Carbapenems

Carbapenems are β-lactam antibiotics — the same family as the penicillins and cephalosporins already covered — and they kill the same way: they bind penicillin-binding proteins and cripple bacterial cell-wall synthesis, so the cell bursts. What sets them apart is spectrum: carbapenems are the broadest-spectrum β-lactams available, covering gram-positives, gram-negatives (including Pseudomonas, except ertapenem), and anaerobes, and resisting many of the β-lactamase enzymes that defeat other β-lactams — notably ESBL-producing organisms.

That power is exactly why they are held in reserve. Using carbapenems for routine infections breeds carbapenem-resistant organisms (CRE) — an urgent public-health threat with limited treatment options. So they are the "last-resort big guns," deployed for multidrug-resistant or severe infection, not first-line.

Doripenem is no longer marketed in the US. Its only US product, Doribax, left the market, and the FDA withdrew its approval at the company’s request in 2018; in 2022 the FDA determined that it was not withdrawn for reasons of safety or effectiveness. Its record still holds a safety lesson: in a trial in ventilator-associated pneumonia, more patients died on doripenem than on imipenem (23% vs 16.7%) and fewer responded, and its US label warned that doripenem is not approved for ventilator-associated pneumonia. The European Union authorization ended in 2014, withdrawn by the holder for commercial reasons, but doripenem was still on the Japanese market in 2018 — a Japanese hospital study lists it among the carbapenems available there and recorded its use through October 2020 — and a 2026 case report from Japan describes a patient treated with doripenem at the approved Japanese adult dose.

The hallmark toxicity of carbapenems is CNS excitation → seizures, greatest with imipenem and in patients with renal impairment (drug accumulates), high doses, or a prior seizure/CNS disorder. A closely related, high-yield interaction: carbapenems significantly lower valproic acid (valproate) levels, which can break seizure control in an epileptic patient — so the combination is avoided.

Imipenem is always paired with cilastatin for a clever reason: the kidney enzyme dehydropeptidase-I would otherwise break down imipenem into metabolites that can injure the kidney tubules, leaving relatively low levels in the urine. Cilastatin inhibits that enzyme, protecting the drug (and possibly the kidney, though human evidence for this is low-certainty) — it is an enzyme inhibitor, not an antibacterial. As β-lactams, carbapenems share the class allergy concern, but cross-reactivity with penicillin allergy is low (<1%).