What is the most common cause of osteomyelitis?

Staphylococcus aureus is the most common cause of osteomyelitis in children and adults, whether the infection arrives through the bloodstream or spreads from nearby tissue. Both methicillin-sensitive strains and MRSA cause it, and MRSA is common in many communities, so empiric therapy covers it where local rates are high. The classic exam exceptions are Salmonella in sickle cell disease, Pseudomonas after a puncture wound through a shoe, and polymicrobial infection in diabetic foot ulcers.

Why do people with sickle cell disease get Salmonella osteomyelitis?

Repeated sickling damages the spleen until it infarcts, leaving the patient functionally asplenic. Without a working spleen, people with sickle cell disease are more susceptible to pneumococcal and Salmonella infections, including Salmonella osteomyelitis. On exams, a child with sickle cell disease, fever and focal bone pain points to Salmonella, and pediatric guidance flags hemoglobinopathies as a reason to cover Salmonella in addition to S. aureus.

What organism causes osteomyelitis after stepping on a nail?

Pseudomonas aeruginosa is the classic answer when a nail or other sharp object punctures the sole of the foot, especially through a sneaker. Deep puncture wounds of the foot can lead to draining sinuses, cellulitis and osteomyelitis. S. aureus can still infect any wound, so bone cultures guide treatment, but in a USMLE stem a nail through a rubber-soled shoe means Pseudomonas.

What is the best imaging test for osteomyelitis?

MRI is the imaging test of choice because it shows bone marrow edema early and maps abscesses, soft-tissue spread and epidural involvement; the IDSA vertebral, PIDS/IDSA pediatric and IWGDF/IDSA diabetic foot guidelines all prefer it. Plain X-rays come first but are often normal early: changes can take 1 to 2 weeks to appear (Merck says 2 to 4 weeks) because a large share of the bone must be destroyed before lysis shows. A bone scan turns positive early but cannot distinguish infection from fracture or tumor.

How is osteomyelitis definitively diagnosed?

Bone biopsy with culture, taken percutaneously or at surgery, is the definitive test because it identifies the organism and its antibiotic susceptibilities. Swabs of ulcers or sinus tracts are unreliable because they grow colonizing bacteria. In vertebral osteomyelitis, IDSA advises an image-guided biopsy when blood cultures do not identify a likely organism and, in stable patients, holding empiric antibiotics until the organism is known.

How long is osteomyelitis treated?

Most adults need about 6 weeks of antibiotics. IDSA advises 6 weeks of IV or highly bioavailable oral therapy for native vertebral osteomyelitis, and IWGDF/IDSA suggest about 6 weeks for diabetic foot osteomyelitis when no bone is removed, or up to 3 weeks after a minor amputation with a positive bone margin. Children with uncomplicated acute hematogenous osteomyelitis usually need 3 to 4 weeks, with an early switch to oral antibiotics. Dead bone and abscesses also need surgery.

Osteomyelitis: Organisms by Risk Factor, MRI & Treatment

Osteomyelitis is infection and destruction of bone. Bacteria reach bone through the bloodstream (hematogenous spread: the long-bone metaphyses in children, the vertebrae in adults), by spreading from nearby infected tissue such as a diabetic foot ulcer or an infected joint replacement, or through an open wound such as an open fracture, surgery or a puncture wound; contiguous spread and open wounds together cause about 80% of cases. Staphylococcus aureus is the most common cause in nearly every setting; the classic exceptions are Salmonella in sickle cell disease, Pseudomonas after a puncture wound of the foot and polymicrobial infection in the diabetic foot. X-rays lag behind the infection, MRI is the imaging test of choice, and bone culture identifies the organism so antibiotics can be targeted, usually for about 6 weeks in adults.

Three routes into bone

Route	Who gets it	Where	Usual organisms
Hematogenous (bloodstream)	Children; adults who are older, debilitated, on hemodialysis or inject drugs	Children: metaphysis of the femur, tibia or humerus. Adults: vertebrae	S. aureus (MRSA is common); enteric gram-negative rods in older adults
Contiguous spread (together with open wounds, about 80% of cases)	Diabetic foot ulcers, pressure injuries, infected prosthetic joints	Foot, pressure sites, around implants	Often polymicrobial: S. aureus in at least half, plus streptococci, gram-negative enterics and anaerobes
Direct inoculation	Open fractures, bone surgery, puncture wounds, bites	The wound site	S. aureus; Pseudomonas after a deep foot puncture; Pasteurella or Eikenella after bites

In children, hematogenous infection settles in the metaphysis next to the growth plate. The classic explanation: metaphyseal vessels have leaky endothelium and sluggish flow and end in capillary loops, so bacteria lodge where the physis meets the metaphysis. Long bones dominate, but 10-25% of pediatric cases involve short or non-tubular bones such as the pelvis, vertebrae, clavicle or calcaneus (PIDS/IDSA).

Match the organism to the stem

Clue in the stem	Think	Why it fits
No special risk factor, child or adult	S. aureus	Most common cause overall; cover MRSA based on local rates
Sickle cell disease	Salmonella (the classic answer)	Splenic autoinfarction (functional asplenia) raises the risk of Salmonella infection, including osteomyelitis
Nail through a sneaker (deep plantar puncture)	Pseudomonas aeruginosa	Deep puncture wounds of the foot can cause draining sinuses, cellulitis and osteomyelitis
Injection drug use	S. aureus; also Pseudomonas and Serratia	Pseudomonas bone and joint infection favors the spine, pubic bone and sternoclavicular joint
Diabetic foot ulcer or pressure injury	Polymicrobial	S. aureus, streptococci, gram-negative rods, anaerobes
Prosthetic joint or hardware	S. aureus; coagulase-negative staphylococci (S. epidermidis)	Biofilm on foreign material; Cutibacterium acnes in shoulder implants can need up to 2 weeks of culture
Cat or dog bite / human bite	Pasteurella multocida / Eikenella corrodens	Hand bites, especially clenched-fist injuries, can reach joints and bone
Young child with bone or joint infection	Consider Kingella kingae	PIDS/IDSA lists younger age as a reason to cover it
Subacute back pain with TB risk, paravertebral abscess	M. tuberculosis (Pott disease)	Starts in a vertebral body and spreads to adjacent vertebrae with disc-space narrowing; untreated, vertebrae can collapse onto the cord

More on the bugs: S. aureus toxins and MRSA, Pseudomonas clues and mimics, the infections and crises of sickle cell disease, and tuberculosis.

Why bone infection turns chronic

Vessels occlude. Infection occludes local blood vessels, so bone dies; pus can spread under the periosteum, form subcutaneous abscesses and drain through the skin via a sinus tract.
Sequestrum: a dead, infected bone fragment that separates from living bone. It has no blood supply, so antibiotics reach it poorly and it usually has to be excised for cure. Involucrum: a thick sheath of new periosteal bone that can encase the sequestrum.
Acute vs chronic (PIDS/IDSA): acute is diagnosed within 4 weeks of symptom onset; chronic is marked by a sequestrum and/or relapse at the same site weeks to years after apparently successful treatment.
Biofilm: coagulase-negative staphylococci such as S. epidermidis form biofilms on foreign material, and infected implants are often removed or exchanged; rifampin is added to antistaphylococcal regimens for prosthetic joint infection to improve biofilm penetration.
Marjolin ulcer: squamous cell carcinoma can arise in a chronic osteomyelitic lesion or burn scar, on average about 30 years after the injury. Biopsy an old sinus or ulcer that enlarges, bleeds easily or develops raised margins.

Presentation

Child: fever, focal bone pain and tenderness, limp or refusal to use the limb.
Adult, vertebral: constant localized back pain and tenderness with paravertebral spasm, unresponsive to conservative care; often afebrile. Cord or root compression (for example from an epidural abscess) adds radicular pain, weakness or numbness.
Diabetic foot: a chronic ulcer over a bony prominence, often painless because of neuropathy; exposed bone or a positive probe-to-bone test raises suspicion.
Chronic: intermittent bone pain and draining sinuses over months to years. Labs: leukocytosis, raised ESR and CRP, often anemia and thrombocytosis; markers can be normal with indolent organisms.

Diagnosis: from X-ray to bone culture

Test	What it adds	Exam takeaway
ESR, CRP	Raised but nonspecific	Diabetic foot: ESR ≥70 mm/h supports osteomyelitis (sensitivity 0.81, specificity 0.80); trend CRP to judge response
Blood cultures	Positive in about 31% of children with acute hematogenous osteomyelitis	Draw before antibiotics; in suspected vertebral osteomyelitis, S. aureus, S. lugdunensis or Brucella bacteremia makes a biopsy unnecessary
Plain X-ray	First study; later periosteal elevation, bone destruction, sequestra	Often normal early: changes may not show for 5-7 days in children or 10-14 days in adults (Merck: abnormal after 2-4 weeks); lysis appears only after a large share of bone is lost (30-50% of mineral content per Radiopaedia, 50-75% of matrix per AAFP)
MRI	Marrow edema, abscess, epidural and soft-tissue spread	Imaging test of choice (IDSA, PIDS/IDSA, IWGDF/IDSA)
CT	Cortical destruction, sequestra, involucrum	Surgical planning; PIDS/IDSA prefers MRI for diagnosis
Three-phase bone scan	Turns positive earlier than X-ray	Cannot tell infection from fracture or tumor
Labeled leukocyte scan, PET, SPECT	Localizes infection	Alternatives when MRI is not possible (IWGDF/IDSA)
Bone biopsy for culture and histology	Organism and susceptibilities	Definitive test; percutaneous or surgical

Probe-to-bone test (diabetic foot): sensitivity 0.87, specificity 0.83. A positive probe in a high-risk patient suggests osteomyelitis; a negative probe helps rule it out only in a low-risk patient.
Vertebral osteomyelitis (IDSA 2015): two sets of blood cultures, ESR and CRP, then spine MRI; image-guided aspiration biopsy if blood cultures (or Brucella serology) do not identify a likely organism. In a stable patient with a normal neurologic exam, hold empiric antibiotics until the organism is known; start them at once for sepsis, hemodynamic instability or severe or progressive neurologic deficits. In subacute disease, test for Brucella in endemic areas and for TB in at-risk patients.

Treatment: culture, then targeted antibiotics and source control

Empiric therapy (when it cannot wait): nafcillin or oxacillin, or vancomycin where MRSA is common, plus a third- or fourth-generation cephalosporin (ceftazidime or cefepime). Chronic contiguous infections often get ampicillin-sulbactam or piperacillin-tazobactam, adding vancomycin for severe infection or likely MRSA.
Source control: debride dead bone, drain abscesses (including paravertebral and epidural ones), stabilize the spine, and remove or exchange infected hardware when needed.

Setting	Usual course	Guidance
Child, uncomplicated acute hematogenous (S. aureus)	3-4 weeks; switch to an oral drug rather than outpatient IV therapy when a suitable one exists	PIDS/IDSA 2021
Adult native vertebral osteomyelitis	6 weeks of IV or highly bioavailable oral therapy; 3 months for Brucella	IDSA 2015
Diabetic foot osteomyelitis, no bone resected	About 6 weeks	IWGDF/IDSA 2023
Diabetic foot, minor amputation with a positive bone margin	Up to 3 weeks	IWGDF/IDSA 2023
Prosthetic joint infection with S. aureus	Prosthesis removal, debridement and one- or two-stage replacement, plus 6 weeks of targeted therapy with rifampin	Merck

IV vs oral: classic teaching is 4-6 weeks of IV antibiotics (Merck still lists 4-8 weeks of parenteral therapy for chronic contiguous-spread infection), but AAFP's 2021 review, citing the OVIVA trial, reports similar cure rates with oral antibiotics at lower risk and cost, and IWGDF/IDSA notes that oral regimens for residual diabetic foot osteomyelitis have failure rates similar to IV regimens.
Diabetic foot: resect infected bone plus antibiotics, or antibiotics alone for selected forefoot osteomyelitis without peripheral artery disease or exposed bone; remission is judged at least 6 months after antibiotics end.
Vertebral: operate for progressive neurologic deficits, progressive deformity or spinal instability despite adequate antibiotics; skip routine follow-up MRI when the patient is improving.

How USMLE tests it

Look-alike	What points to it	Key test
Septic arthritis	Hot, swollen joint with effusion; restricted active and passive motion	Arthrocentesis: synovial WBC usually above 50,000/mcL (a lower count does not exclude it), Gram stain, culture, crystals
Gout	Sudden podagra (first MTP joint), recurrent flares	Needle-shaped, negatively birefringent crystals in joint fluid; serum urate is normal in at least 30% of flares
Pott disease	Subacute back pain, TB risk, paravertebral abscess	TB testing and biopsy; MRI shows soft-tissue spread

See septic arthritis organisms and synovial WBC cut-offs and gout vs pseudogout for the joint side of the differential. Classic traps: a normal X-ray does not exclude early osteomyelitis; swabs of an ulcer or sinus mislead, so culture bone; in stable vertebral disease, biopsy before antibiotics.

Practice question

A 61-year-old man with type 2 diabetes and peripheral neuropathy has had an ulcer under his right first metatarsal head for 8 weeks despite dressing changes and offloading. He has no fever. The ulcer is 2 cm wide with a granulating base and minimal surrounding erythema; a sterile metal probe does not reach bone. Dorsalis pedis and posterior tibial pulses are palpable. ESR is 84 mm/h, CRP is raised and the WBC count is normal. Plain radiographs of the foot show no bone abnormality. Which is the most appropriate next step in diagnosis?

A. Arthrocentesis of the first metatarsophalangeal joint B. MRI of the right foot C. Serum uric acid level D. Superficial swab culture of the ulcer base E. Three-phase technetium-99m bone scan

Answer: B. A chronic ulcer over a bony prominence with an ESR above 70 mm/h keeps osteomyelitis likely, even though the probe did not reach bone (a negative probe only helps rule it out in low-risk patients) and the X-ray is normal (lytic change appears only after a large share of bone is lost). IWGDF/IDSA advise MRI when the diagnosis remains in doubt after clinical assessment, X-rays and labs. If MRI shows osteomyelitis, a bone specimen (percutaneous or surgical) for culture comes next so therapy can be targeted.

A: arthrocentesis diagnoses septic or crystal arthritis, which present as an acutely hot, swollen, painful joint; this is a chronic, ulcer-centered process.
C: serum urate is a poor test for gout (normal in at least 30% of flares), and gout does not explain a nonhealing plantar ulcer.
D: superficial swabs grow colonizers; IWGDF/IDSA favor tissue specimens over swabs and bone over soft tissue when osteomyelitis is suspected.
E: a bone scan turns positive early but cannot distinguish infection from fracture or tumor; when MRI is impossible, IWGDF/IDSA suggest labeled leukocyte scintigraphy, PET or SPECT instead.

Key takeaways

S. aureus is the most common cause of osteomyelitis in nearly every group.
Sickle cell → Salmonella; foot puncture through a shoe → Pseudomonas; injection drug use → S. aureus (also Pseudomonas, Serratia); diabetic foot → polymicrobial; hardware → S. aureus and S. epidermidis biofilm.
Children seed the metaphysis of long bones; adults seed the vertebrae.
X-rays lag by days to weeks; MRI is the imaging test of choice; bone biopsy and culture is definitive.
Typical courses: 3-4 weeks for uncomplicated pediatric disease with an early oral switch; 6 weeks for vertebral or unresected diabetic foot osteomyelitis.
Chronic disease means a sequestrum or relapse; a long-draining sinus can become squamous cell carcinoma (Marjolin ulcer).