Osteomyelitis

1. Osteomyelitis Naasha J Talati Oct 2 2008

2. Overview of Talk Definition Classification Organisms Different forms of osteomyelitis Diagnostic modalities Treatment modalities Unusual Scenarios Progressive destruction of the bone and the formation of sequestra are characteristics of this disease. Osteomyelitis can be due to contiguous spread from adjacent soft tissues and joints, hematogenous seeding, or direct inoculation of microorganism into the bone as a result of trauma or surgery. When established, bacteria produce a local inflammatory reaction that promotes bone necrosis and the formation of sequestra. Staphylococcus aureus, the most common microorganism recovered in osteomyelitisProgressive destruction of the bone and the formation of sequestra are characteristics of this disease. Osteomyelitis can be due to contiguous spread from adjacent soft tissues and joints, hematogenous seeding, or direct inoculation of microorganism into the bone as a result of trauma or surgery. When established, bacteria produce a local inflammatory reaction that promotes bone necrosis and the formation of sequestra. Staphylococcus aureus, the most common microorganism recovered in osteomyelitis

3. Cortical destruction of 5th metatarsal head and air in soft tissues

4. Osteomyelitis Infection localized to bone that is progressive and results in inflammatory destruction of bone and new bone formation 2 classification schemes: Lee and Waldvogel: acute vs chronic hematogenous vs contigious presence of vascular insufficiency - does not determine treatment

5. Cierny and Mader classification Stage 1: medullary osteomyelitis (hematogenous) Stage 2: superficial osteomyelitis Stage 3: localized Stage 4: diffuse A: normal host B: immunocompromised C: treatment is worse than disease Stage 2,3 and 4 require surgery

6. Other classifications: Hematogenous seeding Contiguous spread Direct innoculation: trauma or surgery Acute vs chronic: < 1month vs >1month (Typical sign of chronic osteo is a draining sinus tract)

7. Microorganisms

8. Pathogenesis Normal bone is resistant to infection Infection occurs if there is a large innoculum, trauma leading to bone damage, or the presence of a foreign body Factors that determine pathogenesis include: - virulence of organism underlying disease and immune status of host type, location and vascularity of bone

9. Acute Osteomyelitis: pathogenesis Suppurative infection, acute inflammation, edema vascular congestion and small vessel thrombosis Vascular supply to bone is compromised Large areas of dead bone (sequestra) Necrotic ischemic tissue results and bacteria can be hard to eliminate Host defenses absorb necrotic bone and then new bone formation occurs New bone forms either from periosteum (involucrum) or endosteum

10. Bacterial factors Bacterial adherence: S. aureus adheres to fibrinogen, laminin collagen etc. S. aureus has adhesins called MSCRAMM Proteolytic activity: bacteria decrease protein synthesis and cause increased collagenase Resistance to host defenses: S. aureus can survive within osteoblasts, in a dormant and phenotypically altered state S.aureus decreases locomotion of leukocytes

11. Data: Animal Studies Bone sterilization with just antimicrobials: 78% cultures of S. aureus still positive at 14 days, and 16% at 28 days. Presence of biofilm: rifampin can kill organisms in the biofilm Ciprofloxacin was shown to impare fracture healing, so don�t use this in fracture related osteomyelitis Because of the lack of well-designed prospective clinical trials to guide the management of patients with osteomyelitis, recommendations about management of this disease have been primarily derived from experimental animal models, expert opinion, and retrospective cohort studies.Because of the lack of well-designed prospective clinical trials to guide the management of patients with osteomyelitis, recommendations about management of this disease have been primarily derived from experimental animal models, expert opinion, and retrospective cohort studies.

12. DIAGNOSTIC MODALITIES

13. Probe to bone 76 cases of infected foot ulcers Palpating bone on probing of a pedal ulcer with a metal probe Sensitivity 66% Specificity 85% PPV 89% NPV 56%

14. Bone biopsy Open or percutaneous Positive in 86% If negative repeat d/c antibiotics atleast 72 hours before biopsy Open biopsy is preferred Swab culture should not be used (correlation only 20%) Useful if you find MRSA Obtain 2 specimens one for culture one for histopathology

15. Additional Tests Culture to identify the causative agent Histopathology shows necrotic bone and inflammatory exudate Lab tests: Blood cultures positive in 50% Elevated ESR and CRP Radiology is useful for confirming the diagnosis, delineating the extent of disease and planning therapy

16. Imaging: X-RAY useful for chronic osteomyelitis cortical erosion, periosteal reaction, sclerosis, mixed lucency, soft tissue swelling, or sequestra If hardware is in place you may see periprosthetic lucency, or fracture non union Soft tissue changes seen in 3 days Bone changes seen 1-2 weeks Earliest sign is osteopenia Sensitivity 14%, Specificity 70% (review of 140 cases) Contrary to common belief, swab cultures from draining wounds and sinus tracts can be of diagnostic benefit for two main reasons. The identification of certain resistant microorganisms (e.g., methicillin-resistant S. aureus, vancomycin-resistant enterococcus) indicates the need for infection control measures. Second, the isolation of S. aureus from superficial cultures has a high degree of correlation with deep cultures.[17] The recovery of other microorganisms correlates poorly with deep cultures.Contrary to common belief, swab cultures from draining wounds and sinus tracts can be of diagnostic benefit for two main reasons. The identification of certain resistant microorganisms (e.g., methicillin-resistant S. aureus, vancomycin-resistant enterococcus) indicates the need for infection control measures. Second, the isolation of S. aureus from superficial cultures has a high degree of correlation with deep cultures.[17] The recovery of other microorganisms correlates poorly with deep cultures.

17. MRI Positive 3-5 days post infection MRI can show cortical destruction, marrow and soft tissue edema, sinus tracts, fistula, abscesses If MRI negative at >1 week post infection, likely person does not have osteo When MRI shows marrow edema this is non specific and it doesn�t resolve for months after initial injury MRI is superior to x-rays, technetium scans and tagged WBC scan

18. MRI MRI superior for vertebral osteomyelitis On T1 decreased signal in the disk and vertebral bodies, loss of endplate definition On T2 increased signal in the disk Gadolinium causes disk enhancement Use CT when MRI cannot be used (pacemaker, insulin pump, metallic implants)

20. Nuclear Modalities Tend to be better for acute not chronic infection Pick up inflammation 3 phase bone scan, gallium scan and tagged WBC scan

21. Three phase bone scan Uses a radionucleotide tracer such as technetium bound to phosphorous Accumulates in areas of bone turnover and increased osteoblast activity Tracer is injected and immediate flow phase, 15 minute blood pooling phase and 4 hour osseous phase are seen Cellulitis will show increased activity in the first 2 phases and diffusely increased in the 3rd phase

22. Three phase bone scan In osteomyelitis there is intense uptake in all 3 phases 95% sensitive and specific if the x-ray is normal False positive results occur with fracture and charcot False negative occur with early infection or in chronic osteomyelitis

23. Gallium and dual tracer scans Gallium scans utilize affinity of gallium 67 to acute phase reactants such as lactoferrin, transferrin and others to demonstrate inflammation related to infection Scan is performed 24 hours following injection More specific than three phase bone scan Sensitivity (25-80%), Specificity 67% You can perform both technetium and gallium together

24. Tagged WBC scan Tag WBC with indium, gallium or technetium Blood is drawn White cells are seperated for labeling with tracer Tagged cells are returned to the patient circulation via IV injection Images taken at 24 hours Tagged WBC accumulate in marrow, urinary tract and any area of inflammation or infection

25. Tagged WBC scan Not specific particularly if xray is abnormal As sensitive as a bone scan Vertebral bodies have a lot of red marrow and are not visualized reliably Best used for distal extremities False positive in fracture or charcot False negative in chronic osteo

26. Tagged WBC scan Inflammation or bone turnover can be misinterpreted as osteo Trauma, surgery, healed osteo, septic arthritis, DJD, bone tumors can cause false positives False negatives can occur if there are areas of relative ischemia, since radiotracer cannot be delivered to the target site This occurs in pts with comorbidities

27. Ultrasound Elevation and thickening of periosteum Useful in sickle cell disease

28. Approach to diagnosis History and physical Predisposing factors, underlying disease CRP, ESR and Blood cultures Probe to bone positive=Osteomyelitis XRAY positive = Osteomyelitis Xray negative then get more sophisticated image: diabetic: get MRI Spine: get MRI CT is next choice If hardware: get nuclear study Bone biopsy, repeat bone biopsy, empiric abx

29. Metanalysis: diagnosis of osteomyelitis in a diabetic foot(9 studies)

30. Does this diabetic patient have osteomyelitis? Metaanalysis (Jama 2008) Ulcer larger than 2X2 cm LR=7.7 Probe to bone LR 6.4 ESR >70 LR 11 Abnormal xray LR 2.3 Positive MRI LR 3.9

31. Osteo after open fracture Symptoms: appear several months later Fracture non union Poor wound healing

32. Vertebral Osteomyelitis, Discitis and Epidural Abscess Usually hematogenous Can be post operative Age >50, M>F Antimicrobial prophylaxis for spine surgery decreased infection rates from 2.8% to 0.2% Pain 90%, fever 50%, Neuro deficits 15% Organisms: CNS, S. aureus, Brucella, TB

33. Vertebral Osteomyelitis, Discitis and Epidural Abscess X-ray sensitivity is 32% CT guided bx sensitivity is 50% Surgery is needed if: spine is unstable, no response to abx, presence of abscess, neurological compromise MRI may look like progression

34. Vertebral Osteomyelitis, Discitis and Epidural Abscess Treatment is parentral abx 6 weeks, If post- op osteomyelitis then 6 weeks IV and 2 years of po suppressive abx till bone remodeling and fusion is complete ESR declines within 1st month

35. Hematogenous Accounts for 20% osteo in adults More common in males Children, Elderly, IVDU, indwelling central lines sickle cell Affects the metaphysis of long bones and vertebrae Tibia and femur are most commonly affected Lumbar vertebrae most common Caused by Staph aureus, Strep pneumo and H. flu Bartonella candida cocci and proprionibacterium

36. Hematogenous osteo Occurs because capillaries are narrow and don�t anastamose so you get infarcts in bone if capillary gets blocked. Wbc elevated in 35% ESR elevated 92%, CRP 98% Blood cultures are positive 41-67% Treat for 4 -6 weeks Osteo in children treat for 3 weeks and can change to oral once pt defervesces and is clinically improving

37. Osteo in diabetes and vascular insuff Usually affects foot Factors associated with foot infections: duration of diabetes>10y, poor glycemic control, PVD, previous ulcer or amputation, CVS retinal or renal disease, neuropathy, decreased joint mobility Treatment is combination of medical and surgical

38. Grade 0 no ulcer Grade 1 superficial ulcer Grade 2 deep ulcer to muscle Grade 3 deep ulcer with cellulitis, abscess, osteo Grade 4 gangrene Grade 5 extensive gangrene of whole foot

39. TREATMENT

40. Treatment: duration Duration atleast 6 weeks since last debridement which is how long it takes for debrided bone to be covered by vascularized soft tissue If amputation is performed abx can be given till wound has adequately healed If hardware is in place long term oral antibiotic suppression is warranted

41. Antibiotic penetration into Bone 1st generation cephalosporins 7% Vancomycin 14% Quinolones 12.5%

42. Meta-analysis: Quinolones vs Betalactams 7 studies, all were RCT, 194 patients In 4 studies quinolones were given exclusively orally No data on surgical interventions No data provided on microbiology No difference in treatment success, bacteriologic cure, adverse effects or relapse(f/u 6-18m)

43. Metanalysis: Treatment 1966-2000, 22 articles, 927 patients Only 4 studies were double blinded Inclusion: randomized trials comparing 2 treatment options for bone or joint infection Primary endpoint: quiescence of infection 12 months post treatment (resolution of clinical signs and symptoms) 78.6% Secondary endpoint: improved limb function, marked reduction in disease severity (95%)

44. Role of Rifampin 1 trial looked at rifampin+ ciprofloxacin vs ciprofloxacin alone for device associated Staph infections in which the device was left in place Rifampin provided an absolute risk difference of 28%, but had higher side effects Norden et al compared Nafcillin + Rifampin vs Nafcillin alone, and did not find a benefit to use of Rifampin Probably some biofilm activity, never use rifampin alone

45. Metaanalysis: Treatment In osteo caused by psuedomonas and gram negatives ticarcillin vs other antibiotic, ticarcillin caused more rapid improvement in the short term Comparison of quinolones po to iv agents showed that there was no difference in outcome Comparison of unasyn to other drugs or imipenem to other drugs had no advantage

46. MISCELLANEOUS CONDITIONS

47. Osteitis Pubis Infection of pubic symphisis Occurs after gyn or urological surgery Symptom onset is 2-12 months post intervention Pain on ambulation Staph, Enterococcus, Ecoli, Psuedmonas, There is an inflammatory version that is sterile Debride and treat with antibiotics

48. SAPHO syndrome Synovitis, Acne, Plantar pustulosis, hyperostosis and osteitis Cause is unknown Osteitis involves several bones including chest wall (63%), pelvis (40%) and spine(33%) Lower extremity is affected 6% Systemic symptoms are rare Mean number of active lesions per pt is 5 Self limited disease that remits and relapses Does not respond to abx, may respond to nsaids, steroids, pamidronate

49. Brodie�s abscess Subacute osteo Mild to moderate pain, no fever, insidious Distal tibia Patients <25 years Usually hematogenous Can be trauma related Needs surgical debridement Brodie�s Abscess Brodie�s abscess refers to a chronic localized bone abscess. Patient with subacute cases may present with fever, pain, and periosteal elevation, whereas patients with chronic Brodie�s abscess are often afebrile and present with long-standing dull pain. The most common site of involvement is the distal part of the tibia. The lesion is typically single and located near the metaphysis. Of patients, 75% are younger than 25 years old. Surgical d�bridement and culture-directed antibiotics are often curative. Cultures may be negative. Brodie�s Abscess Brodie�s abscess refers to a chronic localized bone abscess. Patient with subacute cases may present with fever, pain, and periosteal elevation, whereas patients with chronic Brodie�s abscess are often afebrile and present with long-standing dull pain. The most common site of involvement is the distal part of the tibia. The lesion is typically single and located near the metaphysis. Of patients, 75% are younger than 25 years old. Surgical d�bridement and culture-directed antibiotics are often curative. Cultures may be negative.

51. Osteomyelitis of the clavicle Organism: Usually S. aureus Usually after bacteremia, central line, or neck surgery Sacroiliac joint DDx ankylosing spondylitis, inflammatory bowel disease S.aureus, Brucella, usually unilateral

52. Osteo in HD Usually catheter related Usually S.aureus Usually affects vertebra Osteo and Sickle cell S.aureus and Salmonella IVDA S.aureus, Psuedomonas, Candida, Eikenella

53. Skeletal TB 20% of TB is extrapulmonary 1-5% of all TB cases Spinal TB (lumbar and thoracic) TB affects the antero-inferior part of the vertebral body Usually after hematogenous spread from pulmonary focus Collapse of vertebrae, disc herniation and abscess formation hematogenous spread from a pulmonary source.[103][104][105][106][107][108][109][110][111][112][113][114] The clinician should consider tuberculous osteomyelitis in patients with a past medical history of treated or untreated tuberculosis with new back pain, patients with a known positive tuberculin skin test, young patients, patients coming from endemic areas with chest-x-ray findings consistent with active tuberculosis or old healed tuberculosis, patients with a household member who had tuberculosis, patients with negative bacterial cultures, or patients whose biopsy specimen of infected bone shows granulomatous inflammation.[108] Clinical features of osteomyelitis due to M. tuberculosis are pain and swelling with abscess and sinus formation. Radiographs reveal irregular cavities and areas of bone destruction with little surrounding sclerosis. Because of the presence of a sinus tract, secondary bacterial infection does occur.[107][112] Vertebral osteomyelitis due to M. tuberculosis, also called Pott�s disease, is among the most common osteoarticular manifestations of tuberculosis. In this form of vertebral osteomyelitis, in contrast to bacterial vertebral osteomyelitis, systemic symptoms are often absent. Back pain or stiffness is commonly the only symptom, and a delay in the diagnosis is often the norm. In 50% of patients with spinal tuberculosis, MRI reveals paravertebral soft tissue abscesses in addition to the bone lesion. The infection has a predilection to the anterior superior or inferior angles of the vertebral bodies, especially in the early phases of the disease.[108][109][113] Significant overlap in imaging appearances between tuberculous osteomyelitis and other forms of osteomyelitis exists. The diagnosis should rely on the presence of M. tuberculosis on stain or culture of a biopsy specimen. Chest radiographs show an abnormality in less than 50% of patients with musculoskeletal tuberculosis but should be obtained routinely because the existence of concomitant pulmonary tuberculosis has infection control ramifications and may provide for an alternative area from which to obtain culture specimens. The therapy of skeletal tuberculosis is discussed in Chapter 246 . Osteoarticular infections with nontuberculous mycobacteria also can occur. It is commonly seen in immunocompromised patients[114] or after contamination of a wound after trauma or surgery. Mycobacterium marinum, Mycobacterium avium-intracellulare, Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium ulcerans, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium haemophilum all have been associated with infection.[114][115][116][117] Disseminated osteoarticular infection with Mycobacterium bovis after bacille Calmette-Gu�rin vaccination and intravesicular installation of bacille Calmette-Gu�rin also has been reported.[118] Medical therapy alone is often curative, although in selected cases surgical d�bridement is required. Antimicrobial agents typically used in the treatment of osteoarticular infection due to atypical mycobacteria are the same as agents used to treat infection at other sites and are discussed in Chapter 249 . hematogenous spread from a pulmonary source.[103][104][105][106][107][108][109][110][111][112][113][114] The clinician should consider tuberculous osteomyelitis in patients with a past medical history of treated or untreated tuberculosis with new back pain, patients with a known positive tuberculin skin test, young patients, patients coming from endemic areas with chest-x-ray findings consistent with active tuberculosis or old healed tuberculosis, patients with a household member who had tuberculosis, patients with negative bacterial cultures, or patients whose biopsy specimen of infected bone shows granulomatous inflammation.[108] Clinical features of osteomyelitis due to M. tuberculosis are pain and swelling with abscess and sinus formation. Radiographs reveal irregular cavities and areas of bone destruction with little surrounding sclerosis. Because of the presence of a sinus tract, secondary bacterial infection does occur.[107][112] Vertebral osteomyelitis due to M. tuberculosis, also called Pott�s disease, is among the most common osteoarticular manifestations of tuberculosis. In this form of vertebral osteomyelitis, in contrast to bacterial vertebral osteomyelitis, systemic symptoms are often absent. Back pain or stiffness is commonly the only symptom, and a delay in the diagnosis is often the norm. In 50% of patients with spinal tuberculosis, MRI reveals paravertebral soft tissue abscesses in addition to the bone lesion. The infection has a predilection to the anterior superior or inferior angles of the vertebral bodies, especially in the early phases of the disease.[108][109][113] Significant overlap in imaging appearances between tuberculous osteomyelitis and other forms of osteomyelitis exists. The diagnosis should rely on the presence of M. tuberculosis on stain or culture of a biopsy specimen. Chest radiographs show an abnormality in less than 50% of patients with musculoskeletal tuberculosis but should be obtained routinely because the existence of concomitant pulmonary tuberculosis has infection control ramifications and may provide for an alternative area from which to obtain culture specimens. The therapy of skeletal tuberculosis is discussed in Chapter 246 . Osteoarticular infections with nontuberculous mycobacteria also can occur. It is commonly seen in immunocompromised patients[114] or after contamination of a wound after trauma or surgery. Mycobacterium marinum, Mycobacterium avium-intracellulare, Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium ulcerans, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium haemophilum all have been associated with infection.[114][115][116][117] Disseminated osteoarticular infection with Mycobacterium bovis after bacille Calmette-Gu�rin vaccination and intravesicular installation of bacille Calmette-Gu�rin also has been reported.[118] Medical therapy alone is often curative, although in selected cases surgical d�bridement is required. Antimicrobial agents typically used in the treatment of osteoarticular infection due to atypical mycobacteria are the same as agents used to treat infection at other sites and are discussed in Chapter 249 .

54. Skeletal TB TB arthritis: hip, small bones of the hand Extraspinal TB: mastoiditis, ribs or sternal Poncet�s disease: acute symmetric polyarthritis in small and large joints secondary to active TB thought to be immune mediated improved with ATT - HIV coinfection may be a risk factor

56. Diagnosis and Management CXR is positive in only 50% Treatment is with ATT Previously concern to treat for 12-18 months Now with Rifampin, three studies from Hong Kong showed that 6months and 9-18 months are comparable IDSA /CDC guidelines are 6 months

57. Fungal Osteomyelitis Most common: Blasto, cocci, sporotrichosis Less common: cryptococcus, candida, aspergillus Local extension, wound contamination Scedosporium and Fusarium Often presents as a cold abscess lytic bone lesion with associated abscess Bone lesions are most common in blastomycosis, disseminated coccidioidomycosis, and extracutaneous sporotrichosis, but are seen occasionally in cryptococcosis, candidiasis, and aspergillosis. The typical epidemiologic risk factors and host characteristics that predispose to mycoses often provides clues as to the fungal etiology. Although most fungal osteomyelitis is hematogenous, trauma with contamination of a wound is a risk factor for fungal osteomyelitis due to molds, including Pseudallescheria boydii, Scedosporium prolificans, and Fusarium spp. Hematogenous fungal osteomyelitis usually presents clinically as a �cold abscess� and radiologically as a well-defined osteolytic lesion with adjacent soft tissue abscess. In contrast, extracutaneous sporotrichosis causes patchy bone loss and commonly extends to contiguous joints. Surgical d�bridement of contiguous soft tissue should be done in patients with large collections of pus, but the role of surgery is usually limited to biopsy for diagnosis. Therapy of specific mycoses is discussed in other chapters and in treatment guidelinesBone lesions are most common in blastomycosis, disseminated coccidioidomycosis, and extracutaneous sporotrichosis, but are seen occasionally in cryptococcosis, candidiasis, and aspergillosis. The typical epidemiologic risk factors and host characteristics that predispose to mycoses often provides clues as to the fungal etiology. Although most fungal osteomyelitis is hematogenous, trauma with contamination of a wound is a risk factor for fungal osteomyelitis due to molds, including Pseudallescheria boydii, Scedosporium prolificans, and Fusarium spp. Hematogenous fungal osteomyelitis usually presents clinically as a �cold abscess� and radiologically as a well-defined osteolytic lesion with adjacent soft tissue abscess. In contrast, extracutaneous sporotrichosis causes patchy bone loss and commonly extends to contiguous joints. Surgical d�bridement of contiguous soft tissue should be done in patients with large collections of pus, but the role of surgery is usually limited to biopsy for diagnosis. Therapy of specific mycoses is discussed in other chapters and in treatment guidelines

58. Questions?