Multidrug Resistant Bacteria

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Multidrug Resistant Bacteria P. Stogsdill, MD, FIDSA Sept 2013

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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 spp P seudomonas aeruginosa E nterbacter spp E nterbacteriaceae. - PowerPoint PPT Presentation

Transcript of Multidrug Resistant Bacteria

Page 1: Multidrug Resistant Bacteria

Multidrug Resistant Bacteria

P. Stogsdill, MD, FIDSASept 2013

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Bad bugs, No drugsNO ESKAPE

• Enterococcus faecium

• Staphylococcus aureus

• Klebsiella pneumoniae Clostridium difficile

• Acinetobacter spp

• Pseudomonas aeruginosa

• Enterbacter spp Enterbacteriaceae

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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)

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KPC in the US 9/9/13

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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 rates

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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

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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

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●AmpC mutants 1 in 104-7 organisms Impaire

d Immun

e System

Intact Immun

e Syste

m

3GC

Ceftazidime

Ceftriaxone

Cefotaxime

Serratia spp. P. aeruginosa Acinetobacter Citrobacter Enterobacter

Induction of AmpC

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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

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ESBL E coli

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Plasmid-mediated Resistance in ESBLs

Typically confers resistance to Multiple classes of ABXs

• TMP-SMX• Tetracyclines• Fluoroquinolones• Aminoglycosides

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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

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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 & clavulanate• Pip/tazo—ok for UTI (high urinary concentrations)• Cephalosporins—not recommended (? Cefepime)

• Fosfomycin—uncomplicated UTI only

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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

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CRE

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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%

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Risk factors for CRE• Exposure to health care and

antimicrobials• Carbapenems, cephalosporins, FQ,

vanco

• Recent organ or stem-cell transplants• Mechanical ventilation• Longer LOS

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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

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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

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CRE breakpoints

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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

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CRE isolate

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CRE Rx Options• Tigecycline

• Limited clinical experience• Avoid in UTI and primary BSI

• Colistin• Emerging resistance

• Fosfomycin• Looks great in vitro

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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

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Cipro +TMP/SMX at MMC

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Questions?

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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

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• By MICHELLE CASTILLO / CBS NEWS/ September 16, 2013, 2:41 PM

• CDC: Hospitals major source of antibiotic-resistant infections

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• 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."

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• 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.

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• 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.

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• 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.

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• 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.

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CDC sets threat levels for drug-resistant 'superbugs'By Miriam Falco, CNNupdated 5:48 PM EDT, Tue September 17, 2013Briefing 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)

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• 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