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Cefepime microbiologic profile and update.

Abstract

BACKGROUND: The evolution of the cephalosporin class of antibiotics through modifications of the basic cephem structure has resulted in a new generation with improved antibacterial activity. Cefepime is a prototypic agent of this new class of fourth generation cephalosporins. OBJECTIVE: To review the microbiologic profile of cefepime. RESULTS: Cefepime, which is a zwitterion, has a net neutral charge that allows it to penetrate the outer membrane of Gram-negative bacteria faster than third generation cephalosporins. It is more stable against beta-lactamases because of the lower affinity of the enzymes for cefepime when compared with third generation cephalosporins. As a result of these structural attributes, cefepime has in vitro activity against pathogens that are prevalent in pediatric infections. This agent offers the advantage of Gram-positive coverage similar to that of cefotaxime and ceftriaxone, as well as good activity against Pseudomonas aeruginosa and many enteric bacilli that are resistant to third generation cephalosporins, including clinical isolates of Enterobacter spp. and Citrobacter freundii. CONCLUSIONS: Based on its spectrum of activity cefepime is an option for the treatment of pediatric infections caused by susceptible pathogens.

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BibTeXRIS

R E Kessler. 2001. Cefepime microbiologic profile and update.. https://doi.org/10.1097/00006454-200103000-00031

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Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms.

The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum beta-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N=39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T>MIC) for the intermittent bolus regimens was >/=40% for piperacillin/tazobactam and >/=60% for cefepime. The desired C(ss)/MIC ratio (where C(ss) is the concentration at steady state) was >/=2 for all continuous infusion (CI) regimens. MIC(50), MIC(90) and %S were, respectively, 64/4mug/mL, 1024/4mug/mL and 33% for piperacillin/tazobactam and 8mug/mL, 16mug/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375g every 4h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5g CI (31%), 3.375g q6h (27%), 4.5g q8h (17%) and 6.75g CI (10%). However, for cefepime, 4g CI had the highest probability of target attainment (77%), followed by 1g q8h (65%), 2g q12h (58%), 3g CI (46%) and 1g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.

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[Rapid identification of the isomeric impurity in raw drug of cefepime dihydrochloride by liquid chromatography-tandem mass spectrometry].

AIM: To establish a sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of isomeric impurity in raw drug material of cefepime dihydrochloride. METHODS: The HPLC separation experiments were performed on a reversed phase C18 column, with acetonitrile-10 mmol x L(-1) ammonium acetate (5:95) as mobile phase (a flow rate of 0.8 mL x min(-1)). The analytes were determined by electrospray ionization tandem mass spectrometry in positive mode. The chromatogram and mass spectra of cefepime dihydrocloride and its isomeric impurity were obtained by LC-MS/MS. RESULTS: The method can be used for the separation and identification of cefepime dihychrocloride and its isomeric impurity, of which the retention times were 15.28 min and 9.18 min, respectively. Based on the MS/MS spectra of their molecular ions, the different fragmentation pathways of cefepime dihydrocloride and its isomeric impurity were compared and proposed. CONCLUSION: The method was rapid, sensitive and specific. It can be used for the identification of the isomeric purity in raw drug material of cefepime dihydrochloride.

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The aim of this study was to determine an in vitro activity of cefepime against ESBL-positive clinical strains of Gram-negative rods isolated from hospitalized patients. Experiments were performed with 100 ESBL-positive strains of Gram-negative rods isolated from clinical samples in 2004. Strains were identified with the use of automatic ATB Expression system and biochemical ID 32 GN tests (bioMdrieux sa). Extended-spectrum beta-lactamases (ESBLs) were detected by means of disc diffusion methods: the double-disc synergy test (DDST) and the diagnostic disc test (DD, Oxoid Ltd, UK). Susceptibility in vitro of ESBL producers to 4th generation--cefepime was determined with gradient diffusion method Etest (AB Biodisk, Solna, Sweden). MIC value of cefepime was assessed for each strain. Among 100 ESBL-producing strains, 94--belonged to enteric rods and 6--to nonfermentative rods. The greatest number of strains belonged to the species Serratia marcescens (27% of all strains) and next--to the species Enterobacter cloacae (21%). Fourteen strains were susceptible (S) in vitro to cefepime, 12--intermediately susceptible (I) and 74--resistant (R). Application of cefepime in a therapy of infections caused by ESBL-positive strains of Gram-negative rods highly susceptible in vitro to this antibiotic, should be considered.

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