Reversal of the Action of Penicillin

Pennington, J. H.; O'Grady, F.

doi:10.1038/213034a0

Cited by 17 publications

(6 citation statements)

References 9 publications

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“…dose attained a peak of 103 ,ug/ml at 15 min but declined to 47 ,ug/ml at 45 min and to 29 ,ug/ml by 1 h. These concentrations would be sufficient to inhibit most gram-negative bacteria studied in- for the serum concentrations to exceed the MIC for maximum activity against a microorganism causing bacteremia is not known. Contact of susceptible Staphylococcus aureus with penicillin for 15 min has been reported to cause marked bacterial damage (9). Since cefamandole is not metabolized in the body and is not as highly protein bound as cefazolin (10), it is possible that cefamandole may diffuse into tissue spaces.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Studies with Cefamandole in Human Volunteers

Meyers

Ribner

Yancovitz

et al. 1976

Antimicrob Agents Chemother

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Serum and urine concentrations were measured after administration of 0.5-and 1-g doses of cefamandole intramuscularly and intravenously to healthy volunteers. Intramuscular doses of 0.5 and 1 g yielded serum concentrations at 1 h of 14.7 and 35.6 ,ug/ml, respectively. Significant antibacterial concentrations persisted through h 8. Intravenous doses of 0.5 and 1 g resulted in respective peak serum levels of 21 ,ug/ml at 45 min and 103 ,ug/ml at 15 min; these serum levels rapidly declined. Very high urine concentrations were achieved during the first 8 h after injection.boxylic acid, is a new cephalosporin derivative with a broad spectrum of antibacterial activity against a wide variety of gram-positive and gram-negative bacteria (3, 5a, 6, 10). Comparative in vitro studies with other presently available cephalosporin antibiotics showed cefamandole to be the most active against most Enterobacteriaceae and Haemophilus influenzae (3, 5a, 6, 10). The drug appears to be more resistant to the action of staphylococcal betalactamase than cefazolin and more resistant than cephalothin to beta-lactamases produced by some gram-negative bacteria (7, 11). We now report studies of the pharmacological behavior of this new antibiotic in normal human volunteers. MATERIALS AND METHODSSerum and urine concentrations after parenteral administration of cefamandole were determined in 15 healthy volunteers, 10 male and 5 female, aged 21 to 35 years. Each of the doses was administered at intervals of 7 or more days. Ten volunteers each received 0.5 and 1 g of cefamandole intramuscularly (i.m.). Serum was collected before injection of cefamandole and then at 0.5, 1, 2, 4, 6, 8, and 24 h. Urine was collected during the first 8 h and then from 8 to 24 h. Cefamandole was administered intravenously (i.v.) by diluting 500 mg in 5% dextrose and water and injecting the drug over a 15-min period. Serum specimens we-re collected before injection and then at 45, 75, 135, and 255 min after the beginning of the infusion. A 1-g dose was administered in the same manner, but serum specimens were collected at 15, 30, 45, 60, 75, 90, 120, and 240 min after the beginning of the infusion. Urine specimens were collected from 0 to 8 and 8 to 24 h. All volunteers were in the fasting state, had voided before injection of cefamandole, and remained sedentary during the study period. All volunteers had normal hemograms and normal values for blood urea nitrogen, serum creatinine, bilirubin, glutamic oxaloacetic acid transaminase, glutamic pyruvic acid transaminase, alkaline phosphatase, uric acid, albumin, and globulin before and after the study.Blood specimens were centrifuged after clotting at room temperature for 1 h; sera and filtered urine specimens were frozen and stored at -70 C. A modifield agar plate assay with paper disks (6.35 mm, Schleicher & Schuell Co.), with Bacillus subtilis spore suspension (Difco), was used to determine cefamandole concentrations (1, 4). All tests were run at least three times.The regression lines of the logs of serum concentratio...

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Section: Discussionmentioning

confidence: 99%

Pharmacological Studies with Cefamandole in Human Volunteers

Meyers

Ribner

Yancovitz

et al. 1976

Antimicrob Agents Chemother

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“…Turning to lytic action, the following facts indicate that autolysin plays an important role in penicillin-induced bacterial lysis (173,187,188): the inhibition of growth and the inhibition of peptidoglycan biosynthesis by subinhibitory concentrations of penicillins are reversible; timely addition of penicillinase to a penicillininhibited culture restores growth, which depicts a curve indistinguishable from normal; and the bactericidal effect of penicillins in Streptococcus and E. coli can be antagonized by the presence of antibiotics, such as chloramphenicol (179).…”

Section: Mode Of Action Of B-lactammentioning

confidence: 99%