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Could Bone Marrow Aspirate Provide Accurate and Timely Diagnosis of Osteomyelitis?
Bone biopsy is currently the gold standard for diagnosis of osteomyelitis.1–4 However, it lacks a standard definition with debated statistical reliability of its microbiological and histopathological analysis. Also, reports vary with regard to its sensitivity and specificity. Meyr and colleagues reported pathology results demonstrating clear disagreement about the reference standard amongst different pathologists.2 In addition, concomitant antibiotic therapy does invalidate biopsy results in certain cases. Speciation and identification of organisms may also pose a complicating factor.
The literature does not yet address identifying pathogenic organisms using DNA probe assay testing on bone marrow aspirate. Here we report a case where bone marrow aspirate expeditiously identified the pathogenic organism and allowed an earlier change in antibiotic regimen not possible with traditional tissue culture.
Case Report
A 72-year-old male with a past medical history significant for type 2 diabetes, hypertension, congestive heart failure, chronic kidney disease, and peripheral vascular disease presented to our institution with altered mental status and a full-thickness heel ulceration. Examination revealed a 4 cm, full-thickness ulceration to the posteromedial heel with serosanguinous drainage. Radiographs showed findings concerning for osteomyelitis. We empirically started him on a course of intravenous vancomycin and cefepime and brought him to the operating room for wide irrigation and debridement of the ulceration. During that procedure, we aspirated 10 mL of bone marrow from the calcaneus, from a zone far outside the ulceration, and sent this to the lab in an aerobic blood culture tube. DNA probe analysis of the specimen revealed Enterococcus faecalis with genes for vancomycin resistance (VRE). Tissue culture also showed Enterococcus faecalis, as well as other organisms consistent with a polymicrobial diabetic foot infection. Pathological analysis revealed bony necrosis.
Identification and susceptibility testing performed on tissue specimens take up to five days at our institution. Utilizing bone marrow aspirate allowed the infectious disease team to make recommendations within 24 hours, as speciation returned within two-and-a-half hours. This led to a recommendation for ampicillin/sulbactam to cover the vancomycin-resistant Enterococcus. The patient’s post operative course was unremarkable as he went on to heal the ulceration after six weeks of intravenous treatment for osteomyelitis and split-thickness skin grafting.
Considering the Impact of DNA Probe Assay Testing
Infectious Diseases Society of America (IDSA) guidelines recommend histopathological analysis and microbiological analysis as the gold standard for the identification of organisms in acute and chronic osteomyelitis.1 The need for a more comprehensive diagnostic protocol for bone infection is even more apparent with individuals with complicated histories. Additional complexity arises with recent or current use of antibiotics, as low yields could produce false negative culture results. While conventional microbiological methods may require 2 to 4 days to produce bacterial identification and susceptibility results, DNA probe assay test provides results within 2.5 hours.
A study by Walker and team retrospectively reviewed 98 cases of gram-negative bacteremia in hospitalized patients prior to implementation of the DNA probe assay system and 97 cases of gram-negative bacteremia after DNA probe assay implementation.3 Organism identifications took place more quickly post-DNA probe assay implementation (mean 10.9 vs. 37.9 hr, P < .001).3 They also found lower length of ICU stay, 30-day mortality, and mortality associated with multidrug-resistant organisms in the post-intervention group (P < .05).3
One of the benefits of this technique is that laboratory staff does not need any new protocols to process the marrow as a blood specimen. DNA probe of blood culture specimens commonly occurs in hospital laboratories. It is possible to create protocols for nucleic acid analysis of bone tissue, but this technique involving the marrow allows processing of the specimen in a manner already familiar to laboratory staff. Another benefit is that marrow aspiration could theoretically be less prone to sampling error than a small core of bone tissue, since the marrow draws from a larger portion of the bone, especially if aspirating a large volume of marrow. Further study is necessary to determine whether bone marrow culture results will correspond to actual bone tissue cultures obtained from the same bone. We hope to publish a case series this year on the utilization of this technique.
Dr. Erik Kissel is a Fellow of the American College of Foot and Ankle Surgeons. He is in private practice in Southeast Michigan and currently serves as the co-assistant director of the Ascension Macomb-Oakland Podiatric Residency Program and the vice-chair of the Michigan Board of Podiatric Medicine and Surgery.
Dr. Brian Kissel is a Fellow of the American College of Foot and Ankle Surgeons. He is in private practice in Southeast Michigan.
Dr. Shamim is the current fellow at the Northwest Illinois Foot & Ankle Fellowship.
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References
1. Lipsky et al. 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis. 2012;54:E132-E173
2. Meyr AJ, Singh S, Zhang X, et al. Statistical reliability of bone biopsy for the diagnosis of diabetic foot osteomyelitis. J Foot Ankle Surg. 2011;50(6):663-7. doi: 10.1053/j.jfas.2011.08.005.
3. Walker J, Dumadag S, Lee CJ, Lee SH, et al. Clinical impact after laboratory implementation of the Verigene gram-negative bacteria microarray for positive blood cultures. J Clin Microbiol. 2016; 54(7):1789–1796.
4. Dinh T, Snyder G, Veves A. Current techniques to detect foot infection in the diabetic patient. Int J Low Extrem Wounds. 2010;9(1):24–30.
5. Game F. Management of osteomyelitis of the foot in diabetes mellitus. Nat Rec Endocrinol. 2010;6:43-47.
6. Sage RA. Limb salvage and amputation. In: Banks AS, Downey MS, Martin DE, Miller SJ (Eds.) McGlamry’s Comprehensive Textbook of Foot and Ankle Surgery (3rd ed). Lippincott, Williams & Wilkins; 2001:1617-163
7. Felsenstein S, Bender JM, Sposto R, et al. Impact of a rapid blood culture assay for gram-positive identification and detection of resistance markers in a pediatric hospital. Arch Pathol Lab Med. 2016; 140(3):267–75.
8. Howard CB, Einhorn M, Dagan R, et al. Fine-needle bone biopsy to diagnose osteomyelitis. J Bone Joint Surg Br. 1994;76(2):311–4.
9. Bates DW, Goldman L, Lee TH. Contaminant blood cultures and resource utilization. The true consequences of false‐positive results. JAMA. 1991;265(3):365–369.
