J Bone Jt Infect 2020; 5(4):198-204. doi:10.7150/jbji.45338
Surgical techniques for Bone Biopsy in Diabetic Foot Infection, and association between results and treatment duration
, Joulie Donatienne2,3, Blondiaux Nicolas2,4, Robineau Olivier1,2
1. Infectious Diseases Department Gustave Dron Hospital F-59200 Tourcoing, and Lille University F-59000, Lille, France.
2. Northern-West French National Referent Centre for Complex Bone and Joint Infections (CRIOAC Lille-Tourcoing).
3. Orthopaedic Surgery Department G. Dron Hospital Tourcoing F-59200 Tourcoing France.
4. Microbiology Laboratory G. Dron Hospital Tourcoing F-59200 Tourcoing France.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Eric S, Donatienne J, Nicolas B, Olivier R. Surgical techniques for Bone Biopsy in Diabetic Foot Infection, and association between results and treatment duration. J Bone Jt Infect 2020; 5(4):198-204. doi:10.7150/jbji.45338. Available from http://www.jbji.net/v05p0198.htm
Click on Go to download the file. In EndNote Library, go to File – Import. Select the file that you have just downloaded and select import option Reference Manager (RIS). Click on Import. File import instruction
Surgery is an important part of the management of patients diagnosed with DFO. It consists in some selected patients, to remove all or part of the infected bone(s) or even to amputate all or part of the foot. Despite the use of sophisticated imaging techniques, it is however difficult to remove all the infected tissue while respecting the principles of an economical surgery. Bone biopsy performed at the margins of the resection permits to identify residual osteomyelitis and to adjust the post-surgical antibiotic treatment. Some recent studies have reported the way to perform bone margin biopsies and have assessed the impact of the bone results on the patient's outcome. However, the real impact of a residual osteomyelitis on the risk of recurrent DFO is still debated and questions regarding the interpretation of the results remain to be solved. Similarly, the consequences in terms of choice and duration of the antimicrobial treatment to use in case of positive bone margin are not clearly established.
Keywords: diabetic foot osteomyelitis, bone margins biopsy, outcome, antibiotic therapy, surgery
Osteoarticular infections occur in 20 to 60% of diabetic foot infections and profoundly worsen the outcome of the patients [ 1 ]. Removal of infected bones has a major place in the management of diabetic foot osteomyelitis (DFO) and has been considered until recently as the unique therapeutic approach [ 2 ]. Some authors, however, recently reported the results of clinical studies suggesting that a medical approach (i.e., without bone resection) could arrest the infection [ 3 ]. Experience from different teams showed that this medical approach only applies to some selected patients and that surgery is still proposed to most patients with DFO [ 1 , 2 ]. Surgical management of DFO has the advantage over the medical approach that the removed infected bones do not need any treatment, and this is of importance given the difficulties in obtaining the sterilisation even a stabilisation of the bone infection. Indeed, DFO associates some risk factors for bad outcome such as the frequent peripheral artery disease, impaired of phagocytic functions and the presence of peripheral neuropathy which participates in delaying the wound healing.
The main limitation of the surgical part of the treatment of DFO is the uncertainty about the persistence of residual osteomyelitis following bone resection. Indeed, if all the infected bone tissues have been removed, the infection is no longer an osteomyelitis (or an osteitis) and can therefore be treated as a soft tissue infection (except periarticular structures such as tendons and ligaments). This is of importance since the prognosis of non-bone infections is better and the antibiotic therapy is easier regarding the choice of the antibiotic regimens and their duration than that of DFO [ 3 ].
The aim of the present narrative literature review is to provide readers with up-to-date knowledge on the different surgical approaches for DFO and the consequences of bone examination results (i.e., histology and culture) in terms of antibiotic treatment. The summary of the recommendations/current state of knowledge regarding surgical bone biopsy in patients treated for DFO is presented in Table 1 .
Surgical treatment of DFO
Surgical removal of the entire infected bone has been considered in the past and even recently as the standard treatment [ 2 ] in patients with DFO because of the poor results obtained by antibiotics alone in these settings. Despite long standing discussions, surgery remains necessary in many (but not all) diabetic foot infections involving bone and joint structures [ 1 , 2 ]. One must however keep in mind that the story does not end as soon as the operative wound is closed. Indeed, the surgical resection of the infected bone tissues cannot remove all the bacteria involved in most of the cases. This means that the surgical management of DFO necessarily includes an antibiotic therapy the choice and the duration of which will be determined by the culture results of the intraoperative samples. In other words, surgery and medical parts of the management of DFO are linked by the results of bone specimen examination. This is true even in case of major amputations since several studies have shown that bone biopsies of the margins of the amputation are positive in a non-neglectable proportion of cases [ 4 , 5 ].
Surgery is the unique means to drastically reduce the amounts of bacteria present in bones and sometimes in contiguous tissues (e.g., in case of an abscess). Surgery consists in these settings in draining pus and removing economically all necrotic tissues [ 6 ]. It can also remove necrotic tissues which antibiotics cannot reach or treat efficiently. Surgery is helpful to remove bacteria in biofilm, which is an important limitation for the antibiotic therapy to be effective. This type of surgery also needs to consider (i) if the coverage of the dehiscence due to resection is feasible, (ii) what is the best level of amputation and (iii) the vascular status of the limb. Given the usual complexity of surgery in these settings, only the most interested and experienced surgeons should be involved [ 6 ].
Should bone biopsy be performed in every patient with a (suspected) DFO?
It is useful to obtain a bone specimen in almost all cases of (suspected) DFO
However, bone biopsy is not always feasible due to lack of time and experience
Bone biopsy seems most important to perform in case of difficulties in identifying the causative pathogen(s) or its (their) antibiotic susceptibility
Bone biopsy may not be needed if a deep tissue specimen grows a single virulent pathogen, especially S. aureus.
Should culture and histology be systematically performed on bone samples?
The diagnosis of DFO is established when one or more bone specimens has both a positive culture and characteristic histopathological findings.
Culture provides useful data for guiding the choice of the antibiotic treatment
Histology is useful in patients on antibiotic therapy because of the risk of false negative culture
In case of limited amount of bone material, it is better to only consider culture than histology as both seem to perform equally in terms of diagnosis accuracy.
Should bone biopsy be performed on each stump in case of a conservative surgery (i.e., joint resection)?
Since the infectious process is likely to have spread towards both distal and proximal direction from the resected bone, performing a biopsy on both stumps seems appropriate.
In case of exarticulation, should the cartilage be removed?
The avascular cartilage material is less able to defend itself against the pathogens (especially S. aureus) and should be removed in case of exarticulation.
What is the optimal duration of the antibiotic therapy in case of positive bone margin culture in case of conservative surgery or amputation?
3-week duration seems enough in these situations
1 to 2-week duration should be enough for patients in whom all infected bone has been resected.
Are rifampicin combinations recommended in patients with a bone margin biopsy positive in culture for Staphylococcus sp.?
In case of conservative surgery or amputation, the presence of biofilm in residual bone tissues is unlikely and therefore is not in favour of the use of rifampicin combinations
Other antibiotics with high bone diffusion can be used such as clindamycin, tetracyclines, fluoroquinolones (in combination), cotrimoxazole, linezolid, fusidic acid (in combination)
What are the histology criteria for the presence of acute or chronic osteomyelitis?
Acute osteomyelitis is defined by necrosis, destroyed bone and infiltration of polymorphonuclear granulocytes usually associated with congestion or thrombosis of medullary or periosteal small vessels.
Chronic osteomyelitis is characterized by destroyed bone and infiltration of lymphocytes, histiocytes and/or plasmatic cells
In all cases of osteomyelitis, areas of fibrosis are described in variable forms as well as medullar edema.
The IWGDF guidance on diabetic foot infection proposes to favour a surgical approach of DFO in case of systemic signs of infection, substantial cortical destruction, osteolysis, macroscopic bone fragmentation (sequestration), an exposed bone within a forefoot ulcer, open or infected joint space and when the patient has prosthetic heart valves [ 1 ]. Importantly, while surgery may be urgently needed in severe soft-tissue infections, osteomyelitis of the diabetic foot is not a reason for either urgent bone resection or amputation. The usual origin of severe and acute complications of DFIs (i.e., gangrene, septicaemia, and septic shock) is soft-tissue infections rather than osteomyelitis. In order to limit the foot biomechanical consequences of aggressive surgical approaches, some teams have proposed the concept of conservative surgery which consists of a bone resection limited to the infected tissues [ 7 - 9 ]. In case of metatarsophalangeal advanced destruction, a resection of the joint is performed without amputation of the whole ray. By keeping the toe in place, it is expected that the adjacent toes are less likely to be deformed due to the dead space created by the missing toe. In addition, this surgery permits to remove the cause of the ulcer at the origin of the soft tissue infection and its spread to the underlying osteo-articular structures. Ha Van et al. showed that limited resection (i.e., “conservative surgery”) of the infected phalanx or metatarsal bone under the wound, together with removal of the ulcer site, was effective to obtain complete wound healing [ 7 ]. Aragon-Sanchez et al. reported a consecutive series of 185 diabetic patients with osteomyelitis of the foot and histopathological confirmation of bone involvement, all treated surgically, including 91 conservative surgical procedures [ 10 ]. Conservative surgery was successful in almost half of the cases and risk factors for failure were exposed bone, the presence of ischemia and necrotizing soft tissue infection [ 10 ].
Conservative surgery does not entirely the risk of transfer syndrome as shown by Aragon-Sanchez et al. who reported new episodes of osteomyelitis in 16.9% of the patients [ 9 ].
Bone margin biopsy in patients operated for DFO
Relapsing osteomyelitis episodes observed in patients operated for a DFO are not univocal. The new osteomyelitis may be in relation with a new episode of infection of the initial foot ulcer or at the adjacent rays in relation with the transfer syndrome. Another cause may be the absence of sterilization of the initial infected site although remission of DFO can be obtained despite the complete excision of the infected bone. The rate of remission may however be lower when there is a residual bone infection [ 11 ]. It seems therefore important to determine whether there is a persistent osteomeylitis following surgery and if additional antibiotic therapy is needed. The use of bone margin biopsy during bone resection or amputation in patients operated for DFO has been reported by some authors. Kowalski et al. studied the rate of residual osteomyelitis in patients who underwent surgery for the treatment of DFO [ 12 ]. They noted that 35.1% of patients had positive culture of the samples taken at bone margins which correlated with partial metatarsal amputations. They found no differences between patients with negative versus positive histopathologic margins in the primary outcome of definite failure which was defined as an infection relapse at the proximal amputation site. Patients with a positive bone margin were found to have a higher risk of re-amputation [ 12 ]. Atway et al. reviewed the medical charts of 27 out of 184 diabetic patients who had undergone toe, partial metatarsal, or transmetatarsal amputation [ 13 ]. To be included in their study, a bone sample had to be taken at the level proximal to the metatarsal amputation or disarticulation at the metatarsophalangeal joint in a standardized fashion, and the amputation had to be primarily closed. The diagnosis of DFO was based on standard imaging modalities, including plain X-rays, magnetic resonance imaging, and/or nuclear bone scan. Based on bone margins culture, DFO was diagnosed in 11 patients (40.7%) including 23.1% (3/13) in patients who underwent toe amputation and 57.1% (8/14) in patients who underwent partial metatarsal or trans-metatarsal amputation (p=0.12). Almost half of the patients had a poor outcome (13/27, 48.2%). Failure was more frequent in patients with positive versus negative culture of the bone margin biopsy (81.8% (9/11) versus 25% (4/16), respectively p=0.0063) [ 15 ]. Fuji et al. reported a series of 28 patients with DFO who were operated with examination of the proximal margins of resected bones with histopathology to ascertain whether osteomyelitis was completely resected [ 14 ]. Complete healing rate of the foot wound was 100% in the non-ischemic patients with negative bone margin cultures versus 84.6% in the ischemic patients [ 14 ]. Patients with positive bone margins had significantly more elevated CRP values in the pre and post-operative periods and a higher chance to be re-operated (100% versus 15.1%; p