Β-lactamases: Difference between revisions
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Β-lactamases
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− | == |
+ | ==Background== |
+ | *Includes a spectrum of molecules that hydrolyze [[β-lactams]], from penicillins to carbapenems |
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− | * Bacteria containing a plasmid that codes for an extended-spectrum beta-lactamase (ESBL) |
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+ | **See also [[extended-spectrum β-lactamases]] and [[carbapenemases]] |
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− | * Most common with ''Escherichia coli'' and ''Klebsiella'' |
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− | == Classification |
+ | ===Ambler Classification=== |
+ | *Classification based on amino acid sequences rather than function |
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− | * Classes A, B, and C: serine β-lactamases |
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− | ** '''Class A''': inhibited by clavulanic acid or tazobactam |
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− | *** Constitutively expressed plasmid |
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− | *** Most common ESBL in Gram-negative bacteria |
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− | *** Resistance to 2nd and 3rd generation cephalosporins |
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− | *** Examples include penicillinase, TEM-1 (common in GNBs), CTX-M, ''K. pneumoniae'' carbapenemase (KPC) family |
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− | *** Common in ''[[E. coli]]'', ''[[Klebsiella]]'', and ''[[Proteus]]'' spp. |
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− | ** '''Class C''': not inhibited by clavulanic acid or EDTA, resistant to cefoxitin, inhibited by clox in vitro |
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− | *** AmpC = chromosomal |
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− | *** Often an inducible AmpC gene present in the genome |
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− | *** Common in ''[[Citrobacter]]'', ''[[Serratia]]'', and ''[[Enterobacter]]'' |
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− | ** '''Class D''': not inhibited by EDTA, variably inhibited by clavulanic acid; hard to identify |
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− | *** Common in ''[[Acinetobacter]]'' |
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− | * '''Class B''': metallo-β-lactamase, inhibited by EDTA, not inhibited by clavulanic acid |
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− | ** Examples include New Delhi metallo-beta-lactamase (NDM-1) |
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+ | {| class="wikitable" |
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− | == Management == |
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+ | !Class |
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+ | !Binding Site |
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+ | !Examples |
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+ | !Inhibitors |
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+ | |- |
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+ | |A |
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+ | |serine |
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+ | |TEM, SHV, KPC, CTX-M, GES |
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+ | |clavulanic acid, tazobactam, avibactam, vaborbactam, relebactam |
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+ | |- |
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+ | |B |
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+ | |metallo |
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+ | |VIM, NDM, IMP |
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+ | | |
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+ | |- |
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+ | |C |
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+ | |serine |
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+ | |AmpC, P99 |
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+ | |avibactam, vaborbactam, relebactam |
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+ | |- |
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+ | |D |
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+ | |serine |
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+ | |OXA (oxacillinase) enzymes |
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+ | |avibactam (OXA-48), ±clavulanic aciid |
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+ | |} |
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+ | ====Serine β-lactamases==== |
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− | * Antibiotic therapy tailored to the resistance pattern |
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− | * Carbapenems, aminoglycosides, fluoroquinolones, and Septra typically work well |
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+ | *'''Amber classes A, B, and C''' are the serine β-lactamases |
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+ | *Contain a serine residue at the active site |
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+ | *'''Class A''': inhibited by [[clavulanic acid]] or [[tazobactam]] |
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+ | **Constitutively expressed plasmid |
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+ | **Most common ESBL in [[Gram-negative bacteria]] |
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+ | **Resistance to 2nd and 3rd generation [[cephalosporins]] |
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+ | **Common in ''[[E. coli]]'', ''[[Klebsiella]]'', and ''[[Proteus]]'' spp. |
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+ | **Examples include: |
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+ | ***Penicillinases: TEM-1 (common in GNBs), SHV-1 |
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+ | ***ESBLs: CTX-M, TEM-3 |
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+ | ***Carbapenemases: ''K. pneumoniae'' carbapenemase (KPC) |
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+ | *'''Class C''': not inhibited by [[clavulanic acid]] or EDTA, resistant to [[cefoxitin]], inhibited by [[cloxicillin]] in vitro |
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+ | **AmpC = chromosomal |
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+ | **Often an inducible AmpC gene present in the genome |
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+ | **Common in ''[[Citrobacter]]'', ''[[Serratia]]'', and ''[[Enterobacter]]'' |
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+ | *'''Class D''': not inhibited by EDTA, variably inhibited by [[clavulanic acid]]; hard to identify |
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+ | **Common in ''[[Pseudomonas]]'' |
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+ | **Difficult to detect with routine screening |
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+ | **Examples include: |
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+ | ***ESBLs: OXA-11 |
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+ | ***Carbapenemases: OXA-23, OXA-48 |
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+ | |||
+ | ====Metallo-β-lactamases==== |
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+ | |||
+ | *'''Ambler Class B''' are the metallo-β-lactamases |
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+ | *Contain a zinc ion at the active site |
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+ | *Inhibited by EDTA, not inhibited by [[clavulanic acid]] |
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+ | *Examples include: |
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+ | **Carbapenemases: |
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+ | ***New Delhi metallo-beta-lactamase (NDM-1) |
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+ | ***Imipenemases (IMP) |
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+ | ***Verona integron-encoded metallo-β-lactamases (VIM) |
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+ | ***L1 β-lactamase, present in the [[Stenotrophomonas maltophilia]] chromosome |
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+ | |||
+ | ===Bush-Jacoby Classification=== |
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+ | {| class="wikitable" |
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+ | ! rowspan="2" |Group |
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+ | ! rowspan="2" |Ambler |
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+ | ! rowspan="2" |Substrates |
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+ | ! colspan="2" |Inhibitors |
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+ | ! rowspan="2" |Definition |
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+ | ! rowspan="2" |Examples |
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+ | |- |
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+ | !CA/TZB |
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+ | !EDTA |
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+ | |- |
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+ | ! colspan="7" |Group 1: Cephalosporinases |
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+ | |- |
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+ | |1 |
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+ | | rowspan="2" |C |
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+ | |[[cephalosporins]] |
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+ | |— |
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+ | |— |
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+ | |hydrolyzes cephalosporins better than benzylpenicillin, and hydrolyzes cephamycins |
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+ | |''E. coli'' AmpC, P99, ACT-1, CMY-2, FOX-1, MIR-1 |
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+ | |- |
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+ | | |
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+ | |[[cephalosporins]] |
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+ | |— |
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+ | |— |
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+ | |increased hydrolysis of ceftazidime and other oxyimino-β-lactams |
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+ | |GC1, CMY-37 |
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+ | |- |
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+ | ! colspan="7" |Group 2: β-Lactamases |
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+ | |- |
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+ | |2a |
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+ | | rowspan="7" |A |
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+ | |[[penicillins]] |
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+ | |yes |
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+ | |— |
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+ | |hydrolyzes benzylpenicillin better than cephalosporins |
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+ | |PC1 |
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+ | |- |
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+ | |2b |
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+ | |[[penicillins]] and early [[cephalosporins]] |
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+ | |yes |
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+ | |— |
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+ | |hydrolyzes benzylpenicillin similar to cephalosporins |
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+ | |TEM-1, TEM-2, SHV-1 |
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+ | |- |
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+ | |2be |
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+ | |extended-spectrum [[cephalosporins]], [[monobactams]] |
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+ | |yes |
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+ | |— |
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+ | |increased hydrolysis of oxyimino-β-lactams (third-generation plus monobactams) |
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+ | |TEM-3, SHV-2, CTX-M-15, PER-1, VEB-1 |
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+ | |- |
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+ | |2br |
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+ | |[[penicillins]] |
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+ | |— |
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+ | |— |
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+ | |resistance to clavulanic acid, sulbactam, and tazobactam |
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+ | |TEM-30, SHV-10 |
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+ | |- |
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+ | |2ber |
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+ | |extended-spectrum [[cephalosporins]], [[monobactams]] |
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+ | |— |
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+ | |— |
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+ | |increased hydrolysis of oxyimino-β-lactams plus resistance to clavulanic acid, sulbactam, and tazobactam |
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+ | |TEM-50 |
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+ | |- |
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+ | |2c |
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+ | |[[carbenicillin]] |
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+ | |yes |
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+ | |— |
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+ | |increased hydrolysis of carbenicillin |
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+ | |PSE-1, CARB-3 |
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+ | |- |
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+ | |2ce |
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+ | |[[carbenicillin]], [[cefepime]] |
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+ | |yes |
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+ | |— |
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+ | |increased hydrolysis of carbenicillin, cefepime, and cefpirome |
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+ | |RTG-4 |
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+ | |- |
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+ | |2d |
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+ | | rowspan="3" |D |
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+ | |[[cloxacillin]] |
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+ | |variable |
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+ | |— |
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+ | |increased hydrolysis of cloxacillin or oxacillin |
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+ | |OXA-1, OXA-10 |
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+ | |- |
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+ | |2de |
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+ | |extended-spectrum [[cephalosporins]] |
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+ | |variable |
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+ | |— |
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+ | |hydrolyzes cloxacillin or oxacillin and oxyimino-β-lactams |
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+ | |OXA-11, OXA-15 |
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+ | |- |
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+ | |2df |
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+ | |[[carbapenems]] |
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+ | |variable |
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+ | |— |
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+ | |hydrolyzes cloxacillin or oxacillin and carbapenems |
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+ | |OXA-23, OXA-48 |
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+ | |- |
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+ | |2e |
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+ | | rowspan="2" |A |
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+ | |extended-spectrum [[cephalosporins]] |
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+ | |yes |
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+ | |— |
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+ | |hydrolyzes cephalosporins, and inhibited by clavulanic acid but not aztreonem |
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+ | |CepA |
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+ | |- |
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+ | |2f |
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+ | |[[carbapenems]] |
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+ | |variable |
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+ | |— |
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+ | |increased hydrolysis of carbapenems, oxyimino-β-lactams, cephamycins |
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+ | |KPC-2, IMI-1, SME-1 |
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+ | |- |
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+ | ! colspan="7" |Group 3: Carbapenemases |
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+ | |- |
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+ | |3a |
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+ | | rowspan="2" |B |
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+ | |[[carbapenems]] |
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+ | |— |
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+ | |yes |
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+ | |broad-spectrum hydrolysis including carbapenems but not monobactams |
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+ | |IMP-1, VIM-1, CcrA, IND-1, L1, CAU-1, GOB-1, FEZ-1 |
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+ | |- |
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+ | |3b |
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+ | |[[carbapenems]] |
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+ | |— |
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+ | |yes |
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+ | |preferential hydrolysis of carbapenems |
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+ | |CphA, Sfh-1 |
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+ | |} |
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+ | |||
+ | ===Epidemiology=== |
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+ | |||
+ | *The most common β-lactamase is TEM-1 |
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+ | *The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases |
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+ | |||
+ | == Common β-Lactamases == |
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+ | {| class="wikitable" |
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+ | !β-lactamase[[CiteRef::cantón2008ir]] |
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+ | !AMX |
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+ | !AMC |
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+ | !TIC |
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+ | !TIM |
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+ | !PIP |
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+ | !TZP |
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+ | !CFZ |
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+ | !FOX |
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+ | !CRO |
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+ | |- |
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+ | |TEM-1 |
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+ | |R |
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+ | |S |
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+ | |R |
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+ | |S |
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+ | |I/R |
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+ | |S |
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+ | |S/I/R |
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+ | |S |
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+ | |S |
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+ | |- |
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+ | |TEM-1 hyperproduction |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |S/I/R |
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+ | |I/R |
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+ | |S |
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+ | |S |
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+ | |- |
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+ | |OXA-1 |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |S |
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+ | |S |
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+ | |- |
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+ | |IRT type |
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+ | |R |
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+ | |I/R |
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+ | |I/R |
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+ | |I/R |
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+ | |S/I/R |
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+ | |S/I/R |
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+ | |S |
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+ | |S |
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+ | |S |
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+ | |- |
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+ | |CMT type |
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+ | |R |
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+ | |R |
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+ | |R |
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+ | |I/R |
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+ | |R |
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+ | |I/R |
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+ | |I/R |
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+ | |S |
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+ | |I/R |
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+ | |- |
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+ | |ESBL type |
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+ | |R |
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+ | |S/I |
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+ | |R |
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+ | |S |
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+ | |I/R |
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+ | |S/I |
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+ | |R |
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+ | |S |
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+ | |R |
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+ | |- |
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+ | |[[AmpC β-lactamase|AmpC hyperproduction]] |
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+ | |R |
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+ | |R |
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+ | |I/R |
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+ | |I/R |
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+ | |I/R |
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+ | |I/R |
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+ | |R |
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+ | |I/R |
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+ | |S/I/R |
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+ | |} |
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+ | |||
+ | ==Management== |
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+ | |||
+ | *Antibiotic therapy tailored to the resistance pattern |
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+ | *[[Carbapenems]], [[aminoglycosides]], [[fluoroquinolones]], and [[TMP-SMX]] typically work well |
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+ | *See also [[Carbapenem-resistant organisms]] |
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+ | |||
+ | ==Further Reading== |
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+ | |||
+ | *Updated Functional Classification of β-Lactamases. ''Antimicrob Agents Chemother''. 2010;54(3):969-976. doi: [https://doi.org/10.1128/AAC.01009-09 10.1128/AAC.01009-09] |
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+ | {{DISPLAYTITLE:β-lactamases}} |
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[[Category:Antibiotics]] |
[[Category:Antibiotics]] |
Latest revision as of 13:46, 19 September 2024
Background
- Includes a spectrum of molecules that hydrolyze β-lactams, from penicillins to carbapenems
- See also extended-spectrum β-lactamases and carbapenemases
Ambler Classification
- Classification based on amino acid sequences rather than function
Class | Binding Site | Examples | Inhibitors |
---|---|---|---|
A | serine | TEM, SHV, KPC, CTX-M, GES | clavulanic acid, tazobactam, avibactam, vaborbactam, relebactam |
B | metallo | VIM, NDM, IMP | |
C | serine | AmpC, P99 | avibactam, vaborbactam, relebactam |
D | serine | OXA (oxacillinase) enzymes | avibactam (OXA-48), ±clavulanic aciid |
Serine β-lactamases
- Amber classes A, B, and C are the serine β-lactamases
- Contain a serine residue at the active site
- Class A: inhibited by clavulanic acid or tazobactam
- Constitutively expressed plasmid
- Most common ESBL in Gram-negative bacteria
- Resistance to 2nd and 3rd generation cephalosporins
- Common in E. coli, Klebsiella, and Proteus spp.
- Examples include:
- Penicillinases: TEM-1 (common in GNBs), SHV-1
- ESBLs: CTX-M, TEM-3
- Carbapenemases: K. pneumoniae carbapenemase (KPC)
- Class C: not inhibited by clavulanic acid or EDTA, resistant to cefoxitin, inhibited by cloxicillin in vitro
- AmpC = chromosomal
- Often an inducible AmpC gene present in the genome
- Common in Citrobacter, Serratia, and Enterobacter
- Class D: not inhibited by EDTA, variably inhibited by clavulanic acid; hard to identify
- Common in Pseudomonas
- Difficult to detect with routine screening
- Examples include:
- ESBLs: OXA-11
- Carbapenemases: OXA-23, OXA-48
Metallo-β-lactamases
- Ambler Class B are the metallo-β-lactamases
- Contain a zinc ion at the active site
- Inhibited by EDTA, not inhibited by clavulanic acid
- Examples include:
- Carbapenemases:
- New Delhi metallo-beta-lactamase (NDM-1)
- Imipenemases (IMP)
- Verona integron-encoded metallo-β-lactamases (VIM)
- L1 β-lactamase, present in the Stenotrophomonas maltophilia chromosome
- Carbapenemases:
Bush-Jacoby Classification
Group | Ambler | Substrates | Inhibitors | Definition | Examples | |
---|---|---|---|---|---|---|
CA/TZB | EDTA | |||||
Group 1: Cephalosporinases | ||||||
1 | C | cephalosporins | — | — | hydrolyzes cephalosporins better than benzylpenicillin, and hydrolyzes cephamycins | E. coli AmpC, P99, ACT-1, CMY-2, FOX-1, MIR-1 |
cephalosporins | — | — | increased hydrolysis of ceftazidime and other oxyimino-β-lactams | GC1, CMY-37 | ||
Group 2: β-Lactamases | ||||||
2a | A | penicillins | yes | — | hydrolyzes benzylpenicillin better than cephalosporins | PC1 |
2b | penicillins and early cephalosporins | yes | — | hydrolyzes benzylpenicillin similar to cephalosporins | TEM-1, TEM-2, SHV-1 | |
2be | extended-spectrum cephalosporins, monobactams | yes | — | increased hydrolysis of oxyimino-β-lactams (third-generation plus monobactams) | TEM-3, SHV-2, CTX-M-15, PER-1, VEB-1 | |
2br | penicillins | — | — | resistance to clavulanic acid, sulbactam, and tazobactam | TEM-30, SHV-10 | |
2ber | extended-spectrum cephalosporins, monobactams | — | — | increased hydrolysis of oxyimino-β-lactams plus resistance to clavulanic acid, sulbactam, and tazobactam | TEM-50 | |
2c | carbenicillin | yes | — | increased hydrolysis of carbenicillin | PSE-1, CARB-3 | |
2ce | carbenicillin, cefepime | yes | — | increased hydrolysis of carbenicillin, cefepime, and cefpirome | RTG-4 | |
2d | D | cloxacillin | variable | — | increased hydrolysis of cloxacillin or oxacillin | OXA-1, OXA-10 |
2de | extended-spectrum cephalosporins | variable | — | hydrolyzes cloxacillin or oxacillin and oxyimino-β-lactams | OXA-11, OXA-15 | |
2df | carbapenems | variable | — | hydrolyzes cloxacillin or oxacillin and carbapenems | OXA-23, OXA-48 | |
2e | A | extended-spectrum cephalosporins | yes | — | hydrolyzes cephalosporins, and inhibited by clavulanic acid but not aztreonem | CepA |
2f | carbapenems | variable | — | increased hydrolysis of carbapenems, oxyimino-β-lactams, cephamycins | KPC-2, IMI-1, SME-1 | |
Group 3: Carbapenemases | ||||||
3a | B | carbapenems | — | yes | broad-spectrum hydrolysis including carbapenems but not monobactams | IMP-1, VIM-1, CcrA, IND-1, L1, CAU-1, GOB-1, FEZ-1 |
3b | carbapenems | — | yes | preferential hydrolysis of carbapenems | CphA, Sfh-1 |
Epidemiology
- The most common β-lactamase is TEM-1
- The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases
Common β-Lactamases
β-lactamase1 | AMX | AMC | TIC | TIM | PIP | TZP | CFZ | FOX | CRO |
---|---|---|---|---|---|---|---|---|---|
TEM-1 | R | S | R | S | I/R | S | S/I/R | S | S |
TEM-1 hyperproduction | R | I/R | R | I/R | R | S/I/R | I/R | S | S |
OXA-1 | R | I/R | R | I/R | R | I/R | R | S | S |
IRT type | R | I/R | I/R | I/R | S/I/R | S/I/R | S | S | S |
CMT type | R | R | R | I/R | R | I/R | I/R | S | I/R |
ESBL type | R | S/I | R | S | I/R | S/I | R | S | R |
AmpC hyperproduction | R | R | I/R | I/R | I/R | I/R | R | I/R | S/I/R |
Management
- Antibiotic therapy tailored to the resistance pattern
- Carbapenems, aminoglycosides, fluoroquinolones, and TMP-SMX typically work well
- See also Carbapenem-resistant organisms
Further Reading
- Updated Functional Classification of β-Lactamases. Antimicrob Agents Chemother. 2010;54(3):969-976. doi: 10.1128/AAC.01009-09
References
- ^ R. Cantón, M.I. Morosini, O. Martin, S. de la Maza, E. Gomez G. de la Pedrosa. IRT and CMT β-lactamases and inhibitor resistance. Clinical Microbiology and Infection. 2008;14:53-62. doi:10.1111/j.1469-0691.2007.01849.x.