Meropenem


Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. It is given by injection into a vein.
Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection. Serious side effects include Clostridium difficile infection, seizures, and allergic reactions including anaphylaxis. Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem as well. Use in pregnancy appears to be safe. It is in the carbapenem family of medications. Meropenem usually results in bacterial death through blocking their ability to make a cell wall. It is more resistant to breakdown by β-lactamase producing bacteria.
Meropenem was patented in 1983. It was approved for medical use in the United States in 1996. It is on the World Health Organization's List of Essential Medicines.

Medical uses

The spectrum of action includes many Gram-positive and Gram-negative bacteria and anaerobic bacteria. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. It works against extended-spectrum β-lactamases, but may be more susceptible to metallo-β-lactamases. Meropenem is frequently given in the treatment of febrile neutropenia. This condition frequently occurs in patients with hematological malignancies and cancer patients receiving anticancer drugs that suppress bone marrow formation. It is approved for complicated skin and skin structure infections, complicated intra-abdominal infections and bacterial meningitis.
In 2017 the FDA granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections.

Administration

Meropenem is administered intravenously as a white crystalline powder to be dissolved in 5% monobasic potassium phosphate solution. Dosing must be adjusted for altered kidney function and for haemofiltration.
As with other ß-lactams antibiotics, the effectiveness of treatment depends on the amount of time during the dosing interval that the meropenem concentration is above the minimum inhibitory concentration for the bacteria causing the infection. For ß-lactams, including meropenem, prolonged intravenous administration is associated with lower mortality than bolus intravenous infusion in persons with whose infections are severe, or caused by bacteria that are less sensitive to meropenem, such as Pseudomonas aeruginosa.

Side effects

The most common adverse effects are diarrhea, nausea and vomiting, injection-site inflammation, headache, rash and thrombophlebitis. Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin. Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported. Meropenem, like other carbapenems, is a potent inducer of multidrug resistance in bacteria.

Pharmacology

Mechanism of action

Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. In contrast to other beta-lactams, it is highly resistant to degradation by β-lactamases or cephalosporinases. In general, resistance arises due to mutations in penicillin-binding proteins, production of metallo-β-lactamases, or resistance to diffusion across the bacterial outer membrane. Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin.
In 2016, a synthetic peptide-conjugated PMO was found to inhibit the expression of New Delhi metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems.

Society and culture

Trade names