半合成青霉素

SEMISYNTHETIC PENICILLINS

我国半合成青霉素的研究工作始于1961年,并于1962年将试制成功的甲氧苯青霉素应用于临床。到目前为止我国己投产和已试制成功的半合成青霉素有16种。现将我室进行的14种半合成青霉素临床应用研究工作分为三组综合报道,结合文献对半合成青霉素的临床应用提出一些看法。

A comprehensive description of the research works on semisynthetic penicillins in our laboratory and comments on different semisynthetic penicillins are given in this paper.Among the penicillinase-resistant penicillins,the antibacterial activity against Staphylococcus aureus of dicloxacillin was the highest,about 1.7 times more active than that of oxaeillin.The average MIC of methicillin and oxacillin were 3.23μg/ml and 0.29/Ag/ml respectively,i.e.the latter had 11 times the in vitro activity of the former against Staphylococcus.Clinical therapeutic results of methicillin,oxacillin,nafcillin and dicloxacillin were all quite satisfactory.Because of.the comparatively poor antibacterial activity,production of methicillin was already stopped in the early seventies in our country,Parenteral preparations of oxacillin and cloxacillin as well aa oral preparation of dicloxacillin are introduced into clinic nowadays.In order to obtain better elinioal.results with lower cost,it is advisable to produce parenteral preparation of dicloxacillin.Bacteria resistant to penicillinase-stable antibiotics were increased steadily in recent years;therefore,new semisynthetic penicillins or other antibiotics without exhibiting bacterial cross-resistance are urgently needed clinically.Ampicillin,the first discovered broad-spectrum semisynthetio penicillin,is still widely used now.It is the drug of choice in treating suppurative meningitis in children,and infective endocarditis caused by Streptococcus viridans and enterococci when combined with an aminoglycoside.Pivampicillin and hetacillin had their antibacterial activity only after hydrolysis into ampicillin.Hetaoillin had no superiorities over ampicillin.After oral administration,the blood concentrations of amoxicillin and pivampicillin were more than 2 times that of ampicillin and were not affected by food intake.The bactericidal power of amoxicillin is more rapid and stronger than that of ampicillin.Semisynthetic penicillins with antipseudomonas activity are developing at present.The antibacterial activity of carbenicillin is too weak and comparatively large doses should be used clinically.The therapeutic result of carbenicillin was not very satisfactory and side effects such as electrolyte disturbances and neurotoxicity will appear sometimes.Carfecillin,thephenylesterof carbenicillin,is of limited value in the treatment of urinary tract infections because of its low blood levels.BL-P1597(Furbenicillin)has a much stronger antibacterial activity than carbenicillin and is also more active than its analogue,BL-P1654.The preliminary therapeutic result of BL-P1697 was also satisfactory.However,the evaluation of this antibiotic needs further clinical observations as to the problems of bacterial resistance and sides effects on liver and kidney.Initial laboratory studies of piperacillin and antibiotic 771 Can analogue of PC-904 or apalcillin in our country)were promising.