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Abstract

Purpose

Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures; they remain a significant clinical challenge. Here, we aimed to investigate the viability of focusing on soft-tissue management in patients suspected of chronic FRI, who exhibit no significant bony uptake on bone single photon emission computed tomography (SPECT)/computed tomography (CT) scans.

Methods

Between January 2016 and January 2022, we managed 25 patients with chronic FRI or post-traumatic osteomyelitis using technetium 99m-methyl diphosphonate bone SPECT/CT to assess infection depth. Among them, 13 patients showing negligible bony uptake were included and categorized into two groups based on wound discharge reaching the bone/implant (Criteria 1, n = 6) or not (Criteria 2, n = 7).

Results

Patients in the Criteria 1 group were treated with antibiotics and soft tissue debridement without bony procedure. The average duration of antibiotic therapy was 6.7 weeks. Treatments were individualized, including implant changes, local flaps, skin grafts, and negative pressure wound therapy. No recurrence was reported in the mean follow-up of 21.3 months. Patients in the Criteria 2 group were treated with oral antibiotics (mean duration: 5.9 weeks) and daily wound dressings. No recurrence was reported in the mean follow-up of 26.0 months, and no surgical interventions were required.

Conclusion

This study demonstrates the feasibility of focusing on soft-tissue management in patients with chronic FRI showing minimal bony uptake on bone SPECT/CT. Our treatment protocol avoided unnecessary surgical bone procedures, resulting in successful clinical outcomes with no recurrences.

Keywords

Introduction

Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures, including those occurring around implants, in post-healing hematogenous infections, and in those without internal fixation.¹ Despite preventive measures, FRIs remain a significant clinical challenge, affecting 1–30% of patients with orthopedic trauma.² Management of such infections often necessitate extensive treatment, including prolonged antibiotic use, multiple surgeries (e.g., reconstructive procedures), and potential limb amputation in severe cases.²

Accurate diagnosis and appropriate interventions are crucial for effective FRI treatment.² While treatment strategies are relatively straightforward in cases with clear signs of deep infection, ambiguity regarding the presence or extent of the infection poses a significant challenge.¹ This is especially apparent given the limited accuracy of traditional imaging techniques, including radiography, computed tomography (CT), and magnetic resonance imaging (MRI), by the presence of metal hardware or surgical alterations.^1,3

Recent advancements in nuclear imaging, particularly single photon emission computed tomography (SPECT)/CT with a hybrid camera system, have greatly improved the ability to differentiate between infected and non-infected tissues, allowing better anatomical detail and diagnostic accuracy.^4–6 Bone SPECT/CT, a specialized nuclear medicine imaging technique, has proven valuable for its effectiveness in the diagnosis and management of post-traumatic osteomyelitis (PTO).^3,4,7 Previous studies have documented its utility in identifying the presence and extent of bone infection.^8–11 Particularly, Arican et al. highlighted its high sensitivity, specificity, and predictive values in diagnosing bone infections.¹²

In our practice, bone SPECT/CT has been instrumental in evaluating patients suspected of FRI and guiding the design of treatment plans. For patients with definitive bony uptake indicating bone infection, targeted treatment plans with successful clinical outcomes have been developed.⁴ Conversely, in cases where bone SPECT/CT does not show definitive bone uptake, we prioritized the management of the soft tissues with customized treatment strategies. This study aimed to evaluate the effectiveness of focusing on soft-tissue management in patients suspected with FRI but exhibiting minimal or no bony uptake on bone SPECT/CT by analyzing clinical outcomes.

Materials and methods

Patient characteristics and study design

This retrospective case series was approved by our institutional review board and adhered to all relevant guidelines and regulations. Between January 2016 and January 2022, we managed 25 patients diagnosed with chronic FRIs based on clinical history (e.g., previous open fracture, surgical interventions) and specific diagnostic criteria.¹ The criteria included confirmatory signs of FRI, such as wound breakdown reaching the bone/implant or the presence of at least three out of the five suggestive criteria¹: clinical symptoms (local and systemic), radiologic evidence (radiography and/or MRI findings), new joint effusion, elevated serum inflammatory markers, and persistent wound discharge.¹

To determine the depth of infection, all patients underwent bone planar scintigraphy followed by bone SPECT/CT 2–4 h after technetium 99m-methyl diphosphonate injection. Among them, 13 patients with minimal or no bony uptake in the suspected area were included in this study (6 male and 7 female patients; average age, 56.0 years; range, 20–89 years). The remaining 12 patients with significant bony uptake on bone SPECT/CT were treated accordingly. Some of the clinical outcomes for these patients have been previously reported.⁴

Treatment strategies and evaluation of clinical outcome

Given the significant lack of bony uptake on the bone SPECT/CT of the included patients, we inferred the absence of deep bone infections and tailored our treatment strategies accordingly.

Patients were categorized into two distinct groups based on the specific criteria for management. The Criteria 1 group encompassed patients exhibiting wound breakdown reaching the bone/implant, which is a confirmatory sign of FRI. These patients underwent antibiotic treatment, implant removal or replacement (as necessary), and soft tissue coverage procedures. Meanwhile, the Criteria 2 group encompassed patients with wound problems that did not reach the bone/implant. These patients received oral antibiotics and appropriate wound dressing. The choice of antibiotics for both groups was based on the recommendations of our hospital’s infection specialists. Patient demographics are presented in Table 1, and treatment protocols are illustrated in Figure 1.

Table 1.

Characteristic of patients according to the criteria.

Case no.	Age	Sex	Site	Brief history	Previous treatment	Onset (MA)
Criteria 1
1	84	F	Wrist	FRI after open fracture (4MA)	Implant removal (ulna) and debridement	3
2	65	M	Lower leg	Open fracture (4 YA)	CRIF with IM nail	3
3	20	M	Ankle	Open fracture (4 MA)	ORIF with plate and screws, maintained implant	2
4	46	F	Ankle	FRI after open fracture (4 MA)	ORIF with plate and screw, multiple debridement, maintained implant	3
5	46	F	Lower leg	FRI after open fracture (5 YA)	Multiple debridement, flap, and skin grafting	1
6	89	M	Ankle	Open fracture (2 MA)	ORIF with plate and screws, maintained implant	1
Criteria 2
1	52	M	Lower leg	Open fracture (5YA)	ORIF with plate and screws, maintained implant	1
2	46	M	Lower leg	FRI after open fracture (2YA)	Infected bone resection and bone transport using the ilizarov frame	2
3	62	F	Thigh	Open fracture (5 YA)	ORIF with plate and screws, maintained implant	2
4	62	F	Ankle	Open fracture (2 YA)	ORIF with screws, maintained implant	1
5	40	M	Ankle	Open fracture (1 YA)	ORIF with plate and screws, maintained implant	1
6	56	F	Lower leg	Open fracture (5YA)	ORIF and implant removal	1
7	60	F	Lower leg	FRI after open fracture (4YA)	Multiple debridement, flap, and skin grafting	1

FRI; fracture-related infection, CRIF: closed reduction and internal fixation, ORIF: open reduction and internal fixation, YA: years ago, MA: month(s) ago, M: male, F: female.

Figure 1.

Treatment algorithm based on bone SPECT/CT. FRI, fracture-related infection; PTO, post-traumatic osteomyelitis; SPECT, single photon emission computed tomography

The effectiveness of the treatment was evaluated based on several key criteria⁴: (1) alleviation of pain and other symptoms, (2) normalization of blood parameters (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] level), (3) improvement and normalization of wound status or soft tissue conditions, and (4) ability to resume normal daily activities without infection recurrence during the minimal observation period of 1 year.

Results

Outcomes for criteria 1 patients

A total of six patients were placed in the Criteria 1 group, comprising three male and three female patients, with a mean age of 58.6 years (range, 20–89 years). They were treated with soft tissue debridement without bony procedure, and with intravenous antibiotic therapy, with additional oral antibiotics as recommended by an infection specialist. The average antibiotic duration was approximately 6.7 weeks (range, 6–8 weeks). Pathogens identified in four patients included Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus dysgalactiae, and Enterococcus faecalis. Treatments included one case of implant change and primary closure, three of local flap and skin grafting, and two of implant removal and local flap and skin grafting with negative pressure wound therapy. The average hospital stay was 4.8 weeks (range, 3–6 weeks). All patients achieved successful clinical outcomes without recurrence at a mean follow-up of 21.3 months (range, 13–30 months).

Outcomes for criteria 2 patients

A total of seven patients were placed in the Criteria 2 group, comprising three male and four female patients, with a mean age of 54.0 years (range, 40–62 years). They were treated with oral antibiotic therapy and regular wound dressing. The pathogen was identified in only one patient (Serratia marcescens). The average oral antibiotic duration was 5.9 weeks (range, 5–7 weeks), and none of them required hospitalization or surgical intervention. All patients achieved successful clinical outcomes without recurrence at a mean follow-up of 26.0 months (range, 12–60 months).

Case description

Case No. 1 (criteria 1)

An 84-year-old female patient presented with complications following open reduction and internal fixation for open distal radius and ulnar fractures 4 months prior in another hospital (Figure 2(a) and (b)). Approximately 2 weeks post-operatively, wound dehiscence and pus drainage were noted on the ulnar side. Subsequent debridement and removal of the ulnar hook plate were performed to control the infection. However, despite 1 month of intravenous and oral antibiotics with daily wound dressing, persistent wound discharge and metal failure were observed (Figure 2(c) and (d)). Given the suspicion for PTO at the distal radius and ulna, the patient was referred to our hospital. On admission, we conducted a wrist MRI, bone scan, and bone SPECT/CT to evaluate the extent of infection. MRI findings revealed fluid collection and bone marrow signal abnormalities at the non-union sites, indicative of osteomyelitis. The bone scan supported this diagnosis, showing increased uptake in the same suspected areas (Figure 2(g)). In contrast, bone SPECT/CT showed no significant bony uptake in the suspected areas, except for a mild increase in uptake (greenish color) around the loosened screw (Figure 2(h) and (i)). This uptake was assessed as a reactive change due to screw-loosening rather than infection, according to our nuclear medicine specialist. Given these findings, we concluded that soft tissue infection and mechanical instability were the primary issues, excluding the diagnosis of a bone infection. Accordingly, we performed soft tissue debridement and fixation using a longer locking plate to enhance stability (Figure 2(j)). Intra-operatively, gross inspection confirmed infection localized to the soft tissues, without any signs of bone infection and non-union. Wound healing was achieved 2 weeks post-operatively, and no signs of infection recurrence were noted. Bony union was achieved 3 months post-operatively, and assessment at 18 months post-operatively demonstrated successful clinical outcomes without infection recurrence (Figure 2(k) and (l)).

Figure 2.

An 84-year-old female with chronic FRI after an operative management for open distal radius and ulnar fractures. (a and b) Initial radiography after open reduction and internal fixation for the open distal radius and ulnar fractures. (c and d) Persistent wound discharge and metal failure at the distal radius despite 1 month of treatment including multiple debridement, metal removal, and antibiotics. (e and f) MRI shows fluid collection and bone marrow signal abnormalities at nonunion sites, suggestive of osteomyelitis. (g). Bone scan indicates increased uptake in the areas corresponding to MRI findings. (h and i) Bone SPECT/CT scans show no significant bony uptake in suspected areas of osteomyelitis, as well as mild uptake near the loosened screw, which is interpreted as a reactive change. (j). Postoperative image after soft tissue debridement and fixation using a longer locking plate. (k and l). Plain radiography at 18 months post-treatment demonstrating no infection recurrence and successful bony union. FRI, fracture-related infection; MRI, magnetic resonance imaging; SPECT, single photon emission computed tomography.

Case No. 2 (criteria 1)

A 65-year-old male patient with a 2-year history of an open wound exposing the tibial bone presented with complaints of aggravated pain, redness, and a 3-month history of wound discharge with elevated ESR and CRP levels, all of which were suggestive of chronic FRI. Approximately 4 years prior, the patient underwent intra-medullary nail fixation for an open tibial fracture in another hospital. At 2 years post-operatively, he developed FRI and underwent multiple surgeries without implant removal, but a soft tissue defect remained (Figure 3(a) and (b)). Although he was recommended to undergo flap surgery for the soft tissue defect, he opted for a management with self-dressing at home until recent signs of infection prompted him consult to our hospital (Figure 3(c)). Radiographic evaluation indicated the presence of a sinus tract and remnant wire, and bone scan showed increased uptake (Figure 3(a), (b), and (d)). However, bone SPECT/CT revealed only mild bony uptake (green and yellow color) in the suspected area, suggesting no bone involvement that required bony procedures (Figure 3(e)–(g)). Accordingly, we excised the exposed necrotic bone and removed the remnant wire while retaining the implant. Soft tissue coverage was then performed using local flap and skin grafting (Figure 3(h)). No micro-organisms were identified on wound culture, and empirical antibiotics were used for 6 weeks, as guided by our infection specialist. Follow-up at 14 months post-operatively showed that the patient was able to continue his normal daily activities without infection recurrence (Figure 3(i) and (j)).

Figure 3.

A 65-year-old male with a 2-year history of an open wound exposing the tibial bone. (a, b and c). Plain radiography and medical photos showing a persistent soft defect exposing the tibial bone with a retained tibial nail and suspicious sinus tract, all of which suggest chronic FRI involving the bone. (d). Bone scan shows increased uptake at the suspected area. (e, f and g). Bone SPECT/CT scans show only mild bony uptake (green and yellow colour) in the suspected area, suggesting that there is no active bone infection that required bony procedures. (f). Medical photo showing successful coverage of soft tissue defect and eradication of infection after partial excision of exposed necrotic bone and soft tissue coverage procedure through local flap and skin grafting. (i and j). Plain radiography at 14 months postoperatively. The patient is able to continue his normal daily activities without infection recurrence. FRI, fracture-related infection; SPECT, single photon emission computed tomography.

Case No. 7 (criteria 2)

A 60-year-old female patient presented to our hospital with tibial wound discharge, redness, and pain that started one month ago. She had a history of FRI 4 years ago due to an open fracture of the tibia and underwent multiple surgical treatments in another hospital. Following bone debridement and antibiotic treatment, her infection was resolved without any recurrence since then. On admission, discharge was noted from the scar of the previous surgery (Figure 4(a)). Elevated ESR and CRP levels and findings on radiography, MRI, and bone scan were all suggestive of chronic FRI with bone involvement (Figure 4(b)–(e)). However, since bone SPECT/CT revealed no significant uptake (Figure 4(f) and (g)), we determined the diagnosis to be a soft tissue infection. We instructed daily self-dressing, and prescribed oral antibiotics based on previous bacteriological results. Wound culture was negative, and wound discharge was resolved 1 month after. Follow-up at 39 months post-treatment showed that the patient was able to continue her normal daily activities without infection recurrence.

Figure 4.

A 60-year-old female patient with tibial wound discharge, redness, and pain that started 1 month ago. (a). Medical photo showing tibial wound discharge from the previous surgical site. (b, c, d, and e). A series of diagnostic images including plain radiography, MRI, and bone scans showing signs of chronic FRI and suggesting possible bone involvement. (f and g). Bone SPECT/CT scans reveal no significant bony uptake in the areas of concern, leading to a diagnosis of soft tissue infection.

Discussion

In this study, we evaluated patients with suspected chronic FRI presenting wound complications using bone SPECT/CT to determine the depth of infection and establish treatment plans. All patients in this study exhibited minimal or no bony uptake in the suspected areas, indicating that the infection had no bone involvement. Consequently, we addressed them as soft tissue infections, resulting in successful clinical outcomes with non-operative management or surgical treatment focusing on soft tissue problems.

FRI encompasses a wide range of infections affecting both the soft tissue and bone.¹ Although PTO falls within this spectrum, not every FRI can be considered as a PTO.¹³ FRI stratification involves various factors, including the causative organisms, depth of infection (superficial or. Deep), and chronicity.^2,14 Deep infections, or PTO are characterized by the infection of the fracture site, implant, or bone, whereas superficial infections are limited to the soft tissue.^2,14,15 However, accurately determining the depth of infection remains a challenge despite advancements in medical imaging.^14,15

In established chronic FRI with definitive deep infection, which is referred to as chronic osteomyelitis or PTO, evaluation should focus on assessing the extent of bone involvement for sufficient bone debridement and resection.^4,16–18 As these procedures can be as extensive and complex as those performed for malignant bone tumors, careful planning and evaluation are essential in cases where bone infections are uncertain. This is important to ensure that proper interventions are done and unnecessary bony procedures are avoided, as emphasized in our study.

Diverse radiologic tools have been utilized to evaluate the presence of infection, including radiography, CT, MRI, and nuclear imaging.^19,20 If the presence of the bone infection is suspected, advanced imaging techniques, such as MRI or nuclear imaging, are usually recommended.¹ While MRI is known for its high sensitivity in detecting acute osteomyelitis, it exhibits moderate specificity in chronic cases due to factors such as architectural bone distortion, intra-medullary signal changes from previous trauma or surgical interventions, and the presence of implants.¹⁹ On the contrary, nuclear imaging is recognized for its superior accuracy in distinguishing bone infections.^4,7 Indeed, the integration of nuclear imaging with SPECT/CT in hybrid camera systems has further enhanced diagnostic accuracy, providing clearer anatomical details and more precise localization.⁴

Several studies have reported the utility of bone SPECT/CT in the diagnosis and management of the chronic FRI by evaluating the presence and extent of bone infection.^4,5,8,12 In particular, Arican et al. reported its excellent sensitivity, specificity, and positive and negative predictive values of 100%, 95.4%, 97.6%, and 100%, respectively.¹² Overall, these studies collectively underscore its advantage of achieving actual anatomical localization, extension, and activity of infection, making it valuable for differentiating soft tissue and bone infections.^4,8,12

Our patients were suspected to have chronic FRI due to their presentation of wound complications, clinical findings that were consistent with the diagnostic criteria of FRI, and history of previous open fracture and/or surgery. As they were strongly suspected of having bone infection, we could consider aggressive surgical treatment. While achieving definitive results through aggressive treatment is important for suspected chronic FRI cases, we believe that it would be more beneficial if we could rule out bone infection with a more detailed evaluation and achieve satisfactory clinical outcome using less invasive treatments. Therefore, according to the suggested treatment protocol based on bone SPECT/CT (as illustrated in Figure 1), we treated these patients by focusing mainly on their soft tissue infections.

If we pursued an aggressive treatment plan for bone infection, differences would be made to the management of the aforementioned cases. For Case No. 2 in Criteria 1, we would perform tibial nail removal and subsequent segmental resection, followed by reconstructive procedures (e.g., bone transport and flap surgery). For Case No. 1 (Criteria 1), we would perform extensive bone debridement with insertion of antibiotic-impregnated cement beads, followed by bony union procedures after the infection is controlled. Similarly, for Case No. 6 (Criteria 2), tibial segmental resection followed by bone transport, flap surgery, or limb amputation may have been performed. However, we could achieve satisfactory outcomes using less invasive and simpler treatment without additional bony procedure in this study. Furthermore, we could shorten the required treatment period and achieve an earlier return to normal daily activities as compared to surgical management. Given our successful clinical outcomes over a follow-up period of more than 1 year, we believe that our treatment protocol based is a feasible approach for managing patients with suspected chronic FRI presenting with unclear bone infection.

The duration of infection is also an important indicator in determining the treatment strategy.^2,15,21 While initially limited to soft tissue infection, certain cases may progress to bone infection. However, classifying treatment strategies based on the duration of infection has been mostly based on empirical clinical outcomes from previous studies,^2,15,21 rather than objective and systematic evaluations. Surgical management of FRI typically focuses on two principal approaches: (1) debridement, antimicrobial therapy, and implant retention; and (2) debridement, antimicrobial therapy, and implant removal or exchange (particularly when the fracture has healed).² Bone SPECT/CT is known not only to provide information for determining the presence of bone infection, but also to offer insights regarding fracture consolidation and implant stability by revealing specific anatomical details critical in the context of bone infection, including the presence of sinus tracts, sequestra, and cloacae.⁴ Thus, bone SPECT/CT is expected to be valuable in determining the depth of infection and establishing suitable treatment plans for FRI.

Despite the insights offered by our study, several limitations should be acknowledged. First, the follow-up period was relatively short, which means the possibility of infection recurrence several years later cannot be entirely ruled out. However, infection control failure and re-emergence typically occur with 3 months after stopping antibiotics,²¹ and approximately 95% of recurrences occur within a year post-eradication.²² Second, the retrospective design and small number of patients limit the power of our study. Finally, because this study lacks a control group, it is difficult to quantitatively assess the effectiveness of our treatment protocol. Future studies involving larger patient cohorts, randomized controlled trials, and long-term follow-up are essential to validate and refine our findings, which will further increase our understanding and aid in the management of chronic FRI.

Conclusion

In conclusion, prioritizing soft-tissue management in patients suspected of chronic FRI but without significant uptake on bone SPECT/CT was shown to be a feasible approach. Using our suggested treatment protocol, we could avoid additional bony procedures and achieve successful clinical outcomes without recurrence.

Footnotes

Acknowledgements

We would like to thank Editage () for the English-language editing and reviewing of this manuscript.

Author contributions

All authors fulfill authorship requirements according to ICMJE. Each author contributed to the work as follows: Seung Hoo Lee, MD.: conception of the work, the acquisition, analysis and interpretation of data for the work, and drafting the work and revising it critically for important intellectual content, final approval of the version to be published, and agreement to be accountable of all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Min Bom Kim, MD., PhD: conception of the work, the acquisition, analysis and interpretation of data for the work, and drafting the work and revising it critically for important intellectual content, final approval of the version to be published, and agreement to be accountable of all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Yeong June Jeon, M.D.: the acquisition, analysis and interpretation of data for the work, and drafting the work and revising it critically for important intellectual content, final approval of the version to be published, and agreement to be accountable of all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical statement

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the images in all figures in the submitted manuscript.

ORCID iDs

Seung Hoo Lee

Min Bom Kim

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, MB Kim. The data are not publicly available due to information that could compromise the privacy of research participants.*

References

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Role of bone single photon emission computed tomography/computed tomography in managing chronic fracture-related infections: Determining the depth of infection and avoiding unnecessary bone procedures

Abstract

Purpose

Methods

Results

Conclusion

Keywords

Introduction

Materials and methods

Patient characteristics and study design

Treatment strategies and evaluation of clinical outcome

Results

Outcomes for criteria 1 patients

Outcomes for criteria 2 patients

Case description

Case No. 1 (criteria 1)

Case No. 2 (criteria 1)

Case No. 7 (criteria 2)

Discussion

Conclusion

Footnotes

Acknowledgements

Author contributions

Declaration of conflicting interests

Funding

Ethical statement

Consent to publish

ORCID iDs

Data availability statement

References