Meropenem

Meropenem, sold under the brand name Merrem among others, is an intravenous β-lactam antibiotic used to treat a variety of bacterial infections.[1] Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.[1]

Meropenem
Clinical data
Trade namesMerrem, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B2
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability100%
Protein bindingApproximately 2%
Elimination half-life1 hour
ExcretionKidney
Identifiers
IUPAC name
  • (4R,5S,6S)-3-(((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.169.299
Chemical and physical data
FormulaC17H25N3O5S
Molar mass383.46 g·mol−1
3D model (JSmol)
SMILES
  • O=C3N2\C(=C(\S[C@H]1C[C@@H](C(=O)N(C)C)NC1)[C@H](C)[C@@H]2[C@H]3[C@H](O)C)C(=O)O
InChI
  • InChI=1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1 Y
  • Key:DMJNNHOOLUXYBV-PQTSNVLCSA-N Y
  (verify)

Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection.[1] Serious side effects include Clostridioides difficile infection, seizures, and allergic reactions including anaphylaxis.[1] Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem as well.[1] Use in pregnancy appears to be safe.[1] It is in the carbapenem family of medications.[1] Meropenem usually results in bacterial death through blocking their ability to make a cell wall.[1] It is more resistant to breakdown by β-lactamase producing bacteria.[1]

Meropenem was patented in 1983.[2] It was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines.[3][4] The World Health Organization classifies meropenem as critically important for human medicine.[5]

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. It works against extended-spectrum β-lactamases, but may be more susceptible to metallo-β-lactamases.[6] 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 U.S. Food and Drug Administration (FDA) granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections.[7]

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.[8]

As with other β-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.[9] For β-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.[9][10]

Side effects

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%).[11] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[12][13] Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.[14][15]

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.[16]

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.[11] Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin.

In 2016, a synthetic peptide-conjugated PMO (PPMO) was found to inhibit the expression of New Delhi metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems.[17][18]

Society and culture
Meropenem vial

Trade names
Trade names
CountryNameMaker
IndiaUNOMEROScutonix Lifesciences, Bombay
IndiaInzapenumDream India
Aurobindo Pharma
PenmerBiocon
MeronirNirlife
MerowinStrides Acrolab
AktimerAktimas Biopharmaceuticals
NeopenemNeomed
MexopenSamarth life sciences
MeropeniaSYZA Health Sciences LLP
IvpenemMedicorp Pharmaceuticals
Merofit
LykapiperLyka Labs
WinmeroParabolic Drugs
Bangladesh
MerojectEskayef Pharmaceuticals Ltd.
MeroconBeacon Pharmaceuticals
IndonesiaMerofenKalbe
BrazilZylpenAspen Pharma
Japan, KoreaMeropen
AustraliaMerem
TaiwanMepem
GermanyMeronem
NigeriaZironemLyn-Edge Pharmaceuticals
Ukraine[19]MeropenemLekhim-Kharkiv
Panlaktam (Panlaktam)"Darnytsia"
MepenamKyivmedpreparat
MerobicideBorshchahiv HFZ
USMeronemAstraZeneca
...MerosanSanbe Farma
MerobatInterbat
Zwipen
Carbonem
RonemOpsonin Pharma, BD
Neopenem
MeroconContinental
CarnemLaderly Biotech
PenroBosch
MerozaGerman Remedies
MerotrolLupin)
MeromerOrchid Chemicals
MepenoxBioChimico
MeromaxEurofarma
RopenMacter
mirageadwic
MeropexApex Pharma Ltd.
Merostarkyl Hefny Pharma Group[20]

References
  1. "Meropenem". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  2. Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 497. ISBN 9783527607495.
  3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  5. World Health Organization (2019). Critically important antimicrobials for human medicine (6th revision ed.). Geneva: World Health Organization. hdl:10665/312266. ISBN 9789241515528.
  6. AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006.
  7. "FDA approves new antibacterial drug". U.S. Food and Drug Administration (FDA) (Press release). 24 March 2020. This article incorporates text from this source, which is in the public domain.
  8. Bilgrami, I; Roberts, JA; Wallis, SC; Thomas, J; Davis, J; Fowler, S; Goldrick, PB; Lipman, J (July 2010). "Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration" (PDF). Antimicrobial Agents and Chemotherapy. 54 (7): 2974–8. doi:10.1128/AAC.01582-09. PMC 2897321. PMID 20479205.
  9. Yu Z, Pang X, Wu X, Shan C, Jiang S (2018). "Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis". PLOS ONE. 13 (7): e0201667. Bibcode:2018PLoSO..1301667Y. doi:10.1371/journal.pone.0201667. PMC 6066326. PMID 30059536.
  10. Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME (January 2018). "Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials". Lancet Infect Dis. 18 (1): 108–120. doi:10.1016/S1473-3099(17)30615-1. PMID 29102324.
  11. Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006.
  12. Erden, M; Gulcan, E; Bilen, A; Bilen, Y; Uyanik, A; Keles, M (7 March 2013). "Pancytopenýa and Sepsýs due to Meropenem: A Case Report" (PDF). Tropical Journal of Pharmaceutical Research. 12 (1). doi:10.4314/tjpr.v12i1.21.
  13. "Meropenem side effects - from FDA reports". eHealthMe.
  14. Margolin, L (2004). "Impaired rehabilitation secondary to muscle weakness induced by meropenem". Clinical Drug Investigation. 24 (1): 61–2. doi:10.2165/00044011-200424010-00008. PMID 17516692. S2CID 44484294.
  15. Bharti, R; Gombar, S; Khanna, AK (2010). "Meropenem in critical care - uncovering the truths behind weaning failure". Journal of Anaesthesiology Clinical Pharmacology. 26 (1): 99–101. doi:10.4103/0970-9185.75131. S2CID 54127805.
  16. Al-Quteimat O, Laila A (June 2020). "Valproate Interaction With Carbapenems: Review and Recommendations". Hospital Pharmacy. 55 (3): 181–187. doi:10.1177/0018578719831974. PMC 7243600. PMID 32508355.
  17. "New molecule knocks out superbugs' immunity to antibiotics". newatlas.com. 20 January 2017. Retrieved 2017-01-25.
  18. K., Sully, Erin; L., Geller, Bruce; Lixin, Li; M., Moody, Christina; M., Bailey, Stacey; L., Moore, Amy; Michael, Wong; Patrice, Nordmann; M., Daly, Seth (2016). "Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo". Journal of Antimicrobial Chemotherapy. 72 (3): 782–790. doi:10.1093/jac/dkw476. PMC 5890718. PMID 27999041.
  19. "МЕРОПЕНЕМ (MEROPENEMUM)". compendium.com.ua (in Ukrainian). Compendium. Retrieved 21 May 2022.
  20. "Hefny Pharma Group". hefnypharmagroup.info. Retrieved 2018-05-22.
  • "Meropenem". Drug Information Portal. U.S. National Library of Medicine.
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