Meropenem

Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections.[1] Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.[1] It is given by injection into a vein.[1]

Meropenem
Clinical data
Trade namesMerrem, others
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
    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
    ExcretionRenal
    Identifiers
    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 mass383.464 g/mol g·mol−1
    3D model (JSmol)
      (verify)

    Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection.[1] Serious side effects include Clostridium 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.[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 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, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is between 3.44 and 20.58 USD per one gram vial as of 2015.[4] In the United Kingdom this amount costs the NHS about £16 in 2015.[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 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 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.[9] 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.[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] 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.[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.[16][17]

    Society and culture
    Meropenem vial

    Trade names
    Trade names
    CountryNameMaker
    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
    BangladeshInpenNavana pharma
    I-PenamIncepta
    MerocilPharmacil
    IndonesiaMerofenKalbe
    BrazilZylpenAspen Pharma
    Japan, KoreaMeropen
    AustraliaMerem
    TaiwanMepem
    GermanyMeronem
    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[18]

    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. "WHO Model List of Essential Medicines (20th List)" (PDF). World Health Organization. March 2017. Retrieved 29 June 2017.
    4. "Single Drug Information". International Medical Products Price Guide. Retrieved 9 December 2017.
    5. British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 379. ISBN 9780857111562.
    6. AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006.
    7. Commissioner, Office of the. "Press Announcements - FDA approves new antibacterial drug". www.fda.gov.
    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. 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.
    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.
    16. "New molecule knocks out superbugs' immunity to antibiotics". newatlas.com. Retrieved 2017-01-25.
    17. 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.
    18. "Hefny Pharma Group". hefnypharmagroup.info. Retrieved 2018-05-22.
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