These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter‐ and intraspecies susceptibility patterns can vary. Sulfonamide is the first‐line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.
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.
Purpose: To evaluate the safety of repifermin (keratinocyte growth factor-2) administered before and after autologous hematopoietic stem cell transplantation (auto-HSCT). A preliminary analysis of the ability of keratinocyte growth factor-2 to prevent mucositis was also done.Experimental Design: Forty-two patients received intravenous repifermin (25 g/kg or 50 g/kg) or placebo for 3 days before their auto-HSCT conditioning regimen and for up to 10 days after auto-HSCT. Within each dose level, 14 patients were randomized to repifermin and 7 patients to placebo. Clinical evaluations of mucositis were scheduled before auto-HSCT conditioning regimen, on the day of transplant, and three times per week until mucositis resolved.Results: In general, the incidence of adverse events was similar for patients treated with repifermin and placebo. No clinically meaningful differences were noted among treatment groups for clinical laboratory variables. Treatment groups experienced similar time to engraftment. The frequency of Grade 2 to 4 mucositis was 100% for patients in the placebo group, 64% for patients in the 25 g/kg group (P ؍ 0.041 versus placebo), and 50% for patients in the 50 g/kg group (P ؍ 0.006 versus placebo). Results of other endpoints, including pain on swallowing and use of pain medication specifically for mucositis, suggested a better outcome for patients in the 50 g/kg group compared with the placebo and 25 g/kg groups.Conclusions: Repifermin was well tolerated. Repifermin given before and after auto-HSCT seems to be active in reducing mucositis, but a larger trial will be necessary to determine the efficacy of repifermin with this dose schedule.
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