Candida parapsilosis in a case of canine otitis media

Abstract

Candida parapsilosis, commonly present on the skin and mucous membranes, has been described as an opportunistic pathogen increasingly associated with infections. We present the first documented case of severe otitis media caused by this yeast species in a French Bulldog with a history of atopic dermatitis and seborrhea. The diagnosis was confirmed by culture and molecular methods. Susceptibility testing showed resistance only to fluconazole; however, antifungal therapy could not be initiated, as the patient died in an emergency room. This case highlights the potential of C. parapsilosis to cause serious ear infections and underscores the importance of early identification.

1. Introduction

Over the last ten years the number of infections caused by yeasts of the genus Candida has increased considerably in both humans and animals. Although this genus comprises more than 100 species [1], only a few of them are responsible for most fungal infections, including Candida albicans [2], Candida parapsilosis, Candida tropicalis, and Candida auris among others [3,4]. Candida parapsilosis commonly inhabits the skin and mucous membranes of healthy animals and humans [3,[5], [6], [7], [8], [9]]. This species has emerged as an opportunistic pathogen in immunocompromised or immunosuppressed patients or with predisposing factors such as chronic trauma, excessive moisture, concomitant infectious diseases, and prolonged use of broad-spectrum antibiotics [[10], [11], [12]].

In dogs, candidiasis can be associated with both systemic and invasive infections, accounting for approximately 10 % of cases. Localized infections of the urinary tract, skin, external ear canal, peritoneum, cornea, joints, or heart valves can also occur [13]. Candida parapsilosis has been reported in cases of seborrheic dermatitis, rhinitis, pneumonia, and external otitis [3,4,[14], [15], [16], [17]]. To date, this species has not been linked to otitis media in dogs. However, Mousavi Mohammadi et al. documented an unusual case in a 54-year-old woman with necrotizing otitis media and mastoiditis caused by this yeast, highlighting its role as a pathogen in these types of infections [18]. Otitis of the middle ear includes various inflammatory conditions such as: acute otitis, recurrent and chronic otitis, exudative otitis, acute necrotizing otitis and cholesteatoma [19].

We present a case of severe otitis media in a French Bulldog. The diagnosis was C. parapsilosis-driven acute candidiasis. The identification of the yeast strain was confirmed by isolation, culture, and molecular testing.

2. Case

On July 15, 2024 (day 0), a 5-year-old male French Bulldog presented to the clinic with a history of right unilateral otitis media and a previous diagnosis of atopic dermatitis associated with seborrhea, which had been treated with oclacitinib 16 mg (Zoetis, Las Condes, Chile) at 0.4 mg/kg/BID since February 2024.

Dermatological examination revealed purulent otitis media in the right ear with inflammation, erythema, and pain. Cytology of the ear canal discharge revealed the presence of free and intracellular neutrophils (4/field). A complete blood count also showed neutrophilia and lymphopenia.

That same day, a topical otic cleansing with Tris-EDTA (Clean up, União Química, São Paulo, Brazil) and a prescription enrofloxacin 5 % otic solution and 5.26 mg dexamethasone (Ahumada, Santiago, Chile). The patient was scheduled for weekly follow-up visits but did not return until the end of treatment (day +35). On the follow-up day, a purulent, stringy discharge, erythema, and pain associated with anatomical changes in the cartilage of the external auditory canal were observed, with probable ossification detected by palpation, due to chronic inflammation.

A helical tomographic study of the skull was performed (day +35) in simple and contrast phase of 3 mm thickness and 1.5 mm overlap from the nose to the occipital foramen, on brilliance computed tomography CT16 slice - DS equipment (Philips, Holland, Netherlands), which revealed otitis media of the right middle ear with irreversible bone changes (Fig. 1), requiring surgical intervention.

Fig. 1.

Helical tomography of the skull, in simple (A) and contrast phase (B). Right tympanic bulla with contents completely filling the cavity. Thickening of the bony plate; the auditory canal appears uniformly thickened with areas of mineralization.

On day +40, a total excision of the external auditory canal was performed with osteotomy of the tympanic bulla. At this time, a new cytology examination of the contents of the tympanic bulla was performed during surgery, revealing abundant cocci and ovoid fungal structures. At this time, tissue samples were collected for bacterial and fungal culture. Postoperative treatment included metamizole sodium 300 mg (Laboratorio Chile, Chile) 25 mg/kg/BID for 4 days, dermisolone 10 mg (Dragpharma, Chile) 1 mg/kg/SID for 10 days in tapering doses, and cephalexin 500 mg (Holliday-Scott, Buenos Aires, Argentina) 22 mg/Kg/BID for 14 days. Bacterial culture identified cephalexin-sensitive Staphylococcus aureus, so antibiotic therapy was continued. Wound healing was complete 20 days after surgery (day +60).

Mycological examination revealed ovoid, budding blastoconidia in chains forming pseudohyphae upon direct examination. The sample was plated on Sabouraud glucose agar and CHROMagar Candida and incubated at 37 °C, revealing a single morphotype suggestive of C. parapsilosis in both media. From a pure culture, DNA extraction was performed using the Quick-DNA Fungal/Bacterial Miniprep kit (ZYMO Research, Irvine, CA, USA) following the manufacturer's instructions. 10 ng of the extracted DNA was used for PCR amplification of the nuclear ribosomal internal transcribed spacer (ITS) region, using primers ITS4 5′-TCCTCCGCTTATTGATATGC-3′ and ITS5 5′-GGAAGTAAAAGTCGTAACAAGG-3′ [10]. The obtained sequence was compared with freely available sequences from GenBank using the basic local alignment search tool (BLAST). Confirmation of the correct identification of the pathogenic species was based on a percentage of identity and coverage of 100 %, validating the presence of C. parapsilosis, whose GenBank accession number is PX121644. In addition, identification was performed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF, Bruker, Billerica, MA, USA), the result of which identified C. parapsilosis sensu stricto. In parallel, the antifungal susceptibility was determined using the Sensititre YeastOne™ colorimetric panel (Trek-Thermo Scientific™, Argentina). This panel allows determining the minimum inhibitory concentration (MIC) by broth microdilution for the following antifungals: 5-Flucytosine (0.06–64), amphotericin B (0.12–8), anidulafungin (0.015–8), caspofungin (0.08–8), fluconazole (12–256), itraconazole (0.015–16), micafungin (0.08–8), and posaconazole (0.008–8), using C. parapsilosis ATCC 22019 as the reference strain. The tissue sample for this study identified C. parapsilosis (day +70), susceptible to all antifungals tested, with exception of fluconazole. On day 72, the owner was called for a follow-up appointment to initiate antifungal therapy. However, she reports that the patient had died in an emergency room due to systemic decline.

3. Discussion

Canine otitis media commonly occurs as a complication of unresolved otitis externa and is reported in more than 80 % of cases in dogs [20]. The symptoms of this infection are similar regardless of the causative agent, whether bacterial or fungal. Among the latter, yeasts of the genus Malassezia have been the most frequently found, followed by Candida spp. [21]. Therefore, early diagnosis, along with the detection and identification of the etiological agent, is crucial to initiate treatment and achieve disease remission.

Although Malassezia pachydermatis was traditionally the only yeast associated with otitis in domestic animals, C. parapsilosis has been identified as a concurrent species [22]. In 1998, Martins et al. detected this yeast in cases of otitis externa in dogs, in addition to Cryptococcus laurentii and Trichosporon cutaneum [17].

The presence of this species suggests that, while it is a common commensal of the skin and mucous membranes, it can act as an opportunistic pathogen. The infection may spread from the external auditory canal to the middle ear and mastoid, potentially causing serious complications that require surgical intervention [19,20]. The opportunistic nature of C. parapsilosis and Candida spp. have been previously documented in pets, including cases of pneumonia in dogs and cats [15], granulomatous rhinitis in a feline [16], seborrheic dermatitis in a dog [23], and disseminated candidiasis in a healthy dog [24].

Although this species is considered susceptible to azoles and polyenes, in recent years there has been increasing global concern about the emergence of resistance to fluconazole [18], a finding consistent with the present study, in which C. parapsilosis showed resistance to fluconazole. In this regard, C. parapsilosis resistance to fluconazole has been reported in Greece, Italy, France, Israel, Turkey, India, Korea, and Latin America [25]; particularly in Spain there is concern about the emergence of difficult-to-manage outbreaks in different regions of the country [26]. In this regard, a recent study confirms that echinocandins and liposomal amphotericin B are a treatment option for candidemia caused by C. parapsilosis, even in patients with fluconazole-resistant strains [27].

Therefore, obtaining an antifungal susceptibility profile prior to treatment is essential. It is recommended to adjust the antifungal dose according to the time and severity of the infection, the virulence of the microorganism and the underlying comorbidities [16,18,23,25]. Another aspect is that C. parapsilosis can form biofilms, which contribute to antifungal resistance and persistence in systemic infections, associated with fatal cases in immunosuppressed individuals [23]. Unfortunately, this patient's death prevented us from evaluating the efficacy of the treatment, despite his susceptibility profile. The prior diagnosis of atopy and seborrheic dermatitis, the use of oclacitinib as maintenance therapy, and prior treatment with antibiotics and corticosteroids are factors that could have perpetuated the infection in this patient.

This report documents, for the first time, the isolation and identification of C. parapsilosis in canine otitis media in a patient with atopic dermatitis associated with seborrhea.

CRediT authorship contribution statement

Belén Rivera Gómez-Barris: Writing – original draft, Methodology, Investigation. Ronar López: Writing – original draft, Investigation. Leslye Camila del Río: Methodology. Ailén Dumont Viollaz: Writing – original draft, Methodology, Formal analysis. Claudio Moreno: Methodology, Investigation. Pamela Thomson: Writing – review & editing, Writing – original draft, Visualization, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization.

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Written informed consent was obtained from the legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

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Sources of funding

This work received financial funding from the National Agency for Research and Development (ANID, Chile), by grant Initiation FONDECYT 11231174.

Declaration of competing interest

The authors declare there are no conflict of interest that could influence the work presented.