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Carbapenem resistant enterobacteriaceae update 2012. Dr.T.V.Rao MD. What are Carbapenem resistant enterobacteriaceae ?. E enterobacteriaceae strains resistant to Carbapenem have emerged in the past decade Wide-spread outbreaks have been reported in recent years No reliable treatment options

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what are carbapenem resistant enterobacteriaceae
What are Carbapenem resistant enterobacteriaceae ?
  • Eenterobacteriaceae strains resistant to Carbapenem have emerged in the past decade
  • Wide-spread outbreaks have been reported in recent years
  • No reliable treatment options
  • Huge reservoir of carriers in healthy population
  • Easy species-to-species spread
  • Potential devastating health consequences

Dr.T.V.Rao MD

how are carbapenems used
Uses by Clinical Syndrome

Bacterial meningitis

Hospital-associated sinusitis

Sepsis of unknown origin

Hospital-associated pneumonia

How are Carbapenems Used?

Use by Clinical Isolate

  • Acinetobacter spp.
  • Pseudomonas aeruginosa
  • Alcaligenes spp.
  • Enterobacteriaceae
    • Mogenella spp.
    • Serratia spp.
    • Enterobacter spp.
    • Citrobacter spp.
    • ESBL or AmpC + E. coli and Klebsiella spp.

Reference: Sanford Guide

Dr.T.V.Rao MD

how are carbapenems used1
Uses by Clinical Syndrome

Bacterial meningitis

Hospital-associated sinusitis

Sepsis of unknown origin

Hospital-associated pneumonia

How are Carbapenems Used?

Use by Clinical Isolate

  • Acinetobacter spp.
  • Pseudomonas aeruginosa
  • Alcaligenes spp.
  • Enterobacteriaceae
    • Mogenella spp.
    • Serratia spp.
    • Enterobacter spp.
    • Citrobacter spp.
    • ESBL or AmpC + E. coli and Klebsiella spp.

Reference: Sanford Guide

Dr.T.V.Rao MD

emerging carbapenem resistance in gram negative bacilli
Significantly limits treatment options for life-threatening infections

No new drugs for gram-negative bacilli

Emerging resistance mechanisms, carbapenemases are mobile,

Detection of carbapenemases and implementation of infection control practices are necessary to limit spread

Emerging Carbapenem Resistance in Gram-Negative Bacilli

Dr.T.V.Rao MD

defining carbapenem resistance
Defining Carbapenem resistance
  • Definitions for CRE are complicated by a number of factors including the diversity of the genera. Another important challenge to developing a standardized definition of CRE is a recent (mid-2010) change in the Clinical and Laboratory Standards Institute (CLSI) interpretative criteria (breakpoints) for determining susceptibility to Carbapenems among Enterobacteriaceae.

Dr.T.V.Rao MD

kpc s in enterobacteriaceae
KPC’s in Enterobacteriaceae

Pseudomonas aeruginosa – Columbia & Puerto Rico

surveillance definition cdc
Surveillance definition - CDC
  • CDC has developed the following interim surveillance definition for CRE. CRE are defined as Enterobacteriaceae that are: Nonsusceptible to one of the following Carbapenems: doripenem, meropenem, or imipenem AND Resistant to all of the following third-generation cephalosporin that were tested: ceftriaxone, cefotaxime, and ceftazidime. (Note: All three of these antimicrobials are recommended as part of the primary or secondary susceptibility panels for Enterobacteriaceae)

Dr.T.V.Rao MD

kpc enzymes
KPC Enzymes
  • Located on plasmids; conjugative and nonconjugativeblaKPC is usually flanked by transposon sequences
  • blaKPC reported on plasmids with:
    • Normal spectrum b-lactamases
    • Extended spectrum b-lactamases
    • Aminoglycoside resistance

Dr.T.V.Rao MD

changing breakpoints no need for hodge test
Changing breakpoints – no need for Hodge test
  • These new recommendations lowered the breakpoints and removed the requirement for testing for carbapenemases (e.g., modified Hodge Test) to determine susceptibility.

Dr.T.V.Rao MD

cre are epidemiologically important for several reasons
CRE are epidemiologically important for several reasons:
  • CRE have been associated with high mortality rates (up to 40 to 50% in some studies). In addition to β-lactam/Carbapenem resistance, CRE often carry genes that confer high levels of resistance to many other antimicrobials, often leaving very limited therapeutic options. “Pan-resistant” KPC-producing strains have been reported. • CRE have spread throughout many parts of the United States and have the potential to spread more widely.

Dr.T.V.Rao MD

screening for cre
Screening for CRe
  • Screening is used to identify unrecognized CRE colonization among epidemiologically-linked contacts of known CRE colonized or infected patients as clinical cultures will usually identify only a fraction of all patients with CRE. Generally, this screening has involved stool, rectal, or peri-rectal cultures and sometimes cultures of wounds or urine (if a urinary catheter is present).

Dr.T.V.Rao MD

a new carbapenemases
A new carbapenemases
  • New Delhi metallo-b-lactamase (NDM-1)
  • class B b-lactamase
  • plasmid carrying encoding gene blaNDM
  • first detected in 2009 from an isolate of K. pneumoniae
  • Swedish patient with antibiotic-resistant infection acquired and unsuccessfully treated in New Delhi, India
  • novel gene identified in Sweden

Dr.T.V.Rao MD

a new carbapenemases1
A new carbapenemases

14 out of 24 patients come from ICU

“New Delhi Metallo-β lactamase (NDM-1) in Enterobacteriaceae: Treatment options with Carbapenems Compromised”. Journal of Association of Physicians of India 58: 147–150, March 2010

Dr.T.V.Rao MD

  • New Delhi metallo-b-lactamase (NDM-1)
  • over a 3-month period in Mumbai, India, 24 cases of carbapenam resistant isolates were identified
  • 22 carry the NDM-1 gene
    • K. pneumoniae (10)
    • E. coli (9)
  • 14 samples from ICU
  • Carbapenem-resistance 0%  8%

in 3 years

some isolates are inherently resistant to imipenem
Some isolates are inherently resistant to Imipenem
  • For bacteria that have intrinsic imipenem nonsusceptibility (i.e., Morganella morganii, Proteus spp., Providencia spp.), requiring nonsusceptibility to Carbapenems other than imipenem as part of the definition might increase specificity.

Dr.T.V.Rao MD

screening for carbapenem resistant enterobacteriaceae
Screening for Carbapenem resistant Enterobacteriaceae
  • Screening is used to identify unrecognized CRE colonization among epidemiologically-linked contacts of known CRE colonized or infected patients as clinical cultures will usually identify only a fraction of all patients with CRE. Generally, this screening has involved stool, rectal, or peri-rectal cultures and sometimes cultures of wounds or urine

Dr.T.V.Rao MD

testing other drugs
Tigecycline:

Test by Etest if possible – disk diffusion tends to overcall resistance

No CLSI breakpoint, but there are FDA breakpoint

Susceptible ≤ 2 mg/ml

Intermediate = 4 mg/ml

Resistant ≥ 8 mg/ml

Testing Other Drugs

Dr.T.V.Rao MD

testing other drugs1
Polymyxin B or Colistin

Could test either, but colistin used clinically

Disk diffusion test does not work – don’t use!

Etest – works well, but not FDA cleared

Broth micro dilution – reference labs

Breakpoints - none

MIC ≤ 2 mg/ml, normal MIC range

MIC ≥ 4 mg/ml indicates increased resistance

Testing Other Drugs

Dr.T.V.Rao MD

surveillance
Surveillance
  • Inpatient facilities should have an awareness of whether or not CRE (at least E. coli and Klebsiella spp.) have ever been cultured from patients admitted to their facility and, if so, whether these positive cultures were collected within 48 hours of admission.
  • If CRE have been present, facilities should also determine: If there is evidence of intra-facility transmission Which wards/units are most affected

Dr.T.V.Rao MD

what is our role contain spread
What is our role – contain spread
  • Carbapenem-Resistant Enterobacteriaceae is an emerging threat to hospitalized patients
  • Global spread
  • High mortality
  • Treatment options are limited
  • Active surveillance should be performed for high risk patients with overseas hospitalization in past 6 months
  • Contact tracing / screening for confirmed cases
  • Importance of infection control measures
  • High vigilance in critically ill ICU patients

Dr.T.V.Rao MD

hand washing still the best option to prevent spread of cre
Hand washing still the best option to prevent spread of CRE
  • Hand hygiene is a primary part of preventing multidrug-resistant organism (MDRO) transmission. Facilities should ensure that healthcare personnel are familiar with proper hand hygiene technique as well as its rationale.

Dr.T.V.Rao MD

slide26

Programme Created by Dr.T.V.Rao MD for Medical and Paramedical students in the Developing World

  • Email
  • doctortvrao@gmail.com

Dr.T.V.Rao MD