Azole resistance in A. fumigatus is evolving to a global health problem.

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in immunosuppressed patients. Timely diagnosis of IPA improves survival but is difficult to make. We examined the analytical and clinical validity of galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in diagnosing IPA in a mixed population by retrospectively reviewing records of 251 consecutive at-risk patients for whom BAL fluid GM testing was ordered. The performance of the enzyme immunoassay was evaluated by using a range of index cutoffs to define positivity. Three samples were associated with proven IPA, 56 were associated with probable IPA, 63 were associated with possible invasive fungal disease (IFD), and 129 were associated with no IFD. Using a BAL fluid GM index of >0.8 (optimal optical density [OD] index cutoff identified by a receiver operating characteristic curve), the sensitivity in diagnosing proven and probable IPA was 86.4%, and the specificity was 90.7%. At this cutoff, positive and negative predictive values were 81% and 93.6%, respectively. However, an OD index value of >3.0 corresponded to a 100% specificity, thus ruling the disease in, irrespective of the pretest probability. Conversely, an OD index cutoff of <0.5 corresponded to a high sensitivity, virtually always ruling the disease out. For all values in between, the posttest probability of IPA depends largely on the prevalence of disease in the at-risk population and the likelihood ratio of the OD index value. Detection of GM in BAL fluid samples of patients at risk of IPA has an excellent diagnostic accuracy provided results are interpreted in parallel with clinicoradiological findings and pretest probabilities.

i Aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental Aspergillus strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on Aspergillus resistance among patients with Aspergillus disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patient's inclusion. A total of 220 Aspergillus isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (n ‫؍‬ 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n ‫؍‬ 39 patients), chronic pulmonary aspergillosis (n ‫؍‬ 10 patients), Aspergillus bronchitis (n ‫؍‬ 7 patients), and aspergilloma (n ‫؍‬ 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of Aspergillus fumigatus resistance was limited in our patient population with Aspergillus diseases.