In this page:

Revision of beta lactamases

What are Beta Lactamase Inhibitors (BLIs)?

• Group of chemicals structurally similar to beta lactams
• No significant antimicrobial activity (mostly)
• Compete with beta lactam to access beta-lactamase binding site —> render enzyme inoperative —> bug now susceptible to beta lactam
• Examples:
  • MSSA - ~85% have constitutive penicillinase (BlaZ) - therefore not S to Pen/Amox/Amp - but with BL/BLI BlaZ is neutralised, and MSSA becomes susceptible again
  • Klebsiella spp. - constitutive penicillinsase, so intrinsically R Amox, but S to co-amoxiclav (and Piperacillin-Tazobactam).

Spectrum of currently available BLIs

See also Luke Turner’s table in the References

Types

First-Generation BLIs

Second-Generation BLIs

Comparison of targets of BL, BLI and combination

G-:  H.influenzae, M.catarrhalis, Klebsiella spp, Anaerobes | | Clavulanic acid | N.gonorrhoeae, H.influenzae | Amoxicillin | G+: Streptococci, Enterococci, Listeria

G-: E.coli, H.influenzae, P.mirabilis, Salmonella spp., Shigella spp. | G+: S.aureus

G-: H.influenzae, M.catarrhalis, N.gonorrhoeae, Klebsiella spp, Bacteroides spp. | | Clavulanic acid | As above | Ticarcillin | G-: Haemophilus spp., E.coli, Proteus spp, Enterobacter spp, Morganella spp, Providencia spp, P.aeruginosa. | G+: S.aureus

G-: H.influenzae, M.catarrhalis, N.gonorrhoeae, Klebsiella spp, Bacteroides spp | | Tazobactam | Borrelia burgdorferi | Piperacillin | G-: Streptococci, Enterococci / G-: P.aeruginosa, Enterobacterales / Anaerobes | G+: S.aureus

G-: Enterobacterales, H.influenzae, M.catarrhalis, N.gonorrhoeae | | Avibactam | E.coli, H.influenzae | Ceftazidime | Enterobacterales, Pseudomonas | As for Ceftazidime |

Mechanisms of resistance to BLIs

• Intrinsic (e.g. 1st-Gen BLIs don’t work against AmpC or Carbapenemases)