History and Physical Examination Findings
A 3.5-year-old intact female bearded dragon presented with a 2-week history of a firm left-sided mandibular swelling. Mild dental disease had been diagnosed 1 year earlier, and treatment included an anesthetized dental cleaning and chlorhexidine swabbing (0.125%, applied twice a week). The bearded dragon’s diet consisted of 5 to 6 superworms 3 to 4 times a week supplemented daily with leafy greens and fruit.
On physical examination, tooth discoloration and unilateral gingival recession with significant pocketing of the maxillary and mandibular gingiva were found (Figure 1). Cytology of mandibular surface debris revealed the presence of fungal hyphae.
A—Abnormal mandibular gingival pocketing in a bearded dragon with fungal osteomyelitis. B—Fungal hyphae on cytology (at time of diagnosis). Bar = 20 µm.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.12.0774
Diagnostic Findings and Interpretation
Skull radiographs and a mandibular bone biopsy were performed. Left mandibular osteomyelitis and extensive infiltration of necrotic bone and soft tissue by fungal hyphae and arthroconidia were evident.
There was a 5-month period between identification of a fungal component contributing to the bearded dragon’s oral osteomyelitis and fungal species identification. During this time, additional diagnostics included CBCs, which demonstrated severe leukocytosis (29.4 X 109 to 38.5 X 109/L; reference range, 1.45 X 109 to 19.0 X 109/L) characterized by lymphocytosis (17.1 X 109 to 26.6 X 109/L; reference range, 0.29 X 109 to 11.3 X 109/L; Supplementary Table S1), and a CT scan, which demonstrated progressive left maxillary and mandibular osteomyelitis. Differential diagnoses included bacterial or fungal infection or neoplasia.
Treatment during this period included a 16-week course of voriconazole (10 mg/kg, PO, q 24 h), 8 weeks of terbinafine (20 mg/kg, PO, q 24 h), 5 weeks of ceftazidime (25 mg/kg, IM, q 72 h), and 5 anesthetized surgical debridement procedures. An antibiotic synthetic polymer matrix, doxycycline hyclate, and a specialty compounded terbinafine poloxamer gel (50 mg/mL, dosed at 10 mg/kg) were applied to the gingival pocketing. Extralabel drug use was performed with owner consent and complied with provisions of AMDUCA and 21 CFR §530. Compounded products were prepared from FDA-approved products to provide a more appropriate matrix for occupying and treating the oral defect. Veterinarians should adhere to compounding regulations and be aware that properties may differ between compounded and FDA-approved products. Despite these treatments, there was minimal response, characterized by static gingival pocketing and persistence of fungal hyphae on cytology.
Because of the lack of response to treatment, fungal identification and susceptibility testing were performed (University of Texas Health Science Center at San Antonio Long School of Medicine). Species identification was performed by DNA sequence analysis of ITS, LSU, EF-1α, and RPB2. GenBank BLASTn identified it as Fusarium solani species complex (FSSC), while the curated Fusarium reference database (Westerdijk Fungal Biodiversity Institute) gave a definitive identification as Fusarium epipeda (Neocosmospora epipeda; 99.56% match with CBS 146523). The sequences were deposited in GenBank (accession Nos. ITS = PQ623040, LSU = PQ623048, EF-1α = PQ629524, and RPB2 = PQ629523). Susceptibility testing was performed by Clinical and Laboratory Standards Institute broth microdilution methods,1 which demonstrated resistance to fluconazole, itraconazole, posaconazole, voriconazole, and terbinafine but not amphotericin B, which had an MIC of 1 µg/mL (Table 1). Additional testing prior to antifungal treatment included next-generation DNA sequencing (MiDOG Animal Diagnostics LLC), which demonstrated a relative abundance of 66.2% fungi in the oral microbial population dominated by Fusarium cyanescens (99.94%).
Antifungal susceptibility testing results for Fusarium epipeda, a member of the Fusarium solani species complex.
| Drug | Results (µg/mL) |
|---|---|
| Amphotericin B | 1 |
| Fluconazole | > 64 |
| Itraconazole | > 16 |
| Posaconazole | > 16 |
| Voriconazole | > 16 |
| Terbinafine | > 2 |
Treatment and Outcome
Following identification of F epipeda, treatment with deoxycholate amphotericin B was initiated. Dosing was extrapolated from canine and feline medicine,2 and a dose of 1 mg/kg (5.5 mL total volume) was administered every 3 days. Four doses were administered IV once a week in hospital, and 7 doses were administered SC every 72 hours by the client. The jugular veins were used over the ventral coccygeal vein because of concern for amphotericin nephrotoxicity.
To evaluate amphotericin B serum concentrations, antifungal drug levels were measured at 0, 24, and 48 hours after administration at the University of Texas Health Center at San Antonio with a validated HPLC assay (Shimadzu Scientific Instruments). Amphotericin B (Fisher Scientific) quality control samples at 3 concentrations (0.25, 4, and 8 mg/mL) were included in each run of the assay, and an internal control (m-nitrophenol; Sigma-Aldrich) was added to each sample and the quality controls. Protein precipitation was accomplished by combining 0.2 mL of each sample and quality controls with 0.4 mL of methanol, followed by vortexing and centrifugation for 10 minutes at 16,000 X g. Then, 0.2 mL of each supernatant was placed into amber-colored tubes and the samples and quality controls were dried under a stream of nitrogen, reconstituted with 0.2 mL of the mobile phase (60:40 N,N,N’,N’-tetramethyl-ethylenediamine to acetonitrile; Fisher Scientific and Sigma-Aldrich, respectively), and analyzed isocratically by HPLC with UV detection at 406 nm. The analytical measurement range of this assay is 0.05 to 10 mg/mL. Drug levels remained below the MIC (1 µg/mL) at all time points (0 hours, 0.42 µg/mL; 24 hours, 0.92 µg/mL; 48 hours, 0.6 µg/mL; Figure 2). Due to insufficient therapeutic levels, treatment was transitioned to the liposomal formulation of amphotericin B. Twenty days after the final deoxycholate administration, the patient received a single 4-mg/kg dose of liposomal amphotericin B IV in the right jugular vein. Serum levels were measured at 0, 24, and 72 hours and 7 days. Values were above the 1-µg/mL MIC only at 24 hours (0 hours, 0.27 µg/mL; 24 hours, 2.63 µg/mL; 72 hours, 0.65 µg/mL; 7 days, 0.25 µg/mL).
Amphotericin B serum concentrations graph: antifungal drug levels in a bearded dragon infected with oral Fusarium epipeda treated with IV and SC deoxycholate amphotericin B and IV liposomal amphotericin B.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.12.0774
Throughout treatment, fasted plasma biochemistry panels performed before amphotericin administration confirmed no abnormalities, and no adverse effects were observed. Clinical assessment and fungal cultures (Sabouraud dextrose agar) from oral swabs showed no improvement in lesions and substantial fungal growth.
Given the impracticality and expense of frequent (q 24 h) liposomal amphotericin B dosing, injectable therapy was discontinued in favor of palliative topical chlorhexidine gluconate therapy (2% applied daily). This full-strength concentration was chosen because of the lack of historical response to the more commonly used 0.125% concentration. For the first time during treatment, fungal culture showed no growth, but growth recurred after a 12-day discontinuation. The patient underwent trials of chlorhexidine swabbing at various concentrations (1% to 2%) and intervals (24 to 72 hours over 14 to 30 days) for a 6-month period with varying success. Complications included oral ulceration and discomfort, the formation of a suborbital swelling that communicated with the oral cavity, and progressive gingival erythema, tooth staining, and secondary oral bacterial infection (Figure 3). An aerobic culture of the facial swelling confirmed bacterial growth, and cytology demonstrated fungal hyphae. The swelling resolved with 2 gauze packings soaked with ceftazidime (20 mg/kg) and deoxycholate amphotericin B (1 mg/kg) and 4 weeks of injectable ceftiofur crystalline-free acid treatment (30 mg/kg, SC, q 7 d). Next-generation DNA sequencing confirmed Pseudomonas aeruginosa infection in the oral cavity, which was treated with a 28-day course of ceftazidime (20 mg/kg, SC, q 72 h). When comparing results from next-generation DNA sequencing from before fungal identification and after amphotericin B and chlorhexidine treatment, there was a reduction in the relative abundance of fungal growth from 66.2% to 1.5% for a total percentage decrease of 97.8%. Seventeen months after initial diagnosis, the patient remained clinically stable and had monthly oral sedated debridement procedures performed with no other systemic treatments.
A—Oral ulcer after administration of 2% chlorhexidine (50 weeks after diagnosis). B—Suborbital swelling OS (51 weeks after diagnosis). C through D—Progressive ulceration and tooth discoloration of left mandibular and maxillary quadrants (78 weeks after diagnosis).
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.12.0774
Comments
Bearded dragons can be predisposed to dental disease because of their acrodont dentition. Contributing factors include age, body condition score, diet, and other health issues.3 This case was the first documented instance of a specific fungal pathogen, F epipeda, associated with gingivitis and oral osteomyelitis in a bearded dragon and attempted treatment with amphotericin B.
Initial treatment in this case included voriconazole and terbinafine after identifying fungal organisms. However, after a lack of response with prolonged treatment, species identification confirmed F epipeda. In hindsight, fungal speciation and susceptibility should have been pursued immediately upon identifying a dominant fungal presence in the oral cavity. The FSSC is known to be resistant to antifungals other than amphotericin B,4 which matched the resistance pattern in this case.
To the authors’ knowledge, clinical use of IV or SC amphotericin B administration and serum concentrations have not been documented in reptiles. Although amphotericin B is known to be nephrotoxic and warrants caution before administration, this patient exhibited no clinical or biochemical evidence of drug-related adverse effects. However, the dosing reached MIC only for a short period (liposomal form) in this case, suggesting that future treatment might require either an increased dose or more frequent administration.
Due to the impracticality and expense of administering injectable amphotericin, topical treatment with chlorhexidine gluconate, known as a broad-spectrum biocide, was performed.5 Historically, the patient was treated with 0.125% oral rinse, which is the recommended concentration to avoid the ulceration and burns commonly seen with higher concentrations.5 After a lack of response, treatment with a higher concentration was elected in an attempt to reduce fungal growth. While treatment with 1% to 2% oral chlorhexidine demonstrated side effects, there was short-term fungal growth inhibition, which was not achieved with other treatments. If attempting treatment with topical chlorhexidine, choosing as low a concentration as possible to prevent secondary side effects and closely monitoring the patient are recommended.
During the patient’s treatment with amphotericin B and topical chlorhexidine, efficacy was monitored with fungal cultures and in-house oral cytology. While this did not provide an exact fungal identification, it was a cost-effective method to monitor response to treatment and can be easily performed in clinical practice.
This case report describes the first reported case of an FSSC member associated with gingivitis and oral osteomyelitis in a bearded dragon and attempted treatment with IV and SC amphotericin B with no adverse effects. No curative treatment was identified. In future cases of oral disease involving fungal organisms in bearded dragons, speciation and antifungal susceptibility testing are recommended to avoid ineffective treatment attempts.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
None reported.
Disclosures
Dr. Mans is a member of the JAVMA Scientific Review Board, but was not involved in the editorial evaluation of or decision to accept this article for publication.
No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
ORCID
References
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Alastruey-Izquierdo A, Cuenca-Estrella M, Monzón A, Mellado E, Rodríguez-Tudela JL. Antifungal susceptibility profile of clinical Fusarium spp. isolates identified by molecular methods. J Antimicrob Chemother. 2008;61(4):805-809. doi:10.1093/jac/dkn022
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