Tissue Expander for Pediatric Scalp Reconstruction Complicated by Fungal Infection With Aspergillus terreus

Tissue expansion is a valuable tool for reconstruction of large scalp defects while allowing for restoration of hair in the involved region. Despite this significant benefit, the procedure remains time and energy-intensive for both the patient and the surgeon due to the need for frequent clinic visits for expansion and a moderately high complication rate for the procedure. Prior studies have had conflicting data regarding complication rates of expander placement, ranging from 4% to 63%. However, a large meta-analysis showed a mean complication rate of 17.4%, with the most common complication rate after tissue expander placement being implant exposure followed by infection.^1,2Risk factors for the development of expander infection include large expander size (200-400 mL), disease duration ≤1 year before expander placement, and hematoma evacuation after placement.³ Presence of infection often leads to a prolonged course of surgical management due to the need for antibiotics and surgical intervention, including expander debridement, replacement, or removal. A recent study analyzing tissue expander infections showed a 9.5% removal rate after expander infection due to recalcitrant infection.³ 

Tissue expander infections are predominantly due to bacterial pathogens; in 1 report, Staphylococcus aureus was found in three-quarters of exudate samples cultured.⁴ In contrast, infection of fungal origin is rarely reported.^5-7 Prolonged treatment courses, common to tissue expansion-based reconstructive cases, provide numerous opportunities for pathogen introduction. Chlorohexidine solutions to prep skin before outpatient expansion lack sufficient fungicidal activity. Albeit more effective, alcohol and iodine-based solutions lack full sporicidal efficacy.⁵ Furthermore, recent literature suggests that antibiotic treatment of bacterial infections may contribute to subsequent fungal infection due to the hyphae-inducing properties of peptidoglycan released from dying bacteria.⁸ Therefore, a postoperative course complicated by bacterial infection may contribute to expander infection with atypical organisms.

Unfortunately, the treatment of fungal tissue expander infections is currently complicated by the relative lack of literature detailing appropriate management strategies, but implant removal and cultures should be considered paramount. The present report informs management strategies for the treatment of fungal tissue expander infections in the pediatric population.

This report presents the case of a 12-year-old female patient with a history of asthma and hypothyroidism who was undergoing craniofacial reconstruction following accidental blunt force head trauma. Initial evaluation at an outside facility revealed multiple severe, depressed, calvarial fractures, including the frontal sinus and multiple facial fractures, and atlanto-occipital disassociation injury. Shortly after her injury, she required an emergent craniectomy and was treated with a 10-day course of ampicillin-sulbactam prophylaxis and a 7-day course of erythromycin eye drops due to multiple facial fractures. Despite antibiotic prophylaxis, she subsequently suffered multiple infections, including Escherichia coli infection of the scalp wound, which was treated with ceftriaxone, and a subsequent soft tissue infection with a rare staphylococcal species.

Cerebrospinal fluid (CSF) cultures taken approximately 2 months after the injury revealed Candida infection requiring amphotericin B and fluconazole treatment. Ultimately, she was transferred to a tertiary care hospital for management and reconstruction due to visible deterioration of the scalp wound (Figure 1) and ongoing complex care requirements. Following transfer, she required wound debridement and obliteration of the frontal sinus before large adjacent tissue transfer to gain vascularized coverage of the previous craniectomy site. The soft tissue defect was successfully closed with local flap advancement (Figure 2).

Approximately 6 months after her initial injury, 2 remote port subgaleal tissue expanders were placed to facilitate later bony reconstruction. In consideration of her numerous postinjury infections, she was discharged on oral cephalexin and topical bacitracin ointment. Initially, tissue expansion proceeded without incident until threatened exposure of the anterior expander necessitated a repeat operation to reestablish expander coverage. One month postoperatively, she was prescribed amoxicillin/clavulanic acid due to periorbital swelling noted during an outpatient expansion appointment. One week later, she returned to the clinic reporting a 3-day history of purulent drainage from her incision sites (Figure 3) with increased incisional pain. She underwent expander removal, at which time copious purulence was encountered throughout the expander pockets with severe infectious compromise of the galea. Pediatric infectious disease was consulted, and she was started on ceftazidime and clindamycin for broad-spectrum coverage while awaiting results of intraoperative cultures. Initial culture grew S aureus, and she was discharged on cephalexin. Results returned following discharge revealed fungal coinfection that triggered empiric treatment with fluconazole while awaiting species identification and susceptibility. Final results identified Aspergillus terreus, prompting a transition to voriconazole.

Due to the atypical pathogen identified, a thorough literature review was conducted to inform appropriate management. The treatment team encountered a lack of evidence-based recommendations for managing Aspergillus infection of tissue expanders in the pediatric population. A treatment duration of 23 days was derived from a similar case report detailing infection of tissue expanders of the breast with Candida species.⁷

The patient improved rapidly following expander removal and treatment with voriconazole. This regimen was well tolerated, with no medication-associated adverse events reported throughout the treatment interval. Expansion was reattempted 10 months later with the placement of 3 expansion devices. She received intravenous clindamycin prophylaxis during her hospitalization due to her previous culture results and sensitivities.

Expansion protocol proceeded without incident across approximately the next 17 weeks (Figure 4), and the expanders were subsequently removed, followed by reconstructive cranioplasty of the right frontal bone utilizing a polyetheretherketone implant. She experienced an uncomplicated postoperative course throughout 3 months of close follow-up, after which follow-up in 1 year was deemed adequate (Figure 5). An immunologic evaluation was recommended due to the astounding number of postoperative infections this patient had experienced; a thorough workup did not uncover any immunodeficiency.

Invasive fungal infections have been traditionally considered opportunistic infections associated with immunocompromised states.⁹ However, emerging literature has begun to identify additional risk factors, including prolonged treatment with broad-spectrum antibiotics and head injury.^8,9 While currently rare, Aspergillus terreus infections are increasing in frequency and are associated with a 51% to 70% mortality rate in the setting of disseminated infection.^10,11 Yet, appropriate treatment regimens for this pathogen are poorly characterized in current literature. Antifungal susceptibility of Aspergillus is species-specific,¹² and Aspergillus terreus displays only intermediate susceptibility to amphotericin B—a broad-spectrum agent often used for suspected invasive fungal infections while awaiting cultures.¹² Voriconazole is generally the first-line therapy for invasive aspergillosis, with superb central nervous system (CNS) penetrance that makes it particularly effective for infections of the head and neck in which direct invasion of the CNS is of concern.¹³ However, voriconazole is known to cause neurotoxicity (eg, confusion, hallucinations, visual disturbances.)¹⁴ Therefore, alternative azole antifungal medications may be selected due to their superior tolerability^15,16 despite their narrower spectrum of activity relative to voriconazole.¹⁷ Providers must carefully weigh the benefit of providing superior coverage with the risk of increased toxicity when choosing appropriate therapy while awaiting sensitivity testing. As highlighted by the present discussion, the initial selection of a milder agent may prolong treatment course due to treatment failure and eventual escalation to a more robust antifungal (ie, voriconazole).

Previous reports of tissue expander infection by Aspergillus species have detailed asymptomatic fungal colonization of the fluid-filled expander cavity discovered at the time of planned expander removal.^5,18 In contrast, the patient in the present case study experienced infection of the soft tissue envelope external to the expansion devices and significant compromise of the surrounding soft tissue secondary to the infective process. In a prior case report of tissue expander-associated fungal infection, Candida was reported to cause a similar infective process in a pediatric patient.⁶ However, the present case report is the first published case of Aspergillus infection presenting in this manner.

This report details successful treatment of an Aspergillus terreus tissue expander infection in a pediatric patient using 23 days of voriconazole given at a dose of 200 mg twice daily. Though this treatment protocol may inform the management of future patients with similar infective processes, additional studies are needed to establish evidence-based best practices for such patients. Precise species identification, careful selection of targeted antifungal treatment, and device removal were vital to this patient’s successful reconstruction in the setting of atypical infective process and a highly complicated postoperative course. Whereas invasive fungal infections are dogmatically associated with immunocompromised status, they may also lead to infection in immunologically intact patients. Extensive treatment of bacterial infections without complete resolution may prompt consideration for underlying fungal coinfection.

Soft-tissue infections are not uncommon in pediatric patients undergoing expander-based scalp reconstruction. However, atypical fungal infections are rare, and minimal literature is available to guide appropriate antifungal selection. To the authors’ knowledge, the case study is the first report of tissue expander infection with Aspergillus terreus in a pediatric patient undergoing scalp reconstruction. Complete resolution of the detailed infection was achieved with 200 mg voriconazole given twice daily. This report informs management in the setting of similar atypical infective processes in this patient population and highlights the need for future studies to determine evidence-based best practice.

Affiliations: ¹University of Mississippi Medical Center, Division of Plastic and Reconstructive Surgery, Jackson, MS; ²University of Mississippi Medical Center, Department of Pediatrics, Jackson, MS

Correspondence: Shelley R Edwards, BS; sredwards@umc.edu

Presented at: 44th Annual John A Bostwick Burn and Wound Symposium, January 2022

Ethics: To ensure the rights and dignity of the patient, the possible publication of this case report was discussed with the patient and their guardian(s), and written consent was given for the use of the accompanying clinical images for this purpose. A signed statement of informed consent has been submitted alongside this publication. The present work was written in accordance with all appropriate institutional guidelines.

Funding: There were no sources of funding supporting this work.

Disclosures: There were no financial interests, products, devices, or drugs used in the manuscript.