The difference between imipenem, meropenem and biapenem.👀

Carbapenems are a class of atypical β-lactam antibiotics with the broadest
antibacterial spectrum. They have strong antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria. At present, imipenem, meropenem and biapenem are commonly used in clinical practice. Carbapenems bind to a variety of bacterial penicillin binding proteins (PBPs). This will prevent the synthesis of the cell wall and play a role, which has a relatively significant post antibiotic effect (PAE).

Characteristics of imipenem, meropenem and biapenem.

Imipenem: It is the first carbapenem approved for clinical use. It is metabolically inactivated by dehydrogenase I (DHP-I) in human kidney epithelial cells. Therefore, a specific enzyme inhibitor, cilastatin, was added to block the metabolism of imipenem in the kidneys, thereby ensuring sufficient antibacterial concentration of imipenem in urine. At the same time, cilastatin can also prevent imipenem from entering renal tubular epithelial cells to reduce its excretion and reduce renal toxicity. Imipenem and Cilastatin are β-lactamase stable. It has a broad antibacterial spectrum. It has strong activity against most Gram-positive and Gram-negative bacteria.

Meropenem: It is more stable to DHP-I and more active against Gram-negative bacteria than imipenem, especially Pseudomonas aeruginosa. Meropenem easily penetrates the blood-brain barrier and can effectively treat intracranial infections. At the same time, it has no affinity for γ-aminobutyric acid receptors. Its safety in the central nervous system is better than that of imipenem. It is more suitable for the treatment of the elderly, children and patients with central nervous system infection or severe infection accompanied by mental symptoms.

Biapenem: Compared with other carbapenems, it has lower nephrotoxicity and central nervous system toxicity.

• Anti-Gram-positive bacteria activity: Imipenem > Biapenem, Meropenem.
• Anti-Gram-negative bacteria activity: Meropenem > Biapenem > Imipenem.
• Anti-Pseudomonas aeruginosa activity: Meropenem = Biapenem > Imipenem.
• Anti-anaerobic activity: Biapenem > Imipenem = Meropenem.

Carbapenems are generally resistant to Stenotrophomonas maltophilia (chromosome-mediated β-lactamase that candhydrolyze carbapenems), Burkholderia cepacia, Enterococcus faecium, oxacillin-resistant Staphylococcus aureus and so on are ineffective.

Dosage of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: 1-2 g in 3-4 divided doses daily is recommended for most infections. The maximum dose is 4g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Meropenem: The recommended dose is 0.5 or 1 g every 8 hours. Meningitis patients 2g every 8 hours. The maximum dose is 6g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Biapenem: The recommended dose is 0.3 g every 12 hours. The maximum dose is 1.2g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Precautions of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: When the dose is ≤ 0.5g, the intravenous infusion time should be no less than 20-30 minutes. When the dose is > 0.5g, the intravenous infusion time should not be less than 40-60 minutes. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. This will increase the risk of seizures. Furthermore, increasing the dose of sodium valproate was not sufficient to overcome the interaction between them. Imipenem/Cilastatin can cause central nervous system accumulation and lead to psychiatric symptoms. It may also cause pseudomembranous colitis. If using imipenem/cilastatin while breastfeeding, breastfeeding should be discontinued.

Meropenem: Intravenous push time should be greater than 5 minutes. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. This will increase the risk of seizures. It also competes with probenecid to activate tubular secretion and inhibit renal metabolism. This results in prolonged half-life of meropenem and increased plasma concentrations. Patients with a history of epilepsy or central nervous system dysfunction are more likely to develop central nervous system symptoms. It may also cause symptoms of vitamin K deficiency. If using meropenem while breastfeeding, breastfeeding should be discontinued.

Biapenem: The intravenous infusion time should be 30-60 minutes each time. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. It can cause epileptic seizures. Patients with a history of epilepsy or central nervous system dysfunction are more likely to develop central nervous system symptoms. It may also cause symptoms of vitamin K deficiency. Safety during breastfeeding has not been established.

Clinical application characteristics of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: When it comes into contact with bacteria, it turns the bacteria into a spherical shape. The endotoxin released by bacteria is reduced and the initial bactericidal effect is extremely strong. It is widely distributed in the body. It can cross the placental barrier, but it cannot cross the blood-brain barrier. It can cause central nervous system toxicity, so it should not be used in the treatment of meningitis. Its sterilization speed is fast. 1 hour bactericidal activity is twice that of meropenem. It is ineffective against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. The activity against gram-positive bacteria is stronger than that of meropenem.

Meropenem: When it comes into contact with bacteria, it swells the bacteria. Bacteria release a lot of endotoxin, and the initial bactericidal effect is poor. It can cross the blood-brain barrier. It can reach effective concentrations in cerebrospinal fluid. Common adverse reactions are similar to imipenem, but it may have a slightly lower risk of seizures than imipenem. Meropenem is the first choice for patients with renal insufficiency and central nervous system disease. The activity against Acinetobacter baumannii is lower than that of imipenem. However, the ability to resist Gram-negative bacteria is 2-16 times that of subpulmonary penem and the anti-Pseudomonas aeruginosa effect is 2-4 times that of imipenem.

Biapenem: When it comes into contact with bacteria, it turns the bacteria into a spherical shape. The endotoxin released by bacteria is reduced and the initial bactericidal effect is extremely strong. Multiple doses do not accumulate in the body. It is ineffective against Enterococcus faecium and methicillin-resistant Staphylococcus aureus. Its antibacterial activity is similar to meropenem. The activity of inhibiting Pseudomonas aeruginosa and anaerobic bacteria is 2-4 times that of imipenem. It has extremely low nephrotoxicity and CNS toxicity compared to other carbapenems. It does not induce epilepsy. It can be used in the treatment of bacterial meningitis. Adverse reactions are also relatively few.