Several combination studies have been performed using animal

Several combination studies have been performed using animal models of mucormycosis, principally involving R. arrhizus. In two investigations using diabetic and/or neutropenic mice, a combination of a polyene with an echinocandin was shown to improve survival compared with monotherapies [25], [34]. Combining a polyene with posaconazole resulted in a synergistic effect in one study [32] but was found to offer no therapeutic advantages over the polyene alone in another investigation [27]. A more recent report showed that administration of isavuconazole and micafungin in combination to a neutropenic murine model of R. arrhizus infection does not result in improved survival compared with the corresponding monotherapies [22]. The effects of deferasirox, an iron chelator that exhibits activity against Mucorales fungi, have also been evaluated in double combination with L-AmB [24] and in triple combination with L-AmB and micafungin [26]. Both of these combinations, which were administered to diabetic mice, resulted in synergistic interactions [24], [26]. Despite these interesting results, when L-AmB combined with deferasirox was evaluated in a double-blind multicentre study of patients with mucormycosis, higher mortality was observed in the combination therapy group [47]. Few clinical data are available for other drug combinations. In a retrospective study of patients with rhinocerebral mucormycosis, a polyene + caspofungin combination therapy was found to be associated with improved survival [48]. However, a recent retrospective investigation of patients with mucormycosis and haematological malignancies deemed the use of combination therapy to have no impact on survival [49]. According to current recommendations, combination therapy is not a first-choice treatment [5]. A polyene with caspofungin is merely marginally supported as a first-line treatment and salvage therapy, and a polyene with posaconazole is only supported with moderate strength.
Conclusion Funding: None. Competing interests: ED has received research grants from MSD and Gilead, travel grants from Gilead, MSD and Astellas, and speaker's fee from Gilead, MSD and Astellas. Ethical approval: Not required.
Introduction Fungi can easily colonize on the surfaces of most materials and rapidly spread fungal spores [1]. The formation of fungal contamination seriously threatens human health and may cause huge economic losses [2], [3], [4], [5]. Therefore, effective method against those dopamine antagonist drugs is highly desired. One kind of the most recently developed biocidal nanomaterials is graphene and its derivatives [6], [7], [8], [9], [10], [11], [12], [13], [14]. They are intensively studied as carbon-based antimicrobial materials with many potential applications, such as use in the field of medicine, energy and environment [6], [15], [16]. As a breakthrough, Hu et al. found that metabolic activity of E. coli decreases dramatically in the presence of GO or reduced GO (RGO) sheets [17]. Liu et al. revealed that GO derivative could aggregate and locally damage the cell membrane integrity [18]. Tu et al. made a deeper insight that graphene and GO destruct and extract the phospholipids of E. coli membranes [19]. A comprehensive understanding was reported by Hui et al., they demonstrated the key influence factor of proteins on realizing their antibacterial effects. Presence of proteins can inhibit the antibacterial properties of graphene-based materials (GMs) [20]. However, until now, most of the antimicrobial studies of GMs mainly focus on antibacterial performance, rather than antifungal property [21], [22], [23], [24], [25]. This situation is also in agreement with other antimicrobial materials. More than 90% of the researches are about antibacterial materials, while antifungal materials are less than 10% [26], [27], [28], [29]. Recently, the GO-silver nanocomposite with antifungal performance was reported [30], in which the silver nanoparticles wrapped into graphene nanoscrolls exhibite ideal lengthened activities by durative slow-releasing. Han’s group revealed that GO-silver nanocomposite obtained by electrostatic self-assembly can also be a novel antifungal agent for crop disease prevention [31]. Besides, Chen et al. indicated the antimicrobial activity of GO can be triggered in liquid system, where it can interwind bacteria and fungal spores, resulting in membrane damage of the cells [32]. These studies suggest that the GMs are potential antifungal materials. To achieve superior antifungal performance, two aspects should be taken into account. On the one hand, the use of silver nanoparticles should be cautious. Silver nanoparticles have been demonstrated to cause adverse effects for organism and, especially, humans [33], [34], [35]. On the other hand, antifungal performance on the solid surfaces of the GMs is needed. Filamentous fungi grow on solid surfaces can penetrate progressively deeper into the substrate [36], [37]. Studies showed that surface contamination in hospital is heavy and threaten patients’ lives [38]. Improving antifungal performance of the GMs on solid surface is still a challenge. Therefore, a new strategy is required to enhance the antifungal effect of the GMs on solid surface, meanwhile, ensure its biosafety.