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Point-Counterpoint: Is Surgical Treatment The Best Option For Forefoot Osteomyelitis?
Yes.
Citing anatomical constraints, microbiological issues and the lack of a standard guideline for optimal antibiotic administration, this author says surgical treatment is often the best approach for forefoot osteomyelitis.
By Michael H. Theodoulou, DPM, FACFAS
Surgical management remains the cornerstone of treatment in the care of bone infection. The term osteomyelitis is truly a misnomer for much of what we are seeing as the term relates to bone infection of the human foot. Lipsky correctly points out that the majority of pedal bones have limited marrow and are principally cortical bone.1
With the arrival of systemic antibiotics, we have widely eradicated hematogenous osteomyelitis in the industrialized world. As foot and ankle specialists, the majority of the osteomyelitis we see results from post-traumatic or operative injury, and from the diabetic foot associated with a chronic wound. The progression of involvement extends from initial soft tissue infection to osteitis of the cortical bone and eventual myelitis.
The implication of osteomyelitis in diabetic foot infection is significant. There are associated adverse outcomes with antibiotics including a prolonged need of systemic antibiotics and their associated risks; increased duration of hospitalization and associated costs; and increased time to wound healing in comparison to soft tissue infection only.2 We can mitigate much of this with definitive surgical debridement. Further, by understanding the anatomy of bone, local pathophysiology, host presentation and microbiology, one can truly appreciate the challenge of simply treating this condition medically and why osteomyelitis in the infected diabetic foot wound necessitates invasive debridement.
Understanding The Potential Anatomical, Physiological And Microbiological Issues
In a return to basic science, understanding the anatomy of bone clearly enlightens us to the difficulty in achieving adequate medical management through systemic antimicrobial therapy. The nutrient artery is a high-pressure system that emanates from major arteries and supplies the inner two-thirds of bone via the Haversian system. The outer one-third of bone is supplied through a low-pressure system of the periosteum connected through Volkmann’s canal. If we agree that the majority of our osteomyelitis cases involve the cortical bone, then adequate delivery of antibiotics is already limited through a reduced vascular supply to this area.
Further, the local physiology of bone is compromised by the nature of the condition and the host. In response to infection, there is thrombosis of the local vessels resulting from associated inflammation and injury. If the condition presents as a result of surgical trauma or macrotrauma from injury, then there is compromise of soft tissue envelope and vascularity to the area. In the patient with diabetes, we would all agree that there is an accepted understanding of macrovascular and microvascular impairment inherent to the disease that would also compromise delivery of necessary antibiotics.
From the standpoint of microbiology, the most common organism in diabetic foot infections is S. aureus.3 This organism expresses receptors (adhesins) for bone matrix proteins. There is internalization of S. aureus into osteoblasts, resulting in their inhibition of proliferation with secondary demineralization and apoptosis.4 Research has shown that the bacteria are not killed by osteoblasts when ingested and remained viable when cultured several hours after ingestion.4 This may explain the relapse of infection after medical therapy. Biofilm develops on devitalized tissue and bone, or medically implanted devices. This biofilm is produced by S. aureus and manifests as as a glycocalyx or slime layer. The benefit to the organism is that it can survive in a sessile state, allowing the extracellular matrix to concentrate environmental nutrients, develop innate resistance to antimicrobial factors through low metabolic activity and disperse via detachment.
Accordingly, there are challenges in delivering appropriate antimicrobial therapy and Staph aureus, the most common organism we see in cases of forefoot osteomyelitis, has developed a mechanism to resist medical management. However, the opponents to surgery suggest that transmetatarsal amputation and amputation of the ray may risk architectural reorganization of the foot, resulting in altered biomechanics and the development of transfer lesions. They encourage medical management for forefoot osteomyelitis.
A Closer Look At Recommendations In The Literature
What does the literature suggest we do? There have been multiple studies supporting medical management of osteomyelitis.5-8 Unfortunately, most of these studies are weakened by being non-randomized case series with an inadequate definition of osteomyelitis and a lack of clarity as to the amount of “non-operative” debridement performed.
A prospective study by Lazaro-Martinez and colleagues compared medical and surgical management of forefoot osteomyelitis.9 The authors concluded that medical and surgical treatment had similar outcomes in terms of healing rate, time to healing and short-term complications. However, this study had several weaknesses, including the conservative surgery consisting of only removal of infected bone without definitive amputation, and a failure to obtain clean bone margins. Also, the surgical group only had 10 days of postoperative antibiotics, the primary endpoint was soft tissue healing and not proven eradication of bone infection, and all patients in the study did not have ischemia or necrotizing soft tissue infection.
Lazzarini and coworkers analyzed a 30-year period of clinical trials in the antibiotic management of osteomyelitis.10 They reviewed 93 trials in the child and adult populations with a median follow-up of 12 months. Their review suggested there was no optimal duration for antimicrobial therapy and that the available literature was inadequate to determine the best agent, route and duration. If we accept this to be the case, then to cure this condition, one must consider an “oncologic” approach. The surgeon must arrest infection by eliminating necrotic tissue including bone without concern of defect, try to establish a clean margin and obtain deep cultures to guide antimicrobial therapy.
Consider the 2012 Infectious Diseases Society of America (IDSA) clinical guidelines for the diagnosis and management of diabetic foot infections.11 In the management of osteomyelitis, the guidelines suggest considering bone resection when facing the following conditions: persistent sepsis with no other explanation; an inability to deliver appropriate antibiotic therapy or inability of the patient to withstand antibiotics; progressive bone deterioration despite appropriate medical therapy; and advanced bone destruction irretrievably compromising mechanics of the foot. Clinicians should also consider bone resection to hasten wound healing for a patient who prefers to avoid prolonged antibiotics; in order to achieve a manageable soft tissue and primary closure of the wound; and if prolonged antimicrobial therapy is relatively contraindicated, or the likelihood of the benefit of antibiotics is limited.
In Conclusion
If we accept the premise I initially presented of the anatomical issues, the physiology of the tissue and host, the microbiology involved, and no accepted guideline for type, duration and delivery of antibiotics, then the only conclusion we can make is that surgical treatment is a necessary treatment for much of what we see in forefoot osteomyelitis. Furthermore, it is most often in the best interest of the patient and healthcare delivery system to reduce the risk of creating the “institutionalized” patient and associated adverse outcomes.
Dr. Theodoulou is an Attending Surgeon at Cambridge Health Alliance and an Instructor of Surgery at Harvard Medical School. He is the Section Editor of Forefoot Reconstruction for the Journal of Foot and Ankle Surgery. Dr. Theodoulou is the President-Elect of the Massachusetts Podiatric Medical Society.
References
1. Lipsky BA. Osteomyelitis of the foot in diabetic patients. Clin Infect Dis. 1997;25(6):1318-1326.
2. Mutluoglu M, Sivrioglu AK, Eroglu M, Uzun G, Turhan V, Ay H, Lipsky BA. The implications of the presence of osteomyelitis on outcomes of infected diabetic foot wounds. Scand J Infect Dis. 2013;45(7):497-503.
3. Roy M, Somerson JS, Kerr KG, Conroy JL. Pathophysiology and pathogenesis of osteomyelitis. InTech, Croatia, 2012. Available at https://www.intechopen.com/books/osteomyelitis/pathophysiology-and-pathogenesis .
4. Hudson MC, Ramp WK, Nicholson NC, Williams AS, Nousiainen MT. Internalization of Staphylococcus aureus by cultured osteoblasts. Microb Patho.1995;19(6):409-419.
5. Embil JM, Rose G, Trepman E, et al. Oral antimicrobial therapy for diabetic foot osteomyelitis. Foot Ankle Int. 2006;27(10):771-779.
6. Senneville E, Lombart A, Beltrand E, et al. Outcome of diabetic foot osteomyelitis: a retrospective cohort study. Diabetes Care. 2008;31(4):637-642
7. Game FL, Jeffcoate WJ. Primarily non-surgical management of osteomyelitis of the foot in diabetes. Diabetologia. 2008;51(6):962-967.
8. Acharya S, Soliman M, Egun A, Rajbhandari SM. Conservative management of diabetic foot osteomyelitis. Diabetes Res Clin Pract. 2013; 101 (3):e18-e20.
9. Lazaro-Martinez JL, Aragon-Sanchez J, Garcia-Morales E. Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care. 2014; 37(3):789-795.
10. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials. Int J Infect Dis. 2005;9(3):127-138.
11. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Disease Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis. 2012; 54(12):132-17.
Editor’s note: For related articles, see “Point-Counterpoint: Osteomyelitis: Can It Be Treated With Antibiotic Therapy Alone?” in the January 2015 issue of Podiatry Today or the December 2014 DPM Blog, “Are We Overdoing It With Antibiotics When Treating Osteomyelitis In The Diabetic Foot?,” by David G. Armstrong, DPM, MD, PhD at https://tinyurl.com/n3trtvo .
No.
The availability of bone cultures and the use of guidelines such as the Cierny–Mader classification system can help ensure appropriate patient selection and optimal antibiotic management.
By Jeffrey Karr, DPM, CWS
Antibiotic treatment can be a viable management option for acute or chronic osteomyelitis when bone cultures are available and one ensures appropriate patient selection.
The results of a retrospective study suggest that bone culture-based antibiotic therapy without surgery is an independent factor predictive of remission of foot osteomyelitis in patients with diabetes.1 This study presented an overall clinical remission rate of 64 percent, confirming the efficacy of nonsurgical treatment of diabetic foot osteomyelitis.
Bone resection can be a definitive treatment for osteomyelitis but it does not have to be the only option. The downside to surgical intervention, such as ray resection or transmetatarsal amputations, is the progression to altered biomechanics and the subsequent creation of new ulcers with potentially new sites of osteomyelitis.
A criticism of antibiotic therapy is that it can be difficult to achieve an appropriate level of antibiotic in bone. However, studies have demonstrated that oral antibiotics such as fluoroquinolones, linezolid (Zyvox, Pfizer) and trimethoprim/sulfamethoxazole (Bactrim, Roche) can achieve levels in bone that exceed minimum inhibitory concentrations of targeted organisms at approximate concentrations of 50 percent of serum levels.2-4
What The IDSA Recommends For Nonsurgical Management Of Osteomyelitis
There is a limited number of specific guidelines for the nonsurgical and surgical treatment of lower extremity osteomyelitis.
However, one such guideline is the 2012 Infectious Diseases Society of America (ISDA) Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections.5 This guideline notes the following four situations in which one might consider nonsurgical management of osteomyelitis:
• there is no acceptable surgical target (i.e., radical cure of the infection would cause unacceptable loss of function);
• the patient has limb ischemia caused by unreconstructable arterial vascular disease but wishes to avoid amputation;
• infection is confined to the forefoot and there is minimal soft tissue loss; and
• the patient and healthcare professional agree that surgical management carries excessive risk, or is otherwise not appropriate or desirable.
The IDSA guidelines are a good foundation for the nonsurgical management of osteomyelitis. Additionally, in regard to nonsurgical management of midfoot and rearfoot osteomyelitis, one should consider the overall health of the patient, and whether there is intact bone cortex and soft tissue coverage. With these factors in mind, clinicians should consult the Cierny–Mader classification system.
A Closer Look At The Cierny–Mader Classification System
The Cierny–Mader classification system is based on anatomic, clinical and radiologic features.6 With the Cierny–Mader system, one can classify osteomyelitis by duration (acute or chronic), pathogenesis (trauma, contiguous spread, hematogenous, surgical), site, extent and patient’s health type.
This system characterizes osteomyelitis in one of four anatomic stages. In stage 1 (medullary) osteomyelitis, the bone infection is confined to the medullary cavity of the bone. Stage 2 (superficial) osteomyelitis involves only the cortical bone and most often originates from a direct inoculation or a contiguously focused infection. Stage 3 (localized) osteomyelitis usually involves both cortical and medullary bone. In stage 3, the bone remains stable and the infectious process does not involve the entire bone diameter. Stage 4 (diffuse) osteomyelitis involves the entire thickness of the bone with loss of stability.
The Cierny–Mader classification system further characterizes the host’s health as either A, B or C. The A hosts are patients without systemic or local compromising factors. The B hosts are affected by one or more compromising factors. The C hosts are patients so severely compromised that the aggressive treatment necessary would have an unacceptable risk-benefit ratio. Other options unfortunately are limited. These options are antibiotics as indicated, immobility, chronic wound care, pain management and possibly hospice care/support.
Keys To Selecting An Appropriate Antibiotic Regimen
Antibiotic selection for treating osteomyelitis can be challenging. In the absence of a bone culture, clinicians can rely on wound cultures when they are available, albeit with the understanding that they are not a true representation of the bacteria in the bone. In Cierny–Mader stage 1 osteomyelitis involving children, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae are most common. Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is a growing cause of pediatric osteomyelitis.
In adults, hematogenous osteomyelitis is most often the result of S. aureus and particularly in the elderly, Gram-negative enteric bacteria are present. Empiric antibiotic selection for acute hematogenous osteomyelitis should include an anti-staphylococcal antibiotic such as nafcillin or oxacillin, although one should substitute vancomycin when there is a suspicion of MRSA. In Cierny–Mader stage 2-4 osteomyelitis, which can emerge in patients with diabetic ulcers, contaminated wounds or trauma, the typical bacteria are polymicrobial with S. aureus, Gram-negative enteric bacteria and anaerobes being the most common pathogens that we encounter.7
Overall, Staphylococcus aureus is the most common pathogen in diabetic foot osteomyelitis. However, a polymicrobial infection may be present and with frequent Gram-negative bacterial prevalence, empirical antibiotic choices are difficult. One would initiate empiric therapy with broad-spectrum antibiotics while awaiting culture results. Antibiotics are less effective in treating areas of necrotic bone because of the biofilm formation that impairs the antibiotic penetration into this infective bone.8
Researchers have shown successful treatment of diabetic foot osteomyelitis with antibiotic therapy alone.1,9-11 However, the evidence is not strong when it comes to recommended antibiotic regimens for lower extremity osteomyelitis. Guidelines from the Infectious Diseases Society of America (IDSA) suggest treatment based on likely residual infection.5 The IDSA recommends antibiotics for one to three weeks for any residual soft tissue infection, four to six weeks for residual but viable osteomyelitic bone, or at least three months for non-operative cases.
As I stated previously, antibiotic recommendations for osteomyelitis treatment can come from correct Cierny–Mader staging of the extent of bone infection, identifying the bone involved, and consideration of the medical condition of the patient. In Cierny–Mader stage 1 pediatric osteomyelitis, researchers recommend that children start on two weeks of parental antibiotic therapy followed by an oral regimen.12,13 In the case of an infected rod, remove the rod and follow with a four-week course of antibiotics.14
For Cierny–Mader stage 2 osteomyelitis, Mader advocated a two-week course of antibiotics followed by debridement and soft tissue coverage.14 For Cierny–Mader stage 3 and 4 osteomyelitis, Mader advocated a four- to six-week course of parental antibiotics after the last major bone debridement.14 Physicians need to look at Cierny–Mader stage 3 osteomyelitis cases very closely in regard to the extent of bone infection, the bone involved and the integrity of the infected bone. For infected bone that maintains its integrity, antibiotic therapy can be a viable option when patients are on antibiotics for six weeks.
In regard to the bone integrity, one should give more attention to infected metatarsal and phalangeal bones than the infected midfoot and rearfoot bones. The metatarsal and phalangeal threshold for collapse, fragmentation and pathological fracture is much lower than in the midfoot and rearfoot bones. Antibiotic therapy is a good option in metatarsal and phalangeal osteomyelitis when there is clearly intact cortical bone and no loss of trabecular bone on standard radiographs. It is rare for antibiotic therapy alone to be effective in Cierny–Mader stage 4 osteomyelitis as these cases often require surgical debridement and sometimes stabilization with external fixation.
In Summary
Antibiotic therapy can be the correct treatment choice for the patient with osteomyelitis. One should base antibiotic selection on bone cultures when they are available. Also consider the Cierny–Mader staging of the bone infection, the location and the integrity of infected bone. The duration of antibiotic therapy, as based on aforementioned studies, for lower extremity osteomyelitis should be a minimum of six weeks and longer if clinically indicated. Longer antibiotic therapy is at the clinician’s discretion when clinically indicated.
Dr. Karr is the founder and Medical Director of the Osteomyelitis Center of Central Florida. He is also the Central Florida Limb Salvage Alliance founder and serves as the Medical Director. Dr. Karr is board-certified in podiatric surgery and medicine, and is a Fellow of the American Professional Wound Care Association and the American College of Clinical Wound Specialists.
References
1. Senneville E, Lombart A, Beltrand E, Valette M, Legout L, Cazaubiel M, et al. Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care. 2008;31(4):637–42.
2. Wacha H, Wagner D, Schafer V, Knothe H. Concentration of ciprofloxacin in bone tissue after single parenteral administration to patients older than 70 years. Infection. 1990;18(3):173-6.
3. Von Baum H, Bottcher S, Abel R, Gerner HJ, Sonntag HG. Tissue and serum concentrations of levofloxacin in orthopaedic patients. Int J Antimicrob Agents. 2001;18(4):335-40.
4. Fong IW, Rittenhouse BR, Simbul M, Vandenbroucke AC. Bone penetration of enoxacin in patients with and without osteomyelitis. Antimicrob Agents Chemother. 1988;32(6):834-7.
5. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clinic Inf Dis. 2012;54(12):132–73.
6. Cierny GC III, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003;414:7–24
7. Martinez-Aguilar G, Avalos-Mishaan A, Hulten K, et al. Community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children. Pediatr Infect Dis J. 2004;23(8):701–6.
8. Peters EJ, Lipsky BA. Diagnosis and management of infection in the diabetic foot. Med Clin North Am. 2013;97(5):911–46.
9. Acharya S, Soliman M, Egun A, Rajbhandari SM. Conservative management of diabetic foot osteomyelitis. Diabetes Res Clin Pract. 2013;101(3):18–20.
10. Alabhji J, Oliver N, Samarasinghe D, Mali T, Gibbs RG, Gedroyc WM. Conservative management of diabetic forefoot ulceration complicated by underlying osteomyelitis: the benefits of magnetic resonance imaging. Diabet Med. 2009;26(11):1127–34.
11. Game FL, Jeffcoate WJ. Primarily non-surgical management of osteomyelitis of the foot in diabetes. Diabetologia. 2008;51(6):962–7.
12. Nelson JD. A critical review of the role of oral antibiotics in the management of hematogenous osteomyelitis. In Remington RS, Swartz MN (eds): Current Clinical Topics in Infectious Disease, Volume 4, McGraw-Hill, New York, 1983, p. 64.
13. Tetzloft TR, McCracken GH, Nelson FD. Oral antibiotic therapy for skeletal infections in children. II. Therapy of osteomyelitis and supportive arthritis. J Pediatric. 1978; 92(3):485–90.
14. Mader JT, Mauro MD, Calhoun JH. Update on the diagnosis and management of osteomyelitis. Clin Podiatr Med Surg. 1996; 13(4):701-714.
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