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30-­‐04-­‐15	
  
1	
  
Konrad	
  Adenauer	
  
Chancellor	
  of	
  Germany	
  	
  	
  1949-­‐1963	
  
“Only	
  a	
  stupid	
  man	
  
doesn’t	
  admit	
  to	
  his	
  
mistaken	
  opinions.	
  
	
  	
  	
  
A	
  wise	
  man	
  changes	
  his	
  
opinion	
  upon	
  recognizing	
  
the	
  facts”*	
  
*	
  not	
  an	
  exact	
  quote	
  –	
  I	
  was	
  young	
  at	
  the	
  Mme	
  
	
  
	
  
	
  
*	
  front	
  Against	
  MISuse	
  of	
  ScienMfic	
  data	
   Bode	
  et	
  al.	
  	
  NEJM	
  2010,	
  Januray	
  7th	
  
30-­‐04-­‐15	
  
2	
  
Bode	
  et	
  al.	
  	
  NEJM	
  2010,	
  Januray	
  7th	
  
¤ Did	
  you	
  ever	
  get	
  a	
  clear	
  explanaMon	
  how	
  this	
  
miracle	
  is	
  supposed	
  to	
  work?	
  	
  
¤ Did	
  you	
  ever	
  get	
  a	
  clear	
  explanaMon	
  how	
  this	
  is	
  
supposed	
  to	
  work?	
  	
  
¤ 	
  Why	
  would	
  you	
  only	
  use	
  it	
  for	
  paMents?	
  
30-­‐04-­‐15	
  
3	
  
van	
  Vugt	
  et	
  al.	
  	
  Surg	
  Infect	
  	
  doi.:10.1089/sur.2014.022	
   van	
  Vugt	
  et	
  al.	
  	
  Surg	
  Infect	
  	
  doi.:10.1089/sur.2014.022	
  
van	
  Vugt	
  et	
  al.	
  	
  Surg	
  Infect	
  	
  doi.:10.1089/sur.2014.022	
  
If	
  nearly	
  half	
  of	
  these	
  professionals	
  are	
  S.	
  aureus	
  carriers	
  –	
  
Why	
  wouldn’t	
  we	
  decolonize	
  them,	
  or	
  does	
  anyone	
  actually	
  
believe	
  that	
  those	
  masks	
  stop	
  S.	
  aureus	
  from	
  spreading?	
  
Sh…	
  can’t	
  get	
  
through	
  the	
  mask	
  
…	
  thus,	
  why	
  
wouldn’t	
  you	
  
treat	
  this	
  nose?	
  
¤ 	
  11	
  Dutch	
  centers	
  just	
  started	
  a	
  study	
  	
  
	
  to	
  evaluate	
  the	
  effect	
  of	
  decolonizaMon	
  
¤ 	
  Some	
  university	
  hospitals	
  only	
  	
  
	
  implemented	
  “decolonizaMon”	
  for	
  	
  
	
  cardiothoracic	
  surgery!	
  
¤ 	
  Many	
  hospitals	
  are	
  not	
  doing	
  it!	
  
¤ 	
  Many	
  cannot	
  do	
  PCRs	
  or	
  even	
  
	
  the	
  needed	
  cultures	
  
¤ 	
  Many	
  can’t	
  spare	
  the	
  extra	
  costs	
  
Science 	
   	
   	
   	
   	
   	
   	
   	
   	
   	
   	
   	
  	
  	
  	
  	
  	
  	
  Clinic 	
  	
  
30-­‐04-­‐15	
  
4	
  
¤ 	
  LogisMcal	
  nightmare	
  
¤ 	
  When	
  to	
  do	
  the	
  screening	
  cultures	
  
² 	
  on	
  admission	
  (too	
  late,	
  PCR	
  must)	
  
² 	
  during	
  “in-­‐take”	
  okay,	
  but	
  how	
  to	
  deliver	
  the	
  meds	
  
	
  
¤ 	
  When	
  &	
  how	
  to	
  start	
  the	
  treatment	
  
² At	
  least	
  3-­‐Mmes	
  before	
  the	
  operaMon	
  –	
  aker	
  that	
  
by	
  the	
  nurses	
  in	
  the	
  hospital	
  (they	
  will	
  love	
  you	
  for	
  
the	
  extra	
  work)	
  
² Start	
  on	
  day	
  5	
  before	
  the	
  operaMon	
  –	
  first	
  day	
  in	
  	
  
	
  hospital	
  =	
  last	
  day	
  
¤ 	
  LogisMcal	
  nightmare	
  
The	
  soluMon:	
  
Treat	
  them	
  all	
  !	
  
¤ 	
  Far	
  to	
  expensive	
  
The	
  soluMon:	
  
Treat	
  them	
  all	
  !	
   culture	
  €	
  >	
  treatment	
  €	
  	
  
¤ 	
  Missing	
  the	
  intermediate	
  carriers	
  
The	
  soluMon:	
  
Treat	
  them	
  all	
  !	
  
30-­‐04-­‐15	
  
5	
  
Decolonisation – Is it effective?
•  Decolonisation
– Mupirocin effective for MRSA eradication1
– Reduction in S. aureus infection2,3
(RR 0.55, 95% CI 0.43 - 0.70)2
•  Source control - Chlorhexidine
– Routine bathing in ICU4,5
•  MRSA acquisition decreased by 32%
•  HCAI BSI rates decreased by 28%
1. Ammerlaan et al. Clin Infect Dis 2009; 48: 922-30
2. van Rijen et al. Cochrane Database Syst Rev 2008; 4: CD006216
3. Bode et al. N Engl J Med 2010; 362: 9-17
4. Climo MW et al. Crit Care Med 2009; 37:1858-1865
5. Climo MW et al. N Engl J Med 2013; 368: 533-42
Relationship between mupirocin use
and resistance
Patel et al. Clin Infect Dis 2009; 49: 935-41
… but not if you
give it to 70% of
the people who
don’t need it !
Mupirocin Resistance in MRSA
HUG 1999-2008
0
200
400
600
800
1000
1200
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
No.isolates(1isolateper
patientperyear)
0
10
20
30
40
50
60
70
80
90
100
%isolatesresistant
Sensitive
Resistant
% Resistant
Clinical significance of resistance
•  Mupirocin
•  High-level - decolonization failure1
•  Low-level - unclear
•  Chlorhexidine
•  qacA/B gene carriage - unclear2
1. Robicsek et al. Infect Control Hosp Epidemiol 2009; 30: 623-32
2. Vali L et al. J Antimicrob Chemother 2008; 61: 524-32
30-­‐04-­‐15	
  
6	
  
Epidemiology of
Chlorhexidine Resistance in MRSA
•  qacA/B genes found worldwide in MRSA1
– 10%–20% UK
– 63% European
– 80% Brazilian
– 55% Taiwanese
1. Batra et al. Clin Infect Dis 2010; 50: 210-7
Genotypic chlorhexidine resistance in MRSA blood cultures
HUG 1999 to 2008
0
2
4
6
8
10
12
14
16
18
20
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
NumberofMRSA
bloodcultureisolates
qacA-qacB absent
qacA-qacB present
qacA-qacB in 161/188 (86%) blood cultures
Resistance in Blood Cultures
HUG 1999 to 2008
No. isolates %
Sensitive 25 13
Resistant
Mupirocin only 2 1
Chlorhexidine only 60 32
Both 101 54
Total 188 100
The Question 2
Is there a correlation between
mupirocin use and emergence of
resistance?
Relationship between mupirocin consumption and
mupirocin resistance
0
10
20
30
40
50
60
70
80
90
100
80 100 120 140 160 180 200
Mupirocin consumption (g)
Mupirocinresistance(%)
r = 0.87, p= 0.002
The Question 3
Are low-level mupirocin and
chlorhexidine resistance
associated with
decolonisation failure ?
30-­‐04-­‐15	
  
7	
  
Cases Controls Univariate analysis
Exposure n (%) n (%) OR (95% CI) p value
Mupirocin resistance
L-MuR 49 (64) 26 (35) 3.4 (1.7-7.1) 0.0003
V588F mutation 52 (69) 26/73 (36) 4.6 (2.1-9.9) <0.0001
mupA gene 12/49 (24) 2/26 (8) 5.1 (1.0-25.8) 0.03
Chlorhexidine resistance
qacA/B gene 68 (91) 51 (68) 10.2 (2.6-40.7) <0.0001
Resistance combinations
Fully sensitive 6 (8) 24 (32) 0.1 (0.007-0.37) <0.0001
Mupirocin R only 1 (1) 0 (0) … 0.32
Chlorhexidine R only 21 (28) 25 (33) 0.7 (0.3-1.6) 0.44
Resistant to both 47 (63) 26 (35) 3.2 (1.6-6.5) 0.001
Results - Resistance to
Mupirocin and Chlorhexidine Conclusions
1.  Mupirocin and chlorhexidine resistance
are common in MRSA at HUG (and elsewhere)
2.  Resistance correlates with use of these
agents
3.  Low-level mupirocin and chlorhexidine
resistance are strongly associated with
failure of decolonization therapy
Conclusions (2)
4.  Emergence of resistance and its impact
should be monitored in institutions with
widespread use of these agents
5.  Alternative agents may be required to
effectively prevent S. aureus infections in
settings with high prevalence of
resistance
Steed	
  et	
  al.	
  	
  	
  Am	
  J	
  Infect	
  Control	
  2014	
  
Steed	
  et	
  al.	
  	
  Am	
  J	
  Infect	
  Control	
  2014	
   Steed	
  et	
  al.	
  	
  	
  Am	
  J	
  Infect	
  Control	
  2014	
  
¤ 	
  Very	
  effecMve	
  in	
  reducing	
  the	
  bacterial	
  load,	
  	
  
	
  but	
  …	
  	
  
	
  
¤ 	
  …	
  2	
  hours	
  aker	
  last	
  applicaMon:	
  what	
  is	
  the	
  	
  
	
  	
  	
  	
  	
  bacterial	
  load	
  on	
  the	
  next	
  morning?	
  
¤ 	
  …	
  no	
  informaMon	
  about	
  effect	
  aker	
  mulMple	
  	
  
	
  	
  	
  	
  	
  day	
  use	
  (load	
  reducMon?,	
  side	
  effects?)	
  	
  
¤ 	
  …	
  no	
  informaMon	
  on	
  the	
  percentage	
  of	
  HCWs	
  	
  
	
  	
  	
  	
  	
  that	
  became	
  MRSA-­‐free	
  
30-­‐04-­‐15	
  
8	
  
Bryce	
  et	
  al.	
  	
  J	
  Hosp	
  Infect	
  2014;	
  doi:	
  10.1016/j.jhin.2014.06.017.	
  [Epub	
  ahead	
  of	
  print]	
  
…	
  am	
  I	
  even	
  
needed?	
  
Johnson	
  et	
  al.	
  	
  J	
  Arthroplasty	
  2010;25:Suppl.1	
  
Two	
  wipes,	
  no	
  muprirocin,	
  no	
  infecMon	
  !	
  
…	
  always	
  
thought	
  so	
  –	
  
not	
  needed!	
  
nasal cover-up* 3 g
*	
  for	
  non-­‐compliance	
  with	
  IC	
  measures	
  and	
  paMent	
  miss-­‐management	
  
¤ 	
  PrevenMng	
  HAI?	
  
¤ 	
  Scrub	
  versus	
  wipes	
  
² Significant	
  difference	
  in	
  
acMve	
  concentraMon	
  on	
  skin	
  
Noto	
  et	
  al.	
  	
  JAMA.	
  2015;313(4):369-­‐378	
  
30-­‐04-­‐15	
  
9	
  
Let’s	
  fight	
  S.	
  aureus.	
  
Love	
  to	
  Screen	
  &	
  Scrub.	
  	
  
¤ 	
  Are	
  they	
  convinced	
  that	
  decolonizaMon	
  is	
  	
  
	
  needed?	
  
² 	
  InformaMon	
  only	
  probably	
  doesn’t	
  work	
  	
  
	
  à	
  screening	
  &	
  informaMon	
  probably	
  does	
  
¤ 	
  What	
  is	
  the	
  compliance	
  with	
  decolonizaMon?	
  
² 	
  Unknown	
  à	
  but	
  we	
  sMll	
  see	
  S.	
  aureus	
  infecMons	
  
¤ 	
  What	
  are	
  their	
  abiliMes	
  to	
  apply	
  the	
  	
  
	
  treatment?	
  
² 	
  Can	
  the	
  elderly	
  even	
  use	
  a	
  CHX-­‐scrub?	
  
¤ Since	
  this	
  is	
  not	
  the	
  
typical	
  elderly	
  paMent	
  
q 	
  Nearly	
  impossible	
  logisMcs	
  in	
  hospitals	
  
q 	
  Expensive	
  or	
  as	
  an	
  alternaMve	
  (treat	
  	
  
	
  them	
  all)	
  leading	
  to	
  resistance	
  
q 	
  Frequently	
  not	
  taken-­‐up	
  by	
  paMents	
  
q 	
  Impossible	
  for	
  elderly	
  paMents	
  
q 	
  Not	
  the	
  most	
  acMve	
  CHX	
  chosen	
  
q 	
  All	
  of	
  the	
  above	
  
30-­‐04-­‐15	
  
10	
  
Disclaimer:	
  My	
  personal	
  conclusions	
  on	
  the	
  mauer	
  might	
  be	
  different	
  from	
  the	
  presented	
  content	
  

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ESCMID pro-con on S. aureus decolonization

  • 1. 30-­‐04-­‐15   1   Konrad  Adenauer   Chancellor  of  Germany      1949-­‐1963   “Only  a  stupid  man   doesn’t  admit  to  his   mistaken  opinions.         A  wise  man  changes  his   opinion  upon  recognizing   the  facts”*   *  not  an  exact  quote  –  I  was  young  at  the  Mme         *  front  Against  MISuse  of  ScienMfic  data   Bode  et  al.    NEJM  2010,  Januray  7th  
  • 2. 30-­‐04-­‐15   2   Bode  et  al.    NEJM  2010,  Januray  7th   ¤ Did  you  ever  get  a  clear  explanaMon  how  this   miracle  is  supposed  to  work?     ¤ Did  you  ever  get  a  clear  explanaMon  how  this  is   supposed  to  work?     ¤   Why  would  you  only  use  it  for  paMents?  
  • 3. 30-­‐04-­‐15   3   van  Vugt  et  al.    Surg  Infect    doi.:10.1089/sur.2014.022   van  Vugt  et  al.    Surg  Infect    doi.:10.1089/sur.2014.022   van  Vugt  et  al.    Surg  Infect    doi.:10.1089/sur.2014.022   If  nearly  half  of  these  professionals  are  S.  aureus  carriers  –   Why  wouldn’t  we  decolonize  them,  or  does  anyone  actually   believe  that  those  masks  stop  S.  aureus  from  spreading?   Sh…  can’t  get   through  the  mask   …  thus,  why   wouldn’t  you   treat  this  nose?   ¤   11  Dutch  centers  just  started  a  study      to  evaluate  the  effect  of  decolonizaMon   ¤   Some  university  hospitals  only      implemented  “decolonizaMon”  for      cardiothoracic  surgery!   ¤   Many  hospitals  are  not  doing  it!   ¤   Many  cannot  do  PCRs  or  even    the  needed  cultures   ¤   Many  can’t  spare  the  extra  costs   Science                                    Clinic    
  • 4. 30-­‐04-­‐15   4   ¤   LogisMcal  nightmare   ¤   When  to  do  the  screening  cultures   ²   on  admission  (too  late,  PCR  must)   ²   during  “in-­‐take”  okay,  but  how  to  deliver  the  meds     ¤   When  &  how  to  start  the  treatment   ² At  least  3-­‐Mmes  before  the  operaMon  –  aker  that   by  the  nurses  in  the  hospital  (they  will  love  you  for   the  extra  work)   ² Start  on  day  5  before  the  operaMon  –  first  day  in      hospital  =  last  day   ¤   LogisMcal  nightmare   The  soluMon:   Treat  them  all  !   ¤   Far  to  expensive   The  soluMon:   Treat  them  all  !   culture  €  >  treatment  €     ¤   Missing  the  intermediate  carriers   The  soluMon:   Treat  them  all  !  
  • 5. 30-­‐04-­‐15   5   Decolonisation – Is it effective? •  Decolonisation – Mupirocin effective for MRSA eradication1 – Reduction in S. aureus infection2,3 (RR 0.55, 95% CI 0.43 - 0.70)2 •  Source control - Chlorhexidine – Routine bathing in ICU4,5 •  MRSA acquisition decreased by 32% •  HCAI BSI rates decreased by 28% 1. Ammerlaan et al. Clin Infect Dis 2009; 48: 922-30 2. van Rijen et al. Cochrane Database Syst Rev 2008; 4: CD006216 3. Bode et al. N Engl J Med 2010; 362: 9-17 4. Climo MW et al. Crit Care Med 2009; 37:1858-1865 5. Climo MW et al. N Engl J Med 2013; 368: 533-42 Relationship between mupirocin use and resistance Patel et al. Clin Infect Dis 2009; 49: 935-41 … but not if you give it to 70% of the people who don’t need it ! Mupirocin Resistance in MRSA HUG 1999-2008 0 200 400 600 800 1000 1200 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year No.isolates(1isolateper patientperyear) 0 10 20 30 40 50 60 70 80 90 100 %isolatesresistant Sensitive Resistant % Resistant Clinical significance of resistance •  Mupirocin •  High-level - decolonization failure1 •  Low-level - unclear •  Chlorhexidine •  qacA/B gene carriage - unclear2 1. Robicsek et al. Infect Control Hosp Epidemiol 2009; 30: 623-32 2. Vali L et al. J Antimicrob Chemother 2008; 61: 524-32
  • 6. 30-­‐04-­‐15   6   Epidemiology of Chlorhexidine Resistance in MRSA •  qacA/B genes found worldwide in MRSA1 – 10%–20% UK – 63% European – 80% Brazilian – 55% Taiwanese 1. Batra et al. Clin Infect Dis 2010; 50: 210-7 Genotypic chlorhexidine resistance in MRSA blood cultures HUG 1999 to 2008 0 2 4 6 8 10 12 14 16 18 20 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year NumberofMRSA bloodcultureisolates qacA-qacB absent qacA-qacB present qacA-qacB in 161/188 (86%) blood cultures Resistance in Blood Cultures HUG 1999 to 2008 No. isolates % Sensitive 25 13 Resistant Mupirocin only 2 1 Chlorhexidine only 60 32 Both 101 54 Total 188 100 The Question 2 Is there a correlation between mupirocin use and emergence of resistance? Relationship between mupirocin consumption and mupirocin resistance 0 10 20 30 40 50 60 70 80 90 100 80 100 120 140 160 180 200 Mupirocin consumption (g) Mupirocinresistance(%) r = 0.87, p= 0.002 The Question 3 Are low-level mupirocin and chlorhexidine resistance associated with decolonisation failure ?
  • 7. 30-­‐04-­‐15   7   Cases Controls Univariate analysis Exposure n (%) n (%) OR (95% CI) p value Mupirocin resistance L-MuR 49 (64) 26 (35) 3.4 (1.7-7.1) 0.0003 V588F mutation 52 (69) 26/73 (36) 4.6 (2.1-9.9) <0.0001 mupA gene 12/49 (24) 2/26 (8) 5.1 (1.0-25.8) 0.03 Chlorhexidine resistance qacA/B gene 68 (91) 51 (68) 10.2 (2.6-40.7) <0.0001 Resistance combinations Fully sensitive 6 (8) 24 (32) 0.1 (0.007-0.37) <0.0001 Mupirocin R only 1 (1) 0 (0) … 0.32 Chlorhexidine R only 21 (28) 25 (33) 0.7 (0.3-1.6) 0.44 Resistant to both 47 (63) 26 (35) 3.2 (1.6-6.5) 0.001 Results - Resistance to Mupirocin and Chlorhexidine Conclusions 1.  Mupirocin and chlorhexidine resistance are common in MRSA at HUG (and elsewhere) 2.  Resistance correlates with use of these agents 3.  Low-level mupirocin and chlorhexidine resistance are strongly associated with failure of decolonization therapy Conclusions (2) 4.  Emergence of resistance and its impact should be monitored in institutions with widespread use of these agents 5.  Alternative agents may be required to effectively prevent S. aureus infections in settings with high prevalence of resistance Steed  et  al.      Am  J  Infect  Control  2014   Steed  et  al.    Am  J  Infect  Control  2014   Steed  et  al.      Am  J  Infect  Control  2014   ¤   Very  effecMve  in  reducing  the  bacterial  load,      but  …       ¤   …  2  hours  aker  last  applicaMon:  what  is  the              bacterial  load  on  the  next  morning?   ¤   …  no  informaMon  about  effect  aker  mulMple              day  use  (load  reducMon?,  side  effects?)     ¤   …  no  informaMon  on  the  percentage  of  HCWs              that  became  MRSA-­‐free  
  • 8. 30-­‐04-­‐15   8   Bryce  et  al.    J  Hosp  Infect  2014;  doi:  10.1016/j.jhin.2014.06.017.  [Epub  ahead  of  print]   …  am  I  even   needed?   Johnson  et  al.    J  Arthroplasty  2010;25:Suppl.1   Two  wipes,  no  muprirocin,  no  infecMon  !   …  always   thought  so  –   not  needed!   nasal cover-up* 3 g *  for  non-­‐compliance  with  IC  measures  and  paMent  miss-­‐management   ¤   PrevenMng  HAI?   ¤   Scrub  versus  wipes   ² Significant  difference  in   acMve  concentraMon  on  skin   Noto  et  al.    JAMA.  2015;313(4):369-­‐378  
  • 9. 30-­‐04-­‐15   9   Let’s  fight  S.  aureus.   Love  to  Screen  &  Scrub.     ¤   Are  they  convinced  that  decolonizaMon  is      needed?   ²   InformaMon  only  probably  doesn’t  work      à  screening  &  informaMon  probably  does   ¤   What  is  the  compliance  with  decolonizaMon?   ²   Unknown  à  but  we  sMll  see  S.  aureus  infecMons   ¤   What  are  their  abiliMes  to  apply  the      treatment?   ²   Can  the  elderly  even  use  a  CHX-­‐scrub?   ¤ Since  this  is  not  the   typical  elderly  paMent   q   Nearly  impossible  logisMcs  in  hospitals   q   Expensive  or  as  an  alternaMve  (treat      them  all)  leading  to  resistance   q   Frequently  not  taken-­‐up  by  paMents   q   Impossible  for  elderly  paMents   q   Not  the  most  acMve  CHX  chosen   q   All  of  the  above  
  • 10. 30-­‐04-­‐15   10   Disclaimer:  My  personal  conclusions  on  the  mauer  might  be  different  from  the  presented  content