Bacqure

Indications

• Infection treatment with imipenem
• Prevention of renal toxicity associated with high doses of imipenem

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines as they may vary based on indication and patient factors.

Mechanism of action

Cilastatin inhibits the enzyme renal dehydropeptidase-I, which is responsible for the hydrolysis of imipenem in the renal tubules. This inhibition prevents the degradation of imipenem, allowing it to maintain its antimicrobial activity.

Pharmacodynamics

Cilastatin acts by blocking the action of renal dehydropeptidase, thereby protecting imipenem from being metabolized and increasing its renal excretion as unchanged drug. While cilastatin does not display any direct antibacterial activity, its role in preserving imipenem levels helps mitigate the risk of nephrotoxicity associated with high doses of imipenem.

Pharmacokinetics

The pharmacokinetics of cilastatin involves its administration alongside imipenem, with cilastatin enhancing the pharmacological profile of imipenem. Cilastatin is administered intravenously, and its half-life and metabolic pathways are closely tied to those of imipenem. The renal clearance of cilastatin is significant, and it plays a protective role against renal damage from imipenem.

Pregnancy

Cilastatin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Cilastatin is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Cilastatin sodium for injection

Indications

• Severe bacterial infections
• Intra-abdominal infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections
• Bone and joint infections
• Meningitis

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines for paediatric patients, as doses vary based on age and weight.

Adults: The usual adult dose for imipenem ranges from 250 mg to 1 g administered intravenously every 6 to 8 hours, depending on the severity and type of infection.

Mechanism of action

Imipenem acts as an antimicrobial by inhibiting cell wall synthesis in various Gram-positive and Gram-negative bacteria. This mechanism is achieved through binding to penicillin-binding proteins (PBPs), particularly PBP-2, PBP-1a, and PBP-1b in E. coli and selected strains of Pseudomonas aeruginosa. The binding prevents the addition of peptidoglycan polymer to the bacterial cell wall, ultimately leading to cell lysis and death.

Pharmacodynamics

As a beta-lactam antibiotic, imipenem exhibits bactericidal properties by disrupting the synthesis of the bacterial cell wall. This activity is effective against a broad spectrum of pathogens, providing a crucial therapeutic option for serious infections, particularly those caused by resistant organisms.

Pharmacokinetics

Imipenem is typically administered intravenously due to its instability in acidic environments. It has a rapid distribution throughout the body, with peak plasma concentrations occurring shortly after administration. The drug is primarily excreted unchanged by the kidneys, and dose adjustments may be needed in patients with renal impairment. The half-life of imipenem is approximately 1 hour.

Contra-indications

• Hypersensitivity to imipenem or any of its components
• History of severe allergic reactions to other beta-lactam antibiotics

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Seizures
• Superinfection
• Allergic reactions

Interactions

• Probenecid may increase plasma concentrations of imipenem
• Valproic acid may have decreased effectiveness when used with imipenem

Precautions

• Use with caution in patients with a history of seizures
• Assess renal function prior to use
• Monitor for signs of superinfection

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus, as there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Imipenem is excreted in breast milk, caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and discarded after 24 hours.

Formulations

• Powder for injection

Mechanism of action

Cilastatin is a 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 of imipenem.

Pharmacodynamics

Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Renal Dehydropeptidase degrades the antibiotic [imipenem]. Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. However, cilastatin in and of itself does not have any antibacterial activity. The increased renal excretion of unchanged imipenem appears to prevent proximal tubular necrosis associated with high doses of imipenem.

Mechanism of action

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 penicillin-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 inhibition of PBPs prevents the bacterial cell from adding to the peptidoglycan polymer which forms the bacterial cell wall eventually leading to cell death.

Pharmacodynamics

Imipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems. Imipenem is active against aerobic and anaerobic Gram positive as well as Gram negative bacteria including <i>Pseudomonas aeruginosa</i> and the <i>Enterococcus</i>. It exerts a bactericidal effects by disrupting cell wall synthesis.