Cispenam

Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria. This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to pencillin binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b. This preferential binding to PBP-2 and PBP-1b results in the direct conversion of the individual cell to a spheroblast, which leads to rapid cell lysis and death without filament formation.

Cilastatin is a specific and reversible renal dehydropeptidase-I inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to block the metabolism and thus the inactivation of imipenem so that antibacterial levels of imipenem can be attained in the urine. The drug also prevents the metabolism of leukotriene D4 to leukotriene E4 through the inhibition of leukotriene D4 dipeptidase.

Concurrent admin with probenecid may increase the half-life of cilastatin. Increased risk of generalised seizures when used concurrently with ganciclovir.

Most common side effects with imipenem are nausea and vomiting. Other side effects reported with this drug are diarrhea, rash, thrombophlebitis, thrombocytosis, neutro-penia, eosinophilia and derangements of liver and renal functions. Use of imipenem is not recommended for patient with history of anaphylactic reaction with penicillin.

Pregnancy: Category C. There are no adequate and well controlled studies in pregnant women. Cispenam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Imipenem has been detected in human milk. If the use of Cispenam is deemed essential, the patient should stop nursing.

Caution when used in patients with known hypersensitivity to other β-lactams due to possibility of cross-sensitivity. CNS disorders such as epilepsy; renal, hepatic impairment; pregnancy, lactation.

Dosage adjustment in renal impairment:

• CrCl >71: No changes.
• CrCl 41-70: Max 37.5 mg/kg/day or 3 g/day. (Range: 9.4 – 37.5 mg/kg/day) divided q6-8h.
• CrCl 21-40: Max 25 mg/kg/day or 2 g/day. (Range: 6.25 – 25 mg/kg/day) divided q6-12h.
• CrCl 6-20: Max 12.5 mg/kg/day (max dose 1 g/day). Range: 6.25 – 12.5 mg/kg/day) divided q12h. (Usual: 250mg q12h)
• Dialysis Hemodialysis: 125 – 500 mg q12h. (Max 12.5 mg/kg/day). Give dose after dialysis.
• Peritonial Dialysis: 125 – 250 mg q12h

Other beta-lactam Antibiotics

In the case of overdosage, discontinue Imipenem/Cilastatin, treat symptomatically, and institute supportive measures as required. Imipenem/Cilastatin Sodium is hemodialyzable.