A breath fungal secondary metabolite signature to diagnose invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. METHODS: Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. RESULTS: The monoterpenes camphene, α- and ß-pinene, and limonene, and the sesquiterpene compounds α- and ß-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, ß-trans-bergamotene, a ß-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). CONCLUSIONS: In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia.

Live attenuated varicella-zoster vaccine in hematopoietic stem cell transplantation recipients.

Hematopoietic stem cell transplantation (HSCT) recipients are at risk for varicella-zoster virus (VZV) reactivation. Vaccination may help restore VZV immunity; however, the available live attenuated VZV vaccine (Zostavax) is contraindicated in immunocompromised hosts. We report our experience with using a single dose of VZV vaccine in 110 adult autologous and allogeneic HSCT recipients who were about 2 years after transplantation, free of graft-versus-host disease, and not receiving immunosuppression. One hundred eight vaccine recipients (98.2%) had no clinically apparent adverse events with a median follow-up period of 9.5 months (interquartile range, 6 to 16; range, 2 to 28). Two vaccine recipients (1.8%) developed a skin rash (one zoster-like rash with associated pain, one varicella-like) within 42 days post-vaccination that resolved with antiviral therapy. We could not confirm if these rashes were due to vaccine (Oka) or wild-type VZV. No other possible cases of VZV reactivation have occurred with about 1178 months of follow-up. Live attenuated zoster vaccine appears generally safe in this population when vaccinated as noted; the overall vaccination risk needs to be weighed against the risk of wild-type VZV disease in this high-risk population.

BK virus disease after allogeneic stem cell transplantation: a cohort analysis.

The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.

Risk factors for invasive fungal disease in heart transplant recipients.

BACKGROUND: Heart transplant (HT) recipients are at risk for invasive fungal disease (IFD), a morbid and potentially fatal complication. METHODS: We performed a retrospective cohort study to evaluate the incidence and risk factors for IFD in HT recipients from 1995 to 2012 at a single center. IFD cases were classified as proven or probable IFD according to current consensus definitions of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. We calculated IFD incidence rates and used Cox proportional hazards models to determine IFD risk factors. RESULTS: Three hundred sixty patients underwent HT during the study period. The most common indications were dilated (39%) and ischemic (37%) cardiomyopathy. There were 23 (6.4%) cases of proven (21) or probable (2) IFD, for a cumulative incidence rate of 1.23 per 100 person-years (95% CI 0.78 to 1.84). Candida (11) and Aspergillus (5) were the most common etiologic fungi. Thirteen cases (56%) occurred within 3 months of HT, with a 3-month incidence of 3.8% (95% CI 2.2 to 6.4). Delayed chest closure (HR 3.3, 95% CI 1.4 to 7.6, p = 0.01) and the addition of OKT3, anti-thymocyte globulin or daclizumab to standard corticosteroid induction therapy (HR 2.7, 95% CI 1.1 to 6.2, p = 0.02) were independently associated with an increased risk of IFD. CONCLUSIONS: IFD incidence was greatest within the first 3 months post-HT, largely reflecting early surgical-site and nosocomial Candida and Aspergillus infections. Patients receiving additional induction immunosuppression or delayed chest closure were at increased risk for IFD. Peri-transplant anti-fungal prophylaxis should be considered in this subset of HT recipients.