Meropenem

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). 

Meropenem (Merrem IV) inhibits syndiesis of die bacterial cell wall and causes die deadi of susceptible cells. This drug is used for intra-abdominal infections caused by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and odier susceptible organisms Meropenem also is effective against bacterial meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Hemophilus influenzae. 

The most common adverse reactions widi meropenem include headache, nausea, vomiting, diarrhea, anorexia, abdominal pain, generalized pain, flatulence, rash, and superinfections. This drug also can cause an abscess or phlebitis at die injection site An abscess is suspected if die injection site appears red or is tender and warm to die touch. Tissue sloughing at die injection site also may occur. 

Meropenem is contraindicated in patients who are allergic to cephalosporins and penicillins and in patients widi renal failure This drug is not recommended... 

Meropenem. This drug is administered only by the IV route The nurse gives meropenem every 8 hours over a period of 15 to 30 minutes if die drug is diluted or over a period of 3 to 5 minutes as a bolus injection (5-20 mL). 

C21H33NO4S1) see Meropenem [2S-[2u(S ),3P(S )]]-3-[l-[[(l,l-dimethylethyl)dimethyl-silyl]oxy]ethyl]-a-methyl-4-oxo-2-azetidineacetic acid phe-nylmethyl ester... 

C2,H33N04Si 96035-98-2) sec Meropenem [2R-[2a(/i ),3P(R )]]- S-[3-[l-[[(l,l-dimethylethyl)dime-thylsilyl]oxyJethyll-4-oxo-2-azetidinyl] tetrahydro-2- -furancarhothioate... 

C17H21NO2 60725-36-2) see Nefopam a-[/V-(2-hydroxyethyl)methylamino]propiophenone (C 2H,7N02) see Phendimetrazine l-(2-hydroxyethyl)-4-(2-methylbenzyl)piperazine (C13H20N2O 40004-66-8) see Chlorbenzoxamine [2K-[2a(7f )3P(7t )]]-3-(l-hydroxyethyl)-Y-methyl-p,4-di-oxo-2-azetidinebutanoic acid (4-nitropheiiyl)methyl ester (C,7H2oN207 90822-23-4) see Meropenem... 

C2H4OS 507-09-5) see Acetorphan Captopril Meropenem Omapatrilat Spironolactone Tiomesterone thioacetone... 

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.

Thienamycin (Fig. 5.5E) is a broad-spectrum /3-lactam antibiotic with high /3-lactamase resistance. Unfortunately, it is chemically unstable, although the TV-formimidoyl derivative, imipenem, overcomes this defect. Imipenem (Fig. 5.5E) is stable to most/3-lactamases but it readily hydrolysed by kidney dehydropeptidase and is administered with a dehydropeptidase inhibitor, cilastatin. Meropenem, which has yet to be marketed, is more stable than imipenem to this enzyme and may thus be administered without cilastatin. Its chemical structure is depicted in Fig. 5.5F. 

Piperacillin-tazobactam, cefepime, imipenem, or meropenem plus either. 

Meropenem 2 g IV every 8 hours or Rash, hypersensitivity, diarrhea ... 

Streptococcus gentamicin (5 mg/kg per day, dosing based on serum levels) Alternative Therapies Trimethoprim-sulfamethoxazole (TMP-SMX) 10-20 mg/kgTMP IV per day in divided doses every 6-8 hours or meropenem Standard Therapy TMP-SMX Rash, Stevens-Johnson syndrome, bone marrow suppression, nausea/vomiting, hepatotoxicity 14-21... 

Pseudomonas Moxifloxacin or meropenem orTMP-SMX or ampicillin Standard Therapy seizures At least 21 days... 

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

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