Bone and Joint Infections

1. Bone and Joint Infections July, 2009

2. Case 1 • A 12 year old female soccer player sustained a nasty bruise below her R knee during a particularly physical game. Two weeks later she complained of increased pain over the area accompanied by a low grade fever and sweats. She didn’t tell her parents. Her coach told her to quit complaining. However, her symptoms persisted and 2 weeks later she went to her pediatrician. Physical exam revealed a temperature of 38 C and a slightly swollen and warm left proximal tibia.

3. Case 1 • What tests would you order? Plain film, blood culture, ESR

4. Case 1 www.imc.gsm.com

5. Case 1 • What tests might have been positive 2 weeks earlier? Bone scan, WBC scan, AB-CD15 scan, Gallium scan, MRI

6. Case 1 www.imc.gsm.com

7. Case 1 • What is the most likely organism? • Do you need to perform a needle biopsy for diagnosis? • How would you treat this patient? Does she need debridement? Which antibiotics and for how long? S. aureus > streptococci BC+: no. Needle biopsy culture sensitivity ~ 40%, Histopathology increases yield Antibiotics, probably not, many choices; nafcillin, Ceftriaxone, oral abx. Empiric treatment for MRSA?

8. Case 2 • A 26 year old thrill-seeker suffered an open fracture of his right tibia and fibula while roller-blading behind a motorcycle driven by his ex-girlfriend. The fracture was reduced and fixed with the placement of screws, plates and rods. He did remarkably well until 4 months later when he noted a pimple followed by a little drainage from one of wounds. Four days later he was chasing his ex-girlfriend up some stairs and heard a loud crack and looked down to find hardware and bone protruding through his right leg.

9. Case 2 • Why did his leg break (the second time)? • What is the most likely bug? • What specimens do you want sent to the lab? • Can you rely on cultures taken from the sinus tract? Pathologic fracture S. aureus, CoNS > GNR Bone cultures Generally no If S. aureus or single organism - some + predictive value

10. Diagnosis - Culture • Gold standard is open bone biopsy for histopathology and culture. • Needle biopsy has a sensitivity of 87% and a specificity of 93%. However, in the post-operative or post-trauma setting its performance is compromised. • Histopathology of needle biopsy yields diagnosis even if a specific organism is not identified

11. Diagnosis - Culture • Superficial or sinus tract cultures correlate poorly with bone cultures in most studies (< 50%). • Perry (1991) found a 62% correlation between wound swab and operative cultures and a 55% correlation between needle biopsy and operative cultures. Better correlation demonstrated for mono-microbial infections (80 and 76%) and S. aureus infections (69% and 74%). • Bottom line: don't trust sinus cultures unless the results yields a single organism or S. aureus

12. Case 2 • Should all the hardware be removed or can the leg be set and he be treated with antibiotics alone? • What antibiotics would you recommend, by what route and how long would you treat him? Best: 2 or 3 step procedure: remove hardware, antibiotics, new hardware later Some success without removing hardware if infection detected early, sensitive bug Vancomycin/rifampin/quinolone A long time

13. Clinical Presentation Cierny-Mader staging • Anatomic stage • Stage 1 – medullary infection only, hematogenous spread or spread through an intramedullary prosthesis • Stage 2 – superficial infection, due to a contiguous soft tissue infection, could also be termed osteotis • Stage 3 – localized infection, full thickness infection (one cortex), bone integrity maintained • Stage 4 – diffuse infection (both cortexes), destabilizes bone (or resection would destabilize bone)

14. Treatment Cierny-Mader staging • Stage 1 – Antibiotics alone. Patients with rods in place require removal. Adults without hardware may require medullary reaming. • Stage 2 – Debride to bleeding bone and antibiotics • Stage 3 – Follow principles of removal of necrotic bone, elimination of dead space and soft tissue coverage plus antibiotics • Stage 4 – Same as stage 3 plus fracture stabilization.

15. Case 3 • A 72 yo male who underwent a right THR 6 months ago, then developed an enterococcal UTI 3 months ago and now presents with low grade fevers and pain in the right hip that prevents ambulation.

16. Case 3 • Imaging reveals a peri-prosthetic fluid collection • Culture of this fluid grows MRSA and enterococcus (Lew, Lancet, 2004)

17. Case 3 • How should he be treated? Two stage replacement with 2 - 6 wks between surgeries. Time between operations for tough-to-treat organisms - 6 to 8 wks. Stop abx 1 -2 wks before 2nd operation - if cultures neg - stop, if cultures +, continue abx for 3 months (6 months for knees).

18. Case 3 • Are there situations when the prosthesis can be retained after debridement? Symptoms < 3 weeks Stable implant Easy to treat organism Success rates 82-100%

19. Case 3 • Are there indications for single stage replacement? Symptoms >3 weeks Soft tissue in good shape No co-morbidities Easy to treat organism Success rates 86-100%

20. Treatment • Ciprofloxacin/rifampin for Osteomyelitis (Zimmerli, 1998) • N=33, stable implants • Staphylococcus • All treated with debridement and 2 weeks of rifampin + vancomycin or flucloxacin • Then either cipro/rifampin or cipro/placebo • Prostheses retained • Median duration of symptoms 5d

21. Treatment Prosthesis removed: hips (42%), knees (60%), bone plates (50%) All 11 failures occurred in patients with retained prostheses (8) or resistant staphylococcus (8) or both (6) (Drancourt 1993)

22. Treatment All had native bone infection or prosthesis removal, all treated with 2 weeks of nafcillin, vancomycin or cefazolin initially - then ceftriaxone 2 gms/d for 4 to 5 weeks (Guglielmo, 2000)

23. Case 4 • A 39 year old IVDU reports to the ER with fever and back pain. He mixes his drugs with dirty tap water and does not prep his skin before injecting. On exam his temperature is 39 C, he has a 3/6 holo-systolic murmur and tenderness over his thoracic spine on percussion. Neurological exam is initially normal.

24. Case 4 • Diagnoses? • Likely organisms? • Initial antibiotics? • Imaging studies? Endocarditis, vertebral OM, epidural abscess Staphylococcus > streptococci > GNR > fungi Nafcillin and gentamicin or vancomycin and gentamicin MRI

25. Case 4 • The lab reports that 3/4 blood cultures have turned positive in 4 hours and are growing a GPC, the following day the lab reports that 2 blood cultures are also growing GNR. • Likely organisms? • The patient starts complaining of mid-thoracic radicular pain. What does this represent? S. aureus > streptococci; P. aeruginosa > other GNR Spinal ache - first sign of epidural abscess

26. Case 4 Tomogram CT MRI www.xray.2000

27. Case 4 • What do you recommend? • What are indications for debridement of vertebral osteomyelitis? MRI, decompression (laminectomy or aspiration) Instability Abscess Cord compression Cervical infection Medical failure Neurological signs or symptoms

28. Case 5 • A 56 year old diabetic man visits his PCP for a routine visit. He is noted to have a 2.5 cm ulcer on the plantar surface of his foot at the first metatarsal head, extending up to the great toe. He was unaware of the ulcer although, in retrospect, he recalls that his socks have been stained and foul smelling lately. He has not noted fevers or chills. His physician notes a hard, gritty surface at the base of the ulcer.

29. Case 5 • Recommended work-up In this case, plain films, ESR sufficient Of all imaging modalities - MR is most accurate (sensitivity > 90%, specificity > 80%) Combination of WBC scan or ABscan with MRI can improve specificity

30. Diagnosis • The gold standard is histopathologic evidence for osteomyelitis with supporting microbiologic data • However, in many cases the diagnosis rests on clinical, laboratory and radiographic data

31. Diagnosis Sometimes it’s easy: • Compatible history and physical exam, elevated ESR, elevated WBC (acute osteomyelitis) • Positive blood cultures (50% in cases of acute osteomyelitis) • Classic radiographic findings

32. Diagnosis In many cases the diagnosis is difficult • Atypical presentations • Non-specific symptomatology • Co-morbid local and generalized conditions that confound and obscure the infection

33. Diabetic Foot Infections What are exam findings that predict bone involvement? • Larger (> 2cm, 92% specificity) and deeper ( > 3mm) associated with osteomyelitis • Probe to bone – 66% sensitivity and 85% specificity, PPV around 55%, NPV 98% • ESR > 70: 100% specificity (only 28% sensitivity) (Grayson, JAMA,1995;273:721-3) (Newman, JAMA, 1991;266:1246-51) (Kaleta, J Am Pod Med Assoc, 2001;91:445-50) (Dinh, CID, 2008;47:519-27)

34. Diabetic Foot Infections What are the best imaging modalities? • Plain film • CT scan • MRI scan • Nuclear medicine studies

35. Diabetic Foot Infections Plain films • Need 30 to 50% mineral loss for x-ray changes to be evident - takes at least 14 days • Sensitivity 43-75%, specificity 75-83% • Insensitive with acute osteomyelitis • In chronic infection - sclerosis, periosteal elevation and sequestra. (Lipsky, CID, 1997;25:1318-26) (www.podiatry.files.wordpress.com)

36. Diabetic Foot Infections CT • Best method for detecting small areas of necrosis, gas, foreign bodies • Metallic foreign bodies compromise the image (www.xray.2000)

37. Diabetic Foot Infections MRI • Sensitivity 82-100% • Specificity 53-94% (tumors, fractures, post surgery, sympathetic edema, infarction – all can look the same; light up on T2 weighted image) • BEST SINGLE TEST • Location important - • Heel and malleoli with ulcer = osteo • Midfoot, joint-centered, no ulcer - Charcot • Combine with Ind-111 WBC scans or gallium scans to increase specificity (www.med.harvard.edu) (Eckman, JAMA, 1995;273:712-20) (Croll, J Vasc Surg,1996:24:266-70) (Craig, Radiology, 1997;203:849-55) (Enderle, Diabetes Care, 1999;22:294-9)

38. Diabetic Foot Infections Bone scan (TC-99 labeled phosphorus) • Soft tissue infection will be positive in the immediate (blood flow) and 15 minute (blood pool) phases while osteomyelitis will be positive in these 2 plus the delayed (> 4 hour) images. • Sensitivity 69-100% (> 95% in acute osteomyelitis), specificity 38-82% (tumors, fractures, post-surgery, septic arthritis, Paget’s disease, Charcot foot) (www.postgradmed.com) (Eckman, JAMA, 1995;273:712-20) (Enderle, Diabetes Care, 1999;22:294-9)

39. Diabetic Foot Infections AB + WBC scan (Ind-111) • Will be positive prior to bone scan • Useful p-surgery (better than MRI) which will always be abnormal • When combined with bone scan has specificity in the 90% range, sensitivity in the 70% range and PP value in the 90% range (www.nuclearonline.org) (Becker, QJ Nuc Med, 1999;43:9-20) (Unal, Clin Nuc Med, 2001;26:1016-21)

40. Newer Imaging Tests • Tc-99 monoclonal (Fab fragments) against CD-15: sensitivity and specificity ~ 85% • IND-111 biotin: used and concentrated in bacteria: sensitivity and specificity for vertebral OM ~ 95% • PET: better than WBC scans for chronic vertebral OM. Limited use in patients with diabetes and cancer

41. Case 5 • What organisms are likely responsible for this infection? (www.erc.montana.edu)

42. Diabetic Foot Infections

43. Case 5 • Recommended treatment Surgical debridement (with bone cultures) Re-vascularization if needed Long-term abx Recent retrospective studies suggest abx alone May be sufficient treatment in many cases (Jeffcoate, 04)

44. Diabetic Foot Infections • Which antibiotics should I prescribe and for how long? (www.erc.montana.edu)

45. Diabetic Foot Infections • Basic principles for choosing antibiotics: • Should always include coverage for Gram-positive cocci, especially S. aureus • Add Gram-negative coverage for chronic wounds, for patients previously treated with abx and for wounds classified as moderate to severe • Provide anaerobic coverage for obviously necrotic wounds or those with a feculent odor • Narrow coverage based on culture results (Lipsky, Clin Micro Infect, 2007;13:351-53)

46. Diabetic Foot Infections • Basic principles for choosing antibiotics: • Consider risk factors for MRSA when choosing Gram-positive coverage • Coverage for enterococci usually not necessary unless it is the only organism isolated • Coverage for Pseudomonas may also not be necessary unless the wound had been treated with hydrotherapy or Pseudomonas is present and the patient is not improving without anti-Pseudomonal treatment • Avirulent organisms (e.g. coagulase negative staphylococci, Corynebacterium species) may become real pathogens in immunocompromised hosts with significant tissue necrosis (Lipsky, Clin Micro Infect, 2007;13:351-53)

47. Recent Antibiotic Trials for DFI • Ertapenam Vs Piperacillin/tazobactam (SIDESTEP) (Lipsky, Lancet, 2005;366:1695-1702) • R,DB,MCT, N=586. Mod-severe DFI (not osteo): 5 days or IV Ertapenam or Pip/tazo - then up to 23 days of amoxacillin-clavulanic acid (could add vanco for MRSA or enterococus) • Response rates at DCIV 94%/92%, at 10 day FUA 87%/83% • No difference between groups in those with MRSA or PsA even if not on abx active against these organisms • Linezolid Vs Amp-sulbactam or Amo-clavulinate (Lipsky, CID, 2004;38:17-24) • R,OL,MCT, N=371, All types of DFI: Could add Vanco for MRSA and Aztreonam for GNR if either not covered by study medication • Response rates: L/Pcn: Overall 81%/71% (NS), Subgroups with infected ulcer 81%/68% and those without osteo 87%/72% - both favor linezolid • More anemia and thrombocytopenia in the linezolid group - all reversible

48. Recent Antibiotic Trials for DFI • Daptomycin Vs Vancomycin or Semi-synthetic Pcn (Lipsky, JAC, 2005;55:240-45) • Randomized study, N=133, Infected ulcer (no osteo), Comparator was Vanco if MRSA suspected, could add aztreonam for GNR and metronidazole for anaerobes • Response rates Dapto/Comparator: Overall 66%/70% (NS), Dapto/SS-PCN 64%/70%, Dapto/Vanco 71%/69% • Only one MRSA infection in the daptomycin group • Moxifloxacin Vs Pip-Tazo/Amox-clav • Subset analysis of P,DB study of 617 patients: only 78 with DFI were evaluable for cure 10-42 days after therapy • Response rates Moxi/PT-AC 68%/61% • Piperacillin/tazobactam Vs Ampicillin/sulbactam (Harkless, Surg Infect, 2005;6:27-40) • P,R,OL,MCT, N=314, Mod-severe DFI (ulcers). If MRSA could use vanco • Response rates P-T/A-C 81% 83%

49. Diabetic Foot Infections (Lipsky, Clin Micro Infect, 2007;13:351-53)

50. Diabetic Foot Infections • Duration of therapy • Mild infections 1-2 weeks • Moderate to severe infections: 2-4 weeks • Osteomyelitis: 4-6 weeks (or longer)