Is Surgical Treatment of Osteomyelitis Superior?

Yes. These authors note that although osteomyelitis surgery can come with risks, surgical management can remove pathologic forces while facilitating quicker courses of antibiotics and a shorter hospital stay.

By Madison Ravine, DPM; and Michael Theodoulou, DPM, FACFAS

Osteomyelitis is commonly encountered in the practice of a foot and ankle surgeon. Controversy exists regarding optimal management of osteomyelitis, specific to medical versus surgical treatment options. However, neither is without potential complication, even further concerning in the particularly comorbid patient.

Here, we will argue for the value of surgical management of osteomyelitis, emphasizing the importance of oncologic resection with surgical ablation and excision of necrotic bone.

A Closer Look at the Disease Process of Osteomyelitis

Let us begin by first considering the disease process occurring in osteomyelitic bone. Osteomyelitis, in short, is an inflammatory process involving the bone and its associated structures due to infection with microorganisms, be these bacteria, mycobacteria, or fungi. With the introduction of a large inoculum of bacteria, the bone may become susceptible to infection. This may be via hematogenous spread, contiguous extension, or direct inoculation.¹ For the sake of brevity, we will focus on contiguous spread and bacterial osteomyelitis, seen most commonly in patients with diabetic foot ulcers. In patients with diabetes, this infective process is further cultivated in the distal lower extremity by a compromised vascular supply, peripheral neuropathy, and a locally as well as systemically immunocompromised host.¹

Moreover, Staphylococcus aureus is very commonly involved in these cases. This bacterium is known for producing adhesins, which promote adherence to both bone matrices and retained orthopedic hardware and other implants, as well as creation of a protective biofilm coating the bacteria.^1,2 Furthermore, S aureus is uniquely digested by host osteoblasts, where it can survive intracellularly, not only causing persistent infection, but also developing phenotypic resistance to antibiotic therapy.^1,3

The Importance of Debridement

The above begins to highlight the importance of surgical intervention in the management of osteomyelitis. As the infective process develops and evolves, not only does the bacterial load and bioburden increase, but also the now-dead bone creates a necrotic, anaerobic milieu, harboring further growth of pathogens and opportunistic bacteria alike. This devitalized environment further leads to functional death and destruction of the bone over time. Oftentimes, antibiotics in isolation are challenged to penetrate these areas of dead bone and possible fluid collections well.^1,3,4

As such, surgical debridement and resection of the diseased bone is often required to reduce the bioburden and allow for improved antibiotic penetration. An oncologic-type resection of affected bone is favored in order to reduce the number of bacteria-containing osteoblasts, although sometimes this may be limited due to functional and biomechanical needs of the patient. In cases where retained orthopedic hardware or implants are involved, surgical intervention is required to remove the implant at a minimum.

There are multiple other benefits to surgical intervention, including the ability to obtain accurate deep tissue and bone culture data, deliver local antibiotic therapy to the site via the use of antibiotic powders, antibiotic-containing beads or cement spacers, and in certain cases, address the biomechanical cause of ulceration concomitantly. Following this surgical intervention, the patient may then be managed by targeted antimicrobial therapy as a secondary supportive therapy.

What the Literature Says About Antimicrobial Therapy

Although the literature does support a prolonged course of antimicrobial therapy for medical management of osteomyelitis, the evidence also suggests this is best used not in isolation, but rather when in conjunction with surgical management as well.^1,3,5,6 Nonsurgical management with a 3–6 month course of antibiotics has a reported clinical success rate of 65–80%, although the severity of osteomyelitis is not well-defined in this literature.⁷

This prolonged course of systemic antimicrobial therapy, however, is not without risk, and the physician must perform a risk/benefit analysis specific to each patient.

Further, many of these patients suffer significant medical comorbidities to include renal disease, vascular disease, and repeat previous antibiotic exposure, bringing concerns for nephrotoxicity, bioavailability, and resistance to the forefront of the physician’s mind.

Farhad and colleagues investigated a 6-week course of targeted antibiotic therapy, reporting a 91.5% success rate.⁵ It should be noted, however, that 68% of this patient cohort required management with surgical intervention as well.

Most recently, in 2021, Tardaguila-Garcia and colleagues performed a systematic review of medical versus surgical management of diabetic foot osteomyelitis, reviewing 308 patients across 6 randomized clinical trials.⁶ Three of the 6 reviewed studies reported higher rates of reinfection, amputation, and death rates in antibiotic-only treatment groups as compared to those managed with a combination medical and surgical approach.^6,8-10 This led the authors to conclude that timely containment of infection with effective surgical debridement is paramount in the management of osteomyelitis.⁶ This is further supported by the findings of Henke and colleagues, who noted that aggressive surgical debridement or digital amputation was shown to improve wound healing and limb salvage, whereas the use of antibiotic therapy alone was associated with decreased rates of wound healing and limb salvage across data review of 51,000 patients.¹¹

In Conclusion

Human osteomyelitis has been documented in history since the era of Hippocrates, in 460–370 BCE.³ The discovery of penicillin and the dawn of antimicrobial therapy, however, was not until the 1940s. Throughout this time, osteomyelitis was historically managed with surgical debridement, saucerization, and wound packing followed by healing via secondary intention.³

Today, surgical management remains a mainstay in the management of osteomyelitis, supported by antimicrobial therapy as a secondary supportive therapy. The ideal treatment would eradicate the infection in an inexpensive, highly successful manner with low toxicity and morbidity to the patient. Although surgical management is not without its risks and does not necessarily meet all these criteria, surgical management allows for an overall quicker treatment duration requiring shorter courses of antibiotics and hospital stays, while allowing for removal of pathologic forces and an increased chance to prevent recurrence. As such, surgical management has historically been, and remains today, a cornerstone in the management of osteomyelitis.

Dr. Ravine is a Clinical Fellow in Surgery at Harvard University.

Dr. Theodoulou is the Chief of the Division of Podiatric Surgery, Cambridge Health Alliance, and Assistant Professor of Surgery at Harvard Medical School. He is the Section Editor of the Journal of Foot and Ankle Surgery. Dr. Theodoulou is also the President of the Northeast Region American College of Foot and Ankle Surgeons and the Past President of the Massachusetts Foot and Ankle Society.

References
1.     Momodu II, Savaliya V. Osteomyelitis. [Updated 2022 May 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from https://www.ncbi.nlm.nih.gov/books/NBK532250.
2.    Hudson MC, Ramp WK, Franenburg KP. Staphylococcus aureus adhesion to bone matrix and bone-associated biomaterials. FEMS Microbiol Lett. 1999;173:279-284.
3.    Schmitt SK. Osteomyelitis. Infect Dis Clin North Am. 2017;31(2);325-338.
4.    Lew DP, Waldvoge, FA. Osteomyelitis. N Engl J Med. 1997;336(14):999-1007.
5.    Farhad R, Roger PM, Albert C, et al. Six weeks antibiotic therapy for all bone infections: results of a cohort study. Eur J Clin Microbiol Infect Dis. 2010;29:217-222.
6.    Tardáguila-García A, Sanz-Corbalán I, García-Alamino JM, Ahluwaila R, Uccioli L, Lázaro-Martínez JL. Medical versus surgical treatment for the management of diabetic foot osteomyelitis: a systematic review. J Clin Med. 2021;10(6):1237.
7.    Lipsky BA, Berendt AR, Cornea PB, et al. 2012 Infectious Disease Society of America Clinical Practice Guidelines for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis. 2012;54(12):132-173.
8.    Lazaro-Martinez JL, Aragon-Sanchez J, Garcia-Morales E. Antibiotic versus conservative surgery for treating diabetic foot osteomyelitis: A randomized comparative trial. Diabetes Care. 2014;37(3):789-795.
9.    Lauf L, Ozsvár Z, Mitha I, et al. Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis. Diagn Microbiol Infect Dis. 2014;78(4):469–480.
10.    Tone A, Nguyen S, Devemy F, et al. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: A multicenter open-label controlled randomized study. Diabetes Care. 2015;38(2):302–307.
11.    Henke PK, Blackburn SA, Wainess RW, et al. Osteomyelitis of the foot and toe in adults is a surgical disease. Ann Surg. 2005;241(6):885-894.

No. Citing her success with medical therapy including intravenous antibiotics and aggressive wound care, this author supports surgical treatment for osteomyelitis more for patients do not respond to antibiotics.

By Holly Spohn-Gross, DPM; and Harsh Varshney, BS

Osteomyelitis is a bacterial or fungal infection involving bone and/or bone marrow. Historically, surgeons have been taught that the only way to successfully treat a bone infection was to surgically remove all the infected bone. However, there is a growing body of work that demonstrates success with the medical treatment of osteomyelitis. In my experience, it is critical to exhaust medical therapy first.

I became an advocate for nonsurgical treatment of osteomyelitis after practicing in a rural community for over 22 years. Although I was trained to surgically debride and remove all necrotic and dead bone and tissue, I learned that you do not always need to resort to surgery, at least not as the first line of treatment. As a result, I typically use intravenous antibiotics, aggressive wound care, and close evaluation as a first line approach, and have been satisfied by the outcomes.

Over the years, I found myself with limited or no other options and had to rely heavily on antibiotic therapy alone. These limitations included severe constraints on OR time and staff, no available subspeciality vascular or infectious disease and patients’ unwillingness to seek higher level of care. In addition, the patient’s comorbidities, including vascular and nutritional status, as well as abject poverty made the surgical option less acceptable. To my initial surprise I discovered that this nonsurgical approach successfully eradicated the infection most of the time in these patients.

Insights on the Origin and Staging of Osteomyelitis

Osteomyelitis may be acute or chronic and can result from contiguous or hematogenous spread of infection, or by direct inoculation through an open wound such as a fracture or following surgery. Of the various bacterial pathogens that cause infection in osteomyelitis, Staphylococcus aureus is the most common, with other common pathogens dependent on patient demographics, including Streptococcus pyogenes and Pseudomonas aeruginosa, and in patients with hemoglobinopathies, Salmonella species. Additional pathogens commonly found in patients with chronic osteomyelitis include Staphylococcus epidermidis, Serratia marcescens, and Escherichia coli.¹

Classification of osteomyelitis is most commonly based on the Cierny-Mader staging system, although the Waldvogel system has been historically used.

Cierny-Mader staging system. A four stage system (I-IV) classified primarily by portion of bone affected, and secondarily by the presence or absence of systemic or compromising host factors.  

Waldvogel classification system. Based on pathogenesis, and classified as acute or chronic, whether hematogenous (originating from bacteremia) or contiguous (originating from an infection in a nearby tissue), and on the basis of vascular insufficiency. Diagnosis depends upon combined factors: clinical examination, laboratory tests, bacteriological tests, and radiographic imaging. Management consists of evaluation of the patient, determination of the stage of osteomyelitis, identification of the causative organism and its susceptibility to antimicrobial therapy, and, if required, debridement, dead-space management, and stabilization of bone.¹

Literature and Anecdotal Evidence on Medical Treatment of Osteomyelitis

Although in my observation, many surgeons learned the only successful treatment for a bone infection was to surgically remove all the infected bone, there is a growing body of work that demonstrates success with the medical treatment of osteomyelitis.²

Contrasting examples:

1) A 72-year-old female with type 2 non-insulin diabetes, neuropathy, and peripheral arterial disease developed a nonhealing ulcer on her second digit, which quickly progressed to osteomyelitis involving the second metatarsophalangeal joint. Traditional management would suggest that she undergo surgical intervention, but the patient refused admission into the hospital. I had to resort to a combination of oral and IV antibiotics and office wound care, which resulted in complete remission. This treatment exceeded my expectations and personally changed my practice.

2) A 43-year-old male with diabetes, using insulin, who was the primary income earner, lost his job during the COVID-19 pandemic and was forced to take employment as a food delivery driver. He developed an ulcer under his first metatarsal that became infected. He went to the emergency room and was sent to a surgeon where he underwent a first ray amputation due to osteomyelitis of the medial sesamoid. Subsequently, he is only able to partially bear weight and can no longer perform his job. This outcome reinforced my belief that medical treatment might have resulted in a different, if not better, outcome.

I am certainly not suggesting that surgical options are not necessary. My assertion is that we exhaust all medical therapy first before moving on to surgery. I notice that there is a growing trend for nonsurgical management of diabetic foot osteomyelitis, which has resulted in good results in remission from infection, with rates being higher than 60% in patients managed exclusively with antibiotic therapy.

The published literature is, however, limited to retrospective studies, and in certain selected cases, surgery is essential, for instance, where there is bone exposure and/or severe bone destruction, and/or patients with antibiotic resistance or medical treatment failure. One of the major benefits of medical therapy is that it can maintain the biomechanical function of the foot. Amputation of all or part of the foot can create alterations to foot architecture and potentially compensatory deformities that increase the risk of reulceration and infection.

Specifically, when patients are seen in the ER with an acute infection in the foot, diagnosed with osteomyelitis, and then immediately brought to the OR for removal of bone and all necrotic tissue, they could be left with a nonfunctioning foot or limb. An alternative might be to consider IV antibiotics first.

Venkatesan and colleagues did a retrospective study over a 10-year period measuring the outcomes in patients with diabetes with osteomyelitis having undergone oral antimicrobial therapy.³ Twenty-two patients were identified as meeting the criteria for osteomyelitis based on clinical and radiological exam. Seventeen of these patients were admitted to the hospital, of whom 10 received intravenous antibiotics.³ The most prominent identified agent in these patients was Staphylococcus aureus. Furthermore, in regard to treatment, clindamycin was the preliminary choice as an oral agent and metronidazole was the choice for intravenous regimen. The total duration of all antibiotic treatment was 12 weeks (range 5–72 weeks). Remission was seen in 16 patients based on clinical signs and radiographic resolution.³

Another retrospective study by Game and colleagues examined the outcomes in patients’ treatment with an antibiotic regimen in the setting of osteomyelitis complicating a diabetic foot ulcer.⁴ There was a total of 147 patients included in the study, of whom 113 were managed solely via nonsurgical measures. Of note, 121 (82%) patients were prescribed an oral regimen while 26 (18%) were admitted and started on intravenous antibiotic administration. There were 34 patients in whom nonsurgical management did not suffice and a surgical procedure was warranted. Of the 113 remaining patients, 66 (58.4%) of patient achieved remission while 35 (31%) had a relapse. Of the relapse group, 27 (77%) achieved remission with an additional course of antibiotics. In total, of the 113 patients who underwent nonsurgical management alone, 93 (82.3%) achieved total remission. The initial choice of oral therapy was amoxicillin/clavulanic acid or clindamycin combined with a quinolone. Those patients who underwent a second round of antibiotic treatment received an additional dose of either fusidic acid, doxycycline, or trimethoprim.

Final Words

Both my personal experience as well as the studies presented demonstrate that antibiotic regimen alone can provide remission for osteomyelitis in patients with diabetes. I suggest that the surgical management of osteomyelitis should be reserved for those patients who do not respond to treatment with an antibiotic regimen, or for whom nonsurgical options are contraindicated.

Dr. Spohn-Gross is in practice at the Sienna Wellness Institute in Lake Isabella, CA.

Student Doctor Varney is a fourth-year student at Western University of Health Sciences College of Podiatric Medicine.
 
References

1.    Lew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004 Jul 24-30;364(9431):369-79.
2.    Tardáguila-García A, Sanz-Corbalán I, GarcíaAlamino JM, Ahluwalia R, Uccioli L, Lázaro-Martínez JL. Medical versus surgical treatment for the management of diabetic foot osteomyelitis: a systematic review. J Clin Med. 2021 Mar; 10(6):1237.
3.    Venkatesan P, Macfarlane RM, Fletcher EM, Finch RG, Jeffcoat WJ. Conservative management of osteomyelitis in the feet of diabetic patients. Diabet Med. 1997;14(6):487-490.
4.    Game FL, Jeffcoate WJ. Primarily non-surgical management of osteomyelitis to the foot in diabetes. Diabetologia. 2008;51:962-967.
5.    Truong DH, Bedimo R, Malone M, et al, Meta-analysis: outcomes of surgical and medical management of diabetic foot osteomyelitis. Open Forum Infect Dis. 2022; 9(9):ofac407.