Osteomyelitis of the oral and maxillofacial area is an uncommon inflammatory disease that occurs due to odontogenic causes such as endodontic infection, facial trauma, insufficient blood supply, and iatrogenic postoperative infections [1]. With the development of modern medicine and various antibiotics, the incidence of osteomyelitis, except for medication-related osteonecrosis (MRONJ), has decreased. However, osteomyelitis of the mandible is still considered a difficult disease to treat due to the complexity of its pathophysiology and the need for long-term broad-spectrum antibiotic administration and multiple surgeries [2].

Candida infections were previously reported in immunocompromised patient groups, such as newborns, drug addicts, and patients with catheters; however, candida osteomyelitis was rarely observed [3]. Candida osteomyelitis mainly occurs in the spine, sternum, femur, hip, facial bones, feet, ankles, and tibia. Therefore, it must be diagnosed promptly to avoid its progression to significant mortality [4]. Candida osteomyelitis of the jaw has a low incidence and no clearly established criteria for its diagnosis, treatment, and prognosis. Fungi and yeast are originally normal commensal microorganisms of the oral cavity; however, in the presence of conducive local or systemic factors, they could cause infections, including osteomyelitis. With an aging society, the number of immunocompromised patients is increasing, and more cases of candida osteomyelitis of the jaw will occur [5]. Herein, we present the case of a patient with osteomyelitis of the maxilla and mandible, including the maxillary and ethmoidal sinuses due to candida infection. The study protocol was approved by the Ethics Committee of Chosun University Dental Hospital (approval no. CUDHIRB 2206 002) and the need for written informed consent was waived by the committee.

An 81-year-old male patient visited Chosun University Hospital with a chief complaint of nasal pyorrhea and intermittent epistaxis that had occurred one month earlier. He was diagnosed with osteomyelitis based on a paranasal sinus computed tomography (CT) scan performed by an otorhinolaryngologist. At the time of admission, all his vital signs were stable, and the white blood cell count was 6,480 cells/mm³, showing no signs of an acute infection in the blood test. The patient was taking atenolol and had no underlying disease other than arrhythmia. In the department of otorhinolaryngology, endoscopic sinus surgery was planned under general anesthesia. On the CT image, necrotic tissue in the right maxillary alveolar bone was observed (Fig. 1), and a combined operation was performed after consultation with the department of oral and maxillofacial surgery. During sequestrectomy, the right maxillary sinus and oral cavity were perforated due to bone destruction, and much foreign material looking like a fungus ball was discharged from the inside along with sequestrum (Fig. 2). The patient showed good healing after the operation and was discharged from the hospital; however, two weeks later, during follow-up, the patient complained of decreased sensation in the lower lip and swelling of the right jaw. In the oral cavity, some foreign material looking like the previous fungus ball was drained from the lingual alveolar ridge of the right mandibular molar (Fig. 3). At the time of his discharge, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level approached normal values (close to zero); however, when he was later re-hospitalized and retested, the CRP level had increased to 19.7 mg/dL and the ESR to 34 mm/hr. Testing was performed by collecting the drainage material and some tissue samples. As a result of the microbiological culture, Candida albicans and Enterococcus faecium group D were identified. In addition, on the CT image, the loss of the posterior continuity of the right mandibular alveolar bone and the destruction of the inferior wall of the right maxillary sinus, which was the previous surgical site, could be observed (Fig. 4). Therefore, the final diagnosis was osteomyelitis caused by invasive candida. The re-hospitalized patient consulted a physician at the department of infectious diseases, and curettage was performed on the affected area under local anesthesia, after which Mycamine (micafungin) and Taigasil (Tigecycline) were administered for two weeks, followed by Teiconin (teicoplanin), Maxipime (cefepime), and Difflucan (fluconazole). It was confirmed that the wound healed during hospitalization, and Difflucan was administered as a discharge drug for one month. A CT scan taken two months later confirmed that bone destruction of the mandible did not proceed any further, and the patient showed good healing clinically (Fig. 5, 6).

Osteomyelitis, which could be defined as an inflammatory, progressive lesion in the bone and bone marrow, can occur in any bony part of the body; however, it is relatively common in the jaw bones, including the teeth. This is because causative microorganisms can provide a route for spreading into these bones through the root canal or periodontal ligament of the contaminated tooth. In addition, the prevalence of MRONJ related to drugs such as antiresorptive agents and antiangiogenic agents, is increasing [6]. Since the etiology is so diverse, in the case of patients with osteomyelitis of the jaw, clinicians often monotonically prescribe antibiotics and implement curettage without recording the patient’s medical history in detail and approaching the patient carefully. In most cases, osteomyelitis responds to empirical antibiotics and is effectively treated via surgery; however, as in the above cases, osteomyelitis caused by candida or pathogens resistant to empirical antibiotics does not respond well to antibiotics and continues to recur even after surgery, resulting in a poor prognosis [7].

Candida, one of the commensal oral microorganisms in healthy individuals, often integrates the oropharyngeal, gastrointestinal, and vaginal microflora. Although the incidence of candida osteomyelitis of the jaw is minimal, several cases of C. albicans associated with contaminated root canals have been reported. Baumgartner et al. [5] revealed that C. albicans was found in 5 out of 24 root canal samples. However, not all of them in the mouth and bones are virulent or cause osteomyelitis.

Fifteen candida species that cause illness in mankind are known; however, only five species cause more than 90% of invasive infections: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei. Infections caused by these yeasts that cause serious systemic infections are collectively described as invasive candidiasis. This has previously been known to occur mainly in immunosuppressed individuals who are vulnerable to opportunistic infections, such as newborns, drug addicts, and patients with internal catheters. However, the patient in the above case developed candida osteomyelitis despite the absence of underlying diseases other than arrhythmia. Therefore, even if the infected patient is not in an immunosuppressed state, it is necessary to keep in mind the probability of invasive infection caused by candida.

For successful treatment of candida osteomyelitis, speedy diagnosis and the proper use of antifungal drugs are essential. The diagnosis can be made via microbiological culture, histology, or serology; however, it is hard to distinguish between invasive infection and simple colonization in oral candida [8]. Ideally, in these infections, it is recommended to perform both microbiological culture and biopsy for diagnosis [9]. In this case, C. albicans was identified through microbiological culture, and histological examination was performed several times; however, unfortunately, biopsies could not diagnose candida in this case. Microbiological culture alone provided no information other than the presence of a candida colony. However, in this case, the continuity of the soft tissue of the infected bone site was lost; therefore, exposed bone and many fungus balls were observed inside, making the diagnosis possible.

The mechanisms by which candida induces bone infection can be classified into three categories: hematogenous spread, direct contact, and contiguous infection [10]. Among these, hematogenous spread occurs most commonly; however, as mentioned above, there are many cases that cannot be diagnosed even with blood culture, such as extremely low levels of candidemia, intermittent candidemia, or sterilization by bloodstream [11]. In this case, since the main complaint was nasal pyorrhea and intermittent epistaxis, it can be speculated that candida infection from the right maxillary sinus spread to the surrounding bone and destroyed the maxillary alveolar bone, and then continued to spread osteomyelitis through the oral cavity to the adjacent ipsilateral mandibular posterior bone. As such, osteomyelitis caused by candida is often associated with two or more sites; so, it is necessary to closely observe other bones when a patient is diagnosed with this infection [12].

In addition, C. albicans, as well as E. faecium group D, which are ESKAPE pathogens (E. faecium, Staphylococcus aureus, Klebsiella pneumonia, Actinetobacter baumannii, Pseudomonas aeruginosa, and the Enterobacter species), were identified in the patient in this case report. Unfortunately, infections caused by ESKAPE pathogens have been steadily increasing for the past five years at our hospital [7]. Slenker et al. [13] revealed that 13% of patients with candida osteomyelitis were concomitantly infected with ESKAPE pathogens, methicillin-resistant S. aureus, and 8% with enterococcal species. The ESKAPE pathogens are resistant to beta-lactam antibiotics empirically used during surgery in the dental field, and the period of treatment is significantly increased [7]. The patient in this case also showed resistance to ampicillin, ciprofloxacin, and clindamycin; so, tigecycline and teicoplanin were administered. In the cases of patients with candida osteomyelitis, their immunity is usually compromised due to long-term hospitalization and antifungal medication; so, careful attention should be paid to nosocomial infections such as those caused by ESKAPE pathogens.

According to the 2015 Infectious Diseases Society of America guideline updates for candidiasis, for the treatment of candida osteomyelitis, it is recommended to administer fluconazole (Diflucan; Pfizer-Roerig, New York, NY, USA) 400 mg/day for 2–6 months while performing surgical debridement if necessary [14]. In this patient, micafungin was administered for two weeks, and fluconazole was used for about two months, resulting in good healing progress.

In conclusion, candida osteomyelitis has been considered a rare infectious disease with high mortality and fatality rates; however, it is occurring more and more frequently nowadays due to the change in the population structure and the increase in the number of immunosuppressors [15]. When candida osteomyelitis of the jaw is clinically suspected, prompt diagnosis (through culture tests, biopsies, and multiple blood cultures) and surgical intervention, followed by the use of appropriate antifungal agents and the prevention of opportunistic infections should be performed.

No potential conflict of interest relevant to this article was reported.

Conceptualization: HJP. Data curation: HIC. Funding acquisition: HIC. Methodology: JSO, SYM. Project administration: HJP. Visualization: JYC. Writing original draft: HIC. Writing review & editing: HJP, JSY.