Epidemiology, clinical characteristics, and outcome of invasive aspergillosis in renal transplant patients.

BACKGROUND: Invasive aspergillosis (IA) has been considered an infrequent complication after renal transplantation. We aimed to evaluate the differences in clinical and epidemiologic characteristics of IA between renal and other types of transplantation. METHODS: We reviewed all cases of solid organ transplant (SOT) recipients from Hospital Clinic at Barcelona, who had proven and probable IA, according to the EORTC/MSG criteria, between June 2003 and December 2010. RESULTS: A total of 1762 transplants were performed. From this cohort, 27 cases of IA were diagnosed (1.5%): in 56% (15/27) liver, 33% (9/27) kidney, and 11% (3/27) combined transplant. The median onset time from renal and non-renal transplants to IA was 217 and 10 days, respectively (P < 0.001). There were 6 cases (22%) of late IA (>6 months), all in kidney recipients (P < 0.001). Renal transplant patients with IA more frequently had chronic lung disease (44% vs. 6%) and chronic heart failure (33% vs. 6%); they also had none of the classical risk factors for IA defined for liver transplantation (0% vs. 33%, P = 0.001), and therefore they did not receive antifungal prophylaxis (0% vs. 72%, P = 0.001). In 14/24 patients, serum galactomannan antigen was positive, and this related to higher mortality. CONCLUSIONS: While classical risk factors described for IA in liver recipients are still valid, IA appears later in renal patients and is commonly associated with co-morbid conditions.

Environmental variables associated with an increased risk of invasive aspergillosis.

Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28-42 days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.

Late-onset Pneumocystis jirovecii pneumonia in solid organ transplant recipients.

Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late-onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T-cell lymphopenia should be addressed in future studies.

Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed. METHODS: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed. RESULTS: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05). CONCLUSIONS: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.

Trends in frequency and in vitro susceptibilities to antifungal agents, including voriconazole and anidulafungin, of Candida bloodstream isolates. Results from a six-year study (1996-2001).

The frequency of isolation and antifungal susceptibility patterns to established and two new antifungal agents were determined for 218 Candida spp isolates causing bloodstream infection from 1996 to 2001. Overall, 41.7% of the candidemias were due to C. albicans, followed by C. parapsilosis (22%), C. tropicalis (16.1%), C. glabrata (11.9%), C. krusei (6%) and miscellaneous Candida spp (2.3%). Isolates of C. albicans C. parapsilosis and C. tropicalis (80% of isolates) were highly susceptible to fluconazole (94 to 100% at /= 32 microg/ml).