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Multidrug Resistant Bacteria

P. Stogsdill, MD, FIDSA. Sept 2013. Bad bugs, No drugs. NO ESKAPE. E. nterococcus . faecium. S. taphylococcus . aureus. K. lebsiella. . pneumoniae. . C. lostridium. . difficile. A. cinetobacter.

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Multidrug Resistant Bacteria






Presentation on theme: "Multidrug Resistant Bacteria"— Presentation transcript:

Slide1

Multidrug Resistant Bacteria

P. Stogsdill, MD, FIDSA

Sept 2013Slide2

Bad bugs, No drugs

NO ESKAPE

E

nterococcus

faecium

S

taphylococcus

aureus

K

lebsiella

pneumoniae

C

lostridium

difficile

A

cinetobacter

spp

P

seudomonas

aeruginosa

E

nterbacter

spp

E

nterbacteriaceaeSlide3

New Resistance Patterns

ESBL: extended spectrum

β

-

lactamases

(1978)

AmpC

β

-

lactamases

(1981)

CRE:

Carbapenem

-resistant

Enterobacteriaceae

KPC:

Kle

bsiella

pneumoniae

Enterobacteriaceae

(2001)

NDM: New Delhi

Metallo

β

-

lactamases

(2012)Slide4

KPC in the US 9/9/13Slide5

CRE infections

CRE 2001: 1.2%

4.2% in 2011

Klebsiella

1.6% 10.4%

Urine (89%), blood (10%)

Risk factors:

Health care exposure, recent hospitalization

Very high mortality ratesSlide6

β-

lactamases

Chromosomal-Mediated

(intrinsic)

Inducible enzymes (CTX/

Enterobacter

)

Intrinsic changes in DNA Sequence

Structural changes, target site alteration

Plasmid-mediated

(acquired)

Transferable/acquired (always “on”)

Associated with other resistant genesSlide7

AmpC resistance

Chromosomally-inducible Beta-

lactamases

CTX for

Enterobacter

Produced by

Enterobacteriaceae

sp

Asso w/ “SPICE/SPACE” bacteria

Serratia sppP

seudomonas

aeruginosa

A

cinetobacter

/Indole positive Proteae ( Proteus, Morganella, Providencia spp)Citrobacter sppEnterobacter cloacaeSlide8

AmpC

mutants

1

in 10

4-

7

organisms

Impaired Immune System

Intact Immune System

3GC

Ceftazidime

Ceftriaxone

Cefotaxime

S

erratia spp.

P

. aeruginosa

A

cinetobacter

C

itrobacter

E

nterobacter

Induction of

AmpCSlide9

AmpC

Resistant to

all

β

-

lactams

,

β

-lactamase inhibitors and aztreonam

Exception: cefepimeMIC “creep” over timeInducible in the presence of 3rd gen cephSlide10

ESBL E coliSlide11

Plasmid-mediated Resistance in ESBLs

Typically confers resistance to

Multiple classes of ABXs

TMP-SMX

Tetracyclines

Fluoroquinolones

AminoglycosidesSlide12

ESBLs

Plasmid mediated,

transmissable

, always “on”

Found in all

Enterobacteriae

(

usu

E coli or Klebsiella)

Decr susceptibility to cephalosporins and aztreonam usu suscept

to

cefoxitin

, but avoid

Likely ok to use

cefepime if MIC ≤ 2Best Rx option: carbapenems or pip/tazoSlide13
Slide14

ESBL Rx options

Carbapenems

--no RCT

Tigecycline

--

limited clinical data, not for UTI, concern for

bacteremia

β-lactam/β-Lactamase Inhibitor Combinations

Variable inhibitory activity

Tazobactam>>

sulbactam & clavulanatePip/tazo—ok for UTI (high urinary concentrations)Cephalosporins—not recommended (?

Cefepime

)

Fosfomycin

—uncomplicated UTI onlySlide15

ESBL Rx options (cont

)

AG, FQ, Bactrim:

Avoid—high risk of developing resistance

Colistin

:

No CLSI breakpoints, consider E-test

Fosfomycin

Inhibits bacterial cell wall synthesis

cidal vs GP and GN Uncomplicated UTISlide16

CRESlide17

Carbapenem-Resistant

Enterobacteriaceae

Enterobacteriaceae

GNR, GI tract

CA- and HCA-infections

70 genera, but mostly

E coli,

Klebsiella

,

Enterobacter

spUncommon in US before 2000Complex, multiple resistant mechanismsCarbapenemases (KPC, NDM—India/Pakistan)Mortality rates 40-50%Slide18

Risk factors for CRE

Exposure to health care and antimicrobials

Carbapenems

,

cephalosporins

, FQ,

vanco

Recent organ or stem-cell transplants

Mechanical ventilation

Longer LOSSlide19

CRE

Resistant to most β-lactams

K

pneumoniae

plasmid-borne (KPC)

Most prevalent and widely distributed

carbapenamases

Difficult to detect in the lab

Previously Ertapenem

was “canary in the coal mine”New carbapenem MIC breakpointsSlide20

Definition of CRE

“conservative definition”:

nonsusceptibility

to

Imipenem

,

Meropeneum

or

Doripenem

using the revised 2010 CLSI breakpoints.Elevated MICs to carbapenems

Similar to ESBL-producing organismsAlso resistant to AG and FQSlide21

CRE breakpointsSlide22

CRE diagnosis

CDC:

Resistant to all 3

rd

generation

cephalosporins

AND

Resistant to

Imipenem

/Meropenem/

DoripenemErtapenem not includedNew breakpointsNo modified Hodge test necessarySlide23

CRE isolateSlide24

CRE Rx Options

Tigecycline

Limited clinical experience

Avoid in UTI and primary BSI

Colistin

Emerging resistance

Fosfomycin

Looks great in vitroSlide25

Infection Control and CRE

Contact precautions

Pt

cohorting

?

Use of dedicated staff?

Miami: 1:1 nursing/RT care

Surveillance:

Peri

-rectal swabs and wound cxUrinary cathetersCDC workbookSlide26

Cipro +TMP/SMX at MMCSlide27

Questions?Slide28

Jan-June 2012

3918 hospitals (CAUTI or CLABSI surveillance)

181 (4.6%) with ≥ 1 CRE

infxn

145 (3.9%) short-term

hosp

, 36 (17.8%) LTACH

Highest in large, Northeast teaching hospitalsSlide29

By

MICHELLE CASTILLO / CBS NEWS/

September 16, 2013, 2:41 PM

CDC: Hospitals major source of antibiotic-resistant infectionsSlide30

More than two million people in the U.S. get drug-resistant infections annually. About 23,000 die from these diseases that are becoming increasingly resistant to antibiotics in doctors' arsenals

.

CDC director Dr. Tom

Frieden

said to

CBSNews.com

during a press conference. "If we're not careful, the medicine chest will be empty when we go there to look for a lifesaving antibiotic for someone with a deadly infection. If we act now, we can preserve these medications while we continue to work on lifesaving medications."Slide31

World Health Organization (WHO) Director-General Dr. Margaret Chan said in March 2012 that the overuse of antibiotics was becoming so common that she feared we may come to a day where

any normal infection could become deadly because bacteria have evolved to survive our treatments.Slide32

antibiotic resistance costs $20 billion in excess health care costs in the U.S. each year, with costs to society for lost productivity reaching as much as an additional $35 billion.

CDC estimated in April that enough antibiotics are prescribed each year for

four out of five Americans to be taking them. Doctors and other health care providers prescribed 258 million courses of antibiotics in 2010 for a population a little less than 309 million. They also estimated in this current report that up to 50 percent of antibiotics are prescribed incorrectly or to people who do not need them.Slide33

CRE infections are caused by a family of 70 bacteria that normally live in the digestive system. They are extremely resistant to even the strongest kinds of antibiotics, and

can kill one out of every two patients who develop bloodstream infections caused by them. Thirty-eight states reported at least one case of CRE last year, up from just one state a decade ago.Slide34

Antimicrobial stewardship programs, which measure and promote the correct use of antibiotics, have been shown to lower antibiotic-resistant infections in different facilities by as much as 80 percent.Slide35

CDC sets threat levels for drug-resistant 'superbugs'

By

Miriam Falco

, CNN

updated 5:48 PM EDT, Tue September 17,

2013

Briefing speakers, report: antibiotic resistant infections “pose a catastrophic threat to people in every country”

BY

RABITA AZIZ ON

SEPTEMBER 18, 2013.

But fighting antimicrobial resistance isn’t possible without committed resources, IDSA President Dr. David Relman said. The CDC’s current budget is the lowest it’s been in a decade, risking a future that may resemble the days before “miracle” drugs were developed, when people died of common infections, Dr.

Relman

said.

On superbugs, the CDC sounds an

alarm. (Washington Post Editorial Board) Slide36

CDC director: A disease outbreak anywhere is a risk everywhere

By

Dr. Tom

Frieden

, Special to CNN

updated 7:23 AM EDT, Fri September 20, 2013