ÿþ<HTML><HEAD><TITLE>25º Congresso Brasileiro de Microbiologia </TITLE><link rel=STYLESHEET type=text/css href=css.css></HEAD><BODY aLink=#ff0000 bgColor=#FFFFFF leftMargin=0 link=#000000 text=#000000 topMargin=0 vLink=#000000 marginheight=0 marginwidth=0><table align=center width=700 cellpadding=0 cellspacing=0><tr><td align=left bgcolor=#cccccc valign=top width=550><font face=arial size=2><strong><font face=Verdana, Arial, Helvetica, sans-serif size=3><font size=1>25º Congresso Brasileiro de Microbiologia </font></font></strong><font face=Verdana size=1><b><br></b></font><font face=Verdana, Arial,Helvetica, sans-serif size=1><strong> </strong></font></font></td><td align=right bgcolor=#cccccc valign=top width=150><font face=arial size=2><strong><font face=Verdana, Arial, Helvetica, sans-serif size=1><font size=1>ResumoID:1800-1</font></em></font></strong></font></td></tr><tr><td colspan=2><br><br><table align=center width=700><tr><td>Área: <b>Micologia Médica ( Divisão B )</b><p align=justify><strong><SPAN STYLE="FONT-STYLE: ITALIC;">IN VITRO</SPAN> ACTIVITY OF TERBINAFINE AGAINST <SPAN STYLE="FONT-STYLE: ITALIC;">CRYPTOCOCCUS NEOFORMANS</SPAN> AND <SPAN STYLE="FONT-STYLE: ITALIC;">CRYPTOCOCCUS GATTII</SPAN> ISOLATES. </strong></p><p align=justify><b><u>Caroline Rezende Guerra </u></b> (<i>UFRJ</i>); <b>Amanda da Silva Costa </b> (<i>UFRJ</i>); <b>Sonia Rozental </b> (<i>UFRJ</i>)<br><br></p><b><font size=2>Resumo</font></b><p align=justify class=tres><font size=2> <p><font size="2"><b style="font-family: Arial,Helvetica,sans-serif;"><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt;">The yeasts <span style="font-style: italic;">Cryptococcus neoformans </span>and <span style="font-style: italic;">Cryptococcus gattii </span> cause cryptococosis in imunosuppressed and imunocompetent individuals, respectively. Nowadays, the treatment in <st1:country-region><st1:place>Brazil</st1:place></st1:country-region> is done with amphotericin B, fluconazole or itraconazole. However, frequent clinical failure has been reported. Terbinafine is an antifungal used mostly against dermatophytes but its activity <span style="font-style: italic;">in vitro </span>and <span style="font-style: italic;">in vivo</span> against several fungi has been shown. The aim of this work was to evaluate the effect of terbinafine and its combinations with other antifungals in<span style="font-style: italic;"> C. neoformans</span> and <span style="font-style: italic;">C. gattii</span> isolates.<o:p></o:p></p> </b></font></p><p style="font-family: Arial,Helvetica,sans-serif;"><font size="2"><b><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt;">The antifungals used in this work were: amphotericin B, fluconazole, itraconazole and terbinafine. First, 23 <span style="font-style: italic;">C. neoformans</span> and 11 <span style="font-style: italic;">C. gattii </span>isolates were used for microdilution assays (M27-A3 protocol, CLSI 2008) in order to determine the inhibitory concentrations by spectrophotometric reading at 492nm, after 72h at 35ºC. Second, we determined the minimum fungicidal concentration (MFC) after transferring 5<span style="font-family: Symbol;">m</span>l of each well of the microdilution plates onto sabouraud agar plates. After 72h, the MFC was considered the lowest concentration where there was no colony growth.<span style="">&nbsp; </span>In order to combine the drugs <span style="font-style: italic;">in vitro</span><i style="">,</i> we performed checkerboard assays<i style=""> </i>between terbinafine and the other antifungal agents used in the treatment of cryptococosis. The microplates were incubated and read as described previously. Furthermore, we processed one isolate of each species for conventional transmission electron microscopy (TEM), to observe ultrastrucutural alterations caused by terbinafine treatment. <i style=""><o:p></o:p></i><span style="font-style: italic;" lang="EN-US"><br></span></p></b></font></p><p><font size="2"><b><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt; font-family: Arial,Helvetica,sans-serif;"><span style="font-style: italic;" lang="EN-US">Cryptococcus</span><span style="font-style: italic;"> </span>sp. isolates were more susceptible to terbinafine, where 90% of the isolates had an inhibitory concentration of 50% of growth (IC<sub>50</sub>) up to 0,5<span style="font-family: Symbol;">m</span>g/ml. Also, terbinafine showed a fungistatic effect due to high MFC values. Among the combinations tested, all had a synergistic effect. Moreover, there was a great reduction of the concentration of the drugs combined, compared to the IC<sub>50</sub>. In addition, TEM allowed us to see alterations in the cell wall structure, membrane detachment and an increase of cytoplasmatic vacuoles.<span style=""> <br></span></p><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt; font-family: Arial,Helvetica,sans-serif;"><span style="">Thus, we believe that terbinafine, when used alone or in combination, has a good <span style="font-style: italic;">in vitro </span>activity against <span style="font-style: italic;">Cryptococcus</span> sp. Therefore, terbinafine can be used as an alternative in patients who do not respond to conventional treatment. However, clinical trials are needed.</span><font size="2"><b style="font-family: Arial,Helvetica,sans-serif;"><span style="font-size: 12pt;" lang="EN-US"><span style="font-style: italic;"></span></span></b><b><span style="font-size: 12pt;" lang="EN-US"><span style="font-style: italic;"> <span style="font-style: italic;"></span></span></span></b></font></p></b></font></p><p><font size="2"><b><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt; font-family: Arial,Helvetica,sans-serif;"><font size="2"><b><span style="font-size: 12pt;" lang="EN-US"><span style="font-style: italic;"></span></span></b></font></p></b></font></p><p>Financial support: CNPq and FAPERJ<br></p><p style="font-family: Arial,Helvetica,sans-serif;"><font size="2"><b><p class="MsoNormal" style="text-align: justify; text-indent: 35.4pt; font-family: Arial,Helvetica,sans-serif;"><font size="1"><b><span style="font-size: 12pt;" lang="EN-US"></span></b></font></p></b></font></p> </font></p><br><b>Palavras-chave: </b>&nbsp;Cryptococcus neoformans, Cryptococcus gattii, Terbinafine, Transmission Electron Microscopy</td></tr></table></tr></td></table></body></html>