8/10/2019 Molecular microbial ecology as a diagnostic tool to identify mode of action and new targets for silver wound dressings Dr. Lindsay Kalan, Mi Zhou, Michele Suitor, Rod Precht,

1/1

Acknowledgments must be made to Glenda Motta Associates who coordinated the clinical case series.

"#$%&'$() *+&)#,+($ %$#-. (/ ( 0+(-1#/2& 3##$ 3# +0%124. *#0% #4 (&2#1 (10 1%5 3()-%3/ 4#) /+$6%) 5#'10 0)%//+1-/7+10/(. 8($(19:; "+

"#$%&'()*+%,)(-(.&+/0)%12 #34()'()25-6+7'8298)8382:-;8-8)?@AB>@C>>D2AE+F87'4+)' (G 5.7&%H-'H7+2I((3 8)3 JH'7&K() L%&+)%+/2M)&N+7/&'O(G 5-6+7'82#34()'()25P2 98)8382DQ+/'N&+RS+8-', 9+)'+72L'()OT-8&)2 5P298)838

T(-O4&%7(6&8- %(44H)&K+/ %(-()&U+ 8-- R(H)3/ 8)3 6&(V-4/ 87+ ,OF(',+/&U+3 '( 6+ 8

;+O -&); '( ',+ %,7()&% /'8'+ 8)3 /'8--+3 ,+8-&).1 *,+/+ &)G+%K()/ )++3/ '( 6+ '8%;-+3

6O /'H3O&). 4&%7(6+/ 8)3 ',+&7 +%(-(.O H/&). 4(-+%H-87 4+',(3/ 8/ ()-O 8 /48--

G78%K() (G R(H)3 68%'+7&8 87+ %H-'H7+3 6O %H77+)'-O H/+3 4+',(3/ 8)3 /'H3&+/ ,8N+

/,(R) -&W-+ 8.7++4+)' 6+'R++) %H-'H7+ 8)3 4(-+%H-87 68/+3 8FF7(8%,+/1 L(4+

&)'+7N+)K()/ -&;+ 37+//&). R&', ($&3&U+3 /&-N+7 %8) 7+@8%KN8'+ ',+ /'8--+3 R(H)3 ()'(

',+ )(748- ,+8-&). '78X+%'(7O 6H' ',+ H)3+7-O&). 4+%,8)&/4/ 87+ 3&Y%H-' '(

4+8/H7+1 "#$% %&'() *$+% &, '%- +,.-/'.*0 +-,(% &, $(-123) - +$/0,4$*.

/,+5,%$2,1 $1 /#0,1$/ 6,'1(% *1( +-*%'0- - /#*17-% $1 6,'1( +$/0,4$,&* *1(4$,4'0(-1 *& 50,+,&- #-*.$17 6#-1 %$.8-0 (0-%%$17 /,1&*$1$17 %$.8-0 ,9)%*.&% $%

'%-(:

F13)#0'&2#1 (10 G,D%&26%/

?(*H$+1- ?&=%0'$%

I+-')% 9J *,+ 4&%7(6&8- -&G+/'O-+ &) 8 6&(V-4 %8) 6+ -& );+3 '( F,8/+/ (G 4&%7(6&8- %()'84&)8K()

',7(H., '( &)G+%K() 8)3 /H6/+ZH+)' &4F8&7+3 ,+8-&). &) 8 R(H)31 0)'+7N+)K() ',8' 3&/7HF'/

4&%7(6&8- .7(R',2 &)%-H3&). 6&(V-4 %8) 8--(R ,+8-&). '( 7+/H4+1

Colonization

Contamination

Critical Colonization

Infection

F13%)6%12#1

E%%K 9

E%%K L

I+-')% >J MN [&)&4H4 P&(V-4 0),&6&'(7O 9()%+)'78K() \[P09] 8//8O/

R+7+ F+7G(74+3 () 6&(V-4 F(FH-8K()/ (G FN !"#$%& \^["?_]2 FFN '"

)*+,-&.$/) \T5`"]2 8)3 FFFN0"),+*,/ \5*99 AC_AD] .7(R) &) ',+ F7+/+)%+

(G N87O&). %()%+)'78K()/ (G 5. %(4F(H)3/ G(7 B, &) L&4H-8'+3 Q(H)3

I-H&3 \LQI]1 ) a B b LE1 CN *,+ [&)&4H4 P&(V-4 #783&%8K()

9()%+)'78K() \[P#9] (G AB, +/'86-&/,+3 6&(V-4/ .7(R) G(7 AB, &) LQI

8)3 ',+) '7+8'+3 R&', N87O&). %()%+)'78K()/ (G 5. %(4F(H)3/ G(7 AB,1

) a B b LE1

Harrisonet al.2008.Nature Rev MicroPhillipset al. 2010.Wounds International

CuS

O 4

AgN

O3

Ag2SO4

AgO

Ag2O

AgOxysalts

0

20

40

60

80

500

1000

1500

2000

Conc.

ofMetal[M]

E.coli

P.aeruginosa

S.aureus

CuS

O4

AgN

O3

Ag2SO

4AgO

Ag2O

A

gOxysalts

0

10

20

30

40

50

450

850

1250

Conc.ofMetal[M]

E.coli

P.aeruginosa

S.aureus

MN CN

"] 5. %8) +$&/' R&', 3&c+7+)' ($&38K() /'8'+/ 8)3 8ZH+(H/ 8N8&-86&-&'O

A] 5.AdeDd,8/ 8)K4&%7(6&8- 8)3 8)K6&(V-4 8%KN&'O 8' -(R+7 %()%+)'78K()/ ',8) 5."d&. 1&2+$ \/++ V.H7+ A]1

D] 5.AdeDd7+3H%+/ &)f8448K() 8)3 F7(4('+/ R(H)3 ,+8-&). &. 1&2+$ 8)3 &) 4(H/+ &)%&/&()8- R(H)3/ &) ',+ 86/+)%+ (G 68%'+7&8 \/++ V.H7+ D]1

B)%6+#'/ E#)K

I+-')% @J M)&)G+%'+3 4(H/+ &)%&/&()8- R(H)3/ R+7+ '7+8'+3 R&', (7 R&',(H'

R(H)3 37+//&)./ %()'8&)&). 5. $O/8-'/ 8)3 8//+//+3 8g+7 D (7 = 38O/1 MN Q(H)3

87+8 4+8/H7+4+)'/ 8)3 8//+//4+)' (G +F&',+-&8-&U8K() G(H)3 5. `$O/8-'/

/&.)&V%8)'-O 7+3H%+ R(H)3 87+8 h F7(4('+ 7+@+F&',+-&8-&/8K()1 ) a C b LE1 CN

044H)(,&/'(%,+4&/'7O (G ',+ R(H)3/ 7+N+8-+3 /&.)&V%8)'-O G+R+7 )+H'7(F,&-/

8)3 48%7(F,8.+ &) 5. `$O/8-'/ '7+8'+3 R(H)3/ %(4F87+3 '( H)'7+8'+31 ) a C b

LE

OPO

OPQ

9PO

E#'10M)%(R**>N

BSTOPOQ

BSTOPOQ

U#13)#$

M- GV./($3/

O

9OO

>OO

@OO

LOO

W%'3)#H=+$/R**>N

@ X(./ @ X(./ Y X(./Y X(./MN CN

ZVH%)+*%13($ "%3=#0/ (10 ?3'0. U)+3%)+(

[(,$% >J B(2%13 0%*#-)(H=+& (10 0%/&)+H26% 5#'10 &=()(&3%)+/2&/B(2%13 9 > @ L Q \ Y ]M-%^?%V =>eI =AeI i_e[ i?e[ iie[ B=e[ =?e[ BDe[

_10%)$.+1- 0+/%(/%5`E[j

S*JjEk*j

[(76&3-O

(6+/+j S*J

0EE[j ETJj TkEj

95E

PH7)

*78H48

5`E[j

S*Jj TkEj

ETJ

95Ej TkE 5`E[ lE

E#'10 [.H% klM LL0 563(4+) EIM L;&) '+87 EIM EIM EIM klM

E#'10 X')(2#1 ,%4#)% /3'0. A 4( i 4( D 4( i R;/ L+N+78- O7/ m i R++;/ m i R++;/ C@> O7/A%&'))+1- 5#'10 O+/ )( H);)(R) )( O+/ O+/ O+/ O+/E#'10 ?+`% [SO R&*a@N ?1DA >1"A ?1AB ?1"?> ?1AB ?1A= ?1?=A ?1_"A

E#'10 ?+`% [S L 5%%K/ R&*a@N ?1?B "1"i ?1"BB ? ?1DiB ? ? ?1AiB

b &$#/')% ]YPQO ]QPY9 LOPOO 9OOPOO cQ9P\Y 9OOPOO 9OOPOO Y9POQ34567 38,%2 $./*2 8&)9*2*/ :*%%&2,/ ;* ??@A ?4467 ?./,%&.B8*>*.8).2 8&)9*2*/ :*%%&2,/ ;* ?@A

C*+2*./&$.A 4E 1*&. 2F+$:9$/&/A 4'D7 4&)9*G# >*+&>F*+)% .*,+$>)2F=A 'E47

',%:$.)+= 1)/#,%)+ 8&/*)/*A H347 H$+$.)+= )+2*+&)% 8&/*/)/*A I47 I&1*+ 8&/*)/*

?5(, X%,)+0%*%13

d>

E%%K9 E%%K> E%%K@ E%%KL

X)%//+1- U=(1-%

d@ dL dQ d\

X(. 9[SO

d9

[(,$% 9J F1&$'/+#1 (10 ZV&$'/+#1 U)+3%)+(F1&$'/+#1 ZV&$'/+#1

5.+ m"= O7/ LO/'+4&% 8)K6&(K%/ &) F7+N&(H/ A R++;/

9,7()&% )()@,+8-&). R(H)3 m i R++;/ n)(R) /;&) /+)/&KN&'O '( 37+//&). %(4F()+)'/

o+ZH&7+/ 8' -+8/' R++;-O %87+ T87K%&F8K() &) 8)(',+7 /'H3O

G'3*%/

[(,$% @J ?'**(). #4 )%/'$3/e -%1%)(^/5(, /(*H$% o8).+p _@e -%1%)(^0%,)+0%*%13 /(*H$% o8).+p "i[#3($ 1'*,%) #4 -%1%)( #,/%)6%0

b #4 5#'10/ 5+3= &=(1-% +1 *+&)#,+($ *H#/+2#1 #6%) 2*%

b #4 5#'10/ &$#/+1-

B(2%13 @

T= W4T= W1

C(&3%)+($ f%1%)( J g9O

S&., F7(F(7K() (G 02+*>2$#$##,/ /F1 () 8-- N&/&'/1

I7(4 K//H+ /R86/ _Aq 7+-+N8)' 86H)38)%+ G7(4

*r? \6+G(7+ 5. ($O/8-' 8FF-&%8K()] '( B"q 7+-8KN+

86H)38)%+ () R++; B (G '7+8'4+)'1

W#3%J XWM (1($./+/ 0#%/ 1#3 +10+&(3% $+6%^0%(0 &%$$/P

k&/&6-+/&.)/ (G 7+3)+// 7+3H%+3 Q(H)3 ,+8-&).s /F-&' &)'(B /48--+787+8/

PO Q++; B R(H)3 87+8

7+3H%+3 _?q

9-&+)' R8/ N+7O F-+8/+3

R&', 37+//&).

C(&3%)+($ f%1%)(J g@Q

M3 3SOp m>?q 0" ),+*,/

ELp o+3H%+3 '( ADq 7+-8KN+ 86H)38)%+ &) K//H+ /R86/

Q(H)3 GH--O ,+8-+3 ())+$' G(--(R HF N&/&'

C(&3%)+($ f%1%)(J g>Q

M3 3SOp [(/'-O 6+'8F7('+(68%'+7&8 \9(484()838%+8+]

ELp [8&)-O3%%$9)#,%,:/F1 8)3 H),%$9)#2*+/F1

\8//(%&8'+3 R&', /;&)]1

E+F', &4F7(N+3 \C?q] 6O EB Q(H)3 S+8-+3

9()K)H+3 &4F7(N+4+)'

C(&3%)+($ f%1%)( J gQO

M3 3SOJ S&., 86H)38)%+ (G 02)>F=%$##$#,//F1 8)3

')*.&9)#&%%,//F"E@J 02)>F=%$#$##,//F1 7+3H%+3 '(

tAq 86H)38)%+1

T=0

?q

"?q

A?q

D?q

B?q

C?q

i?q

=?q

>?q

_?q

"??q

LD@" LD@A LD@D

A%$(26%M,'10(1&

%RbNH%)/(*H$%

[SO X9 E9

T=0

B(2%13 Y

T= W2 T= W4

?q

"?q

A?q

D?q

B?q

C?q

i?q

=?q

>?q

_?q

"??q

L=@A L=@D L=@B A%$(26%(,'10(1&%RbNH%)/(*H$%

[S X9 E9 E>

B(2%13 9

?q

"?q

A?q

D?q

B?q

C?q

i?q

=?q

>?q

_?q

"??q

L"@A L"@D L"@i

A%$(26%(,'10(1&%RbNH%)/(*H$% o(/+8'+-+/ /F1

I84&-O 9(484()838%+8+

I84&-O 98H-(68%'+78%+8+

5--(68%H-H4 /F1

L'7+F'(%(%%H/ /F1

l8%'(68%&--H/ /F1

I84&-O o&;+)+--8%+8+

P8%'+7(&3+/ /F1

[SO [S E> [S EL

[SO [S E> [S E@

B(2%13 ]

?q

"?q

A?q

D?q

B?q

C?q

i?q

=?q

>?q

_?q

"??q

L>@" L>@A L>@D L>@B L>@C

A%$(26%(,'10(1&%

RbNH%)/(*H$%

[S X9

[SO X9 E9 E> E@ E

X9 E> EL

U#1&$'/+#1/

[=% ,(&3%)+($ *H#/+2#1 #4 ( 5#'10 ,%0 +/ *H$%V (10 0+6%)/%

F13%)6%12#1 5+3= ( 3#H+&($ /+$6%) #V./($3 0)%//+1- &=(1-%/ 3=% ,(&3%)+($ *H#/+2#1

"#)% 0(3( ($#1- 5+3= &=(1-%/ 3# ,+#*()K%)/ +1 3=% =#/3 )%/H#1/% /=#'$0 ,% $$%&3%0

M&K1ZV&+3#1 [%&=1#$#-+%/F1&

W?ZAUJ 0oEI '(l1n8)3 #

M$,%)3( F11#6(3%/[%&=1

E%/36+%5 h%($3=U%13%)

h#5 +/ 3=+/ *%(/')%0 +1 ( &=)#1+& 5#'10i