Invasive fungal infections following liver transplantation: Incidence, risk factors, survival, and impact of fluconazole-resistant Candida parapsilosis (2003-2007)

Abstract

Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Nonalbicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration 8 l/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) ¼ 2.4, 95% confidence interval (CI) ¼ 1.2-5.0, P ¼ 0.01], a Model for End-Stage Liver Disease score > 25 (OR ¼ 2.4, 95% CI ¼ 1.2-4.9, P ¼ 0.02), pretransplant fungal colonization (OR ¼ 7.0, 95% CI ¼ 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR ¼ 2.8, 95% CI ¼ 1.1-7.4, P ¼ 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR ¼ 7.8, 95% CI ¼ 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.

Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high‐risk liver transplantation recipients: A propensity score analysis

“…and increasing rates of resistance have limited the use of fluconazole. (4) A recent retrospective study at the University of Pittsburgh confirmed that, compared with universal prophylaxis, targeted prophylaxis is effective, feasible, and safe. (26) Therefore, in many transplant groups, prophylaxis targeting Candida spp.…”

“…(1)(2)(3)(4)(5) Although most IFIs are due to Candida spp., the risk and severity of invasive aspergillosis (IA) in LTRs is well known. (6,7) Universal prophylaxis, mainly with fluconazole, is controversial in patients with a low risk of IFIs.…”

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

“…Invasive fungal infection is associated with high morbidity and mortality in liver transplant recipients, 229,230 with candidiasis, aspergillosis and cryptococcosis respectively being the most common fungal infections. 229 It is important to screen liver transplant candidates, if admitted to the intensive care unit (ICU) pretransplant, for fungal colonization, to determine whether targeted pretransplant or posttransplant antifungal prophylaxis is required.…”

“…229 It is important to screen liver transplant candidates, if admitted to the intensive care unit (ICU) pretransplant, for fungal colonization, to determine whether targeted pretransplant or posttransplant antifungal prophylaxis is required. 230 The improvement of perioperative and postoperative care, modification of immunosuppression, use of prophylactic measures such as trimethoprim-sulfamethoxazole against pneumocystic pneumonia, and fluconazole in high-risk patients waiting for a liver graft in the ICU, have led to a reduction in invasive fungal infections postliver transplant. 205,230 CMV infection is also common postliver transplant.…”

Prophylactic Use of Liposomal Amphotericin B in Preventing Fungal Infections Early After Liver Transplantation: A Retrospective, Single-Center Study

“…As the administration of prophylaxis to all patients undergoing LT is questionable, the most recent guidelines identify high-risk groups, in whom the incidence of FI and IFI is much higher [5]. Furthermore, the use of fluconazole is related to the emergence of mon-Candida spp, as well as fluconazole-resistant species [6]. Also, fluconazole is not active against Aspergillus spp.…”