We review the experience at our institution with galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16), there were five cases of proven or probable IPA. All five patients had BAL GM of >2.1 and survived following antifungal therapy. The sensitivity, specificity, and positive and negative predictive values for BAL GM testing at a cutoff of >1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The sensitivity of BAL GM testing was better than that of conventional tests such as serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed IPA several days to 4 weeks before other methods for three patients. Twelve patients had BAL GM of >0.5 but no evidence of IPA. Among these, lung transplant recipients accounted for 41.7% (5/12) of the false-positive results, reflecting frequent colonization of airways in this population. Excluding lung transplants, the specificity and positive predictive value for other solid-organ transplants increased to 92.9% and 62.5%, respectively (cutoff, >1.0). In conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the institution of antifungal therapy among non-lung solid-organ transplant recipients and helped to rule out IPA.

Pulmonary aspergillosis in nonimmunocompromised hosts, although rare, is being increasingly recognized. The diagnosis of pulmonary aspergillosis is difficult, since the recovery of Aspergillus from respiratory samples cannot differentiate colonization from invasion. We assessed the role of bronchoalveolar lavage (BAL) in detecting galactomannan (GM) for diagnosing pulmonary aspergillosis in 73 nonimmunocompromised patients with pulmonary infiltrates for whom the test was ordered. Six patients had pulmonary aspergillosis, two each with acute invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and aspergilloma. All six patients had a BAL GM level of >1.18. The sensitivity, specificity, and negative predictive value (NPV) for a BAL GM level of >1.0 were 100%, 88.1%, and 100%, respectively. Notably, the positive predictive value (PPV) was only 42.9%, likely reflecting the low prevalence of pulmonary aspergillosis among nonimmunosuppressed patients. The combination of BAL microscopy and culture had a sensitivity and NPV similar to those of BAL GM detection but a higher specificity and PPV (92.5% and 54.6%, respectively). Moreover, a BAL GM test did not identify any cases that were not diagnosed by conventional methods like microscopy and culture. In conclusion, there was no conclusive benefit of determining BAL GM levels in the diagnosis of pulmonary aspergillosis among nonimmunocompromised hosts. Given the likelihood of false-positive results, a BAL GM test should not be ordered routinely in this population.

Despite shortcomings, cultures of blood and sterile sites remain the "gold standard" for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant Candida albicans antigens among 60 patients with systemic candidiasis due to various Candida spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acutephase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.