Management of Severe Burn Wounds Colonized With Multi-resistant Pseudomonas aeruginosa and Fusarium Using Marine Omega3 Wound Matrix in a Female Victim of War

ABSTRACT

War-related burns are common injuries, also among the civilian population. Additional trauma such as fractures or shrapnel wounds may add significant morbidity. Burn injuries in war zones are furthermore frequently undertreated and hence prone to complications. We report a case of a young female victim of war, whose severely infected burn wounds could be successfully healed using a combination of targeted antimicrobial therapy, wound conditioning using decellularized fish skin, and subsequent skin grafting.

INTRODUCTION

Burns are common and devastating injuries often resulting in significant long-term physiological and psychological morbidity.^1–3 After decades of research and continuous improvement in burn care, including skin substitution, novel wound dressings, fluid management, and renal replacement therapy, infectious complications remain the primary cause of mortality and additional morbidity.^4,5 Common pathogens associated with extensive burns are gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumoniae, and Proteus mirabilis.⁵ Fungal infections are comparably rare but bear a high risk of mortality as common therapeutic measures including removal of infected tissue and systemic administration of antimicrobial drugs are less effective.⁶

In armed conflicts, burns and multiple shrapnel wounds account for almost 40% of all injuries, with men being more often affected than women.⁷ Throughout the past century, the civilian population has increasingly become the major target in wars. In World War I, civilian mortality approximated 20%, whereas it has increased to 80% nowadays. War-related burns, also among the civilian population, are usually accompanied by other trauma; tend to be more complicated, deeper, and associated with inhalation injury; and are frequently undertreated.⁸

Decellularized fish skin has become increasingly popular as comparable low-cost temporary wound coverage and dermal replacement layer in burn wounds. As fish skin requires only minimal processing before medical use because of the negligible risk of inter-species pathogen transmission, the dermal structure is preserved as is most of its molecular content. Moreover, the contained omega-3 fatty acids are often attributed with anti-inflammatory and anti-infective properties that both should have beneficial effects on wound healing.⁹

We present a case of an adolescent female victim of war, whose severely colonized wounds were eventually healed by wound conditioning using decellularized marine omega3 wound matrix derived from codfish, followed by skin grafting.

CASE

An otherwise healthy 17-year-old woman got injured by a landmine in Ukraine and sustained severe burns averaging 17% total body surface area involving the entire right arm, the left upper arm, the right thigh, and the thorax. The wounds were mostly deep dermal to full thickness, and she received initial care in a local trauma center where partial excision and escharotomy of the burns were done. Furthermore, craniotomy had to be performed to remove shrapnel that had penetrated the frontal bone. Thirteen days after trauma, the patient was transferred to our burn unit for treatment because of the poor survival chance in the war zone.

Upon arrival, the burn wounds were in a detrimental state with clinical signs of severe infection (Fig. 1). Swabs were taken, and the wounds were cleansed and covered with povidone-iodine dressings. A full-body CT scan further showed multiple residual intracerebral shrapnel with a diameter of few millimeters each. There were no signs of intracerebral hemorrhage or elevated intracranial pressure though and the electroencephalogram showed no pathologies; for this, no further actions were taken. Bronchoscopy revealed a longitudinal tracheal rupture of the membranous wall averaging 5 cm in length that was treated conservatively (Fig. 2). The patient suffered acute kidney injury (AKI stage 3 according to KDIGO guidelines) and required renal replacement therapy by continuous veno-venous hemodialysis. Two days later, after stabilization, the patient was taken to the operating theater. She was tracheotomized, and the burns were debrided, thus completing the epifascial excision of the burns on the right arm, epifascial excision of the burns on the right thigh, and tangential excision of the burns on the right hemithorax. As the patient was still in a fragile state at this time, grafting was postponed and the wounds were covered with topical negative pressure wound dressings.

FIGURE 1.

Wounds were in a detrimental state upon admission. (A) Full-thickness burns on the right arm with (B) clinical signs of infection. (C) Full-thickness burns on the right thigh.

FIGURE 2.

(A) Longitudinal tracheal rupture of the membranous wall right at the junction with tracheal cartilages (arrows). (B) Healed tracheal rupture.

On day 19 postburn, the patient was again taken to the theater. At this time, the wounds on the right lower leg and thigh as well as the left arm were grafted with split-thickness skin grafts. As the wound on the right arm was still covered with significant residual debris, further debridement was performed and topical negative pressure dressing was applied. Meanwhile, wound swabs revealed the growth of multi-resistant gram-negative (4MRGN) A. baumanii, 4MRGN P. aeruginosa, and additional Fusarium spp. and mold fungus on the right arm, although there was evidence of 4MRGN K. pneumoniae in the tracheal secret. The initially established empiric systemic antimicrobial regimen consisting of meropenem, linezolid, and voriconazole was then switched to a targeted antibiotic therapy consisting of cefiderocol, isavocunazole, and polymyxin B.

On day 26 postburn, the wound on the right arm had improved but still needed further debridement. In these non-graftable conditions with obvious severe wound colonization and swabs still positive for 4MRGN P. aeruginosa, marine omega3 wound matrix was applied for intermittent wound conditioning. Six days later, the remnants of the partially incorporated marine omega3 wound matrix were removed (Fig. 3). As sufficient wound granulation was evident, the wound was grafted using meshed split-thickness skin grafts on the upper arm and forearm and unmeshed skin on the back of the hand. After 1 week, dressings were removed, and excellent graft take was seen. During the following days, the patient’s general condition improved as well: The renal function recovered and hemodialysis was discontinued; bronchoscopy revealed spontaneous healing of the tracheal rupture. Residual skin defects were covered with split-thickness skin grafts on day 40 postburn. Eventually, the patient could be discharged to enter a rehabilitation program 3 months after injury.

FIGURE 3.

Debrided burn wound on the right arm before (A) and after (B) application of marine omega3 wound matrix and 6 days after application of partially incorporated matrix (C).

DISCUSSION

This case report describes the successful recovery of a 17-year-old severely burned victim of war who had suffered from multiple complications, including infection of undertreated wounds with multi-resistant strains, subsequent renal failure, and a tracheal rupture. Severe wound infection was salvaged with targeted i.v. antibiotic and antimycotic therapy and aggressive debridement, and non-graftable wound conditions were overcome by wound conditioning with marine omega3 wound matrix. Kidney function recovered with progressive skin closure and infection control. The tracheal rupture healed by conservative means.

Burn wound infections remain a major concern in modern burn care with patients being especially susceptible because of the extensive loss of skin barrier and large wound surface together with postburn immunosuppression. Burn wounds are usually colonized rapidly with microorganisms originating from the patient’s endogenous skin, respiratory, and gastrointestinal flora. Early excision of the burn eschar is a mainstay of contemporary burn care and has been seen to effectively reduce burn wound infection rates.¹⁰ Possibly because of the specific wound milieu, burns are especially susceptible to gram-negative strains. In a recent study, P. aeruginosa, A. baumanii, and K. pneumoniae have been described as the most common pathogens in burn wound infection, with minimal regional differences.⁵ Fungal colonization with Fusarium spp. is comparably rare but can significantly add to the burden of the disease.¹¹ In our patient, a large portion of the burn wounds had remained unexcised until admission leading to severe wound infection. In addition, all bacteria isolates showed several resistance patterns, with A. baumanii and K. pneumoniae being resistant to all four common antibiotic classes. The situation was complicated by evident fungal colonization with Fusarium spp. The treatment regimen consisted of application of povidone-iodine dressings, burn wound excision, and targeted i.v. antibiotic and antimycotic therapy.

Decellularized fish skin has been proposed as a promising dermal replacement, especially in burn care because of its structural similarity to human skin and the negligible risk of inter-species pathogen transmission. For this, fish skin can be processed for medical purposes while preserving its molecular and structural integrity. Furthermore, there is evidence that the contained omega-3 fatty acids have anti-infective and anti-inflammatory capabilities.⁹ It has been demonstrated that decellularized marine omega3 wound matrix derived from codfish heals wounds faster than human amnion¹² or porcine submucosa.¹³ Furthermore, it has proven effective in the treatment of chronic extremity wounds.¹⁴ In our patient, a complicated severely colonized full-thickness wound on the right arm was conditioned with one cycle of marine omega3 wound matrix in a situation when the risk of total graft loss was high and there was a lack of sufficient granulation tissue. Only 6 days after matrix application, the wound surface had sufficiently recovered and grafting could be performed successfully. At the follow-up visit 3 months after injury, the scars on the right arm were of acceptable quality without significant contraction of the elbow or armpit (Fig. 4).

FIGURE 4.

Scar quality 3 months after trauma and 2 months after surgery, respectively. Note the only minimal contraction at the elbow and armpit (A, B).

Tracheal ruptures are rare and may occur after blunt trauma^15,16; however, they are sometimes also the result of intubation in the emergency setting. Such iatrogenic tracheal ruptures are often related to difficult airways requiring multiple intubation attempts.¹⁷ The mortality because of tracheal ruptures has been seen to approximate 10% and is closely related to rupture length. Regardless of whether the rupture is managed conservatively or via surgical repair, antibiotic therapy is necessary to prevent mediastinitis.¹⁸ In our patient, the cause for the longitudinal rupture of the membranous part of the trachea is unknown and it only became evident after admission. Conservative management was chosen as the rupture was comparably small and the patient’s general condition did not permit timely thoracotomy.

This case demonstrates that comparably small burns in a young patient can be life-threatening if complicated by additional trauma, wound infection with multi-resistant bacterial strains, and fungal colonization as well as organ failure. Complete debridement, wound conditioning and subsequent coverage of the burn wounds, renal replacement therapy, and targeted antibiotic therapy ultimately allowed the patient to be discharged from hospital and enter a rehabilitation program.

FUNDING

The work was not funded by any governmental or non-governmental source.

CONFLICT OF INTEREST STATEMENT

The authors declare that there are no conflicts of interest of financial or non-financial nature.

DATA AVAILABILITY

All relevant data of this case report are provided in the manuscript.

CLINICAL TRIAL REGISTRATION

Not applicable.

INSTITUTIONAL REVIEW BOARD (HUMAN SUBJECTS)

Not applicable.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE

Not applicable.

INDIVIDUAL AUTHOR CONTRIBUTION STATEMENT

C.S. and J.C.J.H.-G. drafted the original manuscript; D.A. and I.M. contributed valuable clinical and scientific input; C.S., S.P.N., and H.L. reviewed the literature for relevant additional data; and L.-P.K. initiated and supervised the research work. All authors approved the final version of the manuscript and contributed significant scientific input to its final version.

INSTITUTIONAL CLEARANCE

Not applicable.