Carbapenem Resistance in Enterobacteriaceae - PowerPoint PPT Presentation

1 / 34
About This Presentation
Title:

Carbapenem Resistance in Enterobacteriaceae

Description:

Susceptibility Profile of KPC-Producing K. pneumoniae. Tigecycline ... Variable susceptibility to cefoxitin and cefepime. Reading Disk Diffusion & Etest ... – PowerPoint PPT presentation

Number of Views:1006
Avg rating:3.0/5.0
Slides: 35
Provided by: vzp
Category:

less

Transcript and Presenter's Notes

Title: Carbapenem Resistance in Enterobacteriaceae


1
Carbapenem Resistance in Enterobacteriaceae
  • Jean B. Patel, PhD, (D)ABMM
  • Leader, Antimicrobial Resistance Team
  • Division of Healthcare Quality Promotion

2
Carbapenems
Drug Route of Administration FDA Status
Imipenem IV Cleared
Meropenem IV Cleared
Ertapenem IM, IV Cleared
Doripenem IV Application Submitted
3
Spectrum of Activity
Drug Strep spp. MSSA Entero-bacteriaeae Non-fermentors Anaerobes
Imipenem
Meropenem
Ertapenem Limited activity
Doripenem
4
How are Carbapenems Used?
  • Uses by Clinical Syndrome
  • Bacterial meningitis
  • Hospital-associated sinusitis
  • Sepsis of unknown origin
  • Hospital-associated pneumonia
  • 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
5
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

6
Carbapenem Resistance Mechanisms
Enterobacteriaceae Cephalosporinase porin loss
Carbapenemase
P. aeruginosa Porin loss
Up-regulated efflux
Carbapenemase
Acinetobacter spp. Cephalosporinase porin loss
Carbapenemase
7
Carbapenemases
Classification Enzyme Most Common Bacteria
Class A KPC, SME, IMI, NMC, GES Enterobacteriaceae (rare reports in P. aeruginosa)
Class B (metallo-b-lactamse) IMP, VIM, GIM, SPM P. aeruginosa Enterobacteriacea Acinetobacter spp.
Class D OXA Acinetobacter spp.
8
Carbapenemases in the U.S.
Enzyme Bacteria
KPC Enterobacteriaceae
Metallo-b-lactamase P. aeruginosa
OXA Acinetobacter spp.
SME Serratia marcesens
9
Klebsiella Pneumoniae Carbapenemase
  • KPC is a class A b-lactamase
  • Confers resistance to all b-lactams including
    extended-spectrum cephalosporins and carbapenems
  • Occurs in Enterobacteriaceae
  • Most commonly in Klebsiella pneumoniae
  • Also reported in K. oxytoca, Citrobacter
    freundii, Enterobacter spp., Escherichia coli,
    Salmonella spp., Serratia spp.,
  • Also reported in Pseudomonas aeruginosa
    (Columbia)

10
Susceptibility Profile of KPC-Producing K.
pneumoniae
Antimicrobial Interpretation Antimicrobial Interpretation
Amikacin I Chloramphenicol R
Amox/clav R Ciprofloxacin R
Ampicillin R Ertapenem R
Aztreonam R Gentamicin R
Cefazolin R Imipenem R
Cefpodoxime R Meropenem R
Cefotaxime R Pipercillin/Tazo R
Cetotetan R Tobramycin R
Cefoxitin R Trimeth/Sulfa R
Ceftazidime R Polymyxin B MIC gt4mg/ml
Ceftriaxone R Colistin MIC gt4mg/ml
Cefepime R Tigecycline S

11
KPC Enzymes
  • Located on plasmids conjugative and
    nonconjugative
  • blaKPC is usually flanked by transposon sequences
  • blaKPC reported on plasmids with
  • Normal spectrum b-lactamases
  • Extended spectrum b-lactamases
  • Aminoglycoside resistance

12
KPCs in Enterobacteriaceae
Species Comments
Klebsiella spp. K. pneumoniae-cause of outbreaks K. oxytoca-sporadic occurrence
Enterobacter spp. Sporadic occurrence
Escherichia coli Sporadic occurrence
Salmonella spp. Sporadic occurrence
Citrobacter freundii Sporadic occurrence
Serratia spp. Sporadic occurrence
Pseudomonas aeruginosa Columbia Puerto Rico
13
Geographical Distribution of KPC-Producers
Frequent Occurrence Sporadic Isolate(s)
14
Geographical Distribution of KPC-Producers in New
Jersey
15
KPC Outside of United States
  • France (Nass et al. 2005. AAC 494423-4424)
  • Singapore (report from survey)
  • Puerto Rico (ICAAC 2007)
  • Columbia (Villegas et al. 2006. AAC 502880-2882
    ICAAC 07)
  • Brazil (ICAAC 2007)
  • Israel (Navon-Venezia et al. 2006. AAC
    503098-3101)
  • China (Wei Z, et al. 2007. AAC 51 763-765)

16
Inter-Institutional Inter-State Spread of
KPC-Producing K. pneumoniae
17
Intra-institution, Interspecies KPC Plasmid
Transfer
Cf Ko
Cf Ko
18
Laboratory Detection of KPC-Producers
  • Problems
  • 1) Some isolates demonstrate low-level carbapenem
    resistance
  • 2) Some automated systems fail to detect
    low-level resistance

19
Susceptibility of KPC-Producers to Imipenem
S
I
R
12 of isolates test susceptible to imipenem
20
Susceptibility of KPC-Producers to Meropenem
S
I
R
9 of isolates test susceptible to meropenem
21
Susceptibility of KPC-Producers to Ertapenem
S
I
R
None of the isolates test susceptible to ertapenem
22
Can Carbapenem Susceptibility of I or R Detect
KPC-Producers?
Method Sens/Spec () for Detection of KPC-mediated R Sens/Spec () for Detection of KPC-mediated R Sens/Spec () for Detection of KPC-mediated R
Method Imipenem Meropenem Ertapenem
Ref BMD 94/93 94/98 97/89
Disk Diffusion 42/96 71/96 97/82
Etest 55/96 58/96 90/84
Vitek Legacy 55/96 52/98 N/A
Vitek 2 71/98 48/96 94/93
MicroScan 74/96 84/98 100/89
Phoenix 81/96 61/98 N/A
N 76 K. pneum, K. oxy, E. coli 31
KPC-producers 45 non-KPC producers
23
CAP Results (D-05)KPC-producing Klebsiella
pneumoniae
Susceptible Results Susceptible Results
MIC Method Disk Method
Imipenem 63 57
Meropenem 63 18
Ertapenem 0 0
24
Carbapenem MIC 2 mg/ml to Detect KPC-producers
Method Sens/Spec () for Detection of KPC-mediated R Sens/Spec () for Detection of KPC-mediated R Sens/Spec () for Detection of KPC-mediated R
Method Imipenem Meropenem Ertapenem
Ref BMD 100/93 100/93 100/89
Etest 84/89 90/87 100/82
Vitek Legacy NA NA NA
Vitek 2 71/91 93/89 93/89
MicroScan 100/93 100/93 NA
Phoenix 74/96 87/93 NA
N 76 K. pneum, K. oxy, E. coli 31
KPC-producers 45 non-KPC producers
25
When to Suspect a KPC-Producer
  • Enterobacteriaceae especially Klebsiella
    pneumoniae that are resistant to
    extended-spectrum cephalosporins
  • MIC range for 151 KPC-producing isolates
  • Ceftazidime 32 to gt64 mg/ml
  • Ceftriaxone 64 mg/ml
  • Cefotaxime 64 mg/ml
  • Variable susceptibility to cefoxitin and cefepime

26
Reading Disk Diffusion Etest
27
Phenotypic Tests for Carbapenemase Activity
  • Modified Hodge Test
  • 100 sensitivity in detecting KPC also positive
    when other carbapenemases are present
  • 100 specificity

Procedure described by Lee et al. CMI, 7, 88-102.
2001.
28
Modified Hodge Test
Lawn of E. coli ATCC 25922 110
dilution of a 0.5 McFarland suspension
Test isolates
Imipenem disk
Described by Lee et al. CMI, 7, 88-102. 2001.
29
Modified Hodge Test
  • Preliminary results suggest that any of the three
    carbapenem disks work in the Modified Hodge Test

30
What Labs Should Do Now
  • Look for isolates of Enterobacteriaceae
    (especially K. pneumoniae), with carbapenem MIC
    2 mg/ml or nonsusceptible to ertapenem by disk
    diffusion
  • Consider confirmation by Modified Hodge Test
  • Can submit initial isolate to CDC via NJ State
    Lab for confirmation by blaKPC PCR if
    KPC-producers not previously identified in
    hospitals isolate population
  • Alert clinician and infection control
    practitioner to possibility of mobile
    carbapenemase in isolate

31
KPC Questions
  • If I have detect KPC-production, should I change
    susceptible carbapenem results to resistant?
  • Not enough data to make a clear recommendation
  • Clinical outcomes data will be necessary

32
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

33
Testing Other Drugs
  • Polymixin B or Colistin
  • Could test either, but colistin used clinically
  • Disk diffusion test does not work dont use!
  • Etest works well, but not FDA cleared
  • Broth microdilution reference labs
  • Breakpoints - none
  • MIC 2 mg/ml, normal MIC range
  • MIC 4 mg/ml indicates increased resistance

34
Acknowledgements
  • Fred Tenover
  • Roberta Carey
  • Kamile Rasheed
  • Kitty Anderson
  • Brandon Kitchel
  • Linda McDougal
  • David Lonsway
  • Jana Swenson
  • Arjun Srinivasan
  • Susan Mikorski
Write a Comment
User Comments (0)
About PowerShow.com