Osteomyelitis: What tests I believe; When is a debridement a debridement?

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1 9:10 9:20 am The Infection Algorithm: Beating the Spread Better Than Vegas Odds Makers William C. McGarvey, MD Osteomyelitis: What tests I believe; When is a debridement a debridement? Osteomyelitis bone infection Acute inflammatory changes, hyperemia/hypervascularity, edema, cytokinetic attraction of cells, abscess formation. Things you need to know (in no particular order): Organism Bacterial, mycobacterial, fungal Strain Important for treatment, specifically antibiotic sensitivity and selection Virulence Staph. Aureus vs MRSA, etc. Some bugs are now not truly resistant but are requiring near toxic doses of specialized antibiotics for treatment (15-30%, institutionally dependent) Extent What tissues are affected and what is still alive and viable that can effectively ward off mounting infection Length of time Acute vs chronic Longer time to diagnosis, harder to deal with; establishes penetration into tissue; creates own protective barrier (glycocalyx by 3 weeks) Host factors Smoker, drug addict, nutritionally challenged, systemic disease contribution, viable immune system Source Hematogenous Typically kids 4-7% go to talus or calcaneus Brodie s abscess Adjacent site Direct inoculation i.e. trauma, surgery Things at your disposal (again, in no particular order): Patient information History Helpful as to potential toxicity and likelihood of inoculation eg. h/o farm accident, prior injuries, procedures, medical or social issues, etc. Physical exam Location, viability of tissue, vascularity, evidence for other source, eg. piercings, tattoos, old scars, lymph node involvement 113

2 Laboratory studies CBC with differential WBC is relatively useless if negative. Differential improves value to demonstrate evidence for bacterial vs atypical infection based on increase in numbers of PMN s or bands vs monocytes or lymphocytes present in more atypical infections Erythrocyte sedimentation rate Non-specific marker of inflammation. Elevation indicates inflammatory process Sensitivity=93%, specificity=83%, Accuracy=86% C-reactive protein Acute phase reactant. Spikes immediately in face of infection. Declines in 1-2 weeks after successful treatment is initiated Sensitivity=91%, specificity=77%, accuracy=88% Combining studies has recently been shown to be helpful. If either test is positive the sensitivity increases to 95% and this is thought to be helpful in screening for disease If both tests are positive, specificity increases to 93% and this is thought to be good for confirmation of disease presence. Accuracy is best when both tests are positive = 92% (Greidanus, et al. JBJS 07) Hemoglobin A1C Speaks to the compliance and control of the diabetic. BMP Gives physiologic data and a hint as to how long infection s been present and how much it s really affecting the patients organ systems, eg. Na = 128 suggests longer presence of infection leading to hyponatremia and potential for neurotoxic event Procalcitonin Biomarker for inflammation Useful (from metanalysis) Sensitivity 77% Specificity 79% Advantages early detection 3-6 hrs after bacterial challenge Reaches maximum value within 12 hours Felt by many to be THE most useful as a result of it s early detection capacity Differentiation of bacterial infection from other confounding inflammatory conditions Can also be helpful in assessing effectiveness of treatment if followed longitudinally Expect 50% reduction in values as a measure of succcess of therapeutic intervention Persistent elevation indicates lack of successful treatment Microbiology studies Wound cultures (& sensitivities) 114

3 Abscess aspiration or purulent drainage is helpful. Sinus tract specimens are essentially worthless with no reliability Blood cultures (& sensitivities) Helpful if positive. Positive only half the time. Bone cultures (& sensitivities) Best test. If positive sensitivity(95%) and specificity(99%0 are both very high. Accuracy is dependent on specimens obtained prior to antibiotic treatment. Reliability falters if empiric therapy has begun, even if stopped before biopsy. Imaging modalities Plain radiographs Findings include osteolysis (at least 30% bone demineralization must occur to see this), periosteal reaction and elevation, cortical destruction, demonstration of nidus with formation of sequestra and involucra. Evidence takes at least 2 weeks to appear and even then are often so subtle as to be overlooked. Sensitivity = 45-75%; specificity = 75-85% Nuclear studies Three phase bone scan is inexpensive and can be obtained in 2 hours. Changes can be identified within bone in 48 hours. Osteomyelitis is characterized by increased uptake in all 3 phases. Low false negatives but fairly high false positives including fracture, traumatic soft tissue injury, hyperemia due to cellulitis, recent surgery, neuropathic joints. Sensitivity=69-100%, specificity=38-82% Addition of labeled leukocyte scan helps improve sensitivity, specificity and accuracy. Sensitivity =73%-100%, specificity=55%-100% Combined studies are shown to be more helpful with Indium better than Gallium. Combined studies show sensitivity=100%, specificity=80%, and accuracy=91% (Johnson, et al. FAI 96) Problems are lengthier tests (2 separate days to scan) and cost which is greater than standard MRI. In fact, the indium scan alone is better than technetium bone scan. Sens=100%, spec=70%, accuracy=86%. Studies have suggested these scans can be used not only diagnostically, but also prognostically after treatment with debridement and antibiotics. Reportedly, continued positive results on serial scans 3-4 weeks apart in the face of presumed effective treatment is an indication that bone will not heal and that amputation may be necessary. Difficulty remained in differentiating infected vs neuropathic changes in the this population. (Vander Wall, et al. FAI 01) Computed tomography Defines extent of bony erosion, cortical destruction. Magnetic Resonance Imaging Changes in bone are seen earlier than plain films. T1=loss of normal fatty marrow signal(darker) and T2=edema enhancement(brighter) in affected 115

4 areas. More anatomic detail than nuclear studies with information about both bone and soft tissue eg. sinus tract extension, abscess formation, tissue plane dissection, contiguous structure involvement. Sensitivity=77-100%, specificity=80-100% Addition of Gadolinium improves results and gives better detail on soft tissue involvement Tissue monitoring TCpO2 Assess vascular reserve in area of prior injury. Good study because it measures tissue oxygen diffusion capacity i.e. amount of O2 that can get into tissue out of vessels and into tissues at one time. Normal value = chest measurement, usually mmHg. Threshold values for healing > 35-40mmHg. Below this spontaneous healing becomes less predictable. There should be a +100mmHg response by tissues to 100% breathed O2. Less responsiveness indicates some level of peripheral vascular compromise that should be evaluated by a specialist (arteriogram, MRA). Problems are limited availability and reduced accuracy in the face of limb edema Arterial Doppler Assess vascular status of limb. Waveforms and ankle-brachial indices are critical info provided. Waveform should read tri-phasic. Flattened or monophhasic waves indicate sclerosis or stenosis. ABI is ration of lower to upper extremity systolic pressure. Should be >1.0 (Normal= ). Threshold value for spontaneous healing~ <0.45. Individual toe pressures are helpful to determine more distal disease. Greater availability than TcpO2. Problems are most facilities only offer measurement to the level of the ankle so more distal disease has to be extrapolated. Surgical procedures Biopsy Rare indication as isolated procedure. IM/ID doctors regularly ask for bone biopsy to identify organism for purposes of antibiotic therapy. Flaw in thinking is that antibiotics alone are sufficient treatment when thorough debridement is necessary Debridement Done in conjunction with biopsy. Remove all dead and devitalized tissue Amputation Experience/gut reaction See below Treatment for osteomyelitis removal of infected bone (and tissue) Antibiotics = suppression Alone can lead to resistant strains and increased virulence for which, eventually antibiotics will no longer be effective. Should be considered adjunctive therapy. Less effective in acidic, dysvascular, anaerobic environments. 116

5 (Debridement reduces necrotic tissue which is both anaerobic and acidic as a result of dessication byproducts) Method of delivery can be IV through PICC line and/or through local delivery systems with either PMMA or an absorbable biologic ceramic. IV therapy standard 4-6 weeks after last debridement. In convenient, expensive. Some protocols are using oral antibiotics provided that they are able to achieve high enough serum levels and have equivalent bone penetration. Rationale for PMMA, etc. is to provide locally high concentrations of bactericidal drug directly at the site of infection in addition to or instead of relying on diffusion and redistribution in the bloodstream Wound care = palliation Will often improve to a point and then reach a plateau beyond which no further improvement will take place until the underlying problem is eradicated Surgical debridement = treatment Only effective if ALL infected tissue is removed Big whack Treat like cancer operation in which clean margins are the goal Stabilization of fractures/non-unions is critical and necessary for proper healing environment Close down the dead space in which micro-organisms flourish Reconstructive options are dictated by necessary amount of tissue removal Adjuncts Hyperbaric oxygen Increased O2 tension to force oxygen into tissues. Increases intramedullary O2 tension. More oxygen means toxicity for anaerobic organisms and enhancement of cellular phagocytic processes required to fight infection Animal studies have shown that HBO is as good as antibiotics in the tretment of Staph Aureus. Additionally, HBO is adjunctive for many antibiotics. Nutrition Ensure adequate caloric intake to fuel the immune system and provide substrate for the healing and creation of collagen. Vitamins and minerals are essential cofactors in healing pathways eg. vitamin C is a cofactor in the production of collagen triple helix formation Systemic disease/metabolic control Disease control is essential for healing wounds, infections Smoking cessation Nicotine is a potent vasoconstrictor. 1 drag of a cigarette can alter blood flow for up to 17 hours. Smokers are anywhere between 4-16x as likely not to heal or fuse as those who don t as a result of reduced vascularity and impaired release of O2 from Hgb molecules. 117

6 Special situations Osteomyelitis vs Charcot Clinical, laboratory and radiographic presentation can be identical. Need time and strong clinical inclination with frequent re-evaluation of diagnostic tests and treatment efficacy. Positron emission tomography has been suggested to be more effective diagnostically. Evaluates cellular glucose metabolism to recognize increased activity of neutrophils and macrophages. Sensitivity=91-100%, specificity=88-91% Limited availability, expensive and can be inaccurate in the face of elevated blood glucose leading to false negative results. Type C host with documented osteomyelitis No great solutions for compromised host factors Do what you can for nutrition, smoking cessation, medical maximization Amputation is sometimes the best reconstructive option. Uncontrolled infected non-union Salvage requires extensive debridement Radical resection of bone and tissue Stabilization and eradication of dead tissue is key Multidisciplinary approach with ortho, plastic, vascular, wound care, pain management docs. Verbal contract with patient for goals, expectations and end point. No organism infections Hard to treat because adjuvant therapy is not specific Must request all testing for bacteria, AFB, fungus, etc. Biopsy is sometimes helpful to identify cellular reaction to organism As long as patient is not septic, stop the antibiotics and keep the patient off for as long as possible before biopsy and debridement Look for old records of prior injuries and surgeries Deductive reasoning for most plausible pathogen i.e. Sickle cell patients have high predilection for Staph, Salmonella so choose antibiotics based on likelihood. When all else fails, stop all treatments and wait for a flare-up. Start all over. If above fails to be fruitful, consider amputation. Total Joint Infection CBC w/ diff, ESR, CRP blood C&S joint fluid are all helpful Combination ESR/CRP is more useful higher degree of accuracy if both are elevated vs either/or Joint fluid analysis 1100 PMN s/cc 64% PMN s + C&S Suspicion level of surgeon may be the most useful and accurate tool! Newer methods 118

7 Alpha defensin ELISA assay (marketed as Synovasure) Joint fluid aspirate analysis Shows great promise Sensitivity 97.4% Specificity 95.8% (higher if no metallosis) Treatment Like that of any other TJA <3 weeks from surgery or a defined incident debridement w/ poly exchange If > 3 weeks (6 weeks for sure), glycocalyx adherence becomes difficult to overcome Single vs mutli staged GPC s -single stage? GNR s- explant/abx spacer/delayed reimplant This may be the best approach for all types My approach Gather patient information Lab studies - CBC with diff., ESR. CRP, (Hgb A1C in DM) Micro studies - deep tissue off antibiotics Imaging MRI Best detail and most information re: extent of marrow or cortical involvement and soft tissue extension as well as articular surface involvement when infection nears or crosses joint. Can be hyper sensitive with emphasis on reactive edema vs infection, especially in the face of recent injury or surgery. Consider adding Gadolinium to reduce the reader error. Surgery based on extent of disease. This often mimics a cancer operation. Large incisions, large resections, including, at times removing diaphyseal or articular sections. May require plastic surgery coverage, fusion, bone grafting or transport. Early soft tissue coverage and increased blood flow are critical. (low threshold for plastics consult, free tissue transfer or flap coverage) Decision making training & gut reaction. If it looks infected, it probably is. Low threshold for surgical treatment. Longer delays mean more difficulty eradicating infection. When in doubt, take it out 119

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