Evaluation of ceforanide as treatment for staphylococcal and streptococcal endocarditis

Cooper, Ronald H.; Savitch, Cary B.; Joseph, W. Patrick; Mills, John D.

doi:10.1128/aac.19.2.256

Cited by 14 publications

(2 citation statements)

References 9 publications

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“…The slower elimination of both of these drugs during bypass may have been due to the decrease in blood flow from this tissue since the site of the aorta selected for drug assay was below the level of the aortic clamp, or it may have been due to a reduction in the renal (6) 23.6 ± 6.4 (4) 41-60 19.5 ± 9.9 (4) 48.1 ± 3.7 (2) 21.5 ± 8.8 (3) 23.8 ± 8.5 (3) 24.3 (1) 22.5 ± 11.0 (3) 61-80 18.1 ± 6.9 (2) 11.3 ± 7.5 (3) 23.3 ± 1.8 (2) 81-100 9.1 (1) 40.8…”

Section: Discussionmentioning

confidence: 99%

“…The results of an in vitro kinetic study (14) showed that the bactericidal activity of ceforanide was greater than the activity of cephalothin, cefazolin, cefamandole, cefuroxime, or cefoxitin. Moreover, ceforanide administered parenterally twice daily has been found to be an effective agent in the treatment of patients with right-sided endocarditis caused by S. aureus (3).…”

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Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery

Mullany¹,

French²,

Nightingale³

et al. 1982

Antimicrob Agents Chemother

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Doses of 30 mg of ceforanide or cefamandole per kg were administered intravenously to 26 patients just before their chests were opened for coronary artery bypass or cardiac valve replacement surgery. Samples of right atrial appendage, pericardial fluid, plasma, aortic wall, intercostal muscle, and sternum were obtained at different times after the antibiotic was injected, and these samples were assayed for cephalosporin concentration. For ceforanide the prebypass plasma half-life was 2.5 h, and the atrial appendage half-life was 2.1 h; for cefamandole the pre-bypass plasma half-life was 0.75 h and the atrial appendage half-life was 0.72 h. At 3 h the concentrations of ceforanide and cefamandole in atrial appendages were 28.0 and 5.0 pug/g, respectively. Ceforanide achieved higher and more sustained concentrations in other tissues than cefamandole. Considering the minimal inhibitory concentrations of these drugs for staphylococci, cefamandole and ceforanide should provide adequate protection against infection by these organisms for the duration of the surgical procedure.Cephalosponns are often used prophylactically in patients undergoing open heart surgery, since these antibiotics provide coverage against Staphylococcus aureus and Staphylococcus epidermidis, the organisms usually responsible for infection after this type of surgery (15).In this work we compared the tissue distribution of ceforanide, a new long-acting cephalosporin with a plasma half-life (t112) of 3 h (7), with the tissue distribution of cefamandole, a cephalosporin with a t1/2 of approximately 0.75 h (6), to determine whether these drugs achieve adequate concentrations to protect against staphylococcal infections in patients undergoing open heart surgery. MATERIALS AND METHODSThe subjects of this study were 26 patients scheduled for coronary artery bypass or cardiac valve replacement surgery. The mean ages of the cefamandole and ceforanide groups were 58.5 + 6.3 and 57.7 ± 9.2 years, respectively. Each patient gave a complete history, underwent a physical examination, and had the following clinical chemical and hematological tests: complete blood cell count, urinalysis, and measurement of blood urea nitrogen, serum transaminases, bilirubin, and serum creatinine. All of the patients who participated in this study had normal values for these tests.Each patient was assigned randomly to receive a single 30-mg/kg dose of either ceforanide (13 patients) or cefamandole (13 patients) by rapid (<5-min) intravenous injection at different times (32 to 214 min) before the removal of the right atrial appendage.Blood was collected from all patients before the administration of the antibiotic, at the end of infusion of the antibiotic, simultaneously with pericardial fluid or tissue sampling, and at some later time in the procedure. Immediately after collection the heparinized blopd samples were centrifuged (4°C) at 3,250 x g for 10 min. The plasma samples were decanted into tubes and stored at -80°C until they were analyzed. Atrial appendage, sternum, intercos...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery

Mullany¹,

French²,

Nightingale³

et al. 1982

Antimicrob Agents Chemother

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Ceforanide: Antibacterial Activity, Pharmacology, and Clinical Efficacy

Barriere

Mills

1982

Pharmacotherapy

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Ceforanide is a new cephalosporin with a longer elimination half-life than any currently available cephalosporin. Its activity is very similar to that of cefamandole, a second-generation cephalosporin, except that ceforanide is less active against most gram-positive organisms. Many coliforms, including Escherichia coli, Klebsiella, Enterobacter, and Proteus, are susceptible to ceforanide, as are most strains of Salmonella, Shigella, Hemophilus, Citrobacter and Arizona species. However, most strains of Serratia marcescens and all Pseudomonas aeruginosa are resistant to this compound. Peak serum concentrations in excess of 100 micrograms/ml are achieved after a 1 g intravenous dose. The elimination half-life of ceforanide is about 3 hrs in patients with normal renal function; this allows twice daily dosing for the majority of patients. As renal excretion amounts for 85-90% of drug elimination, the serum half-life increases to approximately 20 hours in anuric patients. Tissue penetration studies demonstrate inhibitory concentrations in cardiac tissue, bone, and joint fluid. Minor adverse effects have been reported after large doses of ceforanide. Clinical trials indicate that ceforanide is effective in the treatment of skin and soft tissue, pulmonary and urinary tract infections, bone and joint infections, and endocarditis. Ceforanide also has been shown to be as effective as cephalothin or cephaloridine when given prophylactically for vaginal hysterectomy.

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Staphylococcal endocarditis

Karchmer

1985

The American Journal of Medicine

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Evaluation of ceforanide as treatment for staphylococcal and streptococcal endocarditis

Cited by 14 publications

References 9 publications

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery

Ceforanide: Antibacterial Activity, Pharmacology, and Clinical Efficacy

Staphylococcal endocarditis

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