Carbapenemases: Difference between revisions
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*Enzymes that hydrolyze [[carbapenems]] |
*Enzymes that hydrolyze [[carbapenems]] |
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*Includes members of |
*Includes members of all Ambler classes, and corresponds to Bush-Jacoby classes 2df, 2f, 3a, and 3b |
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**Class A: KPC |
**Class A (2f): KPC, IMI |
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**Class B: NDM, |
**Class B (3a and 3b): NDM, IMP, VIM |
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**Class C: AmpCs |
**Class C: AmpCs (occasionally weakly active against [[carbapenems]]) |
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**Class D: OXA-48 |
**Class D (2df): OXA-48 |
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===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]] |
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**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)''' |
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**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)''' |
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**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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*'''Double disc diffusion''' (using Rosco discs) |
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**Class A: attenuated by boronic acid |
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**Class B: attenuated by diploconic acid |
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**Class C: attenuated by both cloxacillin and boronic acid |
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**Class D: not attenuated by boronic acid, diploconic acid, or cloxacillin |
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***Needs special discs, or PCR testing |
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===Inhibitors=== |
===Inhibitors=== |
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*'''Tazobactam:''' active against [[Pseudomonas]], but limited activity against carbapenemases otherwise |
*'''Tazobactam:''' active against [[Pseudomonas]], but limited activity against carbapenemases otherwise |
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*'''Vaborbactam:''' active against KPC, but limited activity against MBLs and OXA-48, [[Pseudomonas]], or [[Acinetobacter]] |
*'''Vaborbactam:''' active against KPC, but limited activity against MBLs and OXA-48, [[Pseudomonas]], or [[Acinetobacter]] |
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===Specific Carbapenemases=== |
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*Class A carbapenemases |
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**'''KPC''' ([[Klebsiella pneumoniae]] carbapenemase) is the most common carbapenemase, located on a plasmids and found most commonly in [[Klebsiella pneumoniae]] |
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**'''GES-1''' (Guiana extended spectrum) is located on plasmids |
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**'''SME''' ([[Serratia marcescens]] enzyme) is chromasomal and found in [[Serratia marcescens]] |
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**'''NMC-A''' (not metalloenzyme carbapenemase) is chromasomal and found in [[Enterobacter cloacae]] |
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**'''IMI-1''' (imipenem-hydrolyzing β-lactamase) is chromasomal and found in [[Enterobacter cloacae]] and confers resistance to [[carbapenems]] but possibly not to [[cephalosporins]][[CiteRef::teo2013en]] |
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**'''VIM-2''' (Verona integron-encoded metallo-β-lacamase) is the most common metallo-β-lactamase worldwide, is on a multiple-intergron cassette, and is mostly found in [[Pseudomonas aeruginosa]] |
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**'''IMP''' (active on imipenem) is on a conjugative plasmid and is mostly found in [[Pseudomonas aeruginosa]] but has also been found in [[Enterobacterales]] |
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**'''NDM''' (New Delhi metallo-β-lactamase) is transmitted by horizontal gene transfer and is most commonly found in [[Escherichia coli]], [[Klebsiella pneumoniae]], and other [[Enterobacterales]] |
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**'''SPM-1''' (Sao Paulo metallo-β-lactamase) has been found in [[Pseudomonas aeruginosa]] in Brazil |
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**'''GIM-1''' (German imipenemase) is in a class 1 integron on a plasmid and has been found in [[Pseudomonas aeruginosa]] |
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**'''SIM-1''' (Seoul imipenemase) is in a class 1 integron and has been found in [[Pseudomonas]] and [[Acinetobacter]] |
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*Class D |
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**Found mostly in [[Acinetobacter baumannii complex]] |
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==Management== |
==Management== |
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*Directed by susceptibility testing |
*Directed by susceptibility testing |
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*See also [[Carbapenem-resistant organisms#Management|carbapenem-resistant organisms]] |
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*For ESBLs and AmpCs, consider: |
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**[[Ceftazidime-avibactam]] (not active against metallo-β-lactamases) |
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**[[Meropenem-vaborbactam]] (limited activity against metallo-β-lactamases and oxacillinases) |
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**[[Colistin]], though increasing resistance |
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**[[Tigecycline]] |
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**[[Fosfomycin]] |
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**[[Aztreonam-avibactam]] |
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**[[Cefiderocol]] |
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**[[Eravacycline]] |
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**[[Plazomicin]] |
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*For carbapenem-resistant [[Pseudomonas aeruginosa]], consider: |
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**[[Cefiderocol]] |
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**[[Imipenem-relebactam]] |
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[[Category:Gram-negative bacilli]] |
[[Category:Gram-negative bacilli]] |
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Latest revision as of 16:44, 25 January 2022
Background
- Enzymes that hydrolyze carbapenems
- Includes members of all Ambler classes, and corresponds to 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
- Class A carbapenemases
- KPC (Klebsiella pneumoniae carbapenemase) is the most common carbapenemase, located on a plasmids and found most commonly in Klebsiella pneumoniae
- GES-1 (Guiana extended spectrum) is located on plasmids
- SME (Serratia marcescens enzyme) is chromasomal and found in Serratia marcescens
- NMC-A (not metalloenzyme carbapenemase) is chromasomal and found in Enterobacter cloacae
- IMI-1 (imipenem-hydrolyzing β-lactamase) is chromasomal and found in Enterobacter cloacae and confers resistance to carbapenems but possibly not to cephalosporins1
- Class B carbapenemases (metallo-β-lactamases)
- VIM-2 (Verona integron-encoded metallo-β-lacamase) is the most common metallo-β-lactamase worldwide, is on a multiple-intergron cassette, and is mostly found in Pseudomonas aeruginosa
- IMP (active on imipenem) is on a conjugative plasmid and is mostly found in Pseudomonas aeruginosa but has also been found in Enterobacterales
- NDM (New Delhi metallo-β-lactamase) is transmitted by horizontal gene transfer and is most commonly found in Escherichia coli, Klebsiella pneumoniae, and other Enterobacterales
- SPM-1 (Sao Paulo metallo-β-lactamase) has been found in Pseudomonas aeruginosa in Brazil
- GIM-1 (German imipenemase) is in a class 1 integron on a plasmid and has been found in Pseudomonas aeruginosa
- SIM-1 (Seoul imipenemase) is in a class 1 integron and has been found in Pseudomonas and Acinetobacter
- Class D
- Found mostly in Acinetobacter baumannii complex
Management
- Directed by susceptibility testing
- See also carbapenem-resistant organisms
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.
