Meropenem

Meropenem, sold under the brand name Merrem among others, is an intravenous carbapenem antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.[3]

Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection.[3] Serious side effects include Clostridioides difficile infection, seizures, and allergic reactions including anaphylaxis.[3] Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem as well.[3] Use in pregnancy appears to be safe.[3] It is in the carbapenem family of medications.[3] Meropenem usually results in bacterial death through blocking their ability to make a cell wall.[3] It is resistant to breakdown by many kinds of β-lactamase enzymes, produced by bacteria to protect themselves from antibiotics.[4]

Meropenem was patented in 1983.[6] It was approved for medical use in the United States in 1996.[3] It is on the World Health Organization's List of Essential Medicines.[7][8] The World Health Organization classifies meropenem as critically important for human medicine.[9]

Medical uses

The spectrum of action includes many Gram-positive and Gram-negative bacteria (including Pseudomonas) 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. Meropenem is effective against bacteria producing extended-spectrum β-lactamases but may be more susceptible to hydrolysis by metallo-β-lactamases produced by bacteria.[10] β-lactamases are enzymes that bacteria produce to hydrolyze β-lactam antibiotics, breaking the β-lactam ring and rendering these antibiotics ineffective. This mechanism helps bacteria resist the effects of antibiotics like penicillins, cephalosporins, and carbapenems, making treatment more challenging.[11][12][13] While β-lactam ring in meropenem is more accessible to water molecules than in the other β-lactam antibiotics, that facilitates the hydrolysis process and faster degradation of meropenem's antibacterial properties in aqueous solutions, it is more resistant to degradation by β-lactamase enzymes produced by bacteria than the other β-lactam antibiotics.[14]

Administration

Meropenem is administered intravenously as an aqueous solution. Meropenem is stored in vials as white crystalline powder (containing meropenem as the trihydrate blended with anhydrous sodium carbonate).[21] For intravenous administration, if pure meropenem powder is used (rather than the powder blended with sodium carbonate), meropenem is dissolved in 5% monobasic potassium phosphate solution, since meropenem is soluble in 5% monobasic potassium phosphate solution and only sparingly soluble in water[22] .[23][24][25] For intravenous bolus administration, injection vials (that contain meropenem blended with sodium carbonate) are reconstituted with sterile water for injection.[26][22]

Side effects

Among antibiotic drugs, meropenem is relatively safe.[15][46] The most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%) and thrombophlebitis (0.9%). Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[55][56] Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.[57][58]

Interactions

Meropenem rapidly reduces serum concentrations of valproic acid. As a result, people who use valproic acid for epilepsy are at increased risk of seizures during treatment with meropenem. In situations where the use of meropenem cannot be avoided, prescription of an additional anticonvulsant should be considered.[59]

Pharmacology

Research directions

Nebulized meropenem (inhaled route) is researched, but is not approved, for prevention of bronchiectasis exacerbation.[66]

Society and culture