disruption of the third distal pha-
lanx with surrounding periosteal reaction (short thick
shifts from cure to palliation.
arrow), consistent with osteomyelitis. A subtle lucency
involving the soft tissues of the third distal phalanx tip ANTIBIOTICS
(long thin arrow) is consistent with a superficial ulcer The choice of antibiotic therapy is specific to the
that was noted on physical examination. culture results listed in Table 3.2,33-37 It should
Copyright © Timothy G. Russell, MD be tailored to the individual patient based on
susceptibility. Specific antibiotic coverage is

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 399
 OSTEOMYELITIS

usually indicated. In hospitalized patients at severe sepsis, epidural extension, or neurologic

risk of methicillin-resistant S. aureus, empiric involvement. The addition of rifampin to other
antibiotic coverage is recommended. Delaying antibiotics may also improve cure rates, especially
antibiotic therapy until cultures are available is when prosthetic joint or spinal implant infections
recommended except in patients in whom urgent are present.35,36 For adult patients hospitalized
intervention is necessary, such as those with with osteomyelitis, parenteral followed by oral

TABLE 3

Initial Antibiotic Therapy for Osteomyelitis in Adults

Organism Preferred regimens Alternative regimens*

Anaerobes Clindamycin, 600 mg IV every 6 hours Cefotetan (Cefotan), 2 g IV every 12 hours

Ticarcillin/clavulanate (Timentin), 3.1 g IV every Metronidazole (Flagyl), 500 mg IV every 6 hours
4 hours

Cutibacterium acnes Penicillin G, 2 to 4 million units IV every 4 hours Ceftriaxone, 2 g IV every 24 hours
(formerly known as
Propionibacterium
acnes)

Enterobacteriaceae Ticarcillin/clavulanate, 3.1 g IV every 4 hours Ceftriaxone (Rocephin), 2 g IV every 24 hours

(e.g., Escherichia coli), Piperacillin/tazobactam (Zosyn), 3.375 g IV every
quinolone resistant 6 hours

Enterobacteriaceae, Fluoroquinolone (e.g., ciprofloxacin, 400 mg IV Ceftriaxone, 2 g IV every 24 hours

quinolone sensitive every 8 to 12 hours) Ciprofloxacin, 750 mg orally every 12 hours
Levofloxacin (Levaquin), 750 mg orally every
24 hours

Pseudomonas Cefepime, 2 g IV every 8 to 12 hours, plus cipro- Imipenem/cilastatin (Primaxin), 1 g IV every

aeruginosa floxacin, 400 mg IV every 8 to 12 hours 8 hours, plus aminoglycoside
Piperacillin/tazobactam, 3.375 g IV every 6 hours,
plus ciprofloxacin, 400 mg IV every 12 hours

Staphylococcus Vancomycin, 15 to 20 mg per kg per dose IV Daptomycin (Cubicin), 6 mg per kg IV every

aureus, methicillin every 8 to 12 hours 24 hours
resistant For patients allergic to vancomycin:​ Linezolid, 600 mg IV or orally every 12 hours
Linezolid (Zyvox), 600 mg IV every 12 hours Clindamycin, 600 mg IV or orally every 8 hours
or Trimethoprim/sulfamethoxazole, 3.5 to 4.0 mg
Rifampin, 600 mg daily per kg per dose or 2 double-strength tablets (for
an 80-kg [176-lb] adult) IV or orally every 8 to
12 hours

S. aureus, methicillin Nafcillin or oxacillin, 1 to 2 g IV every 4 hours Ceftriaxone, 2 g IV every 24 hours

sensitive Cefazolin, 1 to 1.5 g IV every 6 hours Vancomycin, 1 g IV every 12 hours

Streptococcus Penicillin G, 2 to 4 million units IV every 4 hours Ceftriaxone, 2 g IV every 24 hours

species Clindamycin, 600 mg IV every 6 hours

IV = intravenously.
*—Alternative regimens are available if the patient has an allergy to the preferred regimen, does not have access to the preferred regimen, or does
not tolerate the preferred regimen because of other medical complications (e.g., chronic kidney disease, liver failure, drug interactions).
Adapted with permission from Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Physician. 2011;​84(9):​1031, with
additional information from references 33-37.

400 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 OSTEOMYELITIS

antibiotic therapy appears to be as effective as The opinions and assertions contained herein are the
long-term parenteral therapy. Evidence suggests private views of the authors and are not to be con-
strued as official or as reflecting the views of the U.S.
that oral antibiotics have similar cure rates and Army Medical Department or the U.S. Army at large.
lower risks and costs compared with parenteral
antibiotics.20,37,38 Treatment typically lasts four to
six weeks, but comparisons of treatment duration The Authors
have not been well studied.37 DAVID C. BURY, DO, MPH, FAAFP, is program
director of the Family Medicine Residency Program
DEBRIDEMENT at Martin Army Community Hospital, Fort Benning,
Ga., and is assistant professor in the Department
Surgical bony debridement followed by drain- of Family Medicine at the Uniformed Services Uni-
age of any associated soft tissue abscess contin- versity of the Health Sciences, Bethesda, Md. At the
ues to be a mainstay of therapy, although there time this article was written, Dr. Bury was a fellow
is no clear recommendation about which cases in the Leadership and Faculty Development Fel-
lowship Program at Madigan Army Medical Center,
will require debridement.36 Debridement is typ-
Joint Base Lewis-McChord, Wash.
ically indicated as part of the initial treatment
in the presence of underlying orthopedic hard- TYLER S. ROGERS, MD, FAAFP, is a fellow in the
ware and necrotic bone. Stabilization of the bone Leadership and Faculty Development Fellowship
is an essential component of debridement and Program at Madigan Army Medical Center, an
assistant professor in the Department of Family
can decrease healing time and complications. Medicine at the Uniformed Services University of
Surgical debridement after antibiotic therapy the Health Sciences, and a clinical assistant pro-
shortens hospital stays, reduces medical costs, fessor in the Department of Family Medicine at
provides satisfactory infection control, and pre- the University of Washington School of Medicine,
vents complications of long-term systemic anti- Seattle.
biotic use.39 Debridement can be supplemented MICHAEL M. DICKMAN, DO, MBA, FAAFP, is
with the placement of antibiotic-loaded collagen Chief of the Department of Soldier and Commu-
sponges, which has some evidence supporting nity Health at Madigan Army Medical Center, an
improved outcomes.40 Hyperbaric oxygen ther- assistant professor in the Department of Family
Medicine at the Uniformed Services University of
apy can be used as an adjunctive modality and
the Health Sciences, and a clinical assistant pro-
may be particularly helpful in cases of chronic fessor in the Department of Family Medicine at
osteomyelitis.41 the University of Washington School of Medicine.
At the time this article was written, Dr. Dickman
Special Considerations was a fellow in the Leadership and Faculty Devel-
opment Fellowship Program at Madigan Army
When selecting treatment strategies for osteo-
Medical Center.
myelitis, several groups of patients require spe-
cial considerations, such as children and patients Address correspondence to David C. Bury, DO,
who have prosthetic joints, vertebral osteomyeli- MPH, FAAFP, 6600 Van Aalst Blvd., Fort Ben-
tis, and diabetes. The treatment of these groups is ning, GA 31905 (email:​david.c.bury@​gmail.com).
Reprints are not available from the authors.
beyond the scope of this article.

This article updates a previous article on this topic by References

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402 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021