Should tigecycline be considered for urinary tract infections? A pharmacokinetic re-evaluation

platelets plus amphotericin B achieved significantly greater inhibition of the germination rate (P,0.05) than did amphotericin B or platelets alone (Figure 1a). The effect was additive. These results were found with both tested amphotericin B concentrations, although 1 mg/L revealed a better inhibitory effect than the lower concentration (Figure 1a). With caspofun-gin, the germination rate was not significantly reduced (Figure 1b). When azoles were used in combination with plate-lets, the inhibitory effect was found to be additive in comparison with either azole or platelets alone (Figure 1c and d). As found for the germination rate, human platelets plus amphotericin B achieved significantly greater inhibition of hyphal elongation (P,0.05) than amphotericin B or platelets alone. Hyphal elongation was significantly reduced in all tested aspergilli, either under platelet or caspofungin treatment. When used in combination, the effect was found to be additive. The combination of platelets plus either azole at any concentration tested did not significantly enhance the reduction of hyphal elongation. Platelets decreased the ability of hyphae to reduce XTT; however, the combination of platelets plus antimycotics had no additive effect on hyphal damage (data not shown). Our findings indicate that platelets in combination with anti-mycotics exert additive effects in reducing the germination rate and hyphal elongation of A. fumigatus in vitro. Among the tested antimycotic substances, amphotericin B revealed the best results in combination with human platelets. However, platelets plus antimycotics were not additive for hyphal damage. In the immunocompromised patient, inhaled Aspergillus conidia germinate into hyphae, 1 the growing and invading structures of filamentous fungi. Consequently, blocking fungal germination and delaying hyphal growth is crucial in preventing invasive disease. In our study, the combination of platelets plus amphotericin B synergistically enhanced the antifungal activity (P,0.05) in reducing germination rate and hyphal elongation. Amphotericin B is known to complex with sterols in the fungal cell membrane, 4 leading to pore formation and increased cell membrane permeability. This could support the antifungal activity of human platelets, by enabling the penetration of antifungal platelet factors. 5 A clinical study showed that patients with invasive fungal disease had a significantly longer duration of thrombocytopenia compared with those without infection, 6 suggesting that the low platelet count is related to the infection. Our in vitro data suggest that a normal platelet count contributes to overcome fungal infections and that platelets are capable of enhancing the efficacy of antimycotics. 3 Perkhofer S, Kehrel BE, Dierich …