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A rare case of Candida glabrata spondylodiscitis: case report and literature review

Open AccessPublished:January 12, 2018DOI:https://doi.org/10.1016/j.ijid.2018.01.003

      Highlights

      • The incidence of spondylodiscitis is increasing due to the increase in susceptible population and improved ascertainment.
      • The diagnosis is often delayed or missed.
      • A fungal aetiology is rare.
      • There is a global shift toward invasive candidiasis due to C. glabrata which has a variable susceptibility to antifungal drugs.

      Abstract

      Background

      Spondylodiscitis is an infection of the vertebral column, the incidence of which is increasing due to an increase in the susceptible population and improved ascertainment. This disease has been associated with a wide range of microorganisms. Fungal spondylodiscitis is uncommon (0.5–1.6%) and strongly associated with immunosuppression and diabetes (Gouliouris et al., 2010). A rare case of Candida glabrata spondylodiscitis in a non-neutropenic diabetic patient is reported herein, along with a review of the literature.

      Case report

      A case of C. glabrata spondylodiscitis of L3–L4 metameres was diagnosed. The diagnosis was obtained through open biopsy of an abscess and culture examination. The patient was treated with anidulafungin and surgical debridement of the lesion.

      Conclusions

      The diagnosis of spondylodiscitis is often delayed or missed. Physicians should consider this entity in the differential diagnosis of lumbar pain in order to initiate an appropriate therapy to prevent spinal cord lesions and disability. This is particularly relevant in the case of a fungal aetiology, as there is a recognized global shift towards invasive candidiasis due to non-albicans Candida species, in particular C. glabrata, which has variable susceptibility to antifungal drugs.

      Keywords

      Introduction

      Spondylodiscitis is an infection of the vertebral column, the incidence of which is increasing due to an increase in the susceptible population and improved diagnostic skills. Fungal spondylodiscitis is uncommon (0.5–1.6%) and is usually due to Candida albicans (
      • Gouliouris Theodore
      • Aliyu Sani H.
      • Brown Nicholas M.
      Spondylodiscitis: update on diagnosis and management.
      ,
      • Berbari Elie F.
      • Kanj Souha S.
      • Kowalski Todd J.
      • Darouiche Rabih O.
      • Widmer Andreas F.
      • Schmitt Steven K.
      • et al.
      Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults.
      ). Candida glabrata, formerly known as Torulopsis glabrata, is a common saprophyte in the gastrointestinal, genitourinary, and respiratory tracts and an opportunistic pathogen of low virulence (
      • Berkowitz I.D.
      • Robboy S.J.
      • Karchmer A.W.
      • Kunz L.J.
      Torulopsis glabrata fungemia a clinical pathological study.
      ). There has been a recent significant increase in infections caused by C. glabrata due to the increase in the immunocompromised population (
      • Seravalli Laurent
      • Linthoudt DanielVan
      • Bernet Christian
      • Torrenté Antoinede
      • Marchetti Oscar
      • Porchet François
      • et al.
      Candida glabrata spinal osteomyelitis involving two contiguous lumbar vertebrae: a case report and review of the literature.
      ).
      Risk factors for candidaemia are present in the majority of patients with fungal infections and include prior use of broad-spectrum antibiotics, central venous access devices, immunosuppression, neutropenia, chronic granulomatous disease, and intravenous drug use (
      • Gouliouris Theodore
      • Aliyu Sani H.
      • Brown Nicholas M.
      Spondylodiscitis: update on diagnosis and management.
      ,
      • Berbari Elie F.
      • Kanj Souha S.
      • Kowalski Todd J.
      • Darouiche Rabih O.
      • Widmer Andreas F.
      • Schmitt Steven K.
      • et al.
      Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults.
      ).
      The case presented herein represents the fifteenth case of spondylodiscitis due to C. glabrata reported in the literature and the first treated with anidulafungin. Data reported in the literature concerning the diagnosis and treatment of C. glabrata spondylodiscitis are discussed and this newly reported case is compared to previously reported cases.

      Case report

      A 66-year-old male was admitted to the ward for lumbar pain, progressive difficulty in walking, and immobilization during the previous 2 months. He had a history of diabetes, spondyloarthrosis, hepatitis C virus (HCV) infection with liver sclerosis, depression, and segmental ileitis, and he was overweight (90 kg, body mass index (BMI) 28 kg/m2). He had already been evaluated for lumbar pain in the emergency department, where he had undergone spine radiography that had not shown any evidence of pathology. During the following month, the pain had worsened and had not responded to non-steroidal anti-inflammatory drugs or opiates. The patient was therefore investigated with a computed tomography (CT) scan of the spine, which showed signs of lumbar spondyloarthrosis and suspected spondylodiscitis of L4. He was finally admitted to the ward.
      Physical examination showed fever (37.5 °C), significant functional spine limitation for mobility, and weakness of the muscles of the legs. A blood test revealed a normal white blood cell (WBC) count, normochromic normocytic anaemia, and an increased erythrocyte sedimentation rate (ESR; 46 mm/h) and procalcitonin (12.69 ng/ml), while C-reactive protein (CRP) was within the normal range. Quantiferon and serology for Brucella, Echinococcus, and Treponema pallidum were negative. Blood cultures yielded no pathogens and electrophoresis of serum proteins did not show any monoclonal component. Electromyography (EMG) showed a sensitive and motor neuropathy of the L3–S1 fibres. It was decided to perform a spine magnetic resonance imaging (MRI) scan, which showed hypointensity in T1 sequences and hyperintensity in T2 and STIR sequences at the L3–L4 vertebral bodies, signs of oedema of the disc. Post gadolinium images detected a lesion suspicious of an abscess (Figure 1).
      Figure 1
      Figure 1Spine MRI showing a lesion suspicious of an abscess.
      Based on the laboratory findings, the epidemiological data, and the aetiology of spondylodiscitis, the patient was started on a broad-spectrum antibiotic therapy; however, there was no improvement in his symptoms or the functional impairment. The case was then discussed with neurosurgeons, and a surgical exploration revealed a spinal abscess, which was treated with debridement and stabilization of the vertebrae involved. Biopsy specimens were sent for aerobic, anaerobic, fungal, and mycobacterial culture and yielded C. glabrata. Antifungal susceptibility testing indicated that the isolate was susceptible to caspofungin, anidulafungin (both minimum inhibitory concentrations (MICs) were 0.06 μg/ml), and micafungin (MIC 0.01 6μg/ml), according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The patient was evaluated by an infectious diseases specialist and was started on treatment with anidulafungin 200 mg on the first day, followed by 100 mg daily thereafter. Within a few weeks, a progressive improvement in the lumbar pain, resolution of the fever, and a decrease in ESR were seen, and he was finally mobilized.

      Review of the literature

      A MEDLINE search combining the keywords “Candida glabrata”, “Torulopsis glabrata”, “vertebral osteomyelitis”, “spinal osteomyelitis”, and “spondylodiscitis” was performed and the reference lists of identified articles were reviewed to find additional cases. For all reported cases, special attention was paid to risk factors, localization, methods of diagnosis, treatment, and outcome. This is currently the most complete review on C. glabrata spondylodiscitis (Table 1).
      Table 1Review of Candida glabrata spondylodiscitis.
      AuthorAge (years) and sexRisk factorsLocalizationDiagnosisMedical therapySurgeryOutcome
      • Thurston A.J.
      • Gillespie W.J.
      Torulopsis glabrata osteomyelitis of the spine: a case report and review of the literature.
      60 MDiabetes mellitus

      Broad-spectrum antibiotics

      Obstructive uropathy

      Candiduria
      L4–L5Open biopsyAmphotericin B

      5-Fluorocytosine
      Cured
      • Bruns J.
      • Hemker T.
      • Dahmen G.
      Fungal spondylitis: a case of Torulopsis glabrata and Candida tropicalis infection.
      63 FBroad-spectrum antibiotics

      Obstructive uropathy

      Candidaemia
      T7–T8Open biopsyAmphotericin B

      5-Fluorocytosine

      Ketoconazole
      PerformedCured
      • Morrow J.D.
      • Manian F.A.
      Vertebral osteomyelitis due to Candida glabrata. A case report.
      49 MBroad-spectrum antibiotics

      Alcohol abuse

      Funguria
      T11–T12Needle biopsyAmphotericin BPerformedParaplegic
      • Liudahl K.J.
      • Limbird T.J.
      Torulopsis glabrata vertebral osteomyelitis: case report and review of the literature.
      49 MAlcoholic cirrhosis

      Broad-spectrum antibiotics
      T11–T12Open biopsyAmphotericin BPerformedCured
      • Imahori S.C.
      • Papademetriou T.
      • Ogliela D.M.
      Torulopsis glabrata osteomyelitis: a case report.
      66 FBroad-spectrum antibiotics

      Candidaemia

      Central venous catheter
      L2–L3Needle biopsy5-FluorocytosineCured
      • Owen P.G.
      • Willis B.K.
      • Benzel E.C.
      Torulopsis glabrata vertebral osteomyelitis.
      71 FDiabetes mellitus

      Bowel resection

      Central venous catheter

      Parenteral nutrition

      Candidaemia
      T9–T10Open biopsyAmphotericin BPerformedCured
      • Curran M.P.
      • Lenke L.G.
      Torulopsis glabrata spinal osteomyelitis involving two contiguous vertebrae. A case report.
      74 FColon resection

      Broad-spectrum antibiotics

      Central venous catheter

      Candidaemia
      T7–T8Needle biopsyAmphotericin B

      Fluconazole
      PerformedCured
      • Bonomo R.A.
      • Strauss M.
      • Blinkhorn R.
      • Salata R.A.
      Torulopsis (Candida) glabrata: a new pathogen found in spinal epidural abscess.
      85 FDiabetes mellitus

      Rheumatoid arthritis

      Malignancy Broad spectrum

      antibiotics
      C3–C4Open biopsyAmphotericin B

      Itraconazole
      Cured
      • Bonomo R.A.
      • Strauss M.
      • Blinkhorn R.
      • Salata R.A.
      Torulopsis (Candida) glabrata: a new pathogen found in spinal epidural abscess.
      44 FDegenerative joint diseaseT3–T11Open biopsyAmphotericin BPerformedParaplegic
      • Dwyer K.
      • McDonald M.
      • Fitzpatrick T.
      Presentation of Candida glabrata spinal osteomyelitis 25 months after documented candidaemia.
      43 FGastric bypass

      Central venous catheter

      Parenteral nutrition

      Broad-spectrum antibiotics

      Fungaemia
      L1–L2Needle biopsyAmphotericin B

      Fluconazole
      Cured
      • Hendrickx L.
      • Van Wijngaerden E.
      • Samson I.
      • Peetermans W.E.
      Candidal vertebral osteomyelitis: report of 6 patients, and a review.
      72 MAxillo bifemoral bypass

      Broad-spectrum antibiotics

      Central venous catheter

      Parenteral nutrition
      L1–L2Needle biopsyFluconazole

      Amphotericin B
      Died
      • Seravalli Laurent
      • Linthoudt DanielVan
      • Bernet Christian
      • Torrenté Antoinede
      • Marchetti Oscar
      • Porchet François
      • et al.
      Candida glabrata spinal osteomyelitis involving two contiguous lumbar vertebrae: a case report and review of the literature.
      64 MDiabetes mellitus

      Gastric resection

      Spinal osteoarthritis

      Obstructive uropathy
      L2–L3Needle biopsyAmphotericin B

      Fluconazole

      Amphotericin B lipid complex
      PerformedPresumed cured
      • Dailey N.J.
      • Young E.J.
      Candida glabrata spinal osteomyelitis.
      69 MCandidaemia

      Colon resection

      Broad-spectrum antibiotics

      Central venous catheter

      Parenteral nutrition

      Alcohol abuse
      L1–L2Needle biopsyAmphotericin BPerformedCured
      • Tan Aaron C.
      • Parker Nicholas
      • Arnold Mark
      Candida glabrata vertebral osteomyelitis in an immunosuppressed patient.
      47 MPsoriatic arthritis

      Immunosuppression

      Candidaemia
      L3–L4Needle biopsyCaspofungin

      Posaconazole
      Cured
      Current case66 MDiabetes mellitusL3–L4Open biopsyAnidulafunginPerformedCured
      F, female; M, male.
      From the data in the literature, the mean age of patients at diagnosis was 61.5 years (range 43–74 years). Eight cases involved male patients and seven cases involved female patients (53.3% vs. 46.7%). The most prevalent risk factors were prior use of antibiotics (66.7%), previous candidaemia (46.7%), previous surgery (40%), central venous catheter (40%), and diabetes mellitus (33.3%).
      Eight cases involved the lumbar spine, while one case involved the cervical spine and six cases involved the thoracic spine. The most frequently affected metameres were L2 (33.3%) and L3 (26.6%). The microbiological diagnosis was obtained after needle biopsy in 53.3% of cases and by open biopsy in 46.7% of cases. A needle biopsy failed in the detection of the pathogen involved in three cases and an open biopsy was therefore performed.
      Treatment with amphotericin B plus another antifungal drug was used in 46.7% of the cases. A third of the cases were treated with amphotericin B alone. The remaining 20% of cases were treated with a single antifungal drug different from amphotericin B. Sixty percent of the patients underwent spinal surgery after starting medical therapy, while 40% were treated with medical therapy alone.
      The majority of cases had a good outcome: 80% of the patients were cured at the end of therapy. One patient died and two patients had irreversible nerve damage. Only 46.7% of the cured patients underwent spinal surgery, while all of them were treated with antifungals. However, the literature regarding the treatment of C. glabrata spondylodiscitis is limited and the outcomes may have been affected by the clinical condition of the patient before surgical treatment. Further clinical observations are needed to provide more conclusive evidence regarding the management of these conditions, in particular the role of spinal surgery as a therapeutic option in addition to medical therapy.

      Discussion and conclusions

      The case reported here was a diagnostic challenge because back pain is a non-specific symptom among adults and C. glabrata is a very rare cause of spondylodiscitis. The patient’s chronic ileitis probably contributed to the spinal infection, causing a barrier leakage that promoted the translocation of the pathogen from the bowel into the circulatory system, leading to secondary involvement of the lumbar spine. Nevertheless, further studies are needed to determine whether bowel inflammation could have a role in determining candidaemia.
      The suspicion of spondylodiscitis came from physical signs including fever and neurological impairment, as well as the increase in ESR. Furthermore, risk factors such as diabetes, spondyloarthrosis, age >60 years, and male sex were present. ESR was increased, but as for the anaemia, this could have been explained by the chronic ileitis. The WBC count was within the normal range. A high serum value of procalcitonin (PCT) was found. Blood cultures have low sensitivity, and these were negative in the case patient. Based on the epidemiology, the PCT level, and the findings on spine MRI, the patient was started on a broad-spectrum antibiotic therapy that led to no effective improvement in the symptoms.
      This experience suggests that a high PCT level – a well-known marker of bacterial infection (
      • Pieralli F.
      • Corbo L.
      • Torrigiani A.
      • Mannini D.
      • Antonielli E.
      • Mancini A.
      • et al.
      Usefulness of procalcitonin in differentiating Candida and bacterial blood stream infections in critically ill septic patients outside the intensive care unit.
      ) – does not necessarily rule out a fungal infection and has to be read in the clinical context.
      According to the literature, MRI should be the first imaging modality used for patients suspected of native vertebral osteomyelitis; it has a sensitivity of 97%, specificity of 93%, and accuracy of 94%. Its excellent morphological resolution allows early recognition of spondylitis. Affected vertebral bodies and discs reveal typical alterations in T1- and T2-weighted images.
      Nevertheless, MRI does not clarify the aetiology of the illness, which is crucial for initiating the appropriate therapy. A microbiological diagnosis should be established before any treatment. Biopsies (either open or percutaneous) are often reserved for patients with negative blood cultures and they often establish the microbiological and pathological diagnosis.
      As reported in the literature, microbiological positivity is significantly higher when surgical sampling is provided, even through minimally invasive techniques. A CT- or MRI-guided aspiration biopsy should be the first invasive diagnostic step in the patient suspected of vertebral osteomyelitis. Biopsy samples should be sent for aerobic, anaerobic, fungal, and mycobacterial culture. However, the sensitivity of this procedure varies between 30% and 70%. Furthermore, prior treatment may affect the accuracy of culture (
      • Berbari Elie F.
      • Kanj Souha S.
      • Kowalski Todd J.
      • Darouiche Rabih O.
      • Widmer Andreas F.
      • Schmitt Steven K.
      • et al.
      Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults.
      ).
      Once neurological impairment was proven by EMG and there was no clinical improvement with antibiotic therapy, it was decided to take a surgical biopsy of the abscess in order to establish the aetiology of the infection. According to this experience, open biopsy of the abscess was an effective method to obtain specimens for culture evaluation. The choice between needle and open biopsy was determined by the neurological impairment, which prompted the surgery.
      The diagnosis of spondylodiscitis is often delayed or missed. It is generally misdiagnosed and mismanaged as a degenerative process (
      • Berbari Elie F.
      • Kanj Souha S.
      • Kowalski Todd J.
      • Darouiche Rabih O.
      • Widmer Andreas F.
      • Schmitt Steven K.
      • et al.
      Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults.
      ). Although spondylodiscitis is rare among adults, it should not be overlooked in patients with symptomatic back pain not responding to painkillers, especially in patients with risk factors.
      Spondylodiscitis has a poor prognosis in terms of mortality and morbidity. There is a recognized global shift towards invasive candidiasis due to non-albicans Candida species, in particular C. glabrata, which has variable susceptibility to antifungal drugs (
      • Andes D.R.
      • Safdar N.
      • Baddley J.W.
      • Playford G.
      • Reboli A.C.
      • Rex J.H.
      • et al.
      Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.
      ) and a higher mortality rate (
      • Fidel P.L.
      • Vazquez J.A.
      • Sobel J.D.
      Candida glabrata: review of epidemiology, pathogenesis and clinical disease with comparison to C. albicans.
      ).
      The 2016 recommendations of the Infectious Diseases Society of America for the management of Candida osteomyelitis favour initial therapy with fluconazole (6 mg/kg daily for 6–12 months) or an echinocandin (e.g., anidulafungin 100 mg daily) for at least 2 weeks followed by fluconazole (6 mg/kg daily for 6–12 months) (
      • Pappas P.G.
      • Kauffman C.A.
      • Andes D.R.
      • Clancy C.J.
      • Marr K.A.
      • Ostrosky-Zeichner L.
      • et al.
      Clinical practice guidelines for the management of candidiasis: 106 update by the Infectious Diseases Society of America.
      ). However, there are also reports of resistance of C. glabrata to azoles, caspofungin, and amphotericin B (
      • Thompson III, George R.
      • Wiederhold Nathan P.
      • Vallor Ana C.
      • Villareal Nyria C.
      • Lewis II, James S.
      • Patterson Thomas F.
      Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection.
      ,
      • Owen P.G.
      • Willis B.K.
      • Benzel E.C.
      Torulopsis glabrata vertebral osteomyelitis.
      ).
      Surgical debridement is recommended in selected cases, with the goal of debulking the infected tissue, securing an adequate blood supply for tissue healing, and maintaining or restoring spinal stability. Indications for surgery may include the development of neurological deficits or symptoms of spinal cord compression and evidence of progression or recurrence despite appropriate antimicrobial therapy, instability, large epidural abscess, intractable back pain, or failure of medical treatment (
      • Berbari Elie F.
      • Kanj Souha S.
      • Kowalski Todd J.
      • Darouiche Rabih O.
      • Widmer Andreas F.
      • Schmitt Steven K.
      • et al.
      Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults.
      ).
      The patient presented herein was the first with C. glabrata spondylodiscitis to be treated with anidulafungin. In this case, surgical debridement and anidulafungin were found to be effective in the treatment of C. glabrata spondylodiscitis. This experience could be useful in the case of C. glabrata infections with evidence of resistance to azoles or amphotericin B.

      Conflict of interest

      All authors deny any financial or personal relationships with other people or organizations that could inappropriately have influenced (biased) the work.

      Ethical approval

      No approval was required. All authors complied with the ethics and policy of the journal.

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