A review in NEJM, published on 29 October 2026, sets out how gram-negative bacteria resist antibiotics — reduced entry, efflux, altered targets and, above all, beta-lactamase enzymes — and how mobile genetic elements spread those genes between species and settings.
It names four groups that drive most clinical difficulty: extended-spectrum beta-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa with difficult-to-treat resistance, and carbapenem-resistant Acinetobacter baumannii. Access to effective drugs is limited and resistance to newer agents is already appearing.
The management message is broader than drug choice: fast and accurate diagnostics, targeted use of the newer beta-lactam combinations rather than empirical use, effective source control, and treatment durations no longer than needed. In India, where carbapenem resistance is common in hospital isolates, knowing the local mechanism matters as much as the susceptibility result.
- Send cultures before antibiotics wherever it does not delay treatment in sepsis.
- Ask your laboratory which carbapenemase types are common locally; the right newer agent depends on the enzyme.
- Reserve newer beta-lactam combinations for confirmed or strongly suspected resistant infection.
- Pursue source control — drain, remove, debride — as a treatment in its own right.
- Set a stop date at the start of every course and review it at 48 to 72 hours.
Why it matters
Choosing the newest agent without knowing the enzyme or controlling the source wastes the few drugs left.
Don't overread it
A narrative review; it summarises expert practice rather than presenting new trial evidence.
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