Evaluating the causes associated with false positive Galactomannan assay in suspected cases of respiratory fungal infections.

Abstract

The circulating GM antigen is considered an important and reliable biomarker according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) guidelines. However several possible causes of false-positive reactions have been reported, including intake of certain antibiotics, cross-reactivity with other fungi (e.g. Histoplasma capsulatum, Alternaria spp., Candida spp, and Fusarium spp etc), food (Carba beans and fava beans) and food supplements. In this context, the occurrence of false-positive results may lead to an unjustified invasive investigation and anti-fungal therapy. The study was conducted to analyse of causal association of false positive galactomannan factors. BAL samples from suspected respiratory tract infections were submitted for direct microscopic examination, GM detection and fungal culture. Out of a total of 530 patients, 70 patients were in the case group (False positive GM) and 50 were in the control group (True positive). The average GMI of the case group was 2(1-4.2). and control group was 1.8(1-3.5). At a cut-off index of >1 false positive galactomannan results were observed maximum in patients who received Amoxiclav(48.5%), Piperacillin-tazobactam(33.3%), Amoxicillin(12.5%) followed by Meropenem(8.3%). The results showed a significant association(p-value <0.001) with false positive GM.. Other fungal agent colonization also had a higher GM index in the BAL sample but it is difficult to comment on association as the odds ratio was low (0.187). The odds were also lower (0.167) in dietary history to get false positive results and similarly with those on dietary supplements, but in contrast to these findings it was seen that the odd ratio was higher in patients suffering from tuberculosis(3.777) which can be attributed to increased colonization of aspergillus in TB patients. Galactomannan is the key biomarker of whether to start antifungal therapy for patients with IA and a higher mortality risk. Test results should be critically interpreted in the clinical context concerning potential causes of false-positive findings, especially with concomitant Piperacillin-tazobactam and amoxiclav use, other fungal infections and dietary history to prevent unnecessary antimycotic treatment.