Federation of Infection Societies Conference 2024, Liverpool

AMR

AMR 2024-2029 Action Plan

• Epidemiology
  • 2021: 1.14m deaths
  • By 2050: 39m dead of AMR infection
  • BSI: 21% are AMR
• Prescribing (from ESPAUR):
  • 80% primary care
  • 2ry: increasing Px, particularly ED/Other Specialty Services
  • Overall increase of 2.4%
• AMR action plan outcomes:

• 5 human health targets:
  • Prevent increase in a specific set of Drug-R infections
  • prevent increase in GN BSI (from 2019 baseline)
  • Increase knowledge of AMR by 10%
  • Reduce total use ABx in humans by 5% (cf. 2019)
  • 70% Abx use is Access.

Aztreonam-Avibactam (Pfizer)

• Epid: Colocation over time of serine + MBL carbapenemases.

  • NDM now dominant CPE beta-lactamase

  • Associated with longer ICU stay, LoS, highter mortality

    

• Aztreonam-Avibactam active against all except:

  • Pseudomonas aeruginosa:
    • 30-80% Susc. - has other Res Mechs (despite Pseudo AmpC inactivation, efflux pumps might take over)
    • MBL Pseudomonas: <10% will be Azt-Avi Susc. (MBL rides along other Res Mechs)
  • ABC (Acinetobacter baumanii calcoaceticus complex):
    • Avibactam doesn’t work on intrinsic Oxacillinases (OXA23, OXA51)
    • Aztreo has no activity against ABC!

• EUCAST BP:

  • Steno: None yet
  • Entero: 4/4

• In vitro Susceptibility of Enterobacterales:

  • Azt: 76.2%
  • Azt-avi: 99.9%

• Indications: cUTI, HAP, cIAI

• Dosage:

  • Load: 2g / 0.67g
  • Maintenance: 1.5g / 0.5g, over 3h, 6-hourly
    • 3:1 ratio with loading dose optimises PTA
      • PTA >90%
    • Avibactam threshold varies according to partner ABx (with Avi it’s higher than with Ceftaz)
  • Dosing relative to independent dosing:
    • Aztreonam high dose: 2g QID
    • Ceftaz-Avi high dose: 2g / 0.5g TID
    • So Azt-Avi is 2g Avibactam (more than with Ceftaz) and 6g Aztreo (less than Azt high-dose)
  • Elimination:
    • Aztreonam: 70% renal
    • Avibactam: 100%

• Trials:

  • Rejuvenate
  • Revisit
    • Pros RCT, cIAI (75%), HAP/VAP (25%)
    • 2:1 Azt/Avi +/- MNZ vs Mero +/-Col
    • Outcomes: Clinical Cure
    • Results:
      • Primary
        • mITT + CE: NonInf
      • Secondary:
        • 28d mort: 4.3 vs 7.1% - Nonsig
    • ADRs
      • Transaminitis 5-6%
      • Anaemia
      • Diarrhoea
      • Prolonged PT - watch anticoagulation