Extended-spectrum β-lactamases

Background

• Extended-spectrum β-lactamases (ESBLs) are generally defined as β-lactamases that hydrolyze penicillins, first-, second-, and third-generation cephalosporins, and aztreonam, but not cephamycins or carbapenems
• This definition excludes AmpC (which hydrolyze cephamycins) and carbapenemases (which hydrolyze carbapenems)
• Includes primarily Ambler Class A β-lactamases

Identification

• ESBLs are screened for by identifying organisms with increased MICs to one or more third-generation cephalosporin or monobactam
  • CLSI uses cefpodoxime, ceftazidime, aztreonam, cefotaxime, or ceftriaxone

Screening for ESBL production

Bacterium	Antibiotic	Disc Diffusion	Broth Microdilution
Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli	cefpodoxime	≤17 mm	≥8 μg/mL
	ceftazidime	≤22 mm	≥2 μg/mL
	aztreonam	≤27 mm	≥2 μg/mL
	cefotaxime	≤27 mm	≥2 μg/mL
	ceftriaxone	≤25 mm	≥2 μg/mL
Proteus mirabilis	cefpodoxime	≤22 mm	≥2 μg/mL
	ceftazidime	≤22 mm	≥2 μg/mL
	cefotaxime	≤27 mm	≥2 μg/mL

• Organisms that screen positive have further testing to determine the presence of an ESBL
• Class A, for all organisms that screen positive,
  • A double-disc diffusion method is used to assess whether the third-generation cephalosporin resistance that is attenuated by clavulanic acid
  • CLSI uses either ceftazidime or cefotaxime, with and without clavulanic acid
  • An increase in the zone of ≥5 mm is diagnostic of Class A ESBL production
• Class B, for organisms that are also resistant to carbapenems
  • See Carbapenemases for details
• Class C, for organisms that are non-susceptible to cefoxitin
  • A double-disc diffusion method is used to test if the results for cefoxitin are attenuated by cloxacillin (that is, if the isolate becomes even more susceptible)
  • An increase in the zone of ≥4 mm is positive for AmpC (Class C ESBL) phenotype
• Class D, difficult to identify with phenotypic testing

Management

• Carbapenem, with meropenem or imipenem preferentially, though ertapenem can be considered if no septic shockPichia kudriavzevii
• In some patients, can consider piperacillin-tazobactam, amoxicillin-clavulanic acid, or fluoroquinolones
• For non-severe UTI without septic shock, can consider co-trimoxazole, aminoglycosides, or fosfomycin (IV)
• See also Carbapenem-resistant organisms