Emergence(of(MDR:(Are( wediﬀerentfromthe …of(MDR:(Are(wediﬀerentfromthe restoftheworld(Dr C....

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.

•  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

Need to Iden:fy An:bio:c Resistance?

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.

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

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

Super Bug

Super Bugssss

Super Bugssss

Super Bugssss

Super Bugsssss

0

10

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40

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70

80

90

100

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)

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

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

Blood & Pus-‐ GPC (OPD) 2013

Microbiology NewsleGer vol. 20,No1,2014

% Resistance

Blood & Pus-‐ GPC (Ward) 2013


% Resistance

Blood -‐ GPC (ICU) 2013


% Resistance

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

Time Series Analysis of AMR at a Ter:ary Care Hospital Delhi. India.

Ongoing Trend Analysis: SGRH

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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

Vancomycin

% Resistance -‐ S. aureus -‐ Blood Isolates -‐ IPD

Dutta & Wattal et al Indian J Med Res 135, June 2012, pp 907-912

Ongoing Trend Analysis: SGRH % Resistance -‐ S. aureus -‐ Pus Isolates -‐ IPD

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Penicillin

Oxacillin

Clindamycin

Gentamicin

Erythromycin

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90

100

Penicillin

Oxacillin

Clindamycin

Gentamicin

% Resistance - Staph CONS - Blood Isolates - IPD

% 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

0

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40

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60

70

80

90

100

Ampicillin

Cefriaxone

Gentamicin

Amikacin

Ciprofloxacin

Piperacillin + Tazobactum

Cefaperazone + Sulbactum

Imipenem

% Resistance -‐ Klebsiella -‐ Blood Isolates -‐ IPD

0

10

20

30

40

50

60

70

80

90

100

Cefriaxone

Gentamicin

Amikacin

Ciprofloxacin



Imipenem

0

10

20

30

40

50

60

70

80

90

100

Ampicillin

Cefriaxone

Cefazidime

Gentamicin

Amikacin

Ciprofloxacin



Imipenem

Cotrimoxazole

Tigecycline

Colis:n

% Resistance -‐ Acinetobacter -‐ Blood 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

Cefazidime

Gentamicin

Ne:lmicin/Amikacin

Ciprofloxacin



Imipenem

Colis:n

% Resistance -‐ Pseudomonas -‐ Blood Isolates -‐ IPD

0

10

20

30

40

50

60

70

80

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

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

0

20

40

60

80

100

120

2008 2009 2010


Ceftriaxone

Amikacin


Ceftazidime

Colistin

Ertapenem


Quinolones

Tigecycline

Blood Isolates : Klebsiella -‐ ICU

% Sensitivity


0

20

40

60

80

100

120

2008 2009 2010


Amikacin


Ceftazidime

Colistin


Quinolones

Blood Isolates : Pseudomonas -‐ ICU

% Sensitivity


0

20

40

60

80

100

120

2008 2009 2010


Ceftriaxone

Amikacin



Ceftazidime

Colistin

Quinolones

Tigecycline

Blood Isolates : Acinetobacter -‐ ICU% Sen

si:v

ity


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

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)

“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

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

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

Goel & Wattal et al

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;

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%

Association between carbapenem consumption and resistance in P.aeruginosa and A.

baumannii (SGRH)

p value for A. baumannii< 0.5

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90

2005

2006

2007

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2011

2012

2013

Candida - Annual Number of Blood Isolates by Species

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