REVIEW PAPER Prognostic value of galactomannan: current evidence for monitoring response to antifungal therapy in patients with invasive aspergillosis Laura L. Kovanda 1,2 • Amit V. Desai 1 • William W. Hope 2 Received: 2 September 2016 / Accepted: 3 February 2017 Ó Springer Science+Business Media New York 2017 Abstract Galactomannan (GM) is a polysaccharide pre- sent in the cell wall of Aspergillus spp. that is released during growth of the organism. It has been successfully used to aide in the diagnosis of invasive aspergillosis allowing for earlier recognition of disease compared to conventional methods. Since its implementation in the clinic as a diagnostic tool, GM has been used in experi- mental models to measure therapeutic response. Several clinical studies describe the prognostic value of GM. Herein, we review the evidence supporting the utilization of GM antigen as a biomarker to measure response to systemic antifungal therapy. Keywords Galactomannan Á Biomarker Á Aspergillosis Á Antifungal Á Prognostic tool Introduction Invasive aspergillosis (IA) causes significant morbidity and mortality [1]. Treatment is complicated by the limited number of antifungal classes and agents, antifungal drug toxicity, an incomplete spectrum of antifungal activity, and increasing incidence of antifungal resistance [2–6]. The routine management of patients is usually complicated by uncertainty in the diagnosis, delayed treatment and absence of information on the appropriate duration of therapy. One of the biggest hurdles in clinical care is the assessment of the response to therapy at the bedside. Clinical signs and symptoms are notoriously nonspecific, radiological abnor- malities often worsen before improving and clinical response to therapy occurs over weeks-to-months. Better clinical and laboratory tools that enable the therapeutic response to therapy to be followed would be a considerable advance in the routine care of patients with IA. In addition, objectively assessing clinical outcomes in therapeutic trials of new antifungal drugs is difficult and could be improved with the use of a biomarker such as galactomannan (GM). Galactomannan is a polysaccharide present in the cell wall of Aspergillus spp., and some other fungi [7]. It is released by hyphae, which are the biologically invasive forms of filamentous moulds. A commercial double-sand- wich enzyme-linked immunosorbent galactomannan assay (ELISA) is available to detect Aspergillus GM antigen in body fluids. The assay uses a monoclonal IgM obtained from rats following challenge with mycelial extracts from Aspergillus spp. [7, 8]. The assay has become a standard of care for the diagnosis of invasive disease in high risk patients [9]. Herein, we review the literature on the use of GM as a biomarker of therapeutic response both in experimental models and in the treatment of patients infected with Aspergillus spp. A review of the literature was completed using a standard PubMed search for ‘‘galactomannan and pharmacodynamics’’, ‘‘galactomannan and Aspergillus spp.’’, ‘‘triazole and galactomannan’’, ‘‘echinocandin and galactomannan’’, and ‘‘polyene and galactomannan’’. Articles related to the use of GM as a marker of response to treatment were reviewed. & Laura L. Kovanda laura.kovanda@astellas.com 1 Astellas Pharma Global Development, Inc., Northbrook, IL, USA 2 Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK 123 J Pharmacokinet Pharmacodyn DOI 10.1007/s10928-017-9509-1