In vitro Antimicrobial Activity of Linezolid Tested Against Vancomycin-Resistant Enterococci Isolated in Brazilian Hospitals

F"

In vitro

_{) *!+ ,- !". )+/}

! -! '!

2!5 2!2 (% % % ) "

22'$ 4 2 ,,%+",3

4%),3 '(+",3

/$,' 0' '7 ' ''& !($'' 2/$' $G +$$ !++$%):>2/$ + ,0' ! + + + $' $+ ' ' 2/ + '0' , ! $+ 0' ', $67+ 0' , ' 2$'$ ' , 67+ 0' ''' + '$ 9+H +$002/$+' ' 0$ '0 $ %> $' , ',9+7 +, ' '' $ +2/$7$0' ' &%* %C ( 2 +D # 4 + 4 + 4 + 0 #I' '4 +'J D # 4 +K' #L2/$+ $' $ , $ ' &( ' 2 '+,+7,' +$ &#36(2 $ '0' + ,$ ' ''$ ,%>>@ $ $'+=+ 2M+H +' +$ + '0, $+'2/$ '+,,,$$$

$ ++ 0' ' ,$ +2

/$ $'$ ++ +$+' + $ 0' '7 ' ''' 2

F " 0' '7 ' ''9+H +7 ' ' ' 2

$.L5%* .E

:B9-,))%&%%+ M:%, 1,% 0,?%A :,% '% %/%%2%AT.%5%,)J/%, IM/1$%%ADF)J/%,A)/K:0BF"( E"I%3,/ BL(LD(LDE(F"" 5%7BF"(""D(L

/$5 ' BF"(

O*G %3,%%,%% 07/, ,, .

F"(LED

* *--+** - 1 ,B+0G +*, **- *-* 0*> , 01-*,* L */*1+0*-0 +

, ** * 0 -GU#V4 *1 ,* 0 /*.- 1, * 0 0*, * +G * * / G ** ,"%W*#P'P. #OW*#PP(U!V6." 6."

FF

4 B+* * 10G --* * **+-+ *,--*10G - +*1*-*--*& 0 G0&& 0 D&40 && E* ,*--*& 40 && 0 -+ G+ -*0 * UOV* +*+*-/, *, -0J 310G --* --*10G - + 00+, .0 *1****, 003 00 G*UOV1 *1* *, * 3(4.3(.3(. 3(UO.(V - *+ 6"(06".3 6 .3( 3 03 0/0 * / G *+- , 00G

3(1UO.(V

4 +-.37 1*#P'".1 ,73 0G 0G ** >*0,**0 *, >*0* 7 * +*#PP).*+ >*0U)V; 0G./ 0 ,73 ** ; 0* -* 0*F +0 *G; 3 * 0*> *G - 1. 0** 0*, */ 0*0 ** 0**0 58- .+11*1 0 0 ** *U'V **.7*0 3*1 583 */ 0-* 0 0 *F +0U'V,**1** *- 1 *0G** 3** -* 0 / 1*,,-* 0UOV

1 ** *,7*,1 * -*,7*, * ,0** , -+* 1, *+8 &-**/*, *. -++ 0*>0* B+*+-**L 0,-** / 0G --/, 0** 0+*/ 0 +*,*+ 0*, *1*, * +G *, / G *&* 6." , -0* 2* ,*+*, *UP.#"V* C*1. B+*+-**L 0,-** * 0* - *,* 00G , 2* , *+ *, *. * 0-+* ,6."*, * ]3+1* ---* ^U##V **. * B+*+-**L 0,-** 16."

/* *4* .- * 00G*F +0U'V

*>0*D, 00G&#"")((E* J >0**. ** * 0 0 +0 23 ** * 0 1U##&#%V* -+*** , *,*** * -0J + 3* %"*.4.*** *, 5! 5%. ,;&4U$.#%.#$V(3" "(3"3+* / 0*>0* *1*,* ** * 0 */*G 1 *+0** 8 & -**/- 1* 0+*17.* *00*&* *,'%!1 '%!1 %"$"$". -* *00*&* -+ *.

1("-- 7""(1( 4 + "$" --.

+%%-- +3-- 0 + -*00*>0*U#OV

*>0** * * 1 *+ -*0 1 *.+*-0 G * * 0 */*G 1 * *,-+ *. "$.""0 6 %."(( U#OV **. + * +*B+ * , *. &* 3* 0 , ** * 0 1* *. * 0 ,- ++ ** * /G03* G 0 03* * , * +*1 -GU$.#OV

*+G3 + / 0+ "(3"

*/*G , J >0** 0*>0* 1 * / G *&* **0 * >*0* -* 0

! !

* 0 *

*G&/ G ** *0 3 0G>. #)( ." #(6 ." *3*0 ,- * -* 0*> ,003*1-* 0NF +0 -* 0&5 0*/*G,F +0.F +0 D'6."EM3 0+>-* 0.F +0 D$6 ."EM -* 0 /* 60* + 0. F +0 D!6 ." (6 ."EM ; 0* -* 0.F +0D'

F !%,.*&3,

24** * 0 */**,0*>0* , -+ 1 * 0** 0*0 ,/ G * * *

;** * F +0.F +0D!6."

#6."EM-* 00?* H[ 5 0*/*G, H.+** D#6."E 0G#*0 -- *3 * 0+*+G *0 3**,*- *0/0+*1 /* 0* * 0 *G 5 20 . 0U#(V

+ -**0*G

-03G* *0+* ,003*1 * 0*,0** 0 G DE * U#)V**+***G *D;E3 *,0*>0*.B+*+-**& 0,-**.

!,:µ;0<

:o

< !,50 !,90 # =

( *>0* !" !" #[! #"""

."D#(E A+*+-**L _' _' $&_' "" 0,-**

* -0 * _#( _#( _#( "" 7 G * _#( _#( _#( "" 4-* *00* #O $" "O[' #""" 8 * * _#""" _#""" _#""" "" -G * ≤#""" ≤#""" ≤#""" #""" JG G 0* !" $" ≤"O&$ #""" GG * _' _' _' "" 0 -* 0 _#( _#( '&_#( #'' *, -* !" _!" !&_! ""

( *>0* !" !" #&! #"""

."D#)E A+*+-**L $" _'" #&_' ##' 0,-**

FE !%,.*&3,

%4** * 0+ -**0*G, 0** 0*0 ,/ G ** *

5 a

!m;0:<b

>1c

:o

< 0 d

?;d d

4d

, d

#d

6." !DE _'DE "ODE !DE 'DE ! DE D#(E #DE _'DE #DE !DE _#(DE _! DE #DE 'DE !DE !DE _#(DE ! DE !DE _'DE #DE !DE _#(DE ! DE !DE _'DE #ODE $DE _#(DE _! DE !DE $DE #ODE ≤"ODE 'DE _! DE #DE _'DE #ODE !DE _#(DE ! DE #DE _'DE #ODE $DE _#(DE _! DE !DE _'DE "ODE $DE _#(DE _! DE ; !DE _'DE %DE !DE _#(DE ! DE !DE _'DE (DE !DE _#(DE _! DE #DE 'DE 'DE #DE 'DE ! DE !DE _'DE #ODE $DE _#(DE _! DE !DE 'DE #DE !DE _#(DE ! DE !DE _'DE #DE $DE _#(DE _! DE & #DE _'DE $DE #DE _#(DE ! DE

6." #DE $DE _#(DE ≤"ODE $DE _! DE D#)E ; !DE $DE _#(DE ≤"ODE 'DE _! DE 4!

& !DE $DE _#(DE ≤"ODE 'DE _! DE 4# ; !DE $DE _#(DE ≤"ODE 'DE _! DE 4# ; !DE $DE _#(DE ≤"ODE 'DE _! DE 4% ; !DE $DE _#(DE ≤"ODE 'DE _! DE 4$ &5 !DE #DE _#(DE $DE _#(DE _! DE ; #DE #DE _#(DE !DE _#(DE _! DE !DE $DE _#(DE #DE _#(DE ! DE 4# !DE $DE _#(DE ≤".ODE _#(DE _! DE 4! !DE $DE _#(DE ≤"ODE !DE _! DE 4# & !DE $DE _#(DE ≤"ODE 'DE _! DE 4# !DE $DE _#(DE !DE $DE _! DE 4# ; !DE $DE _#(DE ≤"ODE 'DE _! DE 4# ; !DE $DE _#(DE ≤"ODE 'DE _! DE 8 ; !DE _'DE _#(DE #DE _#(DE _! DE #DE _'DE _#(DE !DE _#(DE _! DE 4#

a

9)/X)J/%,9:%, 9H0XH%,039:%, 9)/MX9:%,)./Y,M%%, )1X)%%1%,% 9:%, )0()/X)%%0%%)J/%, 90(/$I9:%,0,?%/%%2 b

)B:, B!% $B% ,,,% %.%!*10A≥Eµ!&A:,%10A≥E!!&* !*10A≥E!!& % ,.,%%!10AZ!!& c

!%,B>X4:%,: !:X %!:,, 7*X7**, 0 ,X ,%!: , $X%!: d

FD !%,.*&3,

>258- ,'*1 043*1J -0,/ G *&*

(."3*58- D0 #&(E D0 )&#!E,*,,-* 0 3 ***0 * G*,,, G0G3 λN$'OC0 0

FL

-* *00*.JG G 0*. 0 -* 0.*, -*. 1 * *.-G *.GG *./ G * * -0 *U#'V+ 0*3+-* O0,;+00&** "O; 5 0 +**G . O"µ 3 ,#",;+00* *J300 * +0++-*3 -- .#""µ ,*+-*3 , -0 300 -0 3* + %O°* * * * + ,#(!"/ G *+0 3*- ,!$,* + * -0 3 1*> + -*0. ** * . *1+ -**0*G 1 0* ,*0+*GU#'V

2-*,+ -**0*G * . - */0GNB+*+-**L 0,-** ≤#µ1L

≥$µ1LM*, -* ≤#µ1L ≥$µ1LM 0 -* 0 ≤'µ1L ≥%!µ1LM JG G 0* ≤ $µ1L ≥ #(µ1LM * -0 * ≤ 'µ1L ≥ %!µ1LM / G * ≤$µ1L ≥%!µ1LM -* *00*

≤'µ1L ≥#(µ1LMGG * ≤"Oµ1L

≥'µ1L.1 * * ≤O""µ1L _O""µ1LD*10/0EM-G * ≤#"""µ1L _#"""µ1LD*10/0E0*>0* *-*1 ** 3 ,* ≤$µ1L + -**0*G ≥#(µ1L* U#PV B+ 0*G 0 *'64!P!#%

6."4!P!#!3 013* 0** 0*0 * ,

;0 +0 G-*1

*30 +0 G-+*158 *G, 00. 0U!"V* **1* , 043 -,3*'Ι

+0 * *, 130/* #W 1 103*5&GD*& *.* .4.4E-+0* -,O%"/!% #%° (7L 58- 3 *** 0*,G /G .**0 *,G*,,, G0G#% . *,,*,G*,,G$

#

0#3; ***O"W P"W , *0 D;O" ;P". - */0GE.;/ * * - 1, + -*0 *, -+/ 0+ 0G0*>0**** 00*0 ,- * + -*0 2-*D≤$µ1LE *1; ,* -+3 !µ1L 0!-;+0,0*>0* #" ** * 0 1 1 * 00*0 / 0+

4J- .B+*+-**L 0,-**3 -"(3" */*G 1 *."3*#""W , *3*1* * -+U%V 416."0#O,#)*0 D''!WE3 * B+*+-**L 0,-**

*10/0* -G *3 1 *0 / 0+ JG G 0*3J 00"(3" */*G 1 *- *DP$#W+ -**0*G 1

6 ." #""W + -**0*G 16 ."E . *1 0/0 * 1 * *3 /*- *3*#""W ,*

0 -* 03 */*G 1 *6.".3*($)W,+ -**0*G. + - */*G 1 *6 ." D'#!W * ED 0!E

4-* *00*3 /G */ 1 *6."

3* #""W + -**0*G. + , 6 ."*0 3+ -*0 -* *00*

0 +0 - , * 3 0 # , #(( ."

+*0 +0 G-*1.#" +*B+0 +0 - .3* 3 00 ( **1 *0 0 3 +*B+ 0 +0 - ** ,- 3 0030/,#)(."

D)#WE *3 +*B+ 9- 3* 3 004*- -$+G-4#.4!.4% 4$O **1 * ** 58- .3* 3 00.8. ..

F

*>0*3 */ -+ 1 * + 00 *,+0** *3 0G ** * 0 1 */ 1 * 00*0 + -*0 2-*D#""W+ -**0*GED 0#E * 13*-+0* +*3* 3 J +*B+ 0 ,G* ** * 0 * *

"(3" */*G 1 *+0** 8 &-**/ *.* 0+*1/ G *&* *U#OV6

***J 00"(3" */*G."(3"3

+*3** /3+0 - 0 ,/ G *,J-* 0G* , *+ *, * + (- U#%V * * 3* ** * 0 ***,-*G*.+ 0 -* 0. 0*. 0* *. -1 *. *10G *. G 0*. / U$.!#V

4 J- . -1 * * * B+*+-**L 0,-**3- */*G 1 *6 ."U%V3/. -* */*G,* -+D''!W* E 1 *6."+ - *> 0-*: +-U!!V* B+*+-**L 0,-** * 3*- ,4 8 1.3* G0 , G0G> -1 * 4 1 0 G0 , 13.3. 3 -* -G0 -*U#"V-* -1 -* 0 - ,3.4. 1 400 1 / - 1 -G0 **0 .+0G1 * 1 * 1 * 3*- 1 **0 , &* 3* 0* 0* *+ *,* *** 0 1U#"V

* ** * 0 1J**-"(3"

*/*G 1 * *.-*, ,/*, **1 00G* * 10G --* β&0 * *10G *++G. 3* 0#. 1 *10G * +

G* 0*, *.0G-G * 3 B+ "( 3" */*G 1 * / G ** **10/0* -G *3 1*0 / 0+ 3/. 00*0 3*10/0 * 1 * *

*0 0G.-**01G, 0 *, *3 -0G++ 0 2, * ** G G-*1 3/. --0* *,0 +0 0+, 10G --*&* * -/* 1 **1**-0. . 0G. 5 8 3 + , + 0 , -**01* 0 / 0+ * , * 0 0*, *UO.!%V40+1 / +,- * ,*, * + G10G --*&* / * 0+, */0/*1* *10 +0*-0 * ,6 ." . * - * +0 .6."UOV

- , *10 *,7 - , + , 9*G, 0+ / ,* *10 -* 0+*3/.*-* 0- ,7 0-. *3 .** . *+ 0 ,,- *UO.!$V

,**1,/ 0 *3*** 0**0 58- **,,* 0 *++G 10G+11*-* 0- ,/ G * * ." 6."5++* */*1 ,** *, +0** *

*0 0G. -*,- * *, 3*73J0G0**U$.!OV0G 00 L+ 00 0** 0* 0 0 -/ 0+ -+* -*,7*, *. * 0+*1JG G 0*.*, -* *. 0 -* 0. 0 */ *+ * *U%.!OV

**J 00"(3" */*G 1 * 7*0 3*-+G */ 0 */*1 *.* /+ 00*>0* -+ *1 , 0** 0+ * 0** 0* 0 */0/*1-* 0*>- *3*2*,*+ -+* U#OV+.*+G-"(3"

*, * 3*00/G0-,+0* 0,0*>0** ,*, * +G +0** ** >*0

-$

+J-** 28*0 + D3 0+>-* 0E. *8+* F 8* +D-* 0/*+0* + 0E.* 0 0F ; * + D-* 0 ; 0* E.* * ;** D ;** * +0E * ; 00 D-* 00?* HE.32*0G +7*0 ,*+G: 0 2 0 4 8 03-/*+3* * *0+* G. *1;, *

0+--#

&1A)%,%!%)A!(M.%1A%,%( , * !%, 8 % ,3% .%!* % 0,9:M:!,%))) BDE(" !M1A5 &A1%VA%,0,

.%!*(% % % !!* :%,B%*:%%% 0,9:M:!,%))) BE(

" % /. % % H%! =%!*( %M=$MG%!(MTA QH,R :B%:.!Q,*A"rd

A ,%!%* % R

F 0 PAV%1&A)%,%%$T&3,A% 7%3,A %!!,(% 6%!(:. %%, 0,

<>>> "BFE(

P SA /A 1 A ):,, 0::.,*::%0, 1,$.%)); LBL(E

E %:% 1A :% 5A 0.%, /A 1 ):* ,*:: %

%%% ,% ! 0 ! %))C FB(

D %,,%(0%&1A)3%0A1%&G5A%,!

=%!*(%%%%,%B% %,%3%)): BE(" L )%9)A$SA%,,09A%,!%, :,*4:%,:%% 6%!(:.!&%!%B$,! 6,%,)1$G6)1$G).,,%)*%3 <>>% B("

/A P% 1A 9%,,% 6A &.! 1 ):,* 4:%,: % %.%!*(%! TVAD!(!0 ! <>>> FEB(L

3% A &,4 $ M %:%!% %.* 4:(%,:%%%%%,% !0 ! %))) F"BD( &.!1>:%,:%,3,B

A A % [! 0 ! <>>> FEB"FD(

P%/A&.!1.*,3,%% !,(% 6%!(:. %% ! . :%, T V! ! 0 ! <>>> FB("

" ) , GA G %.(M,:, 0A 1,, $0A M,:, 61 . 7%3, ,3,%:3,7:!%,%(%!%, %%%%,%.%!*( %%%% ,%! 0 ! %))) F"BLD"(E

F S86A)45A)=A%,"%. ,3,%%!:%6%!(:.%%,

:% , .%!*(%

! 0 ! %))) F"B(E

0,!A1%8 %!&3,<>>> BL(D E 5%8,%!$A)% !AG7%&1MB 1%*A/$A%AMA/%,,A1A%,( 1%%, 0,%, 1,* Dth

!% )*1,*P% A0AT)%))) :D("

D S%%, 0!! 0,%, &%%* )%% S00&)(1 ,%!%,:,* %% %%%,,*A (::. %%1D(P%*A=,,%.%A/A<>>>

L S%%,0!!0,%,&%%*)%% S00&) ( /!% %% %!%, :,* !%%,::,! 1()P%*A=,,%.%A/A<>>>

9%!,0A)%:A1!%VA50P&3,A %, %%<>>> LBE(F /%,,1A$SA)%9)0 !!%,

%! %%,* * :,(, , ,: BA9(0,%,1,*/ 9%8A)1/P% 0 T)%))< :(

51A&,4$.*,3,%%6%!( :.:% :* !0 ! <>>> FBDD(L

),%1A A/ ,:(9%APS 1 %! % 4:(%,: %!,%%%%,%!%!%,A % !%A % :%, :% P M: !0 ! <>>> FFBF""(E

" )%.0A/%,,1AV3*8*A%,0!:% ! ! % %

%%% ,%B ! ,%, :!,%%0,1,%)): "EB""D(" F *1AH:%,)1A0 1A%,H%8

!,( %%%% ,%

%%,.%,%.%!*%0, 1,%))- "BFL("

1%*MG%!:%* .%!*%M(MTA<>>>QH ,R :B:%!Q,*AFth

AA,% !%* % R