Antony, Suresh MD*; Domínguez, Delfina C. PhD†; Jackson, John DO‡; Misenheimer, Gregory MD‡
*Center for Infectious Diseases and Travel Medicine, †College of Health Sciences, The University of Texas at El Paso and ‡El Paso Specialty Hospital, El Paso, TX.
Address correspondence and reprint requests to Suresh Antony, MD, Center for Infectious Diseases and Travel Medicine, 1205 N Oregon, El Paso TX 79902. E-mail: email@example.com.
Abstract: Candida-associated prosthetic infections account for less than 1% of all infections of joint prosthesis. However, the morbidity and mortality of such infections is considerable. Therefore, a prompt diagnosis and appropriate management of such infections is critical. This article reviews prosthetic infections caused by Candida species and adds 2 more cases to the literature where C. Candida parapsilosis is the etiologic agent. The present review describes the clinical presentations, risk factors, summarizes the treatment options available, and briefly discusses the pathogenesis of Candida infection.
The number of orthopedic prosthetic implants has more than doubled since 1995 and with this there has been an increase in implant related infections.1 The current infection rate of arthroplasties is about 0.5% to 5%.2 Most of the cases are due to Staphylococcus infection (>50%).3 Fungal-associated prosthetic joint infections (PJI) are rare accounting for less than 1% of the cases.1 These infections tend to occur in patients who are immunosuppressed, have underlying disease such as diabetes mellitus or lupus, and in patients that have been on long-term antibiotics or have long-term indwelling intravascular catheters.2,4 There are no guidelines as yet regarding the management of these infections but at the present time include empiric antifungal therapy associated with either surgical debridement with or without exchange arthroplasty of the device.3 This article describes the current knowledge on the epidemiology, clinical presentation, and management of Candida prosthetic join infections and adds 2 more cases to the literature.
PATIENTS AND METHODS
Cases of Candida PJI reported in the English literature from 1998 up to today were reviewed. The cases were identified by Medline, PubMed, and Medscape databases using the terms arthroplasty, candida prosthetic infection, and joint prostheses. Reviewed data included clinical presentation, underlying illnesses, antifungal treatment, and outcome.
This is a 67-year-old white female with a history of severe osteoarthritis, depression, and long-term nicotine abuse who underwent a total shoulder arthroplasty in 2005. In 2006, she presented with persistent pain to the affected shoulder, and she was reevaluated. The diagnosis made at that time was a dysfunctional shoulder arthroplasty, and a revision was done. Cultures that were obtained grew a Staphylococcus species and Candida parapsilosis. The erythrocyte sedimentation rate (ESR) 45 and C-reactive protein (CRP) 5.6 but the other tests including complete blood cell count and liver function were normal. X-rays done on the shoulder were unremarkable. She was treated with daptomycin at 4 mg/kg/d for 6 weeks with improvement in the pain and motion. The C. parapsilosis isolated at the time was thought to be a contaminant. Revision arthroplasty was then performed, and the patient did well for a few months. The patient then presented with pain, swelling and erythema to the shoulder and was treated with a course of oral antibiotics with poor clinical response. Because of the lack of clinical response, she underwent a repeat incision and drainage. Cultures grew again C. parasiplosis. She then underwent removal of the arthroplasty and was initially treated with voriconazole 200 mg/d until the sensitivity was available and then switched to fluconazole 200 mg/d. She responded well to the previous treatment and has since undergone a revision arthroplasty of the shoulder with good success and no signs of clinical failure 6 months into follow up. Her course was complicated with documented nickel allergy. The relationship of this allergy to her presentation is unknown at this time.
This is a 67-year-old female with a history of severe osteoarthritis of the right hip who underwent a total hip arthroplasty 10 years ago. About 1 year ago, she started having pain in the right hip that was not resolved with antiinflammatory or intraarticular steroid injections. Radiographs showed evidence of loosening of the prosthesis. The white blood cell (WBC), ESR and CRP were normal. Physical examination revealed a healthy female with normal vital signs. The only significant finding was that of tenderness to the right hip and restricted range of motion. An aspiration of the joint revealed 10-15,000/μL polymorpholeukocytes with C. parapsilosis detected on the fungal culture. Because of this result, she underwent another aspiration of the joint, which grew the same organism. The patient then underwent removal of the prosthesis after being started on 800 mg/d of fluconazole with reimplantation done in 6 weeks with successful outcome.
A total of 14 Candidal PJI have been reported in the literature from 1998 to 2007. Two new cases of our own were added in this report. The patient population age ranged from 42 to 83 years, with a mean of 67.4 years. Seven cases (50%) involved total knee arthroplasty, 6 cases (42.8%) total hip arthroplasty, and 1 case (7.14%) shoulder arthroplasty. Candida infection was higher in females (61.5%) than in males (38.5%). The median time from implantation of prosthesis to clinical infection was 60 weeks. The clinical characteristics, risk factors, treatment, and outcomes of cases are summarized in Table 1. Eleven patients (78.57%) had identifiable risk factors for Candida infection. These risk factors included lupus, chronic monocytic leukemia, diabetes, long antibiotic treatment, and a Staphylococcus aureus preceded infection. Among the Candida species identified 42.84% were Candida albicans, 35.76% C. parapsilosis, and 21.42% Candida glabrata. Antimicrobial susceptibility values were not available for all cases. Five cases reported susceptibility to fluconazole as determined by E-test and minimal inhibitory concentration (MIC) (Table 2). Fluconazole was used in 76.92% of the cases, whereas amphotericin B in 46.15%. All patients received systemic antifungal therapy and debridement (Table 1). The outcome was favorable for all patients. However, 1 patient had a knee amputation.
Fungal infections have emerged as the most important cause of infection especially among immunocompromised patients or those with underlying disease. Candida species are known to be a major cause of nosocomial infections accounting for 8% to 10% of all bloodstream infections.5 Mortality rate is high and their treatment costly.6 Candida infections are usually related to specific risk factors associated with modern medical procedures such us the use of broad spectrum antibiotics, immunosuppressive agents, and implanted devices of various kinds.6
The number of joint prosthesis has considerably increased during the past few years. Between 1990 and 2000, the rate of total hip arthroplasties per 100,000 persons increased to 50%, whereas total knee arthroplasties tripled.7 Candida infection after joint arthroplasty occurs infrequently. The incidence of Candida PJI is very low less than 1%.1-3 Most cases of Candida infection of prosthetic joint involve the hip or the knee.1 Few cases have reported the involvement of other joint prostheses. To our knowledge, there are only 50 cases of Candida PJI reported since 1969 including our own.2-4,8-12
Candidal PJI is difficult to diagnose its indolent course presentation, lack of clinical signs and symptoms. In addition, the identification of yeast cells by direct microscopic examination from purulent secretions is difficult and rare. Furthermore, when Candida cultures are detected they are often thought of as being contaminants.9,11 Histological evidence of invasive Candidiasis in bone is rarely obtained. Special stains such as Grocott-Gomori's methanmine-silver nitrate or periodic acid Schiff have to be performed to identify yeast cells and mycelium inside the bone.8 C. albicans, C. parapsilosis, and C. glabrata have been reported as the most common causative agents of PJI. C. albicans accounts for 50% of the cases followed by C. parapsilosis (30%), C. glabrata and Candida tropicalis (20%). C. tropicalis and C. parapsilosis appear to be more aggressive and virulent.11
The risk for infection of hip and knee implants is higher than for smaller joint prostheses due to the long duration of surgery, decreased cortical bone blood flow, and more frequent development of hematoma around the implanted device.1 Risk factors for PJI include immunocompromised state, diabetes mellitus, poor nutritional status, long-term antibiotics, preceding bacterial infection, lupus, or rheumatoid arthritis.2,3 Among the case reports there were 11 cases (84.6%) with at least 1 of the predisposing factors. It is interesting to note the relationship of preceding bacterial infection of the prostheses to subsequent Candidal infection. In 5 cases (38.5%) bacterial infection preceded fungal infection.3,8,13 The presence of bacterial PJI, therefore, should alert the clinician of the possibility of a subsequent opportunistic infection as bacterial infections along with antibiotics may be predisposing causes for the development of fungal infections.
The source of Candida infections is controversial, and it is a subject of debate. A gastrointestinal source for Candidiasis was proposed based on experimental, clinical, and molecular studies. However, other studies have shown an endogenous origin in patients with hematological abnormalities and in nonneutropenic patients.14,15 A cutaneous origin has been suggested for C. parapsilosis because this agent is often recovered from skin, but the data to support this hypothesis are somewhat incomplete.1
The route by which Candida reaches the implanted joints has not been determined for most of the cases but may be direct seeding as in trauma, and hematogenous spread.2,4
Candidiasis associated with bioprosthetic devices may be problematic because these devices can act as substrates for biofilm development. Host proteins rapidly adsorb onto implants promoting a film formation, which might enhance the development of Candida biofilm, promoting infection and antibiotic resistance.16
The selection of antifungal therapy varies greatly. But amphotericin B remains the mainstay for ingrained candidal infections. The effectiveness of lipid formulations of amphotericin B compared with conventional amphotericin B for the treatment of PJI has not been reported.3 Successful treatment with fluconazole as a sole antifungal has been reported in several cases.3 But combinations of fluconazole with other antifungals such as amphotericin B, ketoconazole, and voriconazole are common practice. Newer antifungals such as voriconazole, iatroconazole, and caspofungin have not been evaluated long enough. All these are attractive alternative therapy that may be less toxic and may be easy to administer. There is a significant lack of instructive literature on the diagnosis and management ofthese infections. In reviewing the literature, we believe that one's clinical suspicion should be alerted when there is a patient with risk factors such as previous large joint surgeries, multiple surgeries and hospitalizations, previous antibiotics, associated total parental nutrition through central line, and so on. Removal of the device seems to be the best way to avert long-term complications and promote early recovery.
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