emergence(of(mdr:(are( wedifferentfromthe …of(mdr:(are(wedifferentfromthe restoftheworld(dr c....
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Emergence of MDR: Are we different from the rest of the world
Dr C. Wattal, M.D.
Chairman Dept of Clinical Microbiology
Sir Ganga Ram Hospital New Delhi.
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• It is more difficult than ever to eradicate infec4ons caused by an4bio4c-‐ resistant “superbugs,”
• And the problem is exacerbated by a dry pipeline for new an4microbials with bactericidal ac4vity against gram-‐nega4ve bacteria
Cesar A. Arias. NEJM 2009, 360:439-‐443
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Need to Iden:fy An:bio:c Resistance?
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How important ? Development of R is poten4ally a disastrous
situa4on The consequences of resistance :
Higher mortality and morbidity, such as neurologic damage in children with pneumococcal meningi:s not recognized as R or for which alterna4ves to first-‐line an4bio4c therapy are less effec4ve.
Infec4ons with R organisms lead to longer hospitaliza:ons and greater expense, e.g valve replacement in enterococcal endocardi4s or lung resec4on in pulmonary tuberculosis.
More virulent organism such as MRSA acquires R to vancomycin, the consequences s4ll more devasta:ng, because the alterna4ves are few or nonexistent.
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A Til4ng Balance in India
Gram +ve bacteria Major problems….
MRSA Penicillin R pneumococci Vancomycin-‐R enterococci
But Many new an:bio:cs
• Most Infec:ons due to Gram -‐ve bacteria Rising problems….
ESBL producers – Pan R Acinetobacter
& P. aeruginosa
And Few new an:bio:cs
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Most Common Bacteremia Pathogen: SGRH
2008 2013 Rank Pathogen % Rank Pathogen % 1. CNS 20 1. CNS 17 2. Acinetobacter 11 2. Kleb. 17 3. E. coli 10 3. Candida 16 4. Candida/Pse./Kl 9 4. Acineto. 13 7. S.typhi 8 5. E.coli 11 8. Enterococcus 5 6. Enterococcus 9 9. S.paraA 4 7. Pseud. 5 10. S.aureus 3 8. S.typhi 4
9. S.aureus 4 Microbiology NewsleAer 2008-‐2014
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Super Bug
Super Bugssss
Super Bugssss
Super Bugssss
Super Bugsssss
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0
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1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Polymicrobial
Gram Nega:ve Bacteria
Gram Posi:ve Bacteria
Microbiology NewsleWer 1999-‐2014
Trends & Causes of Bacteremia In Hospitalized Pa:ents (SGRH)
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Blood isolates from Ward Jan. -‐ Dec., 2013
Acinetobacter , 22
E. coli , 55 Enterococci spp. , 25
Fungal isolates, 72
Klebseilla , 28
Salmonella paratyphi A , 22
Salmonella typhi , 53
Staph. aureus , 19
Staphylococci , 215
Streptococcus spp. , 15 Others , 43
Acinetobacter
E. coli
Enterococci spp.
Fungal isolates
Klebseilla
Salmonella paratyphi A
Salmonella typhi
Staph. aureus
Staphylococci
Streptococcus spp.
Others
Others: Achromobacter spp. -‐1, Aeromonas-‐3, Burkholderia cepacia-‐1, Chrysobacterium-‐2, Enterobacter spp.-‐5, Ochrobactrum anthropi-‐4, Pantoea sps.-‐1, Providencia spp. -‐1, Pseudomonas pu4da-‐1, Pseudomonas stutzeri.-‐2, Salmonella enter4dis-‐1, Serra4a marscecens-‐8 , Serra4a spp.-‐1, Sphingomonas paucimobilis-‐3, Stenotrophomonas maltophilia-‐4, Strept. pneumoniae-‐3 , Streptococcus agalac4ae-‐1, Streptococcus yogenes Group A -‐1
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Acinetobacter , 88 E. coli , 50
Enterobacter , 13 Enterococci spp. , 49
Klebseilla , 112
Pseudomonas aeruginosa , 17
Staph. aureus , 24
Staphylococci , 219
Stenotrophomonas maltophilia, 15
Others , 76
Candida albicans ,
29
Candida glabrata , 14
Candida pelliculosa , 16
Candida tropicalis , 36
Candida parapsilosis, 15
Candida krusei, 8
Candida haemulonii, 16
Other yeast, 21
Other, 155
Acinetobacter
E. coli
Enterobacter
Enterococci spp.
Klebseilla
Pseudomonas aeruginosa
Staph. aureus
Staphylococci
Stenotrophomonas maltophilia
Others
Candida albicans
Candida glabrata
Candida pelliculosa
Candida tropicalis
Candida parapsilosis
Candida krusei
Candida haemulonii
Other yeast
Others: Achromobacter spp. 4, Aeromonas 4, Alcaligenes faecalis 1, Burkholderia capacia 6, Chrysobacterium spp. 8, Citrobacter spp. 2, Cryptococcus neoformans 2, Elizebethkingia meningosep4ca 8, Group A Streptococcus 1 Ochrobactrum anthropi 3, Pantoea spp. 1, Proteus spp. 2, Providencia spp. 2, Pseudomonas spp. 2, Pseudomonas stutzeri 4, Ralstonia mannitoliy4ca 2, Ralstonia pickee 1, Salmonella spp 2, Salmonella typhi 1, Salmonella typhimurium 1, Serra4a marscecens 6, Serra4a spp. 1, Sphingomonas paucimobilis 1, Strept. Pneumoniae 3 ,Streptococcus pyogenes Group A 2, Streptococcus spp. 6
Blood Isolates from ICU: Jan-‐Dec 2013
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Blood & Pus-‐ GPC (OPD) 2013
Microbiology NewsleGer vol. 20,No1,2014
% Resistance
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Blood & Pus-‐ GPC (Ward) 2013
Microbiology NewsleGer vol. 20,No1,2014
% Resistance
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Blood -‐ GPC (ICU) 2013
Microbiology NewsleGer vol. 20,No1,2014
% Resistance
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0
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80
90
100
Blood Urine Pus Body Fluid Respiratory
OPD
Ward
ICU
%
Microbiology NewsleGer vol. 20, No.1, 2014
Sample Source & MRSA at SGRH : 2013
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Time Series Analysis of AMR at a Ter:ary Care Hospital Delhi. India.
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Ongoing Trend Analysis: SGRH
0
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60
70
80
90
100
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Penicillin
Oxacillin
Clindamycin
Gentamicin
Vancomycin
% Resistance -‐ S. aureus -‐ Blood Isolates -‐ IPD
Dutta & Wattal et al Indian J Med Res 135, June 2012, pp 907-912
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Ongoing Trend Analysis: SGRH % Resistance -‐ S. aureus -‐ Pus Isolates -‐ IPD
0
10
20
30
40
50
60
70
80
90
100
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Penicillin
Oxacillin
Clindamycin
Gentamicin
Erythromycin
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0
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20
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50
60
70
80
90
100
Penicillin
Oxacillin
Clindamycin
Gentamicin
% Resistance - Staph CONS - Blood Isolates - IPD
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% MRSA vs An4bio4c Use
0
20
40
60
80
100
120
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Ant
ibio
tic C
onsu
mpt
ion
(DD
Ds)
% MRSA
Cephalosporin Use
Fluoroquinolone Use
Macrolide Use
p = 0.031
p = 0.026
p = 0.037
% R
esis
tanc
e
20
40
60
Dutta & Wattal et al Indian J Med Res 135, June 2012, pp 907-912
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0
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20
30
40
50
60
70
80
90
100
Ampicillin
Cefriaxone
Gentamicin
Amikacin
Ciprofloxacin
Piperacillin + Tazobactum
Cefaperazone + Sulbactum
Imipenem
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% Resistance -‐ Klebsiella -‐ Blood Isolates -‐ IPD
0
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30
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50
60
70
80
90
100
Cefriaxone
Gentamicin
Amikacin
Ciprofloxacin
Piperacillin + Tazobactum
Cefaperazone + Sulbactum
Imipenem
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0
10
20
30
40
50
60
70
80
90
100
Ampicillin
Cefriaxone
Cefazidime
Gentamicin
Amikacin
Ciprofloxacin
Piperacillin + Tazobactum
Cefaperazone + Sulbactum
Imipenem
Cotrimoxazole
Tigecycline
Colis:n
% Resistance -‐ Acinetobacter -‐ Blood Isolates-‐IPD
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0
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20
30
40
50
60
70
80
90
100
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Cefazidime
Gentamicin
Ne:lmicin/Amikacin
Ciprofloxacin
Piperacillin + Tazobactum
Cefaperazone + Sulbactum
Imipenem
Colis:n
% Resistance -‐ Pseudomonas -‐ Blood Isolates -‐ IPD
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0
10
20
30
40
50
60
70
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90
100
Ampicillin
Chloramphenicol
Co-‐trimoxazole
Nalidixic Acid
Ciprofloxacin
% Resistance -‐ S. Typhi -‐ Blood Isolates-‐IPD
Reena Raveendran & Wattal et al Indian J Med Res , June 2008, pp 50-53
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0
20
40
60
80
100
120
2008 2009 2010
Imipenem / Meropenem
Ceftriaxone
Amikacin
Cefaperazone+Sulbactum
Colistin
Ertapenem
Piperacillin+Tazobactm
Quinolones
Tigecycline
% Sensitivity
BloodIsolates : E.coli -‐ICU
BJID 2013 Jan in press :e-copy www.elsevier.com/locate/bjid
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0
20
40
60
80
100
120
2008 2009 2010
Imipenem / Meropenem
Ceftriaxone
Amikacin
Cefaperazone+Sulbactum
Ceftazidime
Colistin
Ertapenem
Piperacillin+Tazobactm
Quinolones
Tigecycline
Blood Isolates : Klebsiella -‐ ICU
% Sensitivity
BJID 2013 Jan in press :e-copy www.elsevier.com/locate/bjid
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0
20
40
60
80
100
120
2008 2009 2010
Imipenem / Meropenem
Amikacin
Cefaperazone+Sulbactum
Ceftazidime
Colistin
Piperacillin+Tazobactm
Quinolones
Blood Isolates : Pseudomonas -‐ ICU
% Sensitivity
BJID 2013 Jan in press :e-copy www.elsevier.com/locate/bjid
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0
20
40
60
80
100
120
2008 2009 2010
Imipenem / Meropenem
Ceftriaxone
Amikacin
Cefaperazone+Sulbactum
Piperacillin+Tazobactm
Ceftazidime
Colistin
Quinolones
Tigecycline
Blood Isolates : Acinetobacter -‐ ICU% Sen
si:v
ity
BJID 2013 Jan in press :e-copy www.elsevier.com/locate/bjid
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MDR organisms: increasing threat
• Gram nega4ve organisms show mul4-‐ drug resistance by produc4on of numerous beta-‐ lactamases – Extended-‐spectrum β-‐lactamases ( ESBL)
• TEM, SHV & CTX-‐M types
– AmpC • Derepressed chromosomal e.g Enterobacter • Plasmid-‐mediated in E. coli & Klebsiella
– Carbapenemases • Metallo-‐ (MBL) & non-‐metallo-‐ (KPC) types
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ESBL, OXA: Co-production
Mul4center study in 6 Indian ci4es in 2007
Walsh TR et al. J An4microb Chemother 2007; 59:799–820
In India bacteria are frequently co-producing OXA along with ESBL (CTX-M-15)
Which are Resistant to penicillins & 3rd gen cephalosporins cephamycins & BLIs (Cefepime is sensitive)
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“PROBLEM” GRAM-‐NEGATIVE PATHOGENS
• ESBL-‐producing GNR – E. coli – Klebsiella pneumoniae – Enterobacter spp.
• Acinetobacter spp. • P. aeruginosa • Stenotrophomonas maltophila
WaAal et al,Microbiology NewsleAer 1997-‐2005;www.sgrh.com
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Carbapenemases
1. MBL-‐ VIM-‐1 in K.pneumoniae in Greece. 2. KPC in US,Greece, Israel 3. OXA-‐48 in Turkey 4. NDM-‐1 Swinly emerging-‐ India
Lancet Infect Dis 2009;9:228-‐36. An4microb Agents Chemother 2008;52:2950-‐4
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0
50
100
150
200
250
300
350
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Total an:bio:cs
Total cephalosporins
Imipenem/Meropenem/ Ertapenem
Aminoglycosides
Fluoroquinolones
Macrolides
Lincomycins
Glycopep:des
Linezolid
An:bio:c Consump:on at SGRH: 1998-‐2013
DDD/
100 Be
d Da
ys
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Goel & Wattal et al
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2008 Carbapenemases in
Enterobacteriaceae: 35.8%
Organism Number of isolates screened
ESBL positive %
Imipenem Resistance %
Ertapenem Resistance %
E. coli 211 61% 6% 6%
Klebsiella spp.
263 40% 52% 55%
Dutta & Wattal et al Indian J Med Res 135, June 2012, pp 907-912;
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Tigecycline : SGRH Experience Jan- Dec: 2013
Organism Number of isolates screened
Tigecycline Resistance %
E. coli 298 4
Klebsiella spp. 157 42
Acinetobacter spp.
90 30
Enterococci 89 (38 GRE) 0%
Staph aureus 46 (15 MRSA) 0%
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Association between carbapenem consumption and resistance in P.aeruginosa and A.
baumannii (SGRH)
p value for A. baumannii< 0.5
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0
10
20
30
40
50
60
70
80
90
2005
2006
2007
2008
2009
2010
2011
2012
2013
Candida - Annual Number of Blood Isolates by Species
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Thanks