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 ID: 673800
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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/tazoSlide13Slide14
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