|Systematic (IUPAC) name|
3-[5-(dimethylcarbamoyl) pyrrolidin-2-yl] sulfanyl-6- (1-hydroxyethyl)-4-methyl-7-oxo- 1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid
|Protein binding||Approximately 2%.|
|Biological half-life||1 hour|
|Molecular mass||383.464 g/mol|
|(what is this?)|
Meropenem is an ultra-broad-spectrum injectable antibiotic used to treat a wide variety of infections. It is a β-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Dainippon Sumitomo Pharma. It gained US FDA approval in July 1996. It penetrates well into many tissues and body fluids, including cerebrospinal fluid, bile, heart valve, lung, and peritoneal fluid. It was initially marketed by AstraZeneca under the trade name Merrem.
Mechanism of action
Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. It inhibits bacterial 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.
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. 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 cause bone marrow suppression. It is approved for complicated skin and skin structure infections, complicated intra-abdominal infections, and bacterial meningitis.
Meropenem must be administered intravenously. It is supplied 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.
Common adverse 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%). Many of these adverse effects were observed in the setting of severely ill individuals already taking many medications including vancomycin. One study showed Clostridium difficile-associated diarrhea happened in 3.6% of the patients on meropenem. Meropenem also has a reduced potential for causing seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.
Other trade names include Merosan By Sanbe Farma, Merobat By Interbat & Meronem By Kalbe (Indonesia), Merofit (India), Merocil by Pharmacil (Bangladesh), Meronir by Nirlife (India), Merowin by Strides Acrolab (India), PENMER by BIOCON (India), Aktimer by Aktimas Biopharmaceuticals (India), Zwipen, Carbonem, Ronem (Opsonin Pharma, BD),NEOPENEM 1G &500MG Neomed (India), Mepem (Taiwan), Meropen (Japan, Korea), Merem (Australia), Neopenem, Merocon (Continental), Carnem (Laderly Biotech), Penro (Bosch), Meronem (Germany, ICI Pakistan), Meroza (German Remedies), Merotrol (Lupin), and Meromer by Orchid Chemicals, Mexopen (Samarth life sciences in India) and Pharmaceuticals (India),Lykapiper by Lyka Labs ( India ),Winmero by Parabolic drugs (India ) .
L-Hydroxyproline (1) is converted first to its paranitrobenzyl alcohol urethane; treatment of the sodium salt with dianisylmethyl chloride then leads to the doubly protected derivative (2). Mitsunobu reaction of this intermediate with thioacetic acid leads to the displacement of the ring hydroxyl group with net inversion of configuration to give the thioacetate derivative (3). The dianisyl ester is the cleaved with trifluoroacetic acid. The resulting carboxylic acid is then activated as its mixed anhydride with isopropyl formate; treatment of this intermediate with dimethylamine then leads to the corresponding amide (4). Saponification removes the acetyl group to afford the free thiol (5). This is then used to replace the diphenylphosphate grouping in the carbapenam (6) (cf biapenem) to give 7. Hydrogenolysis over palladium then serves to remove the nitrobenzyloxy protecting groups to afford the penam antibiotic meropenam (8).
- Edwards, JR; Turner, PJ; Wannop, C; Withnell, ES; Grindey, AJ; Nairn, K (February 1989). "In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I". Antimicrobial agents and chemotherapy 33 (2): 215–22. doi:10.1128/AAC.33.2.215. PMC 171460. PMID 2655530.
- Creation of Meropenem
- AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006.
- Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006.
- 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". Antimicrobial agents and chemotherapy 54 (7): 2974–8. doi:10.1128/AAC.01582-09. PMC 2897321. PMID 20479205.
- 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.
- Yeung, EYH; Gore JG; Auersperg EV (2012). "A Retrospective Analysis of the Incidence of Clostridium Difficile Associated Diarrhea with Meropenem and Piperacillin-tazobactam" (PDF). International Journal of Collaborative Research on Internal Medicine & Public Health 4 (8): 1567–1576.
- 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.
- 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.
- M. Sunagawa et al., EP 126587 ; M. Sunagawa, U.S. Patent 4,943,569 (1984, 1990 both to Sumitomo).
- Sunagawa, M; Matsumura, H; Inoue, T; Fukasawa, M; Kato, M (1990). "A novel carbapenem antibiotic, SM-7338 structure-activity relationships". The Journal of antibiotics 43 (5): 519–32. PMID 2358404.
- MERREM I.V. (meropenem for injection) Official Site by AstraZeneca