Newer Antibacterial Agents

Introduction — the resistance-driven rationale

• What "newer" means here — the antibacterial pipeline of the last two decades is almost entirely a response to acquired resistance, not a search for new targets — each agent is engineered to evade (e.g. ceftaroline binding the altered PBP2a of MRSA) or neutralise (β-lactamase inhibitors) an existing resistance mechanism rather than to act on a novel pathway.
• Why β-lactams stay central — β-lactams remain "the single most important antibacterial class" (broad spectrum, potent bactericidal kill, good tolerability); steadily rising resistance is what drives development of the new agents — most of this topic is the newer-β-lactam programme.
• The threats these agents target — ESBL-producers, AmpC over-expressers, and above all carbapenemase-producing carbapenem-resistant Enterobacterales (CRE) — potentially "resistant to all or almost all antibacterials in clinical use." The two pivotal carbapenemase families are the KPC type (serine) and the metallo-β-lactamases (MBLs — NDM/VIM/IMP).
• Stewardship is intrinsic — most newer agents are positioned as reserve / last-line options for pathogens resistant to all/almost all alternatives — antimicrobial stewardship is therefore built into their place in therapy (WHO AWaRe "Reserve" tier).