# 15 - 136 Osteomyelitis

### 136 Osteomyelitis

Borzio R et al: Predictors of septic arthritis in the adult population. 
Orthopedics 39:e657, 2016.
Franssila R, Hedman K: Infection and musculoskeletal conditions: 
Viral causes of arthritis. Best Pract Res Clin Rheumatol 20:1139, 
2006.
Harrington JT: Mycobacterial and fungal arthritis. Curr Opin 
Rheumatol 10:335, 1998.
Huotari K et al: High cure rate for acute streptococcal prosthetic joint 
infections treated with debridement, antimicrobials, and implant 
retention in a specialized tertiary care center. Clin Infect Dis 67:1288, 
2018.
Meehan AM et al: Outcome of penicillin-susceptible streptococcal 
prosthetic joint infection treated with debridement and retention of 
the prosthesis. Clin Infect Dis 36:845, 2003.
Mohammad M et al: The role of Staphylococcus aureus lipoproteins in 
hematogenous septic arthritis. Sci Rep 10:7936, 2020.
Osmon DR et al: Diagnosis and management of prosthetic joint infection: 
Clinical practice guidelines by the Infectious Diseases Society of 
America. Clin Infect Dis 56:e1, 2013.
Patel R: Periprosthetic joint infection. N Engl J Med 388:251, 2023.
Ross J et al: Septic arthritis and the opioid epidemic: 1465 cases of 
culture-positive native joint septic arthritis from 1990−2018. Open 
Forum Infect Dis 7:ofaa089, 2020.
Zeller V et al: One-stage exchange arthroplasty for chronic peripros­
thetic hip infection: Results of a large prospective cohort study. J Bone 
Joint Surg Am 96:e1, 2014.
Zimmerli W et al: Prosthetic-joint infections. N Engl J Med 351:145, 
2004.
Werner Zimmerli

Osteomyelitis
Osteomyelitis, an infection of bone, can be caused by various 
microorganisms that arrive at bone through different routes. Spon­
taneous hematogenous osteomyelitis may occur in otherwise healthy 
individuals, whereas local microbial spread mainly affects either indi­
viduals who have underlying disease (e.g., vascular insufficiency) or 
patients who have compromised skin or other tissue barriers, with con­
sequent exposure of bone. The latter situation typically follows surgery 
involving bone, such as sternotomy or orthopedic repair.
The manifestations of osteomyelitis are different in children and 
adults. In children, circulating microorganisms seed mainly long 
bones, whereas in adults, the vertebral column is the most commonly 
affected site.
Management of osteomyelitis differs greatly depending on whether 
an implant is involved. The most important aim of the management 
of either type of osteomyelitis is to prevent progression to chronic 
osteomyelitis by rapid diagnosis and prompt treatment. Therefore, 
unambiguous case definitions are required. Device-related bone and 
joint infection necessitates a multidisciplinary approach requiring 
antibiotic therapy and, in many cases, surgical removal of the device. 
For most types of osteomyelitis, the optimal duration and route of anti­
biotic treatment have not been established in clinical trials. Therefore, 
the recommendations for therapy in this chapter reflect mainly expert 
opinions.
CLASSIFICATION
There is no generally accepted, comprehensive system for classification 
of osteomyelitis, primarily because of the multifaceted presentation 
of this infection. Different specialists are confronted with different 
facets of bone disease. Most often, however, general practitioners or 

internists are the first to encounter patients with the initial signs and 
symptoms of osteomyelitis. These primary care physicians should be 
able to recognize this disease in any of its forms. Osteomyelitis cases 
can be classified by various criteria, including pathogenesis, duration 
of infection, location of infection, and presence or absence of foreign 
material. The widely used Cierny-Mader staging system is useful 
mainly for trauma surgeons. It classifies osteomyelitis according to 
anatomic site, comorbidity, and radiographic findings, with stratifica­
tion of long-bone osteomyelitis to optimize surgical management; this 
system encompasses both systemic and local factors affecting immune 
status, metabolism, and local vascularity.

Any of three mechanisms can underlie osteomyelitis: (1) hematog­
enous spread; (2) spread from a contiguous site following surgery; and 
(3) secondary infection in the setting of vascular insufficiency or con­
comitant neuropathy. Hematogenous osteomyelitis in adults typically 
involves the vertebral column. In only about half of patients a primary 
focus can be detected. The most common primary foci of infection are 
the urinary tract, skin/soft tissue, intravascular catheterization sites, 
and the endocardium. Spread from a contiguous source follows either 
bone trauma or surgical intervention. Wound infection leading to 
osteomyelitis typically occurs after cardiovascular intervention involv­
ing the sternum, orthopedic repair after open fracture, or prosthetic 
joint insertion. Osteomyelitis secondary to vascular insufficiency or 
peripheral neuropathy most often follows chronic, progressively deep 
skin and soft tissue infection of the foot. The most common underlying 
condition is diabetes. In diabetes that is poorly controlled, the diabetic 
foot syndrome is caused by skin, soft tissue, and bone ischemia com­
bined with motor, sensory, and autonomic neuropathy.
CHAPTER 136
Classification of osteomyelitis according to the duration of infec­
tion, although ill defined, is useful because the management of acute 
and chronic osteomyelitis differs. However, not a defined duration of 
infection, but the presence or absence of bone necrosis (sequesters) 
is crucial. Acute osteomyelitis without bone necrosis can generally be 
treated with antibiotics alone. In contrast, for chronic osteomyelitis 
antibiotic treatment should be combined with debridement surgery. 
Acute hematogenous or contiguous osteomyelitis evolves over a short 
period—i.e., a few days or weeks. In contrast, subacute or chronic 
osteomyelitis lasts for weeks or months before treatment is started. 
Typical examples of a subacute course are vertebral osteomyelitis due 
to tuberculosis or brucellosis and delayed implant-associated infections 
caused mainly by low-virulence microorganisms (coagulase-negative 
staphylococci, Cutibacterium acnes). A special form of osteomyelitis is 
Brodie’s abscess, mainly occurring in young males. Chronic osteomy­
elitis develops when insufficient therapy leads to persistence or recur­
rence, most often after sternal, mandibular, or foot infection.
Osteomyelitis
Classification by location distinguishes among cases in the long 
bones, the vertebral column, and the periarticular bones. Long bones 
are generally involved after hematogenous seeding in children or 
contiguous spread following trauma or surgery. The risk of vertebral 
osteomyelitis in adults increases with age. Periarticular osteomyelitis, 
which complicates septic arthritis that has not been adequately treated, 
is especially common in periprosthetic joint infection.
Osteomyelitis involving a foreign device requires surgical manage­
ment for cure. Even acute implant-associated infection calls for pro­
longed antimicrobial therapy. Therefore, identification of this type of 
disease is of practical importance.
VERTEBRAL OSTEOMYELITIS
■
■PATHOGENESIS
Vertebral osteomyelitis, also referred to as disk-space infection, septic 
diskitis, spondylodiskitis, or spinal osteomyelitis, is the most common 
manifestation of hematogenous bone infection in adults. This designa­
tion reflects a pathogenic process leading to involvement of the adja­
cent vertebrae and the corresponding intervertebral disk. In adults, the 
disk is avascular. Microorganisms invade via the segmental arterial cir­
culation in adjacent endplates and then spread into the disk. Alterna­
tive routes of infection are retrograde seeding through the prevertebral 
venous plexus and direct inoculation during spinal surgery, epidural

infiltration, or trauma. In the setting of implant surgery, microorgan­
isms are inoculated either during the procedure or, if wound healing is 
impaired, in the early postoperative period.

■
■EPIDEMIOLOGY
Vertebral osteomyelitis occurs more often in male than in female 
patients (ratio, 1.5:1). Between 1995 and 2008, the incidence rate 
increased from 2.2 to 5.8 cases/100,000 person-years. There is a clear 
age-dependent increase. Men age ≥70 years have a sixfold higher inci­
dence rate than those <70 years. The observed increase in reported 
cases over time may reflect improvements in diagnosis resulting from 
the broad availability of MRI technology. In addition, the fraction of 
cases of vertebral osteomyelitis acquired in association with health care 
is increasing as a consequence of comorbidity and the rising number of 
invasive interventions.
■
■MICROBIOLOGY
Vertebral osteomyelitis is typically classified as pyogenic or nonpyo­
genic. However, this distinction is arbitrary: in “nonpyogenic” cases 
(tuberculous, brucellar), macroscopic pus formation (caseous necrosis, 
abscess) is quite common. A more accurate scheme is to classify cases 
as acute or subacute/chronic. Whereas the microbiologic spectrum of 
acute cases is similar in different parts of the world, the spectrum of 
subacute/chronic cases varies according to the geographic region. The 
great majority of cases are monomicrobial in etiology. Of episodes of 
acute vertebral osteomyelitis, 40–50% are caused by Staphylococcus 
aureus, 12% by streptococci, and 20% by gram-negative bacilli—mainly 
Escherichia coli (9%) and Pseudomonas aeruginosa (6%). Subacute 
vertebral osteomyelitis is typically caused by Mycobacterium tubercu­
losis or Brucella species in regions where these microorganisms are 
endemic. Osteomyelitis due to viridans streptococci also has a subacute 
presentation; these infections most often occur as secondary foci in 
patients with endocarditis. In vertebral osteomyelitis due to Candida 
species, the diagnosis is often delayed by several weeks; this etiology 
should be suspected in IV drug users who do not use sterile parapher­
nalia. In implant-associated spinal osteomyelitis, coagulase-negative 
staphylococci and C. acnes—which, in the absence of an implant, 
are generally considered contaminants—typically cause low-grade 
(chronic) infections. As an exception, coagulase-negative staphylococci 
can cause native spinal osteomyelitis in cases of prolonged bacteremia 
(e.g., in patients with infected pacemaker electrodes or implanted vas­
cular catheters that are not promptly removed).
PART 5
Infectious Diseases
■
■CLINICAL MANIFESTATIONS
The signs and symptoms of vertebral osteomyelitis are nonspecific. 
Only about half of patients develop fever >38°C (>100.4°F), perhaps 
because patients frequently use analgesic drugs. Back pain is the lead­
ing initial symptom (>85% of cases). The location of the pain corre­
sponds to the site of infection: the cervical spine in ~10% of cases, the 
thoracic spine in 30%, and the lumbar spine in 60%. One exception is 
involvement at the thoracic level in two-thirds of cases of tuberculous 
osteomyelitis and at the lumbar level in only one-third. This difference 
is due to direct mycobacterial spread via pleural or mediastinal lymph 
nodes in pulmonary tuberculosis.
Neurologic deficits, such as radiculopathy, weakness, or sensory 
loss, are observed in about one-third of cases of vertebral osteomyelitis. 
Neurologic signs and symptoms are caused mostly by spinal epidural 
abscess. This complication starts with severe localized back pain and 
progresses to radicular pain, reflex changes, sensory abnormalities, 
motor weakness, bowel and bladder dysfunction, and paralysis.
A primary focus should always be sought but is found in only half of 
cases. Overall, endocarditis is identified in ~10% of patients. In osteo­
myelitis caused by viridans streptococci, endocarditis is the source in 
about half of patients.
Implant-associated spinal osteomyelitis can present as either early- 
or late-onset infection. Early-onset infection is diagnosed within 
30 days after implant placement. S. aureus is the most common patho­
gen. Wound healing impairment and fever are the leading findings. 
Late-onset infection is diagnosed beyond 30 days after surgery, with 

low-virulence organisms such as coagulase-negative staphylococci 
or C. acnes as typical infecting agents. Fever is rare. One-quarter of 
patients have a sinus tract. Because of the delayed course and the lack 
of classic signs of infection, rapid diagnosis requires a high degree of 
suspicion.
■
■DIAGNOSIS
Leukocytosis and neutrophilia have low levels of diagnostic sensitivity 
(only 65% and 40%, respectively). In contrast, an increased erythrocyte 
sedimentation rate or C-reactive protein (CRP) level has been reported 
in 98% and 100% of cases, respectively; thus, these tests are helpful in 
excluding vertebral osteomyelitis. The fraction of blood cultures that 
yield positive results depends heavily on whether the patient has been 
pretreated with antibiotics; across studies, the range is 30–78%. In view 
of this low rate of positive blood culture after antibiotic treatment, such 
therapy should be withheld until microbial growth is proven unless the 
patient has sepsis syndrome. In patients with negative blood cultures, 
CT-guided or open biopsy is needed. Whether a CT-guided biopsy 
with a negative result is repeated or followed by open biopsy depends 
on the experience of personnel at the specific center. Bone samples 
should be cultured for aerobic, anaerobic, and fungal agents, with a 
portion of the sample sent for histopathologic study. In cases with a 
subacute/chronic presentation, a suggestive history, or a granuloma 
detected during histopathologic analysis, mycobacteria and brucellae 
also should be sought. When blood and tissue cultures are negative 
despite suggestive histopathology, nonculture techniques (eubacterial 
or multiplex polymerase chain reaction analysis, metagenomics) of 
biopsy specimens or aspirated pus should be considered. These tech­
niques allow detection of unusual pathogens such as Helicobacter spp. 
or Tropheryma whipplei.
Given that signs and symptoms of osteomyelitis are nonspecific, 
the clinical differential diagnosis of febrile back pain is broad, includ­
ing pyelonephritis, pancreatitis, and viral syndromes. In addition, 
multiple noninfectious pathologies of the vertebral column, such as 
osteoporotic fracture, seronegative spondylitis (ankylosing spondylitis, 
psoriasis, reactive arthritis, enteropathic arthritis), and spinal stenosis 
must be considered.
Imaging procedures are the most important tools not only for the 
diagnosis of vertebral osteomyelitis but also for the detection of pyo­
genic complications and alternative conditions (e.g., bone metastases 
or osteoporotic fractures). Plain radiography is a reasonable first step 
in evaluating patients without neurologic symptoms and may reveal an 
alternative diagnosis. Because of its low sensitivity, plain radiography 
generally is not helpful in acute osteomyelitis, but it can be useful in 
subacute or chronic cases. The gold standard is MRI, which should be 
performed expeditiously in patients with neurologic impairment in 
order to rule out a herniated disk or to detect pyogenic complications 
in a timely manner (Fig. 136-1, left). Even if the pathologic findings 
on MRI suggest vertebral osteomyelitis, alternative diagnoses should 
be considered, especially when blood cultures are negative. The most 
common alternative diagnosis is erosive osteochondrosis. Septic bone 
necrosis, gouty spondylodiskitis, and erosive diskovertebral lesions 
(Andersson lesions) in ankylosing spondylitis may likewise mimic ver­
tebral osteomyelitis. CT is less sensitive than MRI but may be helpful in 
guiding a percutaneous biopsy. Positron emission tomography (PET) 
with 18F-fluorodeoxyglucose, which has a high degree of diagnostic 
accuracy, is an alternative imaging procedure when MRI is contra­
indicated (Fig. 136-1, right). 18F-fluorodeoxyglucose PET should be 
considered for patients with implants and patients in whom several 
foci are suspected.
TREATMENT
Vertebral Osteomyelitis
The aims of therapy for vertebral osteomyelitis are (1) elimination 
of the pathogen(s), (2) protection from further bone loss, (3) relief 
of back pain, (4) prevention of complications, and (5) stabilization, 
if needed.

A
FIGURE 136-1  Left: MRI from a 53-year-old man suffering from prosthetic aortic valve endocarditis (Aggregatibacter actinomycetemcomitans). In addition, he experienced 
lumbar pain for 7 weeks. MRI sagittal sequence shows on T1 fat-saturated post-gadolinium image enhancement in the intervertebral disk space (ventral arrow) and a small 
epidural abscess (dorsal arrow). Right: PET/CT from the same patient 4 weeks earlier. PET/CT fusion shows fluorodeoxyglucose uptake at L5 ventral (small arrow) and dorsal 
of S1 (large arrow: epidural abscess). (Figures courtesy of Damien Toia, MD, Kantonsspital Baselland; with permission.)
Table 136-1 summarizes suggested antimicrobial regimens for 
infections attributable to the most common etiologic agents. For 
optimal antimicrobial therapy, identification of the infecting agent is 
required. Therefore, in patients without sepsis syndrome, antibiotics 
should not be administered until the pathogen is identified in a blood 
culture, a bone biopsy, or an aspirated pus collection. Traditionally, 
bone infections are at least initially treated by the IV route. However, 
the preference for the IV route is not evidence based. There are no 
good arguments for the assumption that IV therapy is superior to 
oral administration if the following requirements are met: (1) opti­
mal antibiotic spectrum, (2) excellent bioavailability of the oral drug, 
(3) clinical studies confirming efficacy of the oral drug, (4) normal 
intestinal function, and (5) no vomiting. Indeed, in a controlled 
trial in patients with bone and joint infections, including vertebral 
osteomyelitis, oral antibiotic therapy was noninferior to intravenous 
therapy when used during the first 6 weeks. Nevertheless, a short 
initial course of parenteral therapy with a β-lactam antibiotic may 
lower the risk of emergence of fluoroquinolone resistance, especially 
if P. aeruginosa infection is treated with ciprofloxacin or staphylo­
coccal infection with the combination of a fluoroquinolone plus 
rifampin. These suggestions are based on observational studies and 
expert opinion. A randomized, controlled trial showed that 6 weeks 
of antibiotic treatment is not inferior to a 12-week course in patients 
with pyogenic vertebral osteomyelitis. The cure rate was 90.9% in 
both groups 1 year after therapy. Thus, prolonged antibiotic therapy 
is required only for patients with undrained abscesses and for 
patients with spinal implants. Treatment efficacy should be regularly 
monitored through inquiries about signs and symptoms (fever, pain) 
and assessment for signs of inflammation (elevated CRP concentra­
tions). Follow-up MRI is appropriate only for patients with pyogenic 
complications since the correlation between clinical healing and 
improvement on MRI is very poor.
Surgical treatment generally is not needed in acute hematog­
enous vertebral osteomyelitis. However, it is always necessary in 
implant-associated spinal infection. Early infections (those occur­
ring up to 30 days after internal stabilization) can be cured with 
debridement, implant retention, and a 3-month course of antibi­
otics (Table 136-2). In contrast, in late infection with a duration 

B
CHAPTER 136
of >30 days, implant removal and a 6-week course of antibiotics 
(Table 136-1) are required for complete elimination of the infection. 
If implants cannot be removed, oral suppressive long-term treat­
ment should follow the initial course of IV antibiotics. The optimal 
duration of suppressive therapy is unknown. However, if antibiotic 
therapy is discontinued after, for example, 1 year, close clinical and 
laboratory (CRP) follow-up is needed.
Osteomyelitis
■
■COMPLICATIONS
Complications should be suspected when there is persistent pain, a 
persistently increased CRP level, and new-onset or persistent neuro­
logic impairment. In cases of persistent pain with or without signs 
of inflammation, paravertebral, epidural, or psoas abscesses must be 
sought. Epidural abscesses occur in 15–20% of cases. This complica­
tion is more common in the cervical column (30%) than in the lumbar 
spine (12%). Risk factors for severe neurologic deficit were epidural 
abscess, cervical and/or thoracic involvement, and S. aureus vertebral 
osteomyelitis. Persistent pain despite normalization of CRP values 
indicates mechanical complications such as severe osteonecrosis or 
spinal instability. These patients require a consult with an experienced 
orthopedic surgeon.
■
■GLOBAL CONSIDERATIONS
The incidence rate of acute vertebral osteomyelitis is similar in dif­
ferent regions of the world. In contrast, subacute/chronic vertebral 
osteomyelitis predominates in defined regions. Cases attributable to 
brucellosis predominate in endemic areas such as the Middle East, 
Africa, Central and South America, and the Indian subcontinent. 
Tuberculosis is an especially frequent cause in Africa and Asia (India, 
Indonesia, China), where more than two-thirds of the global tubercu­
losis burden is reported. Thus, specific diagnostic tests are needed in 
patients either living in or having traveled to these regions.
OSTEOMYELITIS IN LONG BONES
■
■PATHOGENESIS
Osteomyelitis in long bones is a consequence of hematogenous seed­
ing, exogenous contamination during trauma (open fracture), or

TABLE 136-1  Antibiotic Therapy for Osteomyelitis in Adults without 
Implantsa
MICROORGANISM
ANTIMICROBIAL AGENT (DOSE,b ROUTE)
Staphylococcus spp.
 
  Methicillin-susceptible
Nafcillin or oxacillinc (2 g IV q6h)
 
followed by
 
Rifampin (300–450 mg PO q12h) plus levofloxacin 
(750 mg PO q24h or 500 mg PO q12h)
  Methicillin-resistant
Vancomycind (15 mg/kg IV q12h) or daptomycin 
(8–10 mg/kg IV q24h)
 
followed by
 
Rifampin (300–450 mg PO q12h)
 
plus
 
Levofloxacin (750 mg PO q24h or 500 mg PO q12h) 
or TMP-SMXe (1 double-strength tablet PO q8h) 

or fusidic acid (500 mg PO q8h)
Streptococcus spp.
Penicillin Gc (5 million units IV q6h) or ceftriaxone 
(2 g IV q24h)
Enterobacteriaceae
  Quinolone-susceptible
  Quinolone-resistantf
Ciprofloxacin (750 mg PO q24h)
Imipenem (500 mg IV q6h) or meropenem (1–2g IV q8h)
Pseudomonas aeruginosa
Cefepime or ceftazidime (2 g IV q8h) plus an 
aminoglycosideg
 
or
 
Piperacillin-tazobactam (4.5 g IV q8h) plus an 
aminoglycosideg for 2–4 weeks
 
followed by
PART 5
Infectious Diseases
 
Ciprofloxacinh (750 mg PO q12h)
Anaerobes
Clindamycin (600 mg IV q6–8h) for 2–4 weeks
 
followed by
 
Clindamycini (300 mg PO q6h)
aUnless otherwise indicated, the total duration of antimicrobial treatment is 
generally 6 weeks. bAll dosages are for adults with normal renal function. cWhen the 
patient has delayed-type penicillin hypersensitivity, cefuroxime (1.5 g IV q6–8h) can 
be administered. When the patient has immediate-type penicillin hypersensitivity, 
the penicillin should be replaced by vancomycin (1 g IV q12h). dTarget vancomycin 
trough level: 15–20 μg/mL. eTrimethoprim-sulfamethoxazole. A double-strength 
tablet contains 160 mg of trimethoprim and 800 mg of sulfamethoxazole. fIncluding 
isolates producing extended-spectrum β-lactamase. gThe need for addition of an 
aminoglycoside has not yet been proven. However, this addition may decrease 
the risk of emergence of resistance to the β-lactam. hThe rationale for starting 
ciprofloxacin treatment only after pretreatment with a β-lactam is the increased 
risk of emergence of quinolone resistance in the presence of a heavy bacterial 
load. iAlternatively, penicillin G (5 million units IV q6h) or ceftriaxone (2 g IV q24h) 
can be used against gram-positive anaerobes (e.g., Cutibacterium acnes), and 
metronidazole (500 mg IV/PO q8h) can be used against gram-negative anaerobes 
(e.g., Bacteroides spp.).
Source: From W Zimmerli: Vertebral osteomyelitis. N Engl J Med 362:1022, 2010. 
Copyright © 2010 Massachusetts Medical Society. Reprinted with permission from 
Massachusetts Medical Society.
perioperative contamination during surgery involving bone. Hematog­
enous infection in long bones typically occurs in children. In adults, 
the leading pathogenic source is exogenous fracture-related infection, 
mainly associated with internal fixation devices. For classification, the 
presence of a sequestrum and the status of the surrounding soft tissue 
are crucial for the decision as to whether a surgical intervention is 
required. Chronic osteomyelitis can be reactivated after a symptomfree interval of >70 years. Such recurrences are most common among 
elderly patients who developed S. aureus osteomyelitis in the preanti­
biotic era.
■
■EPIDEMIOLOGY
In adults, most cases of long-bone osteomyelitis are posttraumatic 
or postsurgical; less frequently, late recurrence arises from hematog­
enous infections during childhood. For postoperative or postsurgical 
osteomyelitis, the term “facture-related infection” was generated. The 
risk of infection depends on the type of fracture. After closed fracture, 
implant-associated infection occurs in fewer than 1% of patients. In 
contrast, after open fracture, the risk of osteomyelitis ranges from ~2% 

up to 30%, with the precise figure depending on the degree of tissue 
damage during trauma and the time between injury and admission to 
a specialized center.
■
■MICROBIOLOGY
The spectrum of microorganisms causing hematogenous long-bone 
osteomyelitis does not differ from that in vertebral osteomyelitis. S. aureus 
is most commonly isolated in each type of osteomyelitis. In rare cases, 
mycobacteria or fungal agents such as Cryptococcus species, Sporothrix 
schenckii, Blastomyces dermatitidis, or Coccidioides species are found in 
patients who live or have traveled in endemic regions. Impaired cellular 
immunity (e.g., in HIV infection or after transplantation) predisposes 
to these etiologies. Coagulase-negative staphylococci are the second 
most common etiologic agents (after S. aureus) in implant-associated 
osteomyelitis. After open fracture, contiguous long-bone osteomyelitis 
is typically caused by gram-negative bacilli or a polymicrobial mixture 
of organisms.
■
■CLINICAL MANIFESTATIONS
The leading symptoms in adults with primary or recurrent hematog­
enous long-bone osteomyelitis are pain and low-grade fever. Infection 
occasionally manifests as clinical sepsis and local signs of inflamma­
tion (erythema and swelling). After internal fixation, osteomyelitis can 
be classified as early (acute; <3 weeks), delayed (3–10 weeks), or late 
(chronic) infection. Early/acute long-bone osteomyelitis manifests as 
signs of surgical site infection, such as erythema and impaired wound 
healing. Acute implant-associated infection may also follow hematog­
enous seeding at any time after implantation of a device. Typical symp­
toms are new-onset pain and signs of sepsis. Delayed or late (chronic) 
infections are usually caused by low-virulence microorganisms or 
occur after ineffective treatment of early-onset infection. Patients may 
present with persisting pain, subtle local signs of inflammation, intermittent 
discharge of pus, or fluctuating erythema over the scar (Fig. 136-2). 
A special form of subacute osteomyelitis is Brodie’s abscess, which is 
characterized by pain (98%) and swelling (53%), mainly in the tibia or 
the femur. Fever and inflammatory markers are typical. The median 
delay from symptoms to diagnosis is 3 months. Thus, a young patient 
with unclear localized pain in the tibia or femur should be worked-up 
with an imaging modality (plain x-ray, MRI, or CT).
■
■DIAGNOSIS
The diagnostic workup for acute hematogenous long-bone osteomy­
elitis is similar to that for vertebral osteomyelitis. Bone remodeling 
and thus marker uptake are increased for at least 1 year after surgery. 
Therefore, the three-phase bone scan is not useful during this interval. 
However, in late recurrences it allows rapid diagnosis at low cost. If the 
results are positive, CT is required to estimate the extent of inflamed 
tissue and detect bone necrosis (sequesters). Implant-associated infec­
tion should be suspected if CRP values do not return to the normal 
range or rise after an initial decrease. Clinical and laboratory suspicion 
should prompt surgical exploration and sampling.
In osteomyelitis of >1 year’s duration, single-photon emission CT 
plus conventional CT (SPECT/CT) is a good option, either with 99mTc 
methylene diphosphonate (99mTc-MDP)–labeled leukocytes or with 
labeled monoclonal antibodies to granulocytes. Surgical debridement 
is needed for diagnostic (biopsy culture, histology) and therapeutic 
reasons.
TREATMENT
Osteomyelitis in Long Bones
Treatment for acute hematogenous infection in long bones is iden­
tical to that for acute vertebral osteomyelitis (Table 136-1). The 
suggested duration of antibiotic therapy is 4–6 weeks. In patients 
with good soft tissue condition and no sequestra or implants, 
generally no surgical intervention is required. According to a 
controlled trial, oral treatment can be given, provided that a regi­
men with excellent oral biocompatibility is available. An initial 
IV course can be as short as a few days, if the microorganism and

TABLE 136-2  Antibiotic Therapy for Osteomyelitis Associated with Orthopedic Devices
MICROORGANISM
ANTIMICROBIAL AGENTa (DOSE, ROUTE)
Staphylococcus spp.
Recommendation for initial treatment phase (2 weeks with implant)
  Methicillin-susceptible
Rifampin (450 mg PO/IV q12hb)
 
plus
 
Nafcillin or oxacillinc (2 g IV q6h)
  Methicillin-resistant
Rifampin (450 mg PO/IV q12hb)
 
plus
 
Vancomycin (15 mg/kg IV q12h) or daptomycin (8–10 mg/kg IV q24h)
Staphylococcus spp.
Recommendation after completion of initial treatment phase
 
Rifampin (450 mg PO q12hb)
 
plus
 
Levofloxacin (750 mg PO q24h or 500 mg PO q12h) or ciprofloxacin (750 mg PO q12h) or fusidic acid (500 mg PO q8h) or 
TMP-SMXd (1 double-strength tablet PO q8h) or minocycline (100 mg PO q12h) or linezolid (600 mg PO q12h) or clindamycin 
(1200–1350 mg/d PO in 3 or 4 divided doses)
Streptococcus spp.e
Penicillin Gc (18–24 million units/d IV in 6 divided doses) or ceftriaxone (2 g IV q24h) for 4 weeks
 
followed by
 
Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses)
Enterococcus spp.f
 
  Penicillin-susceptible
Penicillin Gc (24 million units/d IV in 6 divided doses) or ampicillin or amoxicilling (2 g IV q4–6h)
  Penicillin-resistant
Vancomycin (15 mg/kg IV q12h) or daptomycin (6–10 mg/kg IV q24h) or linezolid (600 mg IV/PO q12h)
Enterobacteriaceae
A β-lactam selected in light of in vitro susceptibility profile for 2 weeksh
 
followed by
 
Ciprofloxacin (750 mg PO q12h)
Enterobacter spp.i and nonfermentersj 
(e.g., Pseudomonas aeruginosa)
Cefepime or ceftazidime (2 g IV q8h) or meropenem (1–2 g IV q8hk) for 2–4 weeks
followed by
Ciprofloxacin (750 mg PO q12h)
Cutibacterium spp.
Penicillin Gc (18–24 million units/d IV in 6 divided doses) or clindamycin (600–900 mg IV q8h) for 2–4 weeks
 
followed by
 
Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses)
Gram-negative anaerobes 

(e.g., Bacteroides spp.)
Metronidazole (500 mg IV/PO q8h)
Mixed bacteria (without 

methicillin-resistant staphylococci)
Ampicillin-sulbactam (3 g IV q6h) or amoxicillin-clavulanatel (2.2 g IV q6h) or piperacillin-tazobactam (4.5 g IV q8h) 

or imipenem (500 mg IV q6h) or meropenem (1–2 g IV q8hk) for 2–4 weeks
followed by
Individualized oral regimens chosen in light of antimicrobial susceptibility
aAntimicrobial agents should be chosen in light of the isolate’s in vitro susceptibility, the patient’s drug allergies and intolerances, potential drug interactions, and 
contraindications to specific drugs. All dosages recommended are for adults with normal renal and hepatic function. See text for total durations of antibiotic treatment. 
bOther dosages and intervals of administration with equivalent success rates have been reported. cWhen the patient has delayed-type penicillin hypersensitivity, 
cefazolin (2 g IV q8h) can be administered. When the patient has immediate-type penicillin hypersensitivity, the penicillin should be replaced by vancomycin (1 g IV q12h). 
dTrimethoprim-sulfamethoxazole. A double-strength tablet contains 160 mg of trimethoprim and 800 mg of sulfamethoxazole. eDetermination of the minimal inhibitory 
concentration (MIC) of penicillin is advisable. fCombination therapy with an aminoglycoside is optional since its superiority to monotherapy for prosthetic joint infection is 
unproved. When using combination therapy, monitor for signs of aminoglycoside ototoxicity and nephrotoxicity; the latter is potentiated by other nephrotoxic agents (e.g., 
vancomycin). gFor patients with hypersensitivity to penicillin, see treatment options for penicillin-resistant enterococci. hCiprofloxacin (PO or IV) can be administered to 
patients with hypersensitivity to β-lactams. iCeftriaxone and ceftazidime should not be administered for treatment targeting Enterobacter species, even strains that test 
susceptible in the laboratory, but can be used against nonfermenters. Strains producing extended-spectrum β-lactamases should not be treated with any cephalosporin, 
including cefepime. Enterobacter infections can also be treated with ertapenem (1 g IV q24h); however, ertapenem is not effective against Pseudomonas spp. and other 
nonfermenters. jAddition of an aminoglycoside is optional. Use of two active drugs can be considered in light of the patient’s clinical condition. kThe recommended dosage 
is in line with the guidelines of the Infectious Diseases Society of America. In Europe, 2 g IV q8h is suggested for P. aeruginosa infections. lNot available as an IV formulation 
in the United States.
Source: Modified from W Zimmerli et al: N Engl J Med 351:1645, 2004. Massachusetts Medical Society.
its antibiotic susceptibility is known. In recurrences of chronic 
osteomyelitis as well as in each type of exogenous osteomyelitis 
(acute, chronic, with or without an implant), a combination of 
surgical debridement, obliteration of dead space, and long-term 
antibiotic therapy is required. The length of therapy depends on 
the completeness of the surgical intervention (removal of seques­
tra, implants, and necrotic tissue).
The therapeutic aims in patients whose infections are associ­
ated with internal fixation devices are consolidation of the fracture 
and prevention of chronic osteomyelitis. Stable implants can be 
maintained except in patients with uncontrolled sepsis. In a sys­
tematic review reporting the outcome of 276 patients, the success 
rate with retention of the implant was 86–100% in early, 82–89% in 
delayed, and only 67% in late fracture-related infection. Appropri­
ate antimicrobial therapies are listed in Table 136-2. The cure rate 

CHAPTER 136
Osteomyelitis
for early staphylococcal implant-associated infections treated with 
a fluoroquinolone plus rifampin is >90%. Rifampin is efficacious 
against staphylococcal biofilms of ≤3 weeks’ duration. Similarly, 
fluoroquinolones are active against biofilms formed by gram-negative 
bacilli. In these cases, a short initial course of IV therapy with a 
β-lactam antibiotic is suggested to minimize the risk of emergence 
of resistance to the oral drugs. The total duration of treatment 
is 3 months, and the device can be retained even after antibiotics 
have been discontinued. In contrast, in cases caused by rifampin-

resistant staphylococci or fluoroquinolone-resistant gram-negative 
bacilli, all hardware should be removed after consolidation of the 
fracture and before discontinuation of antibiotics. These patients 
are treated with an oral antibiotic (suppressive therapy) as long as 
the hardware is retained.

FIGURE 136-2  A 42-year-old man who had sustained a malleolar fracture 6 weeks 
previously had persistent pain and slight inflammation after orthopedic repair. 
His infection was treated with oral antibiotics without debridement surgery. This 
insufficient management of an implant-associated Staphylococcus aureus infection 
was complicated by a sinus tract.
■
■COMPLICATIONS
The main complication of long-bone osteomyelitis is the persistence 
of infection with progression to chronic osteomyelitis. This risk is 
especially high after internal fixation of an open fracture and among 
patients with implant-associated osteomyelitis that is treated without 
surgical debridement. In longstanding osteomyelitis, recurrent sinus 
tracts result in severe damage to skin and soft tissue (Fig. 136-2). 
Patients who have chronic open wounds need a therapeutic approach 
combining orthopedic repair and plastic reconstructive surgery.
PART 5
Infectious Diseases
■
■GLOBAL CONSIDERATIONS
In North American and Western European countries, tuberculous 
osteomyelitis is extremely rare, occurring mainly in very old people, 
HIV-infected patients, and immigrants from endemic countries. In 
contrast, in countries where the prevalence of tuberculosis is high 
(India, Indonesia, China), tuberculous osteomyelitis must routinely be 
considered.
PERIPROSTHETIC JOINT INFECTION
■
■PATHOGENESIS
Implanted foreign material is highly susceptible to local infection due 
to local immunodeficiency around the device. Infection occurs by 
either the exogenous or the hematogenous route. More rarely, con­
tiguous spread from adjacent sites of osteomyelitis or deep soft-tissue 
infection may cause periprosthetic joint infection (PJI). The fact that 
foreign devices are covered with host proteins such as fibronectin 
favors the adherence of staphylococci and the formation of a biofilm 
that resists phagocytosis.
■
■EPIDEMIOLOGY
The risk of infection manifesting during the first 2 postoperative years 
varies according to the joint. It is lowest after hip and knee arthroplasty 
(0.3–1.5%) and highest after ankle and elbow replacement (4–10%). 
The risk of hematogenous PJI is highest in the early postoperative 
period. However, hematogenous seeding occurs throughout life, and 
most cases therefore develop >2 years after implantation. The rate of 
risk for secondary PJI during S. aureus bacteremia is 30–40%.
■
■MICROBIOLOGY
About 50–70% of cases of PJI are caused by staphylococci (S. aureus 
and coagulase-negative staphylococci), 6–10% by streptococci, 4–10% 
by gram-negative bacilli, and the rest by various other microorganisms. 
In patients with hematogenous PJI, the fraction of streptococci and 

FIGURE 136-3  Acute postoperative periprosthetic joint infection of the left hip 
caused by group B streptococci in a 68-year-old woman.
gram-negative bacilli is higher and the fraction of coagulase-negative 
staphylococci is much lower. All microorganisms can cause PJI, includ­
ing fungi and mycobacteria. C. acnes causes up to one-third of episodes 
of periprosthetic shoulder infection.
■
■CLASSIFICATION AND CLINICAL 
MANIFESTATIONS
PJI is traditionally classified as early (<3 months after implantation), 
delayed (3–24 months after surgery), or late (>2 years after implanta­
tion). For therapeutic decision-making (see below), it is more useful to 
classify PJI as (1) acute hematogenous PJI with <3 weeks of symptoms, 
(2) early postinterventional PJI manifesting within 1 month after sur­
gery, or (3) chronic PJI with symptom duration of >3 weeks.
Acute exogenous PJI typically presents with local signs of infection 
(Fig. 136-3). In contrast, acute hematogenous PJI is most often caused 
by S. aureus and is characterized by new-onset pain. Local inflamma­
tory signs are rare in hip PJI but frequent in knee PJI. Fever is rare after 
the initial phase of bacteremia. Key findings in chronic PJI are joint 
effusion, local pain, implant loosening, and occasionally a sinus tract. 
Chronic PJI is most commonly caused by low-virulence microorgan­
isms such as coagulase-negative staphylococci or C. acnes. These infec­
tions are characterized by nonspecific symptoms, such as chronic pain 
caused by low-grade inflammation or early loosening.
■
■DIAGNOSIS
Blood tests such as the measurement of CRP (elevated levels, ≥10 
mg/L) and erythrocyte sedimentation rate (elevated rates, ≥30 mm/h) 
are sensitive (91–97%) but not specific (70–78%). Synovial fluid cell 
counts are ~90% sensitive and specific, with threshold values of 1700 
leukocytes/μL in periprosthetic knee infection and 4200 leukocytes/
μL in periprosthetic hip infection. A biomarker, α-defensin, can be 
tested in synovial fluid; this biomarker is highly specific and therefore 
useful in confirming PJI. However, this test is expensive and its sensi­
tivity is limited; therefore, it should not be used for screening. During 
debridement surgery, at least three but optimally six tissue samples 
should be obtained for culture and histopathology. If implant mate­
rial (modular parts, screws, or the prosthesis) is removed, sonication 
of this material followed by culture and/or use of molecular methods 
to examine the sonicate fluid allows the detection of microorganisms 
in biofilms.
The three-phase bone scan is very sensitive for detecting PJI but is 
not specific. As mentioned above, this test does not differentiate bone 
remodeling from infection and therefore is not useful during at least 
the first year after implantation. CT and MRI detect soft tissue infec­
tion, prosthetic loosening, and bone erosion, but imaging artifacts 
caused by metal implants limit their use. 18F-fluorodeoxyglucose PET 
(18F-FD-PET) is an alternative method with good sensitivity but low 
specificity for the detection of PJI. Therefore, 18F-FDG-PET/CT is use­
ful only in excluding but not confirming PJI.

TREATMENT
Periprosthetic Joint Infection
The outcome following treatment of PJI is better when managed 
using a multidisciplinary approach involving an experienced ortho­
pedic surgeon, an infectious disease specialist, a plastic reconstruc­
tive surgeon, and a microbiologist. Therefore, most patients are 
referred to a specialized center. In general, the goal of treatment is 
cure—i.e., a pain-free functional joint with complete eradication of 
the infecting pathogen(s). However, for patients with severe comor­
bidity, lifelong suppressive antimicrobial therapy may be preferred. 
As a rule, antimicrobial therapy without surgical intervention is 
not curative but merely suppressive. There are four curative surgi­
cal options: debridement and implant retention, one-stage implant 
exchange, two-stage implant exchange, and implant removal with­
out replacement. The least invasive treatment option should be 
selected for each patient without compromising the cure rate. The 
choice can be guided following a treatment algorithm. However, 
the different surgical options have not been tested in a randomized 
controlled trial. Implant retention offers a good chance of infectionfree survival (>80%) only if the following conditions are fulfilled: 
(1) acute infection, (2) stable implant, (3) pathogen susceptible to a 
biofilm-active antimicrobial agent (see below), and (4) skin and soft 
tissue in good condition.
Table 136-2 summarizes pathogen-specific antimicrobial therapy 
for PJI. Initial IV therapy is followed by long-term oral antibiotics. 
Efficacious treatment is best defined in staphylococcal implantassociated infections. Rifampin exhibits excellent activity against 
biofilms composed of susceptible staphylococci. Because of the risk 
of rapid emergence of resistance, rifampin must always be com­
bined with another effective antibiotic. If gram-negative infections 
are treated with implant retention, fluoroquinolones should be used 
because of their activity against gram-negative biofilms.
■
■PREVENTION OF HEMATOGENOUS INFECTION
As mentioned above, hematogenous seeding may occur throughout 
life. This risk is highest during S. aureus bacteremia from a distant 
focus. Therefore, documented bacterial infections should be promptly 
treated in patients with prosthetic joints. However, according to a 
prospective case-control study, the risk of prosthetic hip or knee infec­
tion is not increased following dental procedures. Therefore, antibiotic 
prophylaxis is not needed during dental work.
■
■GLOBAL CONSIDERATIONS
Rifampin and fluoroquinolones are still the only antimicrobial agents 
with good activity against staphylococcal and gram-negative biofilms, 
respectively. Thus, in countries with high rates of rifampin resistance in 
staphylococci and/or high rates of fluoroquinolone resistance in gramnegative bacilli, debridement with implant retention generally does not 
yield a good cure rate.
STERNAL OSTEOMYELITIS
■
■PATHOGENESIS
Sternal osteomyelitis occurs primarily after sternal surgery (with the 
entry of exogenous organisms) and more rarely by hematogenous 
seeding or contiguous extension from adjacent sites of sternocostal 
arthritis. Exogenous sternal osteomyelitis after open sternal surgery is 
also called deep sternal-wound infection. Exogenous infection may fol­
low minor sternal trauma, sternal fracture, and manubriosternal septic 
arthritis. Tuberculous sternal osteomyelitis typically manifests during 
hematogenous seeding in children or as reactivated infection in adults. 
Reactivation is sometimes preceded by blunt trauma. In rare cases, 
tuberculous sternal osteomyelitis is caused by continuous infection 
from an infected internal mammary lymph node.
■
■EPIDEMIOLOGY
The incidence of poststernotomy wound infection varies from 0.5% to 
2%, but figures are even higher among patients with risk factors such 

as diabetes, obesity, chronic renal failure, emergency surgery, use of 
bilateral internal mammary artery grafts, and re-exploration for bleed­
ing. Rapid diagnosis and correct management of superficial sternal 
wound infection prevent its progression to sternal osteomyelitis. Pri­
mary (hematogenous) sternal osteomyelitis accounts for only 0.3% of 
all cases of osteomyelitis. Risk factors are IV drug use, HIV infection, 
radiotherapy, blunt trauma, cardiopulmonary resuscitation, alcohol 
abuse, liver cirrhosis, and hemoglobinopathy.

■
■MICROBIOLOGY
Poststernotomy osteomyelitis is generally caused by S. aureus (10–20% 
of cases), coagulase-negative staphylococci (40–60%), gram-negative 
bacilli (5-15%), or C. acnes (2–10%). The spectrum of microorganisms 
greatly varies in different populations (as represented in different pub­
lications); this is perhaps due to local epidemiologic conditions, such 
as antimicrobial stewardship and the incidence of chronic infections. 
Polymicrobial cases are rare in acute infection and indicate exogenous 
superinfection during therapy. Hematogenous sternal osteomyelitis is 
caused most commonly by S. aureus. Other microorganisms play a role 
in special populations—e.g., P. aeruginosa in IV drug users, Salmonella 
species in individuals with sickle cell anemia, and M. tuberculosis in 
patients from endemic areas who have previously had tuberculosis.
■
■CLINICAL MANIFESTATIONS
Exogenous sternal osteomyelitis manifests as fever, increased local pain, 
erythema, wound discharge, and sternal instability (Fig. 136-4). 
Contiguous mediastinitis is a feared complication, occurring in 
~10–30% of patients with sternal osteomyelitis. Hematogenous sternal 
osteomyelitis is characterized by sternal pain, swelling, and erythema. 
In addition, most patients have systemic signs and symptoms of sepsis.
CHAPTER 136
The differential diagnosis of hematogenous sternal osteomyelitis 
includes immunologic processes typically presenting as systemic or 
multifocal inflammation of the sternum or of the sternoclavicular or 
sternocostal joints (e.g., SAPHO [synovitis, acne, pustulosis, hyperos­
tosis, osteitis], vasculitis, chronic multifocal relapsing osteomyelitis).
Osteomyelitis
■
■DIAGNOSIS
In primary sternal osteomyelitis, the diagnostic workup does not differ 
from that in other types of hematogenous osteomyelitis (see above). 
When a patient has grown up in regions where tuberculosis is endemic, 
a specific workup for mycobacterial infection should be performed, 
especially if osteomyelitis had its onset after a blunt sternal trauma. 
In secondary sternal osteomyelitis, leukocyte counts may be normal, 
but the CRP level is >100 mg/L in most cases. Tissue sampling for 
microbiologic studies is crucial. In osteomyelitis associated with ster­
nal wires, low-virulence microorganisms, such as coagulase-negative 
staphylococci, play an important role. In order to differentiate between 
colonization and infection, samples from at least three deep biopsies 
should be subjected to microbiologic examination. Superficial swab 
cultures are not diagnostic and may be misleading. No studies have 
FIGURE 136-4  Sternal osteomyelitis caused by Staphylococcus epidermidis 5 weeks 
after sternotomy for aortocoronary bypass in a 72-year-old man.

compared the value of the various imaging modalities in suspected pri­
mary sternal osteomyelitis. However, MRI is the current gold standard 
for detection of each type of osteomyelitis.

TREATMENT
Sternal Osteomyelitis
In cases of deep sternal-wound infection, a combined approach 
using both surgery and antibiotic treatment is required. Antimi­
crobial therapy should be started immediately after samples have 
been obtained for microbiologic analyses in order to control clini­
cal sepsis. To protect a newly inserted heart valve, initial treatment 
should be directed against staphylococci, with consideration of the 
local susceptibility pattern. In centers with a high prevalence of 
methicillin-resistant S. aureus, vancomycin or daptomycin should 
be added to a broad-spectrum β-lactam drug. As soon as cultures of 
blood and/or deep wound biopsies have confirmed the pathogen’s 
identity and susceptibility pattern, treatment should be optimized 
and narrowed accordingly. Tables 136-1 and 136-2 show appropri­
ate therapeutic choices for the most frequently identified microor­
ganisms causing sternal osteomyelitis in the absence and presence, 
respectively, of an implanted device. In a recent observational study 
of patients with staphylococcal deep sternal-wound infection, the 
use of a rifampin-containing regimen was predictive of success. The 
optimal duration of antibiotic therapy has not been established. In 
acute sternal osteomyelitis without hardware, a 6-week course is the 
rule. In patients with remaining sternal wires, treatment duration 
is generally prolonged to 3 months (Table 136-2). Like other types 
of tuberculous bone infection, tuberculous sternal osteomyelitis is 
treated for 6–12 months.
PART 5
Infectious Diseases
Primary sternal osteomyelitis can generally be treated without 
surgery. In contrast, in secondary sternal osteomyelitis, debride­
ment is always required. This procedure should be performed by a 
team of experienced surgeons, since mediastinitis, bone infection, 
and skin and soft tissue damage may need to be treated during the 
same intervention.
■
■PROGNOSIS
Primary sternal osteomyelitis poses a minimal mortality risk. In con­
trast, the mortality rates from secondary sternal osteomyelitis during 
the first year after diagnosis are 6–20%.
■
■GLOBAL CONSIDERATIONS
In endemic areas, microorganisms such as M. tuberculosis, Salmonella 
species, and Brucella species should be considered during sampling for 
microbiologic diagnosis.
FOOT OSTEOMYELITIS
■
■PATHOGENESIS
Osteomyelitis of the foot is a feared complication in patients with 
diabetic foot ulcers. It also usually occurs in patients with peripheral 
arterial insufficiency, or peripheral neuropathy and after foot surgery. 
These entities are often linked to each other, especially in diabetic 
patients with late complications. However, foot osteomyelitis is also 
seen in patients with isolated peripheral neuropathy and can manifest 
as implant-associated osteomyelitis in patients without comorbidity 
due to a deep wound infection after foot surgery (hallux valgus surgery, 
arthrodesis, total ankle arthroplasty). Foot osteomyelitis is acquired 
almost exclusively by the exogenous route. It is a complication of deep 
pressure ulcers and of impaired wound healing after surgery.
■
■EPIDEMIOLOGY
About 34% of people with diabetes develop a foot ulcer during their 
lifetime. Among patients with foot ulcer, the annual incidence of pro­
gression to foot osteomyelitis is 5%. The condition starts with skin and 
soft tissue lesions and progresses to osteomyelitis, especially in patients 
with risk factors. Diabetic foot osteomyelitis increases the risk of 

FIGURE 136-5  Neuropathic joint disease (Charcot foot) complicated by chronic 
foot osteomyelitis in a 78-year-old woman with diabetes mellitus complicated by 
severe neuropathy.
amputation. With adequate management of the early stage of diabetic 
foot infections, the rate of amputation can be lowered.
■
■RISK FACTORS
Risk factors for diabetic foot infection are (1) peripheral motor, 
sensory, and autonomic neuropathy; (2) neuro-osteoarthropathic 
deformities (Charcot foot; Fig. 136-5); (3) arterial insufficiency; (4) 
uncontrolled hyperglycemia; (5) disabilities such as reduced vision; 
and (6) maladaptive behavior.
■
■MICROBIOLOGY
The correlation between cultures from bone biopsy and those from 
wound swabs or even deep soft-tissue punctures is poor. In a study 
of 31 patients with simultaneous sampling, the correlation between 
needle biopsy and bone biopsy cultures was only 24%. The correlation 
is better when S. aureus is isolated (40–50%) than when anaerobes 
(20–35%), gram-negative bacilli (20–30%), or coagulase-negative 
staphylococci (0–20%) are identified. When only bone-biopsy samples 
are considered, the leading pathogens are S. aureus (25–40%), anaer­
obes (5–20%), and various gram-negative bacilli (18–40%). The precise 
distribution depends on whether the patient has already been treated 
with antibiotics. Anaerobes are especially prevalent in chronic wounds. 
Pretreatment typically selects for P. aeruginosa, methicillin-resistant S. 
aureus, or enterococci.
■
■DIAGNOSIS
In many cases, foot osteomyelitis can be diagnosed clinically, without 
imaging procedures. Most clinicians rely on the “probe-to-bone” 
test, which has a positive predictive value of ~90% in populations 
with a high pretest probability. Thus, in a patient with diabetes who 
is hospitalized for a chronic deep foot ulcer, the diagnosis of foot 
osteomyelitis is highly probable if bone can be directly touched with 
a metal instrument. In a patient with a lower pretest probability, MRI 
should be performed because of its high sensitivity (80–100%) and 
specificity (80–90%). Plain x-rays have typical features character­
izing diabetic foot osteomyelitis. However, their sensitivity is only 
30–90% and the specificity varies between 50% and 90%; thus, it is 
mainly useful for follow-up of patients with confirmed diabetic foot 
osteomyelitis.
TREATMENT
Foot Osteomyelitis
As mentioned above, correlation between cultures of bone and 
those of wound swabs or wound punctures is poor. Antibiotic 
treatment should be based on bone culture. If no bone biopsy is