imipenem and cilastatin
Regulatory sources consulted
Approved indications
- Complicated intra-abdominal, respiratory, gynecologic, urinary, skin, and osteoarticular infections, and febrile neutropenia, caused by susceptible organisms.
Contraindications
Absolute
- Hypersensitivity to imipenem, cilastatin, or other carbapenems, or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · Severe hypersensitivity or anaphylaxis may occur; review beta-lactam allergy history and discontinue if an allergic reaction develops. — CIMA/AEMPS, ficha técnica 72637
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 72637
- Major warning · Accumulation, especially with renal impairment or unadjusted doses, may cause encephalopathy, myoclonus, or seizures; adjust for renal function and monitor neurologic status. — CIMA/AEMPS, ficha técnica 72637
Drug interactions
- HighValproic acid and valproate
Mechanism: Carbapenems rapidly and markedly lower valproate concentrations, risking loss of seizure control.
Recommendation: Avoid the combination; consider another antibacterial or anticonvulsant. Level monitoring alone may be insufficient.
CIMA/AEMPS, ficha técnica 72637
- HighGanciclovir
Mechanism: Generalized seizures have been reported with the combination.
Recommendation: Avoid the combination unless benefit outweighs risk.
CIMA/AEMPS, ficha técnica 72637
- ModerateProbenecid
Mechanism: Probenecid increases exposure by reducing renal elimination.
Recommendation: Avoid the combination when advised by the label or monitor for adverse reactions.
CIMA/AEMPS, ficha técnica 72637
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
During pregnancy, use only when clinically indicated. Assess breastfeeding according to milk exposure and the infant’s condition described in the product information.
Recent literature (PubMed)
To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL. Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed. A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference -13.2%; 95% CI [-30.0 to 3.5]). Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections. SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.