Osteomyelitis Categories of Osteomyelitis

Transcription

1 Osteomyelitis 2017 David Mushatt, M.D., M.P.H.&T.M. Associate Professor of Medicine Chief, Tulane Adult Infectious Diseases Section Categories of Osteomyelitis Acute vs. Chronic Vertebral Diabetic foot Osteomyelitis under pressure sores Septic joint Prosthetic joint 1

2 Acute vs. Chronic When does acute osteo become chronic? When necrotic bone develops Acute osteo is measured in days Chronic osteo is measured in days, weeks or years Lew and Waldvogel: Chronic = clinical signs of acute osteo for > 10 days Acute vs. Chronic Chronic Osteomyelitis Results from: Trauma Less frequently complication of acute hematogenous Sequestrum Necrotic bone fragment devoid of vascular supply Involucrum Rim of reactive new bone Formed by the periosteum around the sequestrum 2

3 Arrows = sequestrum Arrowheads = involucrum Acute vs. Chronic Chronic Osteomyelitis Complications: Secondary amyloidosis (< 1%) Squamous cell CA in scar tissue Probably < 1% In one series occurred after an average of 27 years of infection with drainage 3

4 Trends in the Epidemiology of Osteomyelitis Olmsted County, MN J Bone Joint Surg Am. 2015; 97: Etiology of Osteomyelitis Infect Dis Clin N Am 2017; 31:

5 Approach to Osteomyelitis 1. Diagnose 2. Bone culture Debrided bone Bone biopsy 3. +/- Surgery 4. Revascularization/angioplasty 5. IV/po ABX Diagnosis 5

6 The Accuracy of Diagnostic Imaging for the Assessment of Chronic Osteomyelitis: A Systematic Review and Meta-Analysis 23 clinical studies CT 1 Gallium 1 MRI 5 Bone scan - 7 WBC scan 13 PET - 4 Termaat M et al. J Bone Joint Surg, 2005;87: The Accuracy of Diagnostic Imaging for the Assessment of Chronic Osteomyelitis: A Systematic Review and Meta-Analysis Modality Pooled Sensitivity Pooled Specificity PET 96% 91% MRI 84% 60% Bone scan 82% 25% WBC scan 61% 77% Bone+WBC 78% 84% 6

7 The Accuracy of Diagnostic Imaging for the Assessment of Chronic Osteomyelitis: A Systematic Review and Meta- Analysis Sensitivity Specificity Axial skeleton Peripheral Axial Peripheral WBC scan 21% 84% 60% 80% Sinus Tract Cultures Staph aureus only organism in sinus tract cx that correlated with bone cultures (PPV 78%) but, found in only 44% of sinus tract cx when in bone Only 44% of sinus tract cx contained operative pathogen Mackowiak P et al. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA, 1978;239:

8 Treatment Determinants of Outcome Acute vs. chronic Presence or absence of hardware Vascularization of site Intrinsic Muscle flap Vascular reconstruction Immune status of host Surgical debridement 8

9 Surgical Therapy for Chronic Osteomyelitis Surgical is primary Debride dead bone and soft tissue Restore vascular supply Muscle flap Peripheral re-vascularization Fill dead space Flap Bone graft: autologous or cadaveric Antibiotic impregnated beads or cement ABX must be heat stable Surgical Therapy for Chronic Osteomyelitis Extent of resection is key Oxford group allocated 50 pts to: Wide excision: > 5 mm clearance Marginal excision: < 5 mm clearance Intralesional bx: I + D only IV ABX for 6 wks then po x 6 wks Simpson et al. J Bone Joint Surg Br, 2001;83:

10 Impact of Surgery in Chronic Osteomyelitis Wide resection Marginal resection Debulking Simpson et al. J Bone Joint Surg Br, 2001;83: Surgical Therapy for Chronic Osteomyelitis Restore continuity of bone When resection creates large defects in long bones Conventional external fixation Distraction osteogenesis Ilizarov technique Taylor spatial frame Uses computerized adjustments of frame Can be done by patient 10

11 Conventional External Fixation ILIZAROV 11

12 Antibiotics 12

13 Cochrane 2013 Selection Criteria RCTs or quasi-rcts Post-surgical debridement Search small trials Data from 248 participants Results Study quality/reporting often inadequate Almost all trials had moderate to high risk of bias due to failure to conceal allocation and inadequate follow-up 4 trials studied IV vs. PO Remission at EOT: RR 1.04 (no sig ) Remission at > 12 months (no sig ) AEs (no sig ) Treatment Systematic Review and Meta-Analysis of Antibiotic Therapy for Bone and Joint Infections Reviewed Medline, Embase, Cochrane databases Clinical trials databases, ICAAC abstracts, textbooks, pharmaceutical company data, unpublished data from experts, etc. Inclusion Criteria: Ideally blinded, placebo-controlled trials This would exclude most studies! Random or quasi-random allocation to treatment arms Primary Outcome Measure Quiescence of infection after 1 year of f/u Stengel D et al. Lancet Infectious Diseases

14 Treatment 22 trials with 927 patients were eligible 18 open-label, 4 double-blind Methodological quality was poor in most Limitations: Small sample sizes Missing descriptions of patients and disease Confounding by concomitant ABX was common Deep puncture or surgical tissue samples in only 7! Treatment Primary Outcome Control of infection after 1 year 78.6 % average (of 771 pts.) Bacteriological Eradication 77 % (454 cases) Adverse Events Available for 730 pts % (mainly mild) 10 had severe AEs Overall, no convincing advantages of one antimicrobial over another! 14

15 Treatment Tice et al (OPAT Outcomes Registry) 454 pts with osteomyelitis ( ) 91% contiguous osteo Foreign body in 69 (15%), removed in 24 Micro: MSSA: 52% MRSA: 2% SCN: 14% Follow-up: mean 28 months Tice A et al. J Antimicrob Chemother 2003 Outcomes Cure: 69% Recurrence rates Treatment Pseudomonas aerug. 2.5 x Staph aureus Staph aureus: Oxacillin/methacillin: 28.6% Ceftriaxone: 27.3% Cefazolin: 34.8% Vancomycin: 53% 15

16 Duration of Treatment More an Art than Science 4-6 weeks IV is standard minimum IDSA MRSA guidelines say 8 weeks but based on 2 old studies of vertebral osteo! 2 wks IV then po? probably quinolones, metro, clinda po from the start? sure, why not follow ESR and CRP Treat until normalization?» Intercurrent illness, drug reactions and external fixators may delay fall in markers Duration of Treatment If good debridement 6 weeks If minimal or no debridement 2-4 months total, often with an oral phase If hardware 3-6 months or more include rifampin, quinolone 16

17 Treatment Is there once-a-day therapy for S. aureus? 31 pts with MSSA osteo at UCSF from Ceftriaxone 2g IV QD in 22/31 17/21 cured 3 ceftriaxone failures: all had necrotic bone Guglielmo et al. Clin Infect Dis 2000 Retrospective cohort study 124 pts with MSSA 52% had orthohardware Ceftriaxone 60% vs. oxacillin 40% Median IV 43 days Outcomes Oxa stopped in 18% due to AEs CTX stopped in 4% due to AEs Treatment success at > 6 months Oxa= 81% (p= 0.6) CTX= 77% 45% longterm ABX post IV Clin Infect Dis 2012; 54:

18 Vertebral Osteomyelitis How Long to Treat? Paul Sax on Duration of ABX 18

19 The answer is that this is highly-specialized knowledge, rarefied information that only 100% Board-Certified, USDAinspected Infectious Diseases Doctors know To figure out how long antibiotics need to be given, use the following rules: 1.Choose a multiple of 5 (fingers of the hand) or 7 (days of the week). 2.Is it an outpatient problem that is relatively mild? If so, choose something less than 10 days. After application of our multiples rule, this should be 5 or 7 days. 3.Is it really mild, so much so that antibiotics probably aren t needed at all but clinician or patient are insistent? Break the 5/7 rule and go with 3 days. Ditto uncomplicated cystitis in young women. 4.Is it a serious problem that occurs in the hospital or could end up leading to hospitalization? With the exception of community-acquired pneumonia (5 or 7 days), 10 days is the minimum. 5.Patient not doing better at the end of some course of therapy? Extend treatment, again using a multiple of 5 or 7 days. 6.Does the infection involve a bone or a heart valve? Four weeks (28 days) at least, often 6 weeks (42 days). Note that 5 weeks (35 days) is not an option here the 5 s and 7 s cancel each other out, and chaos ensues. 7.The following lengths of therapy are inherently weird, and should generally be avoided: 2, 4, 6, 8, 9, 11, 12, 13 days. Also, days. 6 weeks not inferior to 12 wks Lancet 2015; 385:

20 Clinical Infectious Diseases, 2016;62(10):

21 Multivariate Analyses of Risk Factors for Recurrence High Risk aor PValue ESRD MRSA infection Undrained paravertebral/ psoas abscess Low Risk > 6 weeks < 6 weeks High Risk > 8 weeks < 8 weeks 21

22 Recurrence rate: Instrumented Non-Instrumented 6.8% 4.8% (p=0.72) Instrumented recurrence rate: 4-6 weeks= 22% 6-8 weeks= 9.1% > 8 weeks= 2.6% (p= 0.04) Clin Infect Dis. 2015;60:

23 Recurrence Rates The most frequently isolated organisms were Staphylococcus aureus (52.9% [81/153]), and of these, 38.3% (31/81) were methicillin resistant. Thirty-seven (24.2%) cases were caused by aerobic gram-negative bacteria, and 17 (11.1%) cases were caused by Streptococcus species. Rifampin was used in only 1 pt with S.aureus Clinical Radiology 71 (2016):

24 Imaging Does Not Predict the Clinical Outcome of Bacterial Vertebral Osteomyelitis Prospective Study 29 pts with spondylodiscitis Inclusion criteria Symptoms: pain, fever, etc. Positive cultures: spinal, blood or portal of entry Diagnostic CT or MRI Antibiotic duration Average 98 days Median Follow-Up 12 months after completion of treatment Cure rate 100% Zarouk V et al. Rheum, 2007;46: Zarouk V et al. Rheum, 2007;46:

25 Diabetic Foot Osteomyelitis Probe-to-Bone Test for Diagnosing Diabetic Foot Osteomyelitis Reliable or Relic? Enrolled 1,666 diabetic pts 151 developed foot infections 30 osteomyelitis Lavery L et al. Diab Care, 2007:30:

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27 Diabet. Med. 32, (2015) 27

28 Magnetic Resonance Imaging for Diagnosing Foot Osteomyelitis A Meta-analysis Compared MRI vs. technetium Tc 99m bone scanning, plain radiography, and WBC studies 16 studies met inclusion criteria Performed receiver operating characteristic curves (ROC) Diagnostic odds ratio (DOR) for MRI = 42 Specificity = 82.5% at a 90% sensitivity cut point DOR MRI vs. bone scan = 150 vs. 3.6 MRI vs. plain x-ray = 82 vs. 3.3 MRI vs. WBC scan = 120 vs. 3.4 Kapoor A et al. Arch Int Med, 2007;167:

29 Diabetic Foot & Ankle 2016; 7:

30 No diff in 2 nd amputation rate MRI No MRI 4-year survival: 100% vs 73% (p< 0.017) Culture of Percutaneous Bone Biopsy Specimens for Diagnosis of Diabetic Foot Osteomyelitis: Concordance with Ulcer Swab Cultures 76 patients Diabetic foot osteomyelitis All had positive bone bx cultures No ABX for 4 weeks prior 69/76 pts had concomitant ulcer swab cx Results Identical: 12/69 = 17.4% Bone bacteria isolated from swab: 21/69 = 30.4% No complications (fracture, infection, etc.)!! Senneville E. Clin Infect Dis, 2006;42:

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32 IDSA Guideline for Diabetic Foot Infections CID 2012:54 (15 June) e147 32

33 Obtaining a bone specimen for culture (and histology, when available), is most likely to be justified when there is: 1. Uncertainty regarding the diagnosis of osteomyelitis despite clinical and imaging evaluations 2. An absence (or confusing mix) of culture data from soft tissue specimens 3. Failure of the patient to respond to empiric antibiotic therapy, or 4. A desire to use antibiotic agents that may be especially effective for osteomyelitis but have a high potential for selecting resistant organisms (eg, rifampin, fluoroquinolones). 33

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38 Conclusions 1. Anaerobes may be involved in wounds that are deeper or more chronic 2. Anaerobes more frequently identified when using modern molecular techniques, such as 16s PCR and pyrosequencing 3. It remains unclear whether the presence of anaerobes in DFI leads to a) more severe manifestations b) or if these organisms are largely colonizers associated with the presence of greater degrees of tissue ischemia and necrosis 4. Adequate surgical debridement and, when needed, foot revascularization may be at least as important as the choice of antibiotic to achieve a successful treatment outcome What s New? 38

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40 PLOS ONE DOI: /journal.pone December 17,

41 Journal of Clinical Microbiology December 2016 Volume 54 41

42 Median time to positivity = 6 days Range 2 11 days Thioglycolate broth most sensitive Recommend blind subculture day 10 Unresolved Questions Role of adjuvants Antibiotic impregnated PMMA beads/cement Do they improve outcomes? Antibiotic elutes out in 2-4 weeks and leaves behind foreign body Now using bioabsorbable calcium sulfate beads Hyperbaric Oxygen (HBO)? Expensive, complications and dubious benefit 42

43 Avoid Combination of Vancomycin + Piperacillin-tazobactam High rates of AKI! 43