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Chemical Compound Review

AC1NUZ1E     (6R,7S)-7-[[(2E)-2-(2-amino- 1,3-thiazol-4...

Synonyms: BIDD:GT0809, ZINC03871923, AKOS015895225, 149261-27-8, Cefepime, BMY-2, ...
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Disease relevance of cefepime

 

Psychiatry related information on cefepime

 

High impact information on cefepime

  • Clinical and in vitro data indicate that cefepime, a fourth-generation cephalosporin, may be a valuable addition in the treatment of serious infections [1].
  • The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia [5].
  • This review of seven pharmacokinetic studies indicates that the pharmacokinetic disposition of cefepime, administered either intravenously or intramuscularly, is similar to that of other cephalosporins with regard to dose linearity, renal excretion, and low serum protein binding [6].
  • None of the 12 cases of gastrointestinal hemorrhage reported in cefepime patients or five cases reported in ceftazidime patients were judged to be related to treatment drug [3].
  • The incidence of positive Coombs' test was higher in high-dose cefepime recipients than in ceftazidime recipients (14.5% vs 8.7%; p = 0.043), although there was no evidence of hemolysis in either treatment group [3].
 

Chemical compound and disease context of cefepime

 

Biological context of cefepime

  • The pharmacokinetics of intravenously administered cefepime (1000 mg over 30 minutes) were studied in 5 healthy volunteers and 20 patients with various degrees of renal impairment [12].
  • Additionally, our results predict that a phenotype not yet observed among TEM beta-lactamases in nature-resistance to cefepime-is likely to arise in nature [13].
  • Thus, cefepime has the advantage of an improved spectrum of antibacterial activity, and is less susceptible to hydrolysis by some beta-lactamases, compared with third generation cephalosporins [9].
  • Plasmids encoding TEM- and SHV-type ESBLs conferred resistance to cefepime and cefpirome, as well as to earlier oxyimino-beta-lactams [14].
  • After four rounds of mutagenesis and selection for increased cefepime resistance each of eight independent populations reached a level equivalent to clinical resistance [15].
 

Anatomical context of cefepime

 

Associations of cefepime with other chemical compounds

 

Gene context of cefepime

  • Neither the class C Citrobacter freundii CMY-2 AmpC beta-lactamase nor the class A TEM-1 beta-lactamase confer resistance to the beta-lactam antibiotic cefepime, nor do any of the naturally occurring alleles descended from them [25].
  • For 10 of the clinical isolates (two MSSA, three MRSA, two MSSE, three MRSE) and the reference strain, the interaction of cefepime and vancomycin was also determined by the time-kill method [26].
  • The MICs of cefpirome and cefepime of E. coli harboring ampC and ampR genes from CHE were 100--200 times higher than those of E. coli harboring ampC and ampR genes from OUDhyp [27].
  • Indeed, MICs of cefepime and cefpirome remained 10 times higher than those for a stable derepressed clinical isolate (OUDhyp) transformed with an ampD gene [27].
  • Experimental prediction of the evolution of cefepime resistance from the CMY-2 AmpC beta-lactamase [25].
 

Analytical, diagnostic and therapeutic context of cefepime

  • In addition, pretreatment susceptibility testing indicates that >94% of organisms isolated in patients enrolled in clinical trials were susceptible to cefepime [28].
  • Cefepime concentrations in plasma, urine, and hemodialysate were assayed using reverse-phase HPLC with ultraviolet detection [12].
  • While developing a high-pressure liquid chromatography assay for cefepime in plasma, we observed significant drug degradation at 20 and 37 degrees C but not at 4 degrees C. This plasma-related degradation persisted after protein removal [29].
  • In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries [30].
  • Cefepime is removed by haemodialysis (over 3h) and peritoneal dialysis (over 72h) to an appreciable extent, with 40 to 68% and 26% of the drug removed, respectively [31].

References

  1. Treatment of urinary tract infections: selecting an appropriate broad-spectrum antibiotic for nosocomial infections. Sharifi, R., Geckler, R., Childs, S. Am. J. Med. (1996) [Pubmed]
  2. Susceptibility of bacterial isolates to beta-lactam antibiotics from U.S. clinical trials over a 5-year period. Kessler, R.E., Fung-Tomc, J. Am. J. Med. (1996) [Pubmed]
  3. Safety of cefepime: a new extended-spectrum parenteral cephalosporin. Neu, H.C. Am. J. Med. (1996) [Pubmed]
  4. Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999-2001). Mutnick, A.H., Rhomberg, P.R., Sader, H.S., Jones, R.N. J. Antimicrob. Chemother. (2004) [Pubmed]
  5. A new therapeutic option for the treatment of pneumonia. McCabe, R., Chirurgi, V., Farkas, S.A., Haddow, A., Heinz, G., Greene, S. Am. J. Med. (1996) [Pubmed]
  6. The pharmacokinetic profile of a new generation of parenteral cephalosporin. Rybak, M. Am. J. Med. (1996) [Pubmed]
  7. Effect of porins and plasmid-mediated AmpC beta-lactamases on the efficacy of beta-lactams in rat pneumonia caused by Klebsiella pneumoniae. Padilla, E., Alonso, D., Doménech-Sánchez, A., Gomez, C., Pérez, J.L., Albertí, S., Borrell, N. Antimicrob. Agents Chemother. (2006) [Pubmed]
  8. Optimizing pharmacodynamic target attainment using the MYSTIC antibiogram: data collected in North America in 2002. Kuti, J.L., Nightingale, C.H., Nicolau, D.P. Antimicrob. Agents Chemother. (2004) [Pubmed]
  9. Cefepime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Barradell, L.B., Bryson, H.M. Drugs (1994) [Pubmed]
  10. In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. Szabó, D., Máthé, A., Filetóth, Z., Anderlik, P., Rókusz, L., Rozgonyi, F. Antimicrob. Agents Chemother. (2001) [Pubmed]
  11. Mutational replacement of Leu-293 in the class C Enterobacter cloacae P99 beta-lactamase confers increased MIC of cefepime. Vakulenko, S.B., Golemi, D., Geryk, B., Suvorov, M., Knox, J.R., Mobashery, S., Lerner, S.A. Antimicrob. Agents Chemother. (2002) [Pubmed]
  12. Pharmacokinetics of cefepime in subjects with renal insufficiency. Barbhaiya, R.H., Knupp, C.A., Forgue, S.T., Matzke, G.R., Guay, D.R., Pittman, K.A. Clin. Pharmacol. Ther. (1990) [Pubmed]
  13. Predicting evolutionary potential: in vitro evolution accurately reproduces natural evolution of the tem beta-lactamase. Barlow, M., Hall, B.G. Genetics (2002) [Pubmed]
  14. Roles of beta-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Martínez-Martínez, L., Pascual, A., Hernández-Allés, S., Alvarez-Díaz, D., Suárez, A.I., Tran, J., Benedí, V.J., Jacoby, G.A. Antimicrob. Agents Chemother. (1999) [Pubmed]
  15. Experimental prediction of the natural evolution of antibiotic resistance. Barlow, M., Hall, B.G. Genetics (2003) [Pubmed]
  16. Uptake of cefepime by phagocytosing polymorphonuclear neutrophils and subsequent intracellular killing. Pruul, H., McDonald, P.J. Antimicrob. Agents Chemother. (1996) [Pubmed]
  17. Prospective randomized comparison of cefepime and cefotaxime for treatment of bacterial meningitis in infants and children. Sáez-Llorens, X., Castaño, E., García, R., Báez, C., Pérez, M., Tejeira, F., McCracken, G.H. Antimicrob. Agents Chemother. (1995) [Pubmed]
  18. In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum. Conrad, D.A., Scribner, R.K., Weber, A.H., Marks, M.I. Antimicrob. Agents Chemother. (1985) [Pubmed]
  19. Effect of a selective decontamination of the digestive tract regimen including parenteral cefepime on establishment of intestinal colonization with vancomycin-resistant Enterococcus spp. and Klebsiella pneumoniae in mice. Paterson, D.L., Stiefel, U., Donskey, C.J. Antimicrob. Agents Chemother. (2006) [Pubmed]
  20. Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose. Chadha, D., Wise, R., Baldwin, D.R., Andrews, J.M., Ashby, J.P., Honeybourne, D. J. Antimicrob. Chemother. (1990) [Pubmed]
  21. Extended-spectrum beta-lactamases in enterobacteriaceae in Buenos Aires, Argentina, public hospitals. Quinteros, M., Radice, M., Gardella, N., Rodriguez, M.M., Costa, N., Korbenfeld, D., Couto, E., Gutkind, G. Antimicrob. Agents Chemother. (2003) [Pubmed]
  22. Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics. Mimoz, O., Jacolot, A., Padoin, C., Quillard, J., Tod, M., Louchahi, K., Samii, K., Petitjean, O. Antimicrob. Agents Chemother. (1996) [Pubmed]
  23. Modulation of the intestinal flora of mice by parenteral treatment with broad-spectrum cephalosporins. van Ogtrop, M.L., Guiot, H.F., Mattie, H., van Furth, R. Antimicrob. Agents Chemother. (1991) [Pubmed]
  24. Pharmacodynamics of cefepime alone and in combination with various antimicrobials against methicillin-resistant Staphylococcus aureus in an in vitro pharmacodynamic infection model. Huang, V., Rybak, M.J. Antimicrob. Agents Chemother. (2005) [Pubmed]
  25. Experimental prediction of the evolution of cefepime resistance from the CMY-2 AmpC beta-lactamase. Barlow, M., Hall, B.G. Genetics (2003) [Pubmed]
  26. In vitro synergy between cefepime and vancomycin against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. Lozniewski, A., Lion, C., Mory, F., Weber, M. J. Antimicrob. Chemother. (2001) [Pubmed]
  27. Extension of resistance to cefepime and cefpirome associated to a six amino acid deletion in the H-10 helix of the cephalosporinase of an Enterobacter cloacae clinical isolate. Barnaud, G., Labia, R., Raskine, L., Sanson-Le Pors, M.J., Philippon, A., Arlet, G. FEMS Microbiol. Lett. (2001) [Pubmed]
  28. Bacteriologic and clinical applications of a new extended-spectrum parenteral cephalosporin. Segreti, J., Levin, S. Am. J. Med. (1996) [Pubmed]
  29. Pitfalls in cefepime titration from human plasma: plasma- and temperature-related drug degradation in vitro. Bugnon, D., Giannoni, E., Majcherczyk, P., Glauser, M.P., Moreillon, P. Antimicrob. Agents Chemother. (2002) [Pubmed]
  30. Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study. Zanetti, G., Bally, F., Greub, G., Garbino, J., Kinge, T., Lew, D., Romand, J.A., Bille, J., Aymon, D., Stratchounski, L., Krawczyk, L., Rubinstein, E., Schaller, M.D., Chiolero, R., Glauser, M.P., Cometta, A. Antimicrob. Agents Chemother. (2003) [Pubmed]
  31. Cefepime clinical pharmacokinetics. Okamoto, M.P., Nakahiro, R.K., Chin, A., Bedikian, A. Clinical pharmacokinetics. (1993) [Pubmed]
 
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