Imipenem

Extensive carbapenem and penem antibiotic research has been ongoing since thienamycin was discovered in 1978. However, only the imipenem-cilastatin combination has become a commercial product. Launched in 1985 in the United States as a broad-spectmm hospital product under the name Ptimaxin, this product had worldwide sales of some 300 million in 1988. Sales were predicted to rise to 345 million for the year ending 1989 (154). 

L-idose 293, 311 ff. imine formation 57 imine-enamine tautomerization 467 iminium-RhH jt complex 351 f. imipenem 348 indoline ligands 681, 684 indolizomycin 47 Iff. -.retrosynthetic analysis 472ff. 

Furthermore, if the antibiotic passes membranes through a specific port of entry, its mutational loss leads to resistance. The lack of the outer membrane protein OprD in P. aeruginosa causes resistance to the (3-lactam antibiotic imipenem. Fosfomycin passes the cytoplasmic membrane via an L-a-glycerol phosphate permease. This transport system is not essential for bacterial growth and therefore mutants with a reduced expression are frequently selected under therapy. 

AcrAB- TolC Tetracycline, fluoroquinolones, chloramphenicol, p-lactams except imipenem, novobiocin, erythromycin, fusidic acid, rifampicin E. coli Chromosome... 

C2H4O2 107-31-3) see Felbamate Hosequinan Fluphenazine Methyprylon Pyrithyldione Retinol methyl formimidate hydrochloride (CjH ClNO 15755-09-6) see Imipenem methyl ( )-2-formyl-2-phenylacetate sodium salt (C H,NaO, 246180-40-5) see Felbamate iV-methylglycine... 

The 1-caibapenems (Fig. 5.5C) comprise a new family of fused /3-lactam antibiotics. They are analogues of penicillins or clavams, the snlphur (penicilhns) or o gen (calvams) atom being replaced by carbon. Examples are the olivanic acids (section 2.5.1) and thienamycin and imipenem (section 2.5.2). 

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. 

Adjust dose of imipenem/cilastatin based on body weight (refer to package insert). 

It is often difficult to narrow the spectrum of activity of the antibiotic choice since the infections are usually polymicrobial. As such, patients may receive long courses of broad-spectrum antibiotics such as imipenem/cilastatin and... 

Imipenem/cilastatin 500 mg every 6 hours 5% incidence of seizure nausea is also a concern... 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Piperacillin-tazobactam 3.375-4.5 g IV every 6 hours Imipenem-cilastatin 500 mg IV every 6 hours Ceftazidime 2 g IV + clindamycin 600 mg IV every 8 hours... 

If the isolate is determined to be vancomycin-resistant, it is most important to know the exact species because some of the treatment options, such as quinupristin/dalfopristin, are not active against E. faecalis. Currently, the treatment options for vancomycin-resistant enterococci (VRE) are not well established by clinical studies or patient experience. The treatment recommendations for vancomycin-resistant E. faecium include linezolid or quinupristin/dalfopristin for a minimum of 8 weeks. However, newer agents, such as daptomycin, may provide another option for treatment for either enterococci species (E. faecium and E. faecalis). Additionally, guidelines suggest the use of imipenem-cilistatin plus ampicillin or ceftriaxone plus ampicillin for the treatment of E. faecalis with a minimum of 8 weeks of therapy. Consultation with an infectious diseases specialist is recommended. 

Erythromycin is considered the optimal drug for treatment of Campylobacter infections. The rate of resistance of Campylobacter to erythromycin remains low. Other advantages of this drug include ease of administration, low cost, lack of major toxicity, and narrow spectrum of activity.14 The recommended dosage for adults is 250 mg orally four times daily or 500 mg orally twice daily for 5 to 7 days. For very ill patients, treatment with gentamicin, imipenem, cefotaxime, or chloramphenicol is indicated, but susceptibility tests should be performed. 

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