Comparison of a new cephalosporin, BMY 28142, with other broad-spectrum beta-lactam antibiotics

Kessler, R E; Bies, M; Buck, R. E.; Chisholm, D. R.; Pursiano, T. A.; Tsai, Y. H.; Misiek, M.; Price, K. E.; Leitner, F.

doi:10.1128/aac.27.2.207

Cited by 140 publications

(95 citation statements)

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“…In vitro studies performed prior to the commercial availability of cefepime showed that the MIC 90 ranged from 0.06 to 0.5 g/ml (12,25,26). In contrast, an assessment of isolates from North American intensive care units in 2003 showed that the MIC 90 was 2 g/ml, with MICs of some isolates as high as Ͼ16 g/ml (20).…”

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SHV-Type Extended-Spectrum Beta-Lactamase Production Is Associated with Reduced Cefepime Susceptibility in Enterobacter cloacae

et al. 2005

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Cefepime is a potentially useful antibiotic for treatment of infections with Enterobacter cloacae. However, in our institution the MIC 90 for E. cloacae bloodstream isolates is 16 g/ml. PCR amplification of bla genes revealed that one-third (15/45) of E. cloacae bloodstream isolates produced SHV-type extended-spectrum beta-lactamases (ESBLs) in addition to hyperproduction of AmpC-type beta-lactamases. The majority (11/15) of ESBL producers also produced the TEM-1 beta-lactamase. The SHV types included SHV-2, -5, -7, -12, -14, and -30. All but two of the ESBL-producing E. cloacae isolates, but none of the non-ESBL-producing strains, had MICs of cefepime of >2 g/ml. The MIC 90 for cefepime for ESBL-producing strains was 64 g/ml, while for non-ESBL producers it was 0.5 g/ml. Using current Clinical and Laboratory Standards Institute breakpoints for cefepime, two thirds (10/15) of ESBL-producing isolates would have been regarded as susceptible to cefepime. Phenotypic ESBL detection methods were generally unreliable with these E. cloacae isolates. Based on these results, pharmacokinetic, pharmacodynamic, and clinical reevaluation of cefepime breakpoints for E. cloacae may be prudent.

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SHV-Type Extended-Spectrum Beta-Lactamase Production Is Associated with Reduced Cefepime Susceptibility in Enterobacter cloacae

et al. 2005

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“…Similarly, the pharmacokinetic parameters of amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens.Cefepime (BMY-28142) is a new parenteral cephalosporin with significant potential advantages over other new cephalosporins and nontraditional ,3-lactam antibiotics with respect to its antimicrobial spectrum of activity (12,15). In addition, cefepime appears to have a low affinity for chromosomally derived P-lactamases (23).…”

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“…Cefepime (BMY-28142) is a new parenteral cephalosporin with significant potential advantages over other new cephalosporins and nontraditional ,3-lactam antibiotics with respect to its antimicrobial spectrum of activity (12,15). In addition, cefepime appears to have a low affinity for chromosomally derived P-lactamases (23).…”

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Lack of pharmacokinetic interaction between cefepime and amikacin in humans

Barbhaiya

Knupp

Pfeffer

et al. 1992

Antimicrob Agents Chemother

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The interaction potential between cefepime and amikacin was investigated in a steady-state pharmacokinetic study in 16 healthy male subjects. Eight subjects (group A) received a first course of 2,000 mg of cefepime; this was followed by a second course of 2,000 mg of cefepime with 300 mg of amikacin and a third course of 2,000 mg of cefepime. Eight other subjects (group B) received a first course of 300 mg of amikacin, a second course of 300 mg of amikacin with 2,000 mg of cefepime, and a third course of 300 mg of amikacin. Each course consisted of four consecutive doses administered every 8 h as 30-min intravenous infusions. Serial plasma and urine samples, which were collected after administration of the fourth dose of each course, were assayed for cefepime and/or amikacin by validated high-performance liquid chromatographic assays. Trough levels of cefepime and amikacin indicated that these antibiotics attained a steady state prior to administration of the fourth dose of each course. Key pharmacokinetic parameters for each antibiotic were determined by noncompartmental methods. The peak concentrations of cefepime and amikacin in plasma when the drugs were given alone were about 160 and 27 ,g/ml, respectively. Levels of each antibiotic in plasma declined, with an apparent half-life of approximately 2.2 h. Urinary recovery of cefepime and amikacin accounted for more than 85% of the administered dose of each antibiotic. Mean renal clearances for cefepime and amikacin ranged from 79 to 95 ml/min and suggested that glomerular filtration is the primary excretion mechanism. The results of the statistical analyses indicated that the pharmacokinetic parameters of cefepime following the concurrent administration of amikacin and following the discontinuation of the amikacin therapy were not significantly altered. Similarly, the pharmacokinetic parameters of amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens.Cefepime (BMY-28142) is a new parenteral cephalosporin with significant potential advantages over other new cephalosporins and nontraditional ,3-lactam antibiotics with respect to its antimicrobial spectrum of activity (12,15). In addition, cefepime appears to have a low affinity for chromosomally derived P-lactamases (23). Clinical experience indicates that cefepime is safe and well tolerated when single or multiple (every 8 or 12 h) doses of 250 to 2,000 mg are given by the intravenous (4, 5) or intramuscular (9) routes of administration. The pharmacokinetics of this cephalosporin are linear (4, 5, 9). Over 80% of the administered dose of cefepime is recovered in urine in an unchanged form (4, 5, 7-9).In the most severely infected patients, empiric therapy consists of the administration of antibacterial therapy before pathogen identification. The standard approach has been to use an ant...

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“…Escherichia coli CSase- (8) (Cephalothin-sensitive) E. coli CSase+ (9) (Cephalothin-resistant) Klebsiella pneumoniae (10) Proteus mirabilis (10) P. vulgaris (10) Providencia rettgeri (10) Morganella morganii (10) Enterobacter cloacae (7) Serratia marcescens (9) Pseudomonas aeruginosa Enterobacteriaceae were also highly susceptible to BMY-28142, and the MIC values of BMY-28142 against Klebsiella pneumoniae, Providencia rettgeri, Morganella morganii and Enterobacter cloacae were below 0.5 ug/ml. There were some ceftazidime-resistant strains among these bacteria, against which BMY-28142 showed higher activity than cefotaxime.…”

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confidence: 99%