Author: admin, 23.02.2015The incidence of invasive mycoses following SOT ranges from 5% to 42 % with the most common fungi being Candida and Aspergillus (55). Liver transplant recipients as described are high risk for invasive candidiasis which accounts for more than 90% of invasive fungal infections in liver transplant recipients. Pancreas transplant recipients also have high rates on invasive Candida infections, ranging from 6-38%.
Candidiasis in renal transplant recipients represents 76-95% of fungal infections in this group and is mostly confined to the genitourinary tract with disseminated infection occurring in fewer than 5%.
Mucosal candida infection is the most common clinical presentation in patients with solid organ transplant, especially oral candidiasis, but the predominant site of involvement varies with the type of organ transplantation.
In liver transplant patients common presentations of invasive candidiasis are: intra-abdominal abscesses, wound infections, peritonitis and candidemia (23, 64). Distinguishing Candida colonization from infection in solid organ transplant recipients is difficult. Antifungal prophylaxis in organ transplant recipients is controversial, with most studies having numerous limitations and a standardized approach to antifungal prophylaxis for these patients does not exist (56). Mucosal candidiasis, Oropharyngeal candidiasis, can be treated with clotrimazole troche (5 x days).
Treatment of choice for urinary candidiasis, proven cystitis and pyelonephritis, is with oral fluconazole. For treatment of candidemia or invasive candidiasis the IDSA guidelines recommend initial treatment with fluconazole or and echinocandin.
After initiation of azoles in solid organ transplant recipients, close monitoring of their immunosuppressive agents will be required.
Guidelines for the use of antifungal agents in patients with invasive fungal infections in Taiwan.
Most cases of invasive candidiasis are not associated with outbreaks; however, a few hospital-associated clusters linked to common sources have been documented.
Candida is the most common cause of invasive fungal infection in liver, pancreas, renal and small bowel transplant recipients while aspergillosis is higher in heart and lung transplant recipients (26). Intra-abdominal abscesses and deep wound or surgical site infections have been documented at around 7-14% of pancreas transplant recipients. CDC has conducted surveillance in other sites (Connecticut and San Francisco), but only during one time period (Figure 1). For example, several clusters of invasive candidiasis in neonatal intensive care units were due to C. Renal transplant recipients have the lowest incidence of invasive fungal infections and small bowel transplant have the highest risk. Lung transplant recipients are frequently colonized with Candida and the use of extracorporeal membrane oxygenation in the post transplant period is associated with a higher rate of candidiasis.
Oral candidiasis is very common in organ transplant recipients and is greater in the first month after transplantation, however can be present for many months later (9, 24).
Some centers use antifungal prophylaxis for mucocutaneous candidiasis but this approach has not been based on documented evidence.
Risk factors for invasive fungal infections complicating orthotopic liver transplantation. Prophylaxis with caspofungin for invasive fungal infections in high-risk liver transplant recipients. Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study.
Outcome, incidence, and timing of infectious complications in small bowel and multivisceral organ transplantation patients. Esophageal candidiasis after renal transplantation: comparative study in patients on different immunosuppressive protocols. Surgical site infection in living-donor liver transplant recipients: a prospective study. Risk factors of invasive Candida and non-Candida fungal infections after liver transplantation. Use of peptide nucleic acid-fluorescence in situ hybridization for definitive, rapid identification of five common Candida species. Trends in invasive disease due to Candida species following heart and lung transplantation. Candidemia following solid organ transplantation in the era of antifungal prophylaxis: the Australian experience. Surveillance and treatment of liver transplant recipients for candidiasis and aspergillosis.
A recently published study including 1305 thoracic organ transplant recipients, between 1980 and 2004, identified 76 episodes of invasive candidiasis with an overall incidence of 5.2%. There may be also be a close correlation with the presence of underlying cytomegalovirus (CMV) infection, or this may reflect the depth of immunosuppression with the two organisms closely tied together (35). Excluding coagulase negative staphylococci, Candida was the 7th most common organism isolated from blood cultures in their study (34). The same risk factors associated with invasive disease are associated with Candida colonization in both the donor and the recipient, especially with small bowel, liver, lung and lastly kidney (24).
Vulvovaginal candidiasis can be treated with several topical antifungal agents that are effective for most not complicated cases. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study.
Mortality from invasive Candida infections ranges from 11-81% in the solid organ transplant population (56) (Table 1) and this is even higher if the patient is located in an intensive care unit (44, 49).
A recently published meta analysis regarding use of nystatin as prophylaxis for invasive fungal infections in immunosuppressed patients (including patients with liver transplant) didn’t demonstrate any benefit compared to placebo and was inferior compared to fluconazole prophylaxis (13). Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. The incidence and attributable mortality from invasive candidiasis decreased over time in all thoracic organ transplant recipients (50).
In pancreas transplant recipients who have bladder drainage, urinary colonization pre-transplantation because of diabetes and liberation of digestive enzymes into the surgical site predispose to invasive candidiasis (30).
The risk of invasive candidiasis in renal or heart transplant recipients is too low to require prophylaxis. For esophageal candidiasis, oral fluconazole is the preferred agent for 14-21 days, however in patients with prior fluconazole exposure or known fluconazole resistance, an echinocandin should be used.
Candida can enter the bloodstream by direct penetration from the epithelium after tissue damage, or by dissemination from biofilms formed on medical devices introduced into the patient’s organism (catheters, endoprotheses, artificial joints or central nervous system shunts) (18, 55).
Oral thrush may be present in only 43% of cases of esophageal candidiasis and 21.4% of patients may be asymptomatic while 54% will have dysphagia (16). Secondary effects of candidemia that should be evaluated in organ transplant recipients, especially when there are persistently positive cultures include endophthalmitis, endocarditis, meningitis and septic arthritis (6, 32, 36, 43, 45, 62). Vaginal candidiasis may also be increased in female organ transplant recipients and is frequently missed without regular screening (2). A prospective, non-comparative, open-label trial on antifungal prophylaxis with caspofungin (21 days of prophylaxis) in 71 high risk liver transplant patients, showed that only two patients experienced an invasive fungal infections (Mucor and Candida surgical wounds infection).
Overall 8 patients (11%) died during the study period and no death was attributable to an invasive fungal infection or caspofungin prophylaxis (12). A survey of 106 liver transplant centers in North America using an electronic questionnaire reported of the sites that responded (63%) 91% used routine antifungal prophylaxis, 28% universal prophylaxis and 72 % targeted high risk patients with fluconazole being the most commonly used agent (57).
Immunosuppressive therapy, especially with corticosteroids is a major risk factor for invasive candidiasis (22, 39, 55).
Use of Alemtuzumab for treatment of acute graft rejection, conferred and increased risk of invasive fungal infections, mostly esophageal candidiasis within 3 months after the start of therapy (40). There are no randomized trials of antifungal prophylaxis among small bowel transplant recipients, but the risk for invasive Candida infection is high and most experts recommend the use of antifungal prophylaxis.
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