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NDM and Ceftazidime-Avibactam — SCE Infectious Diseases MCQ

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HardAntimicrobial StewardshipNDM and Ceftazidime-AvibactamSCE Infectious Diseases

A 55-year-old man develops Gram-negative bacteraemia from a urinary source. The organism is identified as a carbapenemase-producing Escherichia coli (NDM-type). It is resistant to all beta-lactams including Meropenem, and resistant to Ciprofloxacin. It is sensitive to Colistin, Fosfomycin, and Ceftazidime/Avibactam. However, NDM-type carbapenemases are NOT inhibited by Avibactam. Why might Ceftazidime/Avibactam still appear susceptible on testing?

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Correct answer: C — The isolate may co-produce a serine carbapenemase (e.g. OXA-48) alongside NDM, and Avibactam inhibits the serine enzyme — but the NDM itself is NOT inhibited; laboratory confirmation of the resistance mechanism is essential

Avibactam is a non-beta-lactam beta-lactamase inhibitor that inhibits serine beta-lactamases (KPC, OXA-48, AmpC, ESBLs) but does NOT inhibit metallo-beta-lactamases (NDM, VIM, IMP). If an NDM-producing isolate appears Ceftazidime/Avibactam-susceptible, it may co-produce a serine enzyme (OXA-48 is the most common co-producer with NDM). Avibactam inhibits the OXA-48, while the NDM component may have variable expression. This is complex resistance — detailed molecular characterisation is essential. Cefiderocol or Aztreonam/Avibactam combinations may provide broader coverage.

Reference: BSAC 2023 – CRE treatment; EUCAST 2024 – Carbapenemase detection