Editorial Commentary: Galactomannan Testing During Mold-Active Prophylaxis

Choosing a prophylactic approach is a strategic decision impacting the choice, timing, and even the indication of in vitro diagnostic tests and antifungal treatments. In the past, clinical studies informing clinical decisions were conducted in settings without prophylaxis. One may object, that empiric antifungal treatment trials allowed enrolling patients on antifungal prophylaxis with fluconazole and itraconazole. However, prophylaxis with these older azoles cannot be considered effective in preventing mold infection in pivotal protocols [1–3]. There is a debate on how to treat patients with breakthrough infections during posaconazole or voriconazole prophylaxis. To date, no convincing trial addresses this clinically challenging question, likely because of the very low breakthrough rates observed [4–6]. Today’s diagnostic gold standard still depends on tissue sampling, a principle unchanged since the 19th century [7, 8]. In this issue of Clinical Infectious Diseases, Duarte et al report their experience with posaconazole prophylaxis in hematological populations at high risk. The Catalan Institute of Oncology, Barcelona, is one of the premier cancer centers in Spain and their prospective 4-year study period covers 121 patients and 262 consecutive treatment episodes. The study focuses on the effect of prophylaxis on in vitro diagnostics, namely, serum galactomannan testing in a population on active prophylaxis. During posaconazole prophylaxis, the rate of positive galactomannan screening tests was low, which is in line with previous observations in animal models and in humans [9, 10]. Interference of the posaconazole molecule with the assay itself appears unlikely, although false-negative serum results have been reported in the past [11]. When posaconazole is used prophylactically, the performance of galactomannan screening tests is impacted by the very low pretest probability of invasive fungal infection (IFI); in other words, successful prophylaxis results in low IFI breakthrough rates. In that setting, one hardly detects a case of aspergillosis by galactomannan testing, but falsepositive results become important, as they trigger a diagnostic workup and have the potential to mislead the clinician. It is important to know that we can harm simply by applying in vitro diagnostics, if the false-positive results outnumber the true positives. Actually, galactomannan screening may not be advisable at all during effective antifungal prophylaxis. Many centers must have observed this, but none published their observation as result of a prospective study. Thanks to the very timely study of Duarte et al, we now have evidence to personalize diagnostics according to the initial strategic decision. How do Duarte’s findings affect prophylactic strategies? At the University Hospital of Cologne, galactomannan screening 3 times weekly was routine practice when posaconazole prophylaxis was introduced in January 2006 [11, 12]. In 2003–2005, we ran 6950 serum galactomannan assays on samples of 190 patients, or 35 galactomannan tests per patient. When we abandoned galactomannan screening during prophylaxis in 2009, the average number substantially decreased to 8 galactomannan tests per patient (2391 tests in 273 patients) (Cologne Cohort of Neutropenic Patients, NCT01821456). Should we stop all galactomannan testing? There is at least one caveat: The pretest probability of the galactomannan Received 14 August 2014; accepted 16 August 2014; electronically published 27 August 2014. Correspondence: Oliver A. Cornely, MD, FIDSA, FACP, University Hospital of Cologne, Department I of Internal Medicine, Kerpener Str 62, 50937 Cologne, Germany (oliver.cornely@ ctuc.de). Clinical Infectious Diseases 2014;59(12):1703–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/cid/ciu677