Title: A Case Report: Forearm Both Bone Fractures with Chronic, Rare Fungal Infection. Should Hardware Come Out?

Author(s): Benoit Kindo, DO; Timilehin Ogunjana; John V. Gentile, DO

Email: bkindo@mercy.com

Introduction: Acremonium spp are an uncommon culprit in osteosynthesis associated infections (OAI). There is a paucity of studies investigating fungal infections following fracture fixation and no reports in the literature involving Acremonium infection of this type of fixation. A 27-year-old-male sustaining multiple gunshot wounds to the abdomen and forearm presented with a Grade III open fracture to the radius and ulna with extensive soft tissue damage.

Fungal infections of orthopaedic implants are uncommon and are mostly reported in immunocompromised patients as opportunistic infections.  Within the immunocompetent group, Candida is the most common culprit. Hardware infections can be categorized as fracture-related infections (osteosynthesis associated infections (OAI)) or periprosthetic joint infections (PJIs). However, there are few studies investigating non-arthroplasty peri-implants fungal infections, as most available studies and guidelines in the literature center around periprosthetic joint infections (PJIs). In this case, a rare fungal infection in the setting of an unstable fracture fixation led to conflicting surgical and medical treatment approaches prompting further investigations.

Case Report:  A 27-year-old-male sustaining multiple gunshot wounds to the abdomen and forearm presented as a trauma team.  He emergently underwent an exploratory laparotomy and was transferred to the intensive care unit for appropriate resuscitation prior to orthopedic intervention. Before the exploratory laparotomy, the forearm was irrigated and stabilized in a splint after his tetanus status was updated with a grade 3 open fracture antimicrobial protocol.

The patient underwent a formal operative debridement a day following his presentation. Intraoperative evaluation was favorable for a direct open reduction internal fixation (ORIF) with a bridge plating technique of both the radius and the ulna.  Antibiotics beads were placed intraoperatively. Tenodesis of ruptured brachialis and extensor digiti minimi muscle tendons were also performed. Soft dressings allowing compartment and pulse monitoring were applied and the patient was transferred back to the intensive care unit with care to continue open fracture treatment protocol with 8 hours interval IV antibiotics administration. He continued to experience multiple episodes of febrility with an up trending white blood cell count leading to infectious disease involvement. A repeat exploratory laparotomy was conducted seven (7) days later due to visible evisceration from the previous midline abdominal incision. Twelve days (12) following the initial orthopaedic  I&D and ORIF of the forearm, the patient developed a small quarter size area of skin necrosis from the projectile entry wound. Exposed hardware consisting of the radial fixation plate was visible triggering a repeat intra-operative excisional debridement of nonviable skin, muscle, fascia and fat with application of a wound VAC and tissue collection for microbiological studies. Cultures subsequently grew Candida Albicans and Acremonium species. An Antifungal regimen was then implemented to the existing antibiotic treatment per the infectious disease team. A third intra-operative irrigation and debridement 3 days later showed fresh granulation tissue encouraging for optimistic outcome. The decision was then made to retain the hardware as the fractures remained unstable with no radiographic signs of healing.  Antifungal beads of Amphotericin were also placed in the wound and around the implants at the time, and the wound VAC treatment was also continued. New culture samples were recollected which later grew a new fungal species, Scedosporium Apiospermum. After six (6) weeks of IV antifungal treatment, the patient underwent a 4th excisional irrigation and debridement, placement of amphotericin beads and secondary forearm wound closure with a rotational flap. He was then discharged with the wound VAC switched to an incisional VAC along with weight bearing restrictions and close follow up with the orthopaedic office. He was also to continue the antibiotic/antifungal treatment with infectious disease. The patient was later evaluated in the emergency department twelve (12) weeks since injury with exposed hardware and purulent discharge from a dehisced forearm wound. No consolidated bridging callus was visible on plain radiographs.  He underwent a 5^th   irrigation and debridement of the forearm.  The radial side plate was replaced at that time with an antibiotic impregnated cement spacer to the bony void. A 2.0-millimeter (about 0.08 in) diameter k-wire was inserted into the radius medullary canal to provide some degree of stabilization. The antifungal regimen was reassessed and a new medication Posaconazole was initiated by the infectious disease team. Cultures from the last debridement did not grow any organism to date, most likely due to the masking effect of the longstanding antifungal/antimicrobial treatment.  At the six (6) months follow-up visit, no radiographic evidence of healing was present. He is participating in occupational therapy and is gaining some increased range of motion to the hand and wrist. The current plan of his treatment is to obtain complete eradication of the culprit’s fungi and bacteria followed by a reconstructive autograft of both the radius and the ulna.

Discussion: The Acremonium species are composed of opportunistic fungi, and historically have been associated with mycetoma’s and ocular infections. Although much less reported than its Candida species counterpart, Acremonium implant-infections do occur. Guarro et al. in 1997 tested in vitro antifungal susceptibilities on wild type Acremonium species.  Amphotericin B was found to have the best efficacy on a wide variety of strains. The 50% Minimum Inhibitory Concentration and Minimum Fungicidal Concentration for Amphotericin B were found to be 1.16 and 2.31µg/mL respectively against 33 Acremonium strains.

Our patient was initially started on IV Anidulafungin (Eraxis) at 100mg every 24 hours for empiric treatment of the fungal infection. Eraxis was then stopped and switched to IV Amphotericin B (Ambisome) at 5mg/kg every 24 hours. The Infectious disease team recommended removing the plates because the infection was unlikely to clear with retained hardware. An additional concern was the risk of various organ toxicities including nephrotoxicity, neurotoxicity, and hepatotoxicity with prolonged IV amphotericin B. To their point, clearing the infection took precedence on any surgical plan, and the hardware should clearly be removed to maximize the medical treatment.

The American Academy of Orthopaedic Surgeons’ 2019 Appropriate Use Criteria (AUC) strongest recommendation for managing peri-implant infections is two-fold.  Superficial/deep surgical debridement is crucial followed by a suppressive antimicrobial therapy until removal of hardware. The most important criteria for management of OAI are mechanical stability, time between fixation and infection and the presence of union. The current literature suggests that achieving mechanical stability with union prior to hardware removal takes precedence over eradication of an infection as instability promotes a favorable environment for bacterial/fungal overgrowth. In our case, despite the Infectious Disease service’s recommendations, hardware removal was unsuitable as bone consolidation was not achieved. The unstable nature of the fractures posed a serious risk of sacrificing the limb if deprived of any structural stability.  We elected to monitor the patient while on suppressive therapy until decent stability could be achieved.

The source of this patient’s infection remains unknown. However, non-compliance with his treatment regimen most likely played a role in the resurgence of infections after discharge. He is a known smoker which carries a poor healing prognosis in implant-associated infections.  Bonnevialle et al (2017) recommends a definitive fixation within 6 months after infection control has been achieved. Of note, this patient is yet to achieve bony union prior to consideration of a definitive fixation.

Conclusion: Unstable fractures in the setting of multimicrobial infections present a challenging dilemma to approach. From an orthopedic perspective, stability supersedes all other factors including infection eradication. However, persistent infection does not favor adequate bony union which is required for fracture stabilization. This case perfectly highlights the dilemma with a patient who has non healing unstable fractures seven (7) months post injury in the setting of persisting chronic fungal infection. A multidisciplinary approach has proven to be useful even though a clear and definitive approach to this issue remains elusive.