ESBL VS AMPC

• ESBLs


  Extended-spectrum beta-lactamases
• Most ESBLs are plasmid mediated
• ESBLs


  They are inhibited by clavulanate, sulbactam, tazobactam and Avibactam
• ESBLs can cause a variety of illnesses
• Importance of detecting ESBL producers

  • If an ESBL is detected, all penicillins, cephalosporins and aztrenam is reported as resistant
  • Correct therapy
  • Breakpoints do not reliably detect new β-lactamases
  • Represents an epidemiologic marker of colonization
• Cephalosporin indicator when screening for ESBLs

  • All Esbls - obvious resistance to cepodoxime
  • TEM and SHV – obvious resistance to ceftazidime variable to cefotaxime
  • CTX-M – obvious resistance to cefotaxime, variable to ceftazidime
  • Cefuroxime, cephalexin and cephradine are unreliable indicators
• Detecting ESBLs

  1. Double disc

  2. Combination disc

  3. Etest
• Combination Disc

  • Disc with cephalosporin + clavulanic acid
  • Disc with cephalosporin alone
• If the difference between the inhibition zone diameters of the cephalosporin disc and the cephalosporin-clavulanic acid disc is ≥5mm, it indicates the presence of an ESBL
• Etest

  • Cephalosporin alone
  • Cephalosporin + clavulanic acid
  • Ellipse (positive), Phantom
• AmpC β Lactamases

  • Cephalosporinases, hydrolyze all beta lactam antibiotics except carbapenems and cefepime
  • Not inhibited by clavulanate and sulbactam
  • Chromosomally (E. cloacae, E. aerogenes, C. freundii, S. marcescens, Providencia sp., M. morganii) or plasmid mediated
• Importance of detecting AmpC

  • Infection control opportunities for prevention of spread of important mechanisms of plasmid mediated multi drug resistance
  • Potential treatment failure with broad spectrum cephalosporins
  • Organisms overexpressing AmpC β-lactamases are a major clinical concern because these organisms are usually resistant to all the β-lactam drugs, except for cefepime, cefpirome, and the carbapenems
  • Surveillance & Epidemiology
• Chromosomal AmpC vs Derepressed AmpC

  • E. cloacae expressing Induced Chromosomal AmpC
  • E. cloacae derepressed mutant expressing AmpC
• Plasmid mediated AmpC

  • Derepressed/plasmid AmpC should be suspected when we see: Resistance to 3rd generation cephalosporins – NOT Cefepime
  • Resistance to Cefoxitin (inhibition zone < 16 mm)
  • No cephalosporin / Clav. synergism
  • I / R to Amoxycillin + Clav.
  • AmpC derepressed Serratia are S to ceftazidime
  • Providencia, Morganella and Serratia inducible & derepressed may appear S /I to cefoxitin
  • Strains producing AAC-1 beta-lactamase are susceptible to cefoxitin
• Detection of plasmid-mediated AmpC

  1. Combination disc method

  2. Double disc synergy method

  3. Hodge Fox Test
• Klebsiella spp., P. mirabilis, Salmonella spp., Shigella spp. with ↑ R CFZ (6mm), R POD and ESBL NEG should be tested for plasmid-mediated AmpC
• Steps for detecting plasmid-mediated AmpC

  • FOX R/I (Pmi R/S/I)
  • FEP S
  • TEST FOX - APB - 3rdGC
  • FOX-APB-3rdGC POS
  • Hodge FOX POS
• ESBL vs AmpC

  • Inhibited by clavulanate, sulbactam, tazobactam (ESBL Yes, AmpC No)
  • Hydrolyzes 1st, 2nd, 3rd, Cephalosporins (ESBL Yes (R), AmpC Yes (R))
  • Cephamycins (ESBL No (S), AmpC Yes (R))
  • Cefepime (ESBL Yes (R/S), AmpC No (S))
• ESBLs are difficult to detect in Enterobacter spp., Citrobacter, Morganella, Providencia and Serratia because the AmpC enzymes may be induced by clavulanate and may then attack the cephalosporin, masking synergy arising from inhibition of the ESBL
• Screening criteria for ESBL presence among AmpC producing Enterobacter, C. freundii and Serratia is Cefepime MIC >1µg/ml or >26mm inhibition zone
• The use of Cefepime is more reliable to detect these strains because high AmpC production has little effect on cefepime activity
• Automated systems are unable to detect ESBLs in organisms other than Escherichia coli, Klebsiella pneumonia, Klebsiella oxytoca and Proteus mirabilis, and unable to detect AmpCs
• ESBLs are inhibited by

  Clavulanate, Sulbactam, Tazobactam and Avibactam