Imipenem Cilastatin Relebactam

Imipenem cilastatin relebactam adds a diazabicyclooctane beta-lactamase inhibitor to imipenem cilastatin. It is a reserve agent for KPC-producing Enterobacterales and for multidrug-resistant Pseudomonas aeruginosa.

Classification. Beta-lactam, carbapenem plus relebactam. The full dose contains 500 mg imipenem, 500 mg cilastatin and 250 mg relebactam (1.25 g).

Mechanism. Imipenem blocks penicillin-binding proteins; relebactam inactivates class A (including KPC) and class C enzymes, restoring imipenem activity.

Spectrum. KPC, ESBL and AmpC producing Enterobacterales, Pseudomonas aeruginosa including many strains resistant to ceftazidime and piperacillin tazobactam, plus the imipenem spectrum for Gram-positive and anaerobic organisms. Not active against metallo-beta-lactamase producers, most OXA-48 and Acinetobacter producers, or Stenotrophomonas.

Pharmacokinetics. IV only. Half-life about 1.5 hours for imipenem and 1.7 hours for relebactam. About 63% of imipenem and 90% of relebactam are excreted unchanged in urine.

Reserve agent; specialist use. No loading dose.

Adults, creatinine clearance 90 mL/min or more. 1.25 g IV over 30 minutes every 6 hours. - Complicated urinary tract infection including pyelonephritis: 5 to 14 days. - Complicated intra-abdominal infection (with metronidazole where anaerobes are expected but not covered): 4 to 14 days. - Hospital-acquired and ventilator-associated pneumonia: 7 to 14 days.

Children. Not established in most labels; specialist advice.

Alternatives. Ceftazidime avibactam, meropenem vaborbactam, cefiderocol.

Contraindications. Hypersensitivity to carbapenems or any component; severe hypersensitivity to other beta-lactams.

Adverse effects. Nausea, diarrhoea, headache, phlebitis, raised liver enzymes. Serious: seizures, anaphylaxis, Clostridioides difficile infection, interstitial nephritis, positive direct Coombs test.

Interactions. - Valproate: carbapenems lower valproate levels by 60 to 100% within 24 hours; avoid the combination. - Ganciclovir: increased seizure risk. - Probenecid raises imipenem levels.

Common prescribing errors. Not reducing the dose in renal impairment (a common cause of seizures), using it for metallo-beta-lactamase producers, and giving with valproate.

Special groups.

• Pregnancy and breastfeeding: limited data; use only if the benefit outweighs unknown risk.
• Older adults: adjust by kidney function.
• Kidney impairment, creatinine clearance 60 to 89 mL/min: 1 g (400 mg/400 mg/200 mg) every 6 hours.
• 30 to 59 mL/min: 750 mg every 6 hours.
• 15 to 29 mL/min: 500 mg every 6 hours.
• Haemodialysis: 500 mg every 6 hours, given after the session on dialysis days.
• Liver impairment: no adjustment.
• Region: availability in East Africa is very limited.

Preparation. Reconstitute each vial with 20 mL of 0.9% sodium chloride, then dilute in 100 mL of 0.9% sodium chloride and infuse over 30 minutes.

Baseline and monitoring. - Baseline: allergy history, medication review (valproate), cultures with carbapenemase testing, creatinine. - During treatment: creatinine daily in acute illness; neurological status; liver tests weekly. - No therapeutic drug monitoring.

Stop rules. Stop for seizures, anaphylaxis or severe skin reaction.

Referral and escalation. Infectious diseases consultation is needed before use.