Question 1 · Hard
A 54-year-old man ventilated in a Mumbai ICU has bacteraemia with Klebsiella pneumoniae resistant to meropenem. Meropenem's zone of inhibition increases markedly with EDTA, the isolate is resistant to ceftazidime-avibactam, and aztreonam alone tests resistant. Which regimen is most likely to be effective?
- APiperacillin-tazobactam
- BHigh-dose extended-infusion meropenem
- CCeftazidime-avibactam alone
- DCeftazidime-avibactam plus aztreonam
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Answer: D · Ceftazidime-avibactam plus aztreonam
Enhancement of the meropenem zone with EDTA, which chelates zinc, shows a metallo-beta-lactamase such as NDM, common in India. Metallo-enzymes hydrolyse all beta-lactams except aztreonam and are not inhibited by avibactam, so ceftazidime-avibactam fails. Aztreonam alone also fails here because co-produced ESBLs or AmpC enzymes hydrolyse it; adding avibactam protects aztreonam from these enzymes, so the combination works. Results like these should be reported early so that contact precautions can begin.
- A: Piperacillin-tazobactam is hydrolysed by both NDM and ESBLs.
- B: Meropenem is hydrolysed by NDM regardless of dose or infusion time.
- C: Avibactam does not inhibit metallo-beta-lactamases, as the test shows.