Which carbapenem is most commonly associated with seizures at high doses and is given with cilastatin to protect the kidney?

Which carbapenem is most commonly associated with seizures at high doses and is given with cilastatin to protect the kidney?

• A. Imipenem
• B. Meropenem
• C. Ertapenem
• D. Doripenem

Answer: (A)

Imipenem is unique among carbapenems in that it is routinely given with cilastatin to protect the kidneys. Cilastatin blocks renal dehydropeptidase I, an enzyme in the renal tubules that would rapidly degrade imipenem. By inhibiting this enzyme, cilastatin prevents nephrotoxicity and allows higher, effective levels of imipenem to reach the body’s tissues. The trade-off is that imipenem can cause seizures at high doses because it can lower the brain’s seizure threshold through GABA-related mechanisms. This risk is particularly relevant when dosing is high or renal function is impaired, which can raise drug exposure. Other carbapenems—meropenem, ertapenem, and doripenem—do not require cilastatin because they are less susceptible to renal degradation or have lower CNS penetration and a lower reported risk of inducing seizures. They are therefore less commonly associated with seizures at standard therapeutic doses. So, when you think of a carbapenem paired with a kidney-protective inhibitor to prevent renal degradation and enable higher dosing, imipenem with cilastatin is the classic example, with the caveat that high doses carry a seizure risk.

Imipenem is unique among carbapenems in that it is routinely given with cilastatin to protect the kidneys. Cilastatin blocks renal dehydropeptidase I, an enzyme in the renal tubules that would rapidly degrade imipenem. By inhibiting this enzyme, cilastatin prevents nephrotoxicity and allows higher, effective levels of imipenem to reach the body’s tissues.

The trade-off is that imipenem can cause seizures at high doses because it can lower the brain’s seizure threshold through GABA-related mechanisms. This risk is particularly relevant when dosing is high or renal function is impaired, which can raise drug exposure.

Other carbapenems—meropenem, ertapenem, and doripenem—do not require cilastatin because they are less susceptible to renal degradation or have lower CNS penetration and a lower reported risk of inducing seizures. They are therefore less commonly associated with seizures at standard therapeutic doses.

So, when you think of a carbapenem paired with a kidney-protective inhibitor to prevent renal degradation and enable higher dosing, imipenem with cilastatin is the classic example, with the caveat that high doses carry a seizure risk.