We studied the cross-reactivity of penams and cephems in delayed-type hypersensitivity (DTH) by leucocyte migration inhibition test (LMIT) to test the cross-reactivity of 10 patients displaying ...hypersensitivity to penams and 20 with hypersensitivity to cephems. The cross-reaction rate in the LMIT of penam-sensitive patients was 56%(10/18) to penams, 71%(10/14) to penams with similar structures to the causative drugs in the C-6 side chain, and 0%(0/4) to penams without such similarities. On the other hand, 8%(3/38) to cephems, 16%(3/18) to cephems with similar structures to the causative drugs in the C-7 side chain, and 0%(0/20) to cephems without. The cross-reaction rate in the LMIT of cephem-sensitive patients was 48%(31/64) to cephems, 65%(17/26) to cephems with similar structures in the C-7 side chain, 75%(12/16) to cephems with similar structures in the C-3 side chain and 9%(2/22) to cephems without. On the other hand, 3%(1/34) to penams, (1/26) to penams with similar structures in the C-6 side chain and 0%(0/8) to penams without. Our findings indicate that in DTH there may be incomplete cross-antigenicity between penams and cephems and that the structures of both the side chain and the parent ring itself may play an important part as antigenic determinant; but this kind of cross-reaction is probably induced only at a low rate.
We conducted an investigation in animals to substantiate our previous clinical findings on the cross-reactivity of beta-lactam antibiotics in delayed-type hypersensitivity (DTH) by carrying out ...cross-reactivity testing of patients displaying hypersensitivity to cephems with a tetrazolyl group in the C-3 side chain. We used guinea pigs and three sensitizing agents: latamoxef (LMOX), cefoperazone (CPZ), and methyl-tetrazolethiol (MTT), which is itself the C-3 side chain of both LMOX and CPZ. The delayed-type intradermal skin test and leucocyte migration inhibition test (LMIT) were used to examine the cross-reaction of 14 agents in DTH on sensitized guinea pigs. The results of the skin test and LMIT on sensitized guinea pigs correlated and closely agreed with our human studies. Briefly, our observations suggest that in DTH to LMOX or CPZ they crossreacted not only with cephems with a tetrazolyl group in the C-3 side chain like LMOX or CPZ, but also with MTT, hydroxyethyl-tetrazolethiol (HTT) which is similar to MTT, and 7-aminocephalosporanic acid (7 ACA) which is itself the nucleus of cephems. Also, in DTH to MTT, they crossreacted not only with HTT, but also with cephems with a tetrazolyl group in the C-3 side chain. Our findings indicate that in DTH to caphems with an MTT group in the C-3 side chain, freetyped MTT and the mother nucleus structure may play an important part in the function of the antigenic determinant and consequently they may cross-react at a high rate with other cephems with a tetrazolyl group in the C-3 side chain.
We propose the following hypotheses made from based on the results of a leucocyte migration inhibition test (LMIT) which we performed on 11 patients with hypersensitivity to cephems with a 5-membered ...ring structure (aminothiazolyl, thienyl, furyl) in their C-7 side chain. 1. In delayed type hypersensitivity (DTH) to cephems with an aminothiazolyl group in their C-7 Ade chain, these agents cross-react with cephems with an aminothiazolyl or thienyl group in their C-7 side chain. 2. In DTH to cephems with an aminothiazolyl group in their C-7 sicie chain no cross-reactivity exists between these agents on the one hand and monobactams with an aminothiazolyl group in their C-3 Ade chain, penams with a thienyl group in their C-6 Ade chain and cephems with an amino-phenyl group in their C-7 Ade chain on the other. 3. In DTH to cephems with a thienyl or furyl group in the C-7 Ade chain, cross-reactivity exists between these agents, but they are not moss-reactive with monobactam. Our findings indicate that the mother nucleus structure as well as the Ade chains may play an important part in the function of the antigenic determinant in DTH to cephems with a 5-membered ring structure in their C-7 Ade chain.
Ribostamycin is an aminoglycoside antibiotic produced by Streptomyces ribosidificus, and extracted and isolated by NIIDA et al. 1, 2) It has been used widely clinically with its characteristic of low ...ototoxicity. UMEMURA et al. studied the pharmacokinetics of this antibiotic in animals and reported that it has a similar pharmacokinetic behavior in vivo to kanamycin. 3) In the present studies, the pharmacokinetic behavior of ribostamycin was studied in 5 healthy adult volunteers receiving different doses (0.5g, 1.0gand1.5g) by intramuscular injection, and 0.5 g by intravenous drip infusion.In addition, a similar study was conducted with11patients with varying degrees of renal dysfunction in order to study the application of ribostamycin in such patients.
On two cephalosporin C antibiotics, cephaloridine and cephalothin, comparative studies of pharmaco-kinetics after a single 500 mg intravenous dose were performed in human subjects with renal ...insufficiency. In subjects with normal kidney functions, the mean half life (T/2) of cephaloridine was 1.82 hours and of cephalothin 0.65 hour. In severe renal failures, the mean half life of cephaloridine was 9.79hours, the fall in serum cephalothin activity was biphasic and the mean half life for the curve of the first 9 hours was 5.0 hours; but for the second curve of during the period 9 to 72hours was 14.14 hours. The ratio of the mean rate of removal by the kidney of cephalothin (Kr) to the rate of the removal from serum (Ks), i. e. Kr/Ks was 0.09 much less than 0.48 of cephaloridine. It was suggested that nonrenal mechanism presumably desacetylation played an important role in removal of cephalothin from serum in these patients of severely impaired renal function.In the groups during haemodialysis, T/2 was shortened than those in the groups of severe renal failure without haemodialysis. But in the groups of peritoneal dialysis, T/2 were not shortened, because the clearance rates of cephaloridine and cephalothin by peritoneum (Cp) were nearly equal to the clearance rates by the kidney (Cr) in severe renal failure without dialysis. In the groups administered these antibiotics dissolved in all irrigating fluid (in concentration 62.5 mcg/ml) intraperitoneally during peritoneal dialysis, the mean serum levels after 9 hours of dialysis reached 12.5 mcg/ml with cephaloridine and 13.6 mcg/ml with cephalothin. The mean rates of absorption, across the peritoneum of cephaloridine and cephalothin were 42.5 and 45% when it is administered intraperitoneally.
On three broad-spectrum semisynthetic penicillins, i. e. ampicillin, hetacillin and carbenicillin, comparative studies of pharmacokinetics after a single 500mg intravenous dose were performed in ...human subjects with renal insufficiency. In severe renal failures, the half lives of these antibiotics in the serum were markedly prolonged mainly due to marked decreases of renal clearance (Cr) of these drugs. Both of the rates of removal of these antibiotics from serum (Ks) and through the kidney (Kr), as well as the clearances of these drugs from serum (Cs) were decreased too. Mean relative volume of distribution (RVD) of ampicillin, hetacillin decreased to 1/2-1/3 of normal kidney. These results suggested us that the distribution of these drugs into the tissue are lowered in the patients with severely impaired kidney function. In the groups treated with dialysis, T/2 was shorter than that seen in the groups of severe renal failure without dialysis, T/2 during haemodialysis was shorter than that seen during peritoneal dialy-sis, because the clearance-rates of these antibiotics by artificial kidney (Ck) were higher than the rates by peritoneum (Cp). In the groups administered these antibiotics, dissolved in all irrigating fluid (in concentration of 62.5mcg/ml), intraperitoneally during peritoneal dialysis, the mean serum levels after 9 hours of dia-lysis reached 11.6 to 14.0mcg/ml with all drugs tested. The mean rates of absorption of these drugs across the peritoneum were 35 to 58% when it is administered intraperitoneally.
Antirickettsial activities against R. orientalis of tetracycline, demethylchlortetracycline, methacycline, aminobenzylpenicillin, cephaloridine, cephalothin, mikamycin, spiramycin and ...acetylspiramycin were evaluated. Demethylchlortetracycline and methacycline were more effective, mikamycin, spiramycin and acetylspiramycin were less effective than tetracycline in the treatment of the mice inoculated. with R. orientalis. Aminobenzylpenicillin, cephaloridine and cephalothin had no effect on the infected mice. In clinical use, demethylchlortetracycline and methacycline were administered 33 mg twice daily and then on defervescence once daily for about 3 weeks until the total amount reached 1 g. This dosage was two third of tetracycline applied to small-dose long-term treatment. All six patients were cured without incurring relapse. In three cases mikamycin was administered daily 1g dose, followed by reduced daily 0. 5 g dose after subsidence of fever, and all of these three cases showed relapse after 1 to 3 days. In the use of mikamycin, spiramycin and acetylspiramycin, oral daily dose less than 1 g would be inadequate for the treatment of tsutsugamushi disease.
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