Imipenem–cilastatin !

A very broad carbapenem paired with cilastatin, which stops the kidney from destroying it; it carries the highest seizure risk of its class.

Updated 2026-11-01

Class: Carbapenems
Enzyme: Penicillin-binding proteins (bacterial transpeptidases)
ATC code: J01DH51

Penicillin-binding proteins (bacterial transpeptidases)Imipenem–cilastatin

The figure shows imipenem bound to penicillin-binding protein 3 of Pseudomonas aeruginosa (cilastatin acts on a human kidney enzyme and is not in the structure).

Target in 3D: Penicillin-binding proteins (bacterial transpeptidases). PDB structure 3PBQ (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Imipenem binds many penicillin-binding proteins, with the lethal effect linked to PBP2 and PBP1B, and stops cell-wall cross-linking. On its own it would be hydrolysed by dehydropeptidase I in the brush border of the proximal tubule; cilastatin blocks that enzyme, so imipenem lasts longer and reaches the urine in active form.

Imipenem acylates PBPs and stops wall cross-linking
Cilastatin blocks renal dehydropeptidase I
Imipenem stays active longer, also in urine
The bacterial wall fails and the cell lyses

Pharmacokinetics

Absorption: Intravenous only; not absorbed by mouth.
Metabolism: Without cilastatin, imipenem is hydrolysed in the proximal tubule; cilastatin prevents this.
Elimination: Through the kidney; about 70% of imipenem appears in the urine as active drug when given with cilastatin.
Half-life: About 1 hour for each component.

Indications

Lower respiratory tract infections, including hospital-acquired pneumonia by resistant organisms. Hospital-acquired and ventilator-associated pneumonia →
Complicated and uncomplicated urinary tract infections. Acute pyelonephritis →
Intra-abdominal infections. Peritonitis →
Bone and joint infections, skin infections, septicemia and endocarditis by susceptible bacteria. Osteomyelitis →

Adverse effects

Common

Phlebitis and pain at the infusion site
Nausea, vomiting, diarrhoea
Rash, itching, fever, hypotension, dizziness, somnolence

Contraindications

Hypersensitivity to any component
Not used for meningitis (efficacy and safety not established; seizure risk)

Key interactions

Valproic acid / divalproex: Valproate falls and breakthrough seizures can occur; generally avoided.
Ganciclovir: Generalized seizures reported; given together only if the benefit outweighs the risk.
Probenecid: Raises imipenem levels and half-life; not recommended.

What is monitored

Kidney function; the regimen is adjusted to creatinine clearance
Neurological status: tremor, myoclonus, seizures
Signs of allergy and of C. difficile diarrhoea

Administration and safety

Reconstituted and diluted before IV infusion; not given as a bolus.
Nausea during the infusion often settles by slowing it, as ordered.
Check that the product ordered is imipenem–cilastatin and not the version with relebactam or another carbapenem.

Nursing care

Ask about β-lactam allergy, epilepsy and valproic acid before the first dose.
Seizure precautions in patients with kidney failure or brain lesions.
Inspect the IV site for phlebitis.
Teaching: report twitching, confusion, rash or severe diarrhoea.

Pregnancy and breastfeeding

A small number of human cases do not show a clear risk, and animal studies showed no malformations; it is used in pregnancy when clearly needed.

Test yourself

Think of the answer, then tap the question to see it.

What would happen to imipenem without cilastatin?

Dehydropeptidase I in the proximal tubule would hydrolyse it, shortening its action and lowering active drug in the urine.

Which patients are at highest risk of imipenem seizures?

Those with kidney failure, brain lesions or a seizure history, and those on high doses; children with CNS infection should not receive it.

Which antiviral increases seizure risk when combined with imipenem?

Ganciclovir; generalized seizures have been reported with the combination.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - IMIPENEM AND CILASTATIN- imipenem and cilastatin sodium injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); Imipenem and Cilastatin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 58 (McGraw Hill, 2023); RCSB PDB - 3PBQ: Crystal structure of PBP3 complexed with imipenem (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.