Transcript Multidrug Resistant Bacteria

Multidrug
Resistant Bacteria
P. Stogsdill, MD, FIDSA
Sept 2013
Bad bugs, No drugs
NO ESKAPE
• Enterococcus faecium
• Staphylococcus aureus
• Klebsiella pneumoniae
Clostridium difficile
• Acinetobacter spp
• Pseudomonas aeruginosa
• Enterbacter spp
Enterbacteriaceae
New Resistance Patterns
• ESBL: extended spectrum β-lactamases (1978)
• AmpC β-lactamases (1981)
• CRE: Carbapenem-resistant Enterobacteriaceae
• KPC: Klebsiella pneumoniae Enterobacteriaceae (2001)
• NDM: New Delhi Metallo β-lactamases (2012)
KPC in the US 9/9/13
CRE infections
• CRE 2001: 1.2%
• Klebsiella 1.6%
4.2% in 2011
10.4%
• Urine (89%), blood (10%)
• Risk factors:
• Health care exposure, recent hospitalization
• Very high mortality rates
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 genes
AmpC resistance
• Chromosomally-inducible Beta-lactamases
• CTX for Enterobacter
• Produced by Enterobacteriaceae sp
• Asso w/ “SPICE/SPACE” bacteria
• Serratia spp
• Pseudomonas aeruginosa
• Acinetobacter/Indole positive Proteae ( Proteus,
Morganella, Providencia spp)
• Citrobacter spp
• Enterobacter cloacae
Induction of AmpC
●AmpC mutants
Impaired
Immune
System
1 in 104-7 organisms
Serratia spp.
aeruginosa
Acinetobacter
Citrobacter
Enterobacter
P.
3GC
Intact
Immune
System
Ceftazidime
Ceftriaxone
Cefotaxime
AmpC
• Resistant to all β-lactams, β -lactamase
inhibitors and aztreonam
• Exception: cefepime
• MIC “creep” over time
• Inducible in the presence of 3rd gen ceph
ESBL E coli
Plasmid-mediated
Resistance in ESBLs
Typically confers resistance to
Multiple classes of ABXs
• TMP-SMX
• Tetracyclines
• Fluoroquinolones
• Aminoglycosides
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 ≤ 2
• Best Rx option: carbapenems or pip/tazo
ESBL Rx options
• Carbapenems --no RCT
• Tigecycline-- limited clinical data, not for UTI,
concern for bacteremia
• β-lactam/β-Lactamase Inhibitor Combinations
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•
•
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Variable inhibitory activity
Tazobactam>>sulbactam & clavulanate
Pip/tazo—ok for UTI (high urinary concentrations)
Cephalosporins—not recommended (? Cefepime)
• Fosfomycin—uncomplicated UTI only
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 UTI
CRE
Carbapenem-Resistant
Enterobacteriaceae
• Enterobacteriaceae
• GNR, GI tract
• CA- and HCA-infections
• 70 genera, but mostly E coli, Klebsiella,
Enterobacter sp
• Uncommon in US before 2000
• Complex, multiple resistant mechanisms
• Carbapenemases (KPC, NDM—India/Pakistan)
• Mortality rates 40-50%
Risk factors for CRE
• Exposure to health care and antimicrobials
• Carbapenems, cephalosporins, FQ, vanco
• Recent organ or stem-cell transplants
• Mechanical ventilation
• Longer LOS
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 breakpoints
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 organisms
• Also resistant to AG and FQ
CRE breakpoints
CRE diagnosis
• CDC:
• Resistant to all 3rd generation cephalosporins
• AND
• Resistant to Imipenem/Meropenem/Doripenem
• Ertapenem not included
• New breakpoints
• No modified Hodge test necessary
CRE isolate
CRE Rx Options
• Tigecycline
• Limited clinical experience
• Avoid in UTI and primary BSI
• Colistin
• Emerging resistance
• Fosfomycin
• Looks great in vitro
Infection Control and
CRE
• Contact precautions
• Pt cohorting?
• Use of dedicated staff?
• Miami: 1:1 nursing/RT care
• Surveillance: Peri-rectal swabs and wound cx
• Urinary catheters
• CDC workbook
Cipro +TMP/SMX at MMC
Questions?
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 hospitals
• By MICHELLE CASTILLO / CBS NEWS/
September 16, 2013, 2:41 PM
• CDC: Hospitals major source of antibioticresistant infections
• More than two million people in the U.S. get drugresistant 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."
• World Health Organization (WHO) DirectorGeneral 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.
• 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.
• 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. Thirtyeight states reported at least one case of CRE
last year, up from just one state a decade ago.
• 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.
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
AZIZantimicrobial
ON SEPTEMBER
18, 2013.
But fighting
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)
• 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