Carbapenems meropenem

Two carbapenems, meropenem and panipe-nem + betamipron, reduced serum valproic acid concentrations, and increased the risk of seizures (47,48). The mechanism of the interaction was unclear. Accelerated... 

A number of highly potent DHP-I stable iP-methylcarbapenems having a variety of C-2 substituents have now been described (60,66—69) including SM 7338 [96036-03-2] (42), C yH25N20 S. An acylamiao compound (66) and a iP-methoxy analogue (70) provide other variations. The pyrroHdine substituted iP-methyl-carbapenem SM 7338 (42) is being developed as a broad-spectmm parenteral antibiotic under the name meropenem the synthesis of (42) is by way of the lactone (43) derived by a novel Diels-Alder approach to dihydropyran precursors of (43) (71). 

Fig. 5.5 A, clavulanic acid B, latamoxef C, 1-carbapenems D, olivanic acid (general structure) E, thienamycin F, meropenem G, 1-carbacephems H, loracarbef.

Efforts to produce more-stable compounds have yielded meropenem (5.47), which, although superior to other carbapenems, is less-stable than penicillins or cephalosporins. This lack of stability is confirmed by the formation of breakdown products identified as the dimers (5.48a and b) resulting from intermolecular aminolysis of the /Madam ring [100],... 

Pharmacology Meropenem is a broad-spectrum carbapenem antibiotic. The bactericidal activity of meropenem results from the inhibition of cell-wall synthesis. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. 

Mercaptopurine [6-MP] (Purinethol) [Antineoplastic/ Antimeta lite] Uses Acute leukemias, 2nd-line Rx of CML NHL, maint ALL in children, immunosuppressant w/ autoimmune Dzs (Crohn Dz) Action Antimetabolite, mimics hypoxanthine Dose Adults. 80-100 mg/mVd or 2.5-5 mg/kg/d maint 1.5-2.5 mg/kg/d Peds. Per protocol X w/ renal/hepatic insuff on empty stomach Caution [D, ] Contra Severe hepatic Dz, BM suppression, PRG Disp Tabs SE Mild hematotox, mucositis, stomatitis, D rash, fever, eosinophilia, jaundice. Hep Interactions T Effects W/ allopurinol T risk of BM suppression W/ trimethoprim-sulfamethoxazole X effects OF warfarin EMS May falsely T glucose OD May cause NA and liver necrosis symptomatic and supportive Meropenem (Merrem) [Antibiotic/Carbapenem] Uses lntra-abd Infxns, bacterial meningitis Action Carbapenem X cell wall synth, a [3-lactam Dose Adults. 1 to 2 g IV q8h Peds. >3 mo, <50 kg 10-40 mg/kg IV q 8h in renal insuff Caution [B, ] Contra [3-Lactam sensitivity Disp Inj 500 mg, 1 g SE Less Sz potential than imipenem D, thrombocytopenia Interactions T Effects W/ probenecid EMS Monitor for signs of electrolyte disturbances and... 

Meropenem (Merrem) is another carbapenem antibiotic with a broad spectrum of activity comparable to that of imipenem. A methyl group attached at the one-position on the five-member ring confers stability to dehydropeptidase 1. Consequently, meropenem does not require administration with cilastatin. When compared in human trials, imipenem-cilastatin and meropenem achieve similar clinical outcomes in patients with serious intraabdominal and soft tissue infections. Both imipenem-cilastatin and meropenem are used to treat infections caused by highly resistant Klebsiella pneumoniae producing ESBLs.The major cUnicaUy relevant distinction between imipenem-cilastatin and meropenem... 

L B. The patient has complicated urinary tract infection and nonsevere sepsis syndrome caused by P. aeruginosa. Effective antibiotics for Pseudomonas spp. include mezlocillin, piperacillin, piperacillin-tazobactam, ticarcillin, and ticarciUin-clavulanate. The carbapenems (imipenem and meropenem) and the monobactam (aztreonam) are also active against P. aeruginosa. Ampicillin-sulbactam and cefazolin are ineffective against P. 

The most common adverse effects of carbapenems—which tend to be more common with imipenem—are nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Excessive levels of imipenem in patients with renal failure may lead to seizures. Meropenem, doripenem, and ertapenem are much less likely to cause seizures than imipenem. Patients allergic to penicillins may be allergic to carbapenems as well. 

Extensive carbapenem and penem antibiotic research has been ongoing since thienamycin was discovered in 1978. However, only the iiniperiem-cilaslalin combination has become a conunercial product. Meropenem was expected to be the second carbapenem on the market by 1998. 

Carbapenems penetrate body tissues and fluids well, including the cerebrospinal fluid. All are cleared renally, and the dose must be reduced in patients with renal insufficiency. The usual dose of imipenem is 0.25-0.5 g given intravenously every 6-8 hours (half-life 1 hour). The usual adult dose of meropenem is 1 g intravenously every 8 hours. Ertapenem has the longest half-life (4 hours) and is administered as a once-daily dose of 1 g intravenously or intramuscularly. Intramuscular ertapenem is irritating, and for that reason the drug is formulated with 1% lidocaine for administration by this route. 

Chromosomal metallo-beta-lactamases that hydrolyze carbapenem antibiotics, such as imipenem, meropenem, or biapenem, are present in some Stenotro-phomonas, Bacteroides, andAeromonas strains [26], Some clinical/5, aeruginosa and Serratia marcescens isolates have a plasmid that carries metallo-beta-lactamase genes [26], These enzymes are not inactivated by inhibitors of serine-based beta-lactamases such as clavulanic acid or sulbactam analogs. Enzyme-... 

Similarly, metallo- 3-lactamases share with metallo-proteases activation of a hydrolytic water molecule by interaction with an active-site Zn + ion. These lactamases have gained clinical prominence in the past few years as a result of their association with carbapenem resistance. The carbapenems, such as meropenem and imipenem, are fS-lactam antibiotics that have been introduced to circumvent Ser-fS-lactamase activity. The trans stereochemistry across the 6-5 bond rather than the cis geometry found in most other fS-lactams (Fig. 7) contributes to... 

In the last 25 years, various natural carbapenems have been discovered (1). However, their potential is limited by chemical instability. Imipenem (N-formimidoylthienamycin), the first carbapenem in use, is therefore a stabilized synthetic compound. To overcome a second difficulty, namely inactivation by a kidney dehydropeptidase, imipenem has to be combined with cilastatin, a competitive inhibitor of that enzyme. Meropenem has better stability in the presence of renal dehydropeptidase I (2). The... 

In animals, meropenem (17) and other carbapenems (18,19) were less epileptogenic than imipenem. In 403 children there was no meropenem-associated neurotoxicity (20) and meropenem was well tolerated in children with bacterial meningitis (21). In summary, a larger dose range of meropenem than imipenem appears to be tolerated, but when strictly observing known risk factors for seizure propensity the difference between the two compounds is very small (22,23). 

Carbapenems (imipenem more than meropenem) are believed to increase central nervons system excitation by inhibition of GABA binding to receptors. Combinations with other GABA inhibiting drngs snch as theophylline or qninolones have been reported to provoke seizures (45,46). 

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