### Diagnosis Infection of bone. ### Epidemiologic Risks Trauma or hematogenous seeding ( fromthe usual triad of IVDA, dialysis, and IDDM) are the main ways people acquire bone infections. It can also be chronic or acute. Bone scans and MRI's are very sensitive, sometimes too much so. Many diseases and conditions can lead to a positive MRI. Nearby [[cellulitis]] can lead to a false-positive MRI as one of many examples. So never order an MRI looking for [[osteomyelitis]] in cases of recurrent [[cellulitis]]. It will be positive. And I have NEVER seen [[cellulitis]] lead to bone infection either in practice or in the literature. A tagged WBC may be of benefit for diagnosing infected fractures. [^1] Although I never found tagged WBC scans to be of much help in any infection In the adult, long bone hematogenous infections are very rare and are called a Brodie's abscess. They present with pain and look like a primary bone tumor until, of course, they are biopsied. With vertebral [[osteomyelitis]], the elderly are more likely to have [[endocarditis]], cancer and have an infection due to *Streptococci*. [^2] [[Osteomyelitis]] with sacral pressure ulcers: debride, biopsy and get cultures. Then and only then treat. From an excellent review: > "We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of [[osteomyelitis]] when biopsied, and magnetic resonance imaging may not accurately distinguish [[osteomyelitis]] from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and [[osteomyelitis]] is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the [[osteomyelitis]] is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy." [^3] For vertebral [[osteomyelitis]]: > "The prevalence of [[Staphylococcus]] aureus infections was higher in young patients than in old patients, while gram-negative bacterial infections and [[Enterococcus]] were more prevalent in older patients. Gram-negative bacterial infections were more common in women than in men, in patients with cirrhosis than in those without, and in patients with a solid tumor than in those without. Methicillin-resistant S. aureus infections were more prevalent in patients with chronic renal disease than in those without. [^4] ### Microbiology Varies. *S*. *aureus* leads the list, but anything can infect bone, especially after trauma. A Brodie's abscess is a spontaneous long bone abscess usually due to *S*. *aureus*. Since the microbiology is variable, maybe get cultures? What a concept. [[AIDS]]: *[[Bartonella]]* a common cause of lytic bone lesions as well as *Mycobacterium* *avium*. [^5] ### Therapy Never, ever, ever, never treat empirically. Down that road lies madness. Therapy should be guided by cultures. For vertebral [[osteomyelitis]], open biopsy has a higher yield than needle biopsy (29 [91%] of 32 vs 32 [53%] of 60 and there was no association of prebiopsy antibiotics with culture results. [^6] > "Open biopsy of vertebral tissue had a higher diagnostic yield (70%) than fine needle aspirate (41%) or core biopsy (30%). Despite receiving a median of 6 weeks of intravenous antibiotics, only 15% of patients had a full recovery on discharge from index admission. .... **Obtaining a microbiological diagnosis is associated with a better outcome**." [^7] Debride (No debridement, no cure. Know debridement, know cure) and get cultures, then wait for it. Waaiiitttttt. Then, when you have the infecting organism in your hand (figuratively speaking one hopes) treat with 6 weeks of IV something depending on the organism, and then, if possible or if the labs auger failure (ESR and/or CRP remain elevated), 3-6 months po. No one ever died of [[osteomyelitis]] acutely. If you can't get a debridement at least biopsy the damn thing; yield is not unreasonable: about 33%. I don't know. the literature suggests debridement is the best therapy, but mostly retrospective trials. And I can't get surgeons to operate anyway. [^8] And also consider a second biopsy if the first is negative, it doubles the chance of getting the bug and knowing what to kill. > "To optimize microbiological diagnosis in vertebral [[osteomyelitis]], performing a second PNB (after an initial negative biopsy) could lead to a microbiological diagnosis in nearly 80% of patients." [^9] In one study of vertebral [[osteomyelitis]], three samples (one in anaerobic bc bottle, one in aerobic bc bottle and one in saline followed by three post-biopsy blood cultures found the organism 74% of the time. [^10] I have wondered about sending blood for bacterial DNA testing at the time of biopsy, figuring the biopsy would stir things up. While I am too chicken to try, changing to po something (a quinolone) PLUS [[rifampin]] for S. aureus after a 2 weeks IV was successful in one series. In a small series of chronic [[osteomyelitis]] followed for 10 years, 8 weeks of oral dicloxacillin plus [[rifampin]] has the same cure as IV. Duration?  6-8-12 weeks have all been used.  6 weeks [^11] probably enough for normal hosts with easy to kill bugs and good debridement.  As the confounding factors increase, paranoia tends to lengthen therapy. *S*. *aureus* of the spine: 6 weeks for MSSA. Treat MRSA infection of the spine with 8 weeks and, if possible, debridement. [^12] [^13] The problem with the spine is there is just so much you can remove and unless a senator, you need a spine. Keep the trough > 15. [[daptomycin]] has efficacy equal to [[vancomycin]]. [^14]  For the spine, 6 weeks not inferior to 12. [^15] [[Clindamycin]] not ineffective if that's all you have: > "The cure rate was 67.4% by intention to treat and 84.6% per protocol, with a median follow-up of 398 days." [^16] One study of early post-op spine [[osteomyelitis]], 10 days of IV then po for a total of 6 weeks worked fine; failure was due to anaerobes, which I have never seen. [^17] Is IV therapy mandated? Maybe not if you can use oral agents with good bioavailability. Most oral therapy (8 to 12 weeks) has the same outcomes as IV. [^18] IF IF IF there is good debridement: > Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. [^19] And > "Switching to an oral antibiotic regimen after two weeks intravenous treatment may be safe, provided that CRP has decreased and epidural or paravertebral abscesses of significant size have been drained." [^20] Oral [[Trimethoprim-Sulfamethoxazole]] can be effective for salvage therapy. [^22] This reference [^21], by the way, has all the bone levels of antibiotics. *[[Candida]]* [[osteomyelitis]] - debride and 6 to 12 months of therapy. [^23] ### Pearls I tend to avoid the quinolones where the structural integrity of the bone is important. Quinolones may decrease new bone deposition by 50% (at least in animals). However, their efficacy is probably equal to beta-lactams. I also avoid aminoglycosides as they do not penetrate into the bone and only give toxicity instead of efficacy. In the spine, the bacterial infection starts in the disc and spreads to both adjacent bones. Always. Tumor involves just the bone. Tuberculosis and fungal spondylodiscitis tend to involve the anterior vertebral body, with a predilection for paraspinal infection and tends to spare the intervertebral disc. 20% of *[[Candida]]* vertebral [[osteomyelitis]] does not have disk involvement. Treat MRSA infection of the spine, as well as undrained paravertebral/psoas abscesses and end-stage renal disease,  go with 8 weeks and, if possible, debridement. [^24] And *S*. *aureus* in the spine should warrant a careful (as if I would suggest a sloppy) evaluation for [[endocarditis]]. I rarely get MRI, tagged WBC scans and bone scans when the issue is an infection from trauma (and that includes the diabetic foot) as trauma will lead to positive scans. Plain films often take at least 6 weeks before there are changes. Either debride or wait. [[Osteomyelitis]] of the jaw is best treated with SOMETHING OTHER than [[clindamycin]] and is one of the few bones that can usually be treated with po. Infected hardware around a fracture: the first goal is a good orthopedic result. Wash it out, keep in the hardware, GET CULTURES BEFORE ANTIBIOTICS. Look, it's [[osteomyelitis]]. No one dies of [[osteomyelitis]] (maybe [[cellulitis]]) so have some discipline and hold on the antibiotics until you have a culture, then treat with IV for 6 weeks followed by po until you get good bone healing. At that point, remove the hardware and retreat with 6 weeks IV then po in an attempt to get rid of the infection. With Staphylococcal bone/hardware infections, I would treat add [[rifampin]] to my anti-staphylococcal antibiotic. However, if you have a case of vertebral infection you (or your surgeon) does not need to delay placement of hardware if indicated. As long as there is pathogen-directed prolonged antibiotic therapy [^25] putting a CAGE into an infected back is surprisingly safe. [^26] Diabetes and smoking are the biggest risk factors for failing therapy for [[osteomyelitis]]. Diabetic foot [[osteomyelitis]]: the diagnosis is the cure; if you remove the infected bones, you may save the foot and you do not need long term IV therapy. If you don't remove the infected bone, then the antibiotics will do nothing, and the patient, in the long run, will lose the foot. You do the patient no favor by not being aggressive. I am a hyperbaric oxygen agnostic. Is there [[osteomyelitis]] under that chronic stasis ulcer?  If the platelet count is > 350, you betcha. A  sensitivity of 62.5%, specificity 91.7% and a positive predictive value of 88%. [^27] Curiously, there is an association between chronic [[osteomyelitis]] and dementia, increases risk by 1.73. [^28] But there is a consistent association between chronic inflammation from infection and dementia. [[Osteomyelitis]] increases fracture risk of all bones in men for reasons to be determined. 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Injury, Volume 49, Issue 6, 1085 - 1090 [^2]: Courjon J, Lemaignen A, Ghout I, Therby A, Belmatoug N, Dinh A, Gras G, Bernard L; DTS (Duration of Treatment for Spondylodiscitis) study group. Pyogenic vertebral [[osteomyelitis]] of the elderly: Characteristics and outcomes. PLoS One. 2017 Dec 5;12(12):e0188470. doi: 10.1371/journal.pone.0188470. PMID: 29206837; PMCID: PMC5716588. [^3]: Wong D, Holtom P, Spellberg B. [[Osteomyelitis]] Complicating Sacral Pressure Ulcers: Whether or Not to Treat With Antibiotic Therapy. Clin Infect Dis. 2019 Jan 7;68(2):338-342. doi: 10.1093/cid/ciy559. PMID: 29986022; PMCID: PMC6594415. [^4]: Kim DY, Kim UJ, Yu Y, Kim SE, Kang SJ, Jun KI, Kang CK, Song KH, Choe PG, Kim ES, Kim HB, Jang HC, Jung SI, Oh MD, Park KH, Kim NJ. Microbial Etiology of Pyogenic Vertebral [[Osteomyelitis]] According to Patient Characteristics. Open Forum Infect Dis. 2020 May 20;7(6):ofaa176. doi: 10.1093/ofid/ofaa176. PMID: 32523973; PMCID: PMC7270706. [^5]: Brian R. Wood, Martha O. Buitrago, Sugat Patel, David H. Hachey, Sebastien Haneuse, Robert D. Harrington, _Mycobacterium avium_ Complex [[Osteomyelitis]] in Persons With Human Immunodeficiency Virus: Case Series and Literature Review, _Open Forum Infectious Diseases_, Volume 2, Issue 3, Summer 2015, ofv090, [https://doi.org/10.1093/ofid/ofv090](https://doi.org/10.1093/ofid/ofv090) [^6]: Saravolatz LD 2nd, Labalo V, Fishbain J, Szpunar S, Johnson LB. Lack of effect of antibiotics on biopsy culture results in vertebral [[osteomyelitis]]. Diagn Microbiol Infect Dis. 2018 Jul;91(3):273-274. doi: 10.1016/j.diagmicrobio.2018.02.017. Epub 2018 Feb 26. PMID: 29573841. [^7]: Brian S W Chong, Christopher J Brereton, Alexander Gordon, Joshua S Davis, Epidemiology, Microbiological Diagnosis, and Clinical Outcomes in Pyogenic Vertebral [[Osteomyelitis]]: A 10-year Retrospective Cohort Study, _Open Forum Infectious Diseases_, Volume 5, Issue 3, March 2018, ofy037, [https://doi.org/10.1093/ofid/ofy037](https://doi.org/10.1093/ofid/ofy037) [^8]: Guo, W., Wang, M., Chen, G. et al. Early surgery with antibiotic medication was effective and efficient in treating pyogenic spondylodiscitis. BMC Musculoskelet Disord 22, 288 (2021). https://doi.org/10.1186/s12891-021-04155-2 [^9]: Gras G, Buzele R, Parienti JJ, Debiais F, Dinh A, Dupon M, Roblot F, Mulleman D, Marcelli C, Michon J, Bernard L. Microbiological diagnosis of vertebral [[osteomyelitis]]: relevance of second percutaneous biopsy following initial negative biopsy and limited yield of post-biopsy blood cultures. Eur J Clin Microbiol Infect Dis. 2014 Mar;33(3):371-5. doi: 10.1007/s10096-013-1965-y. Epub 2013 Sep 21. PMID: 24057139. [^10]: Management of vertebral [[osteomyelitis]] over an eight-year period: The UDIPROVE (UDIne PROtocol on VErtebral [[osteomyelitis]]) Russo, Alessandro et al. International Journal of Infectious Diseases, Volume 89, 116 - 121 [^11]: Bernard L, Dinh A, Ghout I, Simo D, Zeller V, Issartel B, Le Moing V, Belmatoug N, Lesprit P, Bru JP, Therby A, Bouhour D, Dénes E, Debard A, Chirouze C, Fèvre K, Dupon M, Aegerter P, Mulleman D; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral [[osteomyelitis]]: an open-label, non-inferiority, randomised, controlled trial. Lancet. 2015 Mar 7;385(9971):875-82. doi: 10.1016/S0140-6736(14)61233-2. Epub 2014 Nov 5. PMID: 25468170. [^12]: Livorsi DJ, Daver NG, Atmar RL, Shelburne SA, White AC Jr, Musher DM. Outcomes of treatment for hematogenous [[Staphylococcus]] aureus vertebral [[osteomyelitis]] in the MRSA ERA. J Infect. 2008 Aug;57(2):128-31. doi: 10.1016/j.jinf.2008.04.012. Epub 2008 Jun 17. PMID: 18562009. [^13]: Park KH, Chong YP, Kim SH, Lee SO, Choi SH, Lee MS, Jeong JY, Woo JH, Kim YS. Clinical characteristics and therapeutic outcomes of hematogenous vertebral [[osteomyelitis]] caused by methicillin-resistant [[Staphylococcus]] aureus. J Infect. 2013 Dec;67(6):556-64. doi: 10.1016/j.jinf.2013.07.026. Epub 2013 Jul 31. PMID: 23916563. [^14]: Liang SY, Khair HN, McDonald JR, Babcock HM, Marschall J. [[Daptomycin]] versus [[vancomycin]] for osteoarticular infections due to methicillin-resistant [[Staphylococcus]] aureus (MRSA): a nested case-control study. Eur J Clin Microbiol Infect Dis. 2014 Apr;33(4):659-64. doi: 10.1007/s10096-013-2001-y. Epub 2013 Nov 3. PMID: 24186726; PMCID: PMC3955410. [^15]: Bernard L, Dinh A, Ghout I, Simo D, Zeller V, Issartel B, Le Moing V, Belmatoug N, Lesprit P, Bru JP, Therby A, Bouhour D, Dénes E, Debard A, Chirouze C, Fèvre K, Dupon M, Aegerter P, Mulleman D; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral [[osteomyelitis]]: an open-label, non-inferiority, randomised, controlled trial. Lancet. 2015 Mar 7;385(9971):875-82. doi: 10.1016/S0140-6736(14)61233-2. Epub 2014 Nov 5. PMID: 25468170. [^16]: Bonnaire A, Vernet-Garnier V, Lebrun D, Bajolet O, Bonnet M, Hentzien M, Ohl X, Diallo S, Bani-Sadr F. [[Clindamycin]] combination treatment for the treatment of bone and joint infections caused by [[clindamycin]]-susceptible, [[erythromycin]]-resistant [[Staphylococcus]] spp. Diagn Microbiol Infect Dis. 2021 Jan;99(1):115225. doi: 10.1016/j.diagmicrobio.2020.115225. Epub 2020 Sep 28. PMID: 33099073. [^17]: Fernandez-Gerlinger MP, Arvieu R, Lebeaux D, Rouis K, Guigui P, Mainardi JL, Bouyer B. Successful 6-Week Antibiotic Treatment for Early Surgical-site Infections in Spinal Surgery. Clin Infect Dis. 2019 May 17;68(11):1856-1861. doi: 10.1093/cid/ciy805. PMID: 30247513. [^18]: Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic [[osteomyelitis]] in adults. Clin Infect Dis. 2012 Feb 1;54(3):393-407. doi: 10.1093/cid/cir842. Epub 2011 Dec 12. PMID: 22157324; PMCID: PMC3491855. [^19]: Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, Lipsky BA, Hughes HC, Bose D, Kümin M, Scarborough C, Matthews PC, Brent AJ, Lomas J, Gundle R, Rogers M, Taylor A, Angus B, Byren I, Berendt AR, Warren S, Fitzgerald FE, Mack DJF, Hopkins S, Folb J, Reynolds HE, Moore E, Marshall J, Jenkins N, Moran CE, Woodhouse AF, Stafford S, Seaton RA, Vallance C, Hemsley CJ, Bisnauthsing K, Sandoe JAT, Aggarwal I, Ellis SC, Bunn DJ, Sutherland RK, Barlow G, Cooper C, Geue C, McMeekin N, Briggs AH, Sendi P, Khatamzas E, Wangrangsimakul T, Wong THN, Barrett LK, Alvand A, Old CF, Bostock J, Paul J, Cooke G, Thwaites GE, Bejon P, Scarborough M; OVIVA Trial Collaborators. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425-436. doi: 10.1056/NEJMoa1710926. PMID: 30699315; PMCID: PMC6522347. [^20]: Babouee Flury B, Elzi L, Kolbe M, Frei R, Weisser M, Schären S, Widmer AF, Battegay M. Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral [[osteomyelitis]]? BMC Infect Dis. 2014 Apr 27;14:226. doi: 10.1186/1471-2334-14-226. PMID: 24767169; PMCID: PMC4012835. [^21]: Antibiotic penetration into bone and joints: An updated review Thabit, Abrar K. et al. International Journal of Infectious Diseases, Volume 81, 128 - 136 [^22]: Deconinck L, Dinh A, Nich C, Tritz T, Matt M, Senard O, Bessis S, Bauer T, Rottman M, Salomon J, Bouchand F, Davido B. Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs). PLoS One. 2019 Oct 17;14(10):e0224106. doi: 10.1371/journal.pone.0224106. PMID: 31622440; PMCID: PMC6797119. [^23]: Gamaletsou MN, Kontoyiannis DP, Sipsas NV, Moriyama B, Alexander E, Roilides E, Brause B, Walsh TJ. [[Candida]] [[osteomyelitis]]: analysis of 207 pediatric and adult cases (1970-2011). 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[^26]: Korovessis P, Vardakastanis K, Fennema P, Syrimbeis V. Mesh cage for treatment of hematogenous spondylitis and spondylodiskitis. How safe and successful is its use in acute and chronic complicated cases? A systematic review of literature over a decade. Eur J Orthop Surg Traumatol. 2016 Oct;26(7):753-61. doi: 10.1007/s00590-016-1803-x. Epub 2016 Jun 20. PMID: 27324195. [^27]: Schattner A, Dubin I, Gelber M. A New Diagnostic Clue to [[Osteomyelitis]] in Chronic Leg Ulcers. Am J Med. 2016 May;129(5):538-9. doi: 10.1016/j.amjmed.2015.10.020. Epub 2015 Nov 17. PMID: 26597669. [^28]: Tseng CH, Huang WS, Muo CH, Kao CH. Increased risk of dementia among chronic [[osteomyelitis]] patients. Eur J Clin Microbiol Infect Dis. 2015 Jan;34(1):153-159. doi: 10.1007/s10096-014-2200-1. Epub 2014 Aug 7. PMID: 25098680. [^29]: Hsieh E, Shiau S, Nolan O, Gibert CL, Bedimo RJ, Rodriguez-Barradas MC, Justice AC, Womack JA, Yin MT. 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