1. No category

Updated SusceptibilityInterpretationGuideline
(CLSI2014)
Important points in current guideline
“Breakpoint Changes”
‐Enterobacteriaceae***
‐Acinetobacter spp.
#Based on CLSI
Effect of Breakpoint Change
Beta‐Lactamases
Penicillinases
Cephalosporinases
for Enterobacteriaceae!
Carbapenemases
ESBL
AmpC
New!
KPC
MBL e.g. IMP, VIM, NDM‐1
Broth dilution
Drug
conc.
1
New Breakpoint ≤ 2
2
4
8
(ug/mL)
Breakpoint
≤ 8
Susceptible
Enterobacteriaceae
Effect of Breakpoint Change
Drug
Disk Diffusion
New Breakpoint
32
Minimal Inhibitory Concentration (MIC)
OXA (some)
MIC breakpoint
<2009 2009
A
16
Susceptible
Zone breakpoint
2014 <2009
2009
Cefazolin
≤ 8
≤ 2
≥ 18
≥ 23 Cefotaxime
≤ 8
≤ 1
≥ 23
≥ 26 Ceftriaxone
≤ 8
≤ 1 ≥ 21
≥ 23 Ceftazidime
≤ 8
≤ 4
≥ 18
≥ 21 Cefepime
≤ 8
≤ 8
≥ 18
≥ 18
≤ 2
2014
≥ 25
Breakpoint
Pattarachai Kiratisin,MDPhD
ForEducationalUseOnly
1
Updated SusceptibilityInterpretationGuideline
(CLSI2014)
Cefepime
Cefepime
Previous breakpoint was based on a higher dose than the normal dose
No new drug available, so need to adjust to current drug to be appropriate for treatment
Clinical failure was found with MIC 4 and 8 ug/mL, or zone 19‐24 mm MIC breakpoint
Zone breakpoint
S
I
R
S
I
R
≤ 8
16
≥ 32
≥ 18
15‐17
≤ 14
REF: CLSI M100‐S24
Susceptible Dose‐Dependent (SDD)
Cefepime
Year
2013
2014
REF: CLSI M100‐S24
MIC breakpoint
Zone breakpoint
S
S
I
≤ 8
16
S
SDD (D)
≤ 2
4‐8
R
≥ 32 ≥ 18
R
S
≥ 16 ≥ 25
I
R
15‐17
≤ 14
SDD (D)
R
19‐24
≤ 18
In vitro interpretation: not similar to “intermediate (I)”
“I”
Lower response rate for isolates with MICs at blood/tissue levels.
A drug may be used if concentrated at that body site,
or at higher dose.
“SDD”
Susceptibility is dependent on the dosing regimen
that is used in the patient.
REF: CLSI M100‐S24
Susceptible Dose‐Dependent (SDD)
Susceptible Dose‐Dependent (SDD)
Clinical interpretation: susceptibility of organism requires “a higher drug exposure” Why SDD?
(higher dose and/or more frequent dose up to max dose)
This information is based on pharmacokinetics‐pharmacodynamics of antimicrobial drugs
related to in vitro testing
To make available drugs be used more effectively
Doctors often misinterpret “I” as resistant (don’t use!)
Increase awareness of antibiotic appropriate us
‐Encourage optimal dose vs. use of broad spectrum
‐Infection control and antimicrobial stewardship
Apply to ALL specimens, ALL patient groups
REF: CLSI M100‐S24
Pattarachai Kiratisin,MDPhD
ForEducationalUseOnly
REF: CLSI M100‐S24
2
Updated SusceptibilityInterpretationGuideline
(CLSI2014)
Cefepime
Cefepime
Need to communicate with user!
If report SDD for cefepime, a comment may be added:
The interpretation of “S” is based on a dosage regimen of 1 g q 12 hr, and “SDD” is based on dosage regimens that result in a higher cefepime exposure (higher doses or more frequent doses or both) up to approved maximum dosing regimens.
REF: CLSI M100‐S24
REF: CLSI M100‐S24
Carbapenem‐resistant
Enterobacteriaceae (CRE)
New! for Enterobacteriaceae
ESBL testing is NOT required with new cephalosporin breakpoints!
‐Report cephalosporin testing results as ONLY suggested by CLSI 2014!
Other cephalosporins are being evaluated for SDD
REF: CLSI M100‐S24
Emerg Infect Dis. 2006;12: 1209‐13.
Carbapenem‐resistant
Enterobacteriaceae (CRE)
Carbapenem‐resistant
Enterobacteriaceae (CRE)
Klebsiella pneumoniae carbapenemase (KPC)
The most common enzyme
New Delhi Metallo‐beta‐lactamase (NDM)
The emerging enzyme
KPC 1/2‐KPC 20 reported!
(As of Aug 2014)
Discovery of “KPC‐13”
in Thailand
Lascols et al.,JCM 2012;50;1632‐9.
Netikul T./Kiratisin P., Int J Antimicrobial Agents, In Press.
Pattarachai Kiratisin,MDPhD
ForEducationalUseOnly
NDM 1‐NDM 12 reported!
(As of Aug 2014)
Nordman P, et al, Trends Microbiol. 2011;19:588.
3
Updated SusceptibilityInterpretationGuideline
(CLSI2014)
Carbapenem‐resistant
Enterobacteriaceae (CRE)
Detection of ESBL / CRE
CRE @ Siriraj
MIC value Ertapenem Imipenem Meropenem Doripenem
>32
8
8
8
KPC‐13 #1
16
1
2
4
KPC‐13 #2
>32
1
8
4
KPC‐13 #3
NDM‐1 #1
>32
>32
>32
>32
NDM‐1 #2
>32
>32
>32
>32
NDM‐1 #3
>32
>32
>32
>32
Routine service
Infection control
Public health
No
Yes
Yes
Netikul T./Kiratisin P., J Antimicrobial Chemother, 2014:69;3161‐3.
Netikul T./Kiratisin P., Int J Antimicrobial Agents, In Press.
New! for Acinetobacter spp.
Important notes: Drug
Laboratory test results for detection of Carbapenems
resistance mechanisms are not perfect! (~10% false negative for ESBL, MHT)
Now, recommended not to report!
Uses of cephalosporins/carbapenems
need a good stewardship
MIC breakpoint Zone breakpoint
S
I
2013
≤ 4
8
≥ 16 ≥ 16 14‐15 ≤ 13 500 mg q 8 h 2014
≤ 2
4
≥ 8
Meropenem 2013
≤ 4
8
≥ 16 ≥ 16 14‐15 ≤ 13 500 mg q 6 hr/ 2014
1 g q 8 hr
≤ 2
4
≥ 8
Imipenem
Doripenem
2013
500 mg q 8 h 2014
R
‐
‐
‐
≤ 2
4
≥ 8
S
I
R
≥ 22 19‐21 ≤ 18 ≥ 18 15‐17 ≤ 14 ‐
‐
‐
≥ 18 15‐17 ≤ 14 REF: CLSI M100‐S24
New, changing breakpoints need attention…
No need to report mechanism (e.g. ESBL, MHT)
How to report commonly used antibiotics?
How to communicate with customers?
Pattarachai Kiratisin,MDPhD
ForEducationalUseOnly
4