In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum

Conrad, Doug; Scribner, R K; Weber, A H; Marks, Melvin I.

doi:10.1128/aac.28.1.58

Cited by 28 publications

(9 citation statements)

References 14 publications

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“…This is in agree ment with reports of other investigators [1,3,11] who have reported high activity of cefepime also against E. cloacae, Serratia marcescens, and M. morganii and against ceftazidime-and cefotaxime-resistant gram-negative bacilli. The compound showed similar activity as that of cefti buten, was twofold or more active than ceftazidime, and was manifold more ac tive than piperacillin/tazobactam against the gram-negative bacilli [7], Strains of Acinetobacter sp.…”

Section: Discussionsupporting

confidence: 82%

In vitro Activity of Cefepime, a New Parenteral Cephalosporin, against Recent European Blood Isolates and in Comparison with Piperacillin/Tazobactam

Dornbusch¹,

Mörtsell²,

Göransson³

1990

Chemotherapy

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Cefepime, a new parenteral cephalosporin with broad antibacterial spectrum and stability to the hydrolysis to many bacterial [3-lactamases, was tested against recent blood culture isolates (369 strains of gram-negative bacilli and 131 strains of staphylococci) collected in 29 European laboratories by the microdilution method in Mueller-Hinton broth. Cefepime was very active against the gram-negative bacilli (MIC₅₀≤0.016–0.064 mg/l; MIC₉₀ 0.064–4 mg/l) and less active against Pseudomonas (MIC₅₀ 4 mg/l; MIC₉₀ > 16 mg/l) or Acinetobacter (MIC₅₀ and MIC₉₀ > 16 mg/l). The staphylococci were also inhibited (MIC₅₀ 8 mg/l; MIC₉₀ 16 mg/l). Cefepime was very active against bacteria producing different plasmid-encoded β-lactamases (MIC 0.016–0.5 mg/l). Piperacillin was not active against the latter strains (MIC from 2 to > 64 mg/ 1), but the presence of the β-lactamase inhibitor tazobactam restored the activity of piperacillin. The bactericidal activity of cefepime and piperacillin/tazobactam against β-lactamase-producing strains was confirmed by the by the killing curve technique.

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Section: Discussionsupporting

confidence: 82%

In vitro Activity of Cefepime, a New Parenteral Cephalosporin, against Recent European Blood Isolates and in Comparison with Piperacillin/Tazobactam

Dornbusch¹,

Mörtsell²,

Göransson³

1990

Chemotherapy

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“…Increases in MICs due to higher inoculum densities are well documented among ,-lactam antibiotics (1,4). The fact that a fourfold or lower increase in the MIC was seen when the inoculum density was increased 100-fold for all organisms tested except beta-lactamase-producing H. influenzae is encouraging.…”

mentioning

confidence: 65%

In vitro activity of BMY-28100 against common isolates from pediatric infections

Scribner¹,

Marks²,

Finkhouse³

1987

Antimicrob Agents Chemother

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The antibacterial activity of BMY-28100, a new oral cephalosporin, was measured against 300 bacterial isolates from pediatric infections by standard agar dilution methodology. The effect of inoculum size on activity was also assessed. BMY-28100 was more active than cephalexin or cefaclor against all bacterial species tested.BMY-28100 {5-thia-1-azabicyclo[4.2.0] oct-2-ene-2 carboxylic acid-7- [[amino(4-hydroxyphenyl)new oral cephalosporin which has shown activity against major pediatric pathogens, both in vitro and in experimental infections

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“…1). The compound has excellent activity against a broad spectrum of clinically important pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa strains resistant to other new, broadspectrum cephalosporins (6,9,24).Extensive preclinical safety evaluations have been conducted with cynomolgus monkeys and rats, the latter being appreciably more susceptible to toxicity at high cefepime doses. The present study was conducted to characterize cefepime disposition in these species after single-dose administration.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacokinetics of the novel cephalosporin cefepime (BMY-28142) in rats and monkeys

Forgue¹,

Shyu²,

Gleason³

et al. 1987

Antimicrob Agents Chemother

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The disposition of the novel cephalosporin cefepime (BMY-28142) was characterized for intravenous administration of single doses to rats and cynomolgus monkeys, the species used most extensively for safety evaluation of the compound. Serial blood samples were collected from individual animals, and plasma was analyzed for intact cefepime by a high-pressure liquid chromatography-UV method. Assay results were evaluated by compartmental and noncompartmental methods to characterize pharmacokinetics for each species and dosage regimen. For intravenous (i.v.) Cefepime (BMY-28142) is a novel, semisynthetic cephalosporin that is under development for parenteral human therapy. It differs from other aminothiazolyl methoxyimino derivatives like cefotaxime and ceftizoxime by having a quaternized N-methyl pyrrolidino moiety attached to the methylene group at C-3 (Fig. 1). The compound has excellent activity against a broad spectrum of clinically important pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa strains resistant to other new, broadspectrum cephalosporins (6,9,24).Extensive preclinical safety evaluations have been conducted with cynomolgus monkeys and rats, the latter being appreciably more susceptible to toxicity at high cefepime doses. The present study was conducted to characterize cefepime disposition in these species after single-dose administration. Dose levels and other administration parameters were selected to mimic those of the toxicologic studies.MATERIALS AND METHODS Antibiotic formulations. Cefepime was provided by the Pharmaceutical Product Deyelopment Department, BristolMyers, Co., Syracuse, N.Y., as the sulfate salt or the lyophilized dipolar ion (Mr, 481).The initial formulation, used for rat bolus doses of 28 and 89 mg/kg (body weight), entailed the combination of cefepime sulfate with NaHCO3 and L-lysine in a 10:1:2.9 weight ratio and dissolution in sterile water for injection. Subsequently, lyophilized dipolar ions were reconstituted with sterile water to yield 250-or 500-mg/ml solutions. These were subsequently diluted with sterile water to prepare solutions used for dosing. Each formulation was prepared on * Corresponding author. the day of dosing; a portion was stored (-20°C) pending analysis for cefepime content by a high-pressure liquid chromatography-UV assay.Rat i.v. bolus study. Male Sprague-Dawley rats [Crl:COBS(SD)BR; Charles River Breeding Laboratories, Inc., Wilmington, Mass.] were housed individ-ually with ad libitum access to food and rodent chow, whidh was withdrawn about 2 h before dosing. The rats weighd 255 to 400 g at dosing. On the day before dosing, a catheter was implanted in the right external jugular vein of each rat, under anesthesia. The catheterization procedure was essentially that described by others (2). The catheter was kept patent with heparinized saline (10 U/ml) overnight and with normal saline during the sampling interval. Each dose of 28, 89, 200, or 386 mg/kg was administered as a bolus (ca. 20-s) injection into a caudal vein. Blood (0.25 ...

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In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum

Cited by 28 publications

References 14 publications

In vitro Activity of Cefepime, a New Parenteral Cephalosporin, against Recent European Blood Isolates and in Comparison with Piperacillin/Tazobactam

In vitro Activity of Cefepime, a New Parenteral Cephalosporin, against Recent European Blood Isolates and in Comparison with Piperacillin/Tazobactam

In vitro activity of BMY-28100 against common isolates from pediatric infections

Pharmacokinetics of the novel cephalosporin cefepime (BMY-28142) in rats and monkeys

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