Carbapenemases: Difference between revisions
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*Enzymes that hydrolyze [[carbapenems]] |
*Enzymes that hydrolyze [[carbapenems]] |
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| − | *Includes members of all Ambler classes |
+ | *Includes members of all Ambler classes, which are in Bush-Jacoby classes 2df, 2f, 3a, and 3b |
| − | **Class A: KPC, IMI |
+ | **Class A (2f): KPC, IMI |
| − | **Class B: NDM, IMP, VIM |
+ | **Class B (3a and 3b): NDM, IMP, VIM |
| − | **Class C: AmpCs |
+ | **Class C: AmpCs (occasionally weakly active against [[carbapenems]]) |
| − | **Class D: OXA-48 |
+ | **Class D (2df): OXA-48 |
===Identification=== |
===Identification=== |
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| − | *Screening is done by identifying isolates with decreased susceptibility to one or more [[carbapenems]] |
+ | *'''Screening''' is done by identifying isolates with decreased susceptibility to one or more [[carbapenems]] |
**Testing "not susceptible" to [[ertapenem]] is the most sensitive indicator |
**Testing "not susceptible" to [[ertapenem]] is the most sensitive indicator |
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**Typically also resistant to third-generation [[cephalosporins]], as well, with the exception of SME in [[Serratia marcescens]] and IMI |
**Typically also resistant to third-generation [[cephalosporins]], as well, with the exception of SME in [[Serratia marcescens]] and IMI |
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*A [[modified Hodge test]] can confirm the presence of a carbapenemase, but is no longer routinely recommended |
*A [[modified Hodge test]] can confirm the presence of a carbapenemase, but is no longer routinely recommended |
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| − | *Modified carbapenem inactivation method (mCIM) |
+ | *'''Modified carbapenem inactivation method (mCIM)''' |
**Place meropenem disc in a suspension of the test isolate, and incubate at 35ºC for 4 hours |
**Place meropenem disc in a suspension of the test isolate, and incubate at 35ºC for 4 hours |
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**Remove disc, squeezing out excess fluid, and place on a lawn of susceptible [[Escherichia coli]] |
**Remove disc, squeezing out excess fluid, and place on a lawn of susceptible [[Escherichia coli]] |
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**Negative if zone diameter is clear ≥19 mm |
**Negative if zone diameter is clear ≥19 mm |
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**Indeterminate if clear diameter 16 to 18 mm, or pinpoint colonies ≥19 mm |
**Indeterminate if clear diameter 16 to 18 mm, or pinpoint colonies ≥19 mm |
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| − | *EDTA-modified carbapenem inactivation method (eCIM) |
+ | *'''EDTA-modified carbapenem inactivation method (eCIM)''' |
**Only done if mCIM is positive, to test for metallo-β-lactamases |
**Only done if mCIM is positive, to test for metallo-β-lactamases |
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**As above for mCIM, but adds EDTA to the tube |
**As above for mCIM, but adds EDTA to the tube |
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**Positive for metallo-β-lactamase if zone diameter increases ≥5 mm from mCIM |
**Positive for metallo-β-lactamase if zone diameter increases ≥5 mm from mCIM |
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***Ignore pinpoint colonies within any zones of inhibition in the eCIM |
***Ignore pinpoint colonies within any zones of inhibition in the eCIM |
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| − | *Rosco discs |
+ | *'''Double disc diffusion''' (using Rosco discs) |
**Class A: attenuated by boronic acid |
**Class A: attenuated by boronic acid |
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**Class B: attenuated by diploconic acid |
**Class B: attenuated by diploconic acid |
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Revision as of 18:48, 17 September 2020
Background
- Enzymes that hydrolyze carbapenems
- Includes members of all Ambler classes, which are in Bush-Jacoby classes 2df, 2f, 3a, and 3b
- Class A (2f): KPC, IMI
- Class B (3a and 3b): NDM, IMP, VIM
- Class C: AmpCs (occasionally weakly active against carbapenems)
- Class D (2df): OXA-48
Identification
- Screening is done by identifying isolates with decreased susceptibility to one or more carbapenems
- Testing "not susceptible" to ertapenem is the most sensitive indicator
- Typically also resistant to third-generation cephalosporins, as well, with the exception of SME in Serratia marcescens and IMI
- A modified Hodge test can confirm the presence of a carbapenemase, but is no longer routinely recommended
- Modified carbapenem inactivation method (mCIM)
- Place meropenem disc in a suspension of the test isolate, and incubate at 35ºC for 4 hours
- Remove disc, squeezing out excess fluid, and place on a lawn of susceptible Escherichia coli
- Positive for carbapenemase if zone diameter is clear ≤15 mm (or pinpoint colonies up to 18 mm)
- Negative if zone diameter is clear ≥19 mm
- Indeterminate if clear diameter 16 to 18 mm, or pinpoint colonies ≥19 mm
- EDTA-modified carbapenem inactivation method (eCIM)
- Only done if mCIM is positive, to test for metallo-β-lactamases
- As above for mCIM, but adds EDTA to the tube
- Positive for metallo-β-lactamase if zone diameter increases ≥5 mm from mCIM
- Ignore pinpoint colonies within any zones of inhibition in the eCIM
- Double disc diffusion (using Rosco discs)
- Class A: attenuated by boronic acid
- Class B: attenuated by diploconic acid
- Class C: attenuated by both cloxacillin and boronic acid
- Class D: not attenuated by boronic acid, diploconic acid, or cloxacillin
- Needs special discs, or PCR testing
Inhibitors
- Avibactam: active against ESBLs, AmpCs, KPC, and OXA-48, but not MBLs and other OXAs
- Only inhibitor with some activity against class D (OXAs)
- Relebactam: active against ESBLs, AmpCs, and KPC, but not OXA-48, VIM, GES, or MBLs
- Tazobactam: active against Pseudomonas, but limited activity against carbapenemases otherwise
- Vaborbactam: active against KPC, but limited activity against MBLs and OXA-48, Pseudomonas, or Acinetobacter
Specific Carbapenemases
- IMI-1 confers resistance to carbapenems but not to cephalosporins1
Management
- Directed by susceptibility testing
- For ESBLs and AmpCs, consider:
- Ceftazidime-avibactam (not active against metallo-β-lactamases)
- Meropenem-vaborbactam (limited activity against metallo-β-lactamases and oxacillinases)
- For metallo-β-lactamases, consider:
- Colistin, though increasing resistance
- Tigecycline
- Fosfomycin
- Aztreonam-avibactam
- Cefiderocol
- Eravacycline
- Plazomicin
- For carbapenem-resistant Pseudomonas aeruginosa, consider:
References
- ^ Jeanette W. P. Teo, My-Van La, Prabha Krishnan, Brenda Ang, Roland Jureen, Raymond T. P. Lin. Enterobacter cloacae producing an uncommon class A carbapenemase, IMI-1, from Singapore. Journal of Medical Microbiology. 2013;62(7):1086-1088. doi:10.1099/jmm.0.053363-0.
