Emerging evidence supports the concept that T helper type 17 (T H 17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T H 17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony-stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury.

Receipt of high-dose steroids, history of cytomegalovirus disease, and high levels of calcineurin inhibitors are independent risk factors for Nocardia infection in organ transplant recipients. Our study provides insights into the epidemiology of Nocardia infection in the current era, a period in which immunosuppressive and prophylactic regimens have greatly evolved.

Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

No abstract

These updated AST‐IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid‐organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post‐transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12‐week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non‐lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.

No abstract

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.