6059-S, A'new oxa cephalosporin; its antimicrobial activity and efficapy on respiratory tract infections

Akira Watanabe, Seiichi Aonuma, Kikuo Onuma, Masako Sasaki, Kotaro Oizumi, Kiyoshi Kohno, Kiichi Kaishio

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    A new oxacephem antibiotic was developed in Research Laboratory, Shionogi & Co. Ltd., Japan, in 1976, The chemical structure of this substance, in addition to having a methoxy group at 7 position, is quite unique in that the sulfur at cephalosporanic acid is substituted with oxygen. This new substance, which has a cephalosporin like structure, is now designated “oxadethiacephem” or more simply “oxacephem”. We examined antimicrobial activities of this substance, the first oxacephem antibiotic available So far, against clinical isolates of several species and then evaluated clinical efficacy of it on various types of, respiratory tract infections. From the results of our in vitro examinations it was revealed that the in vitro activities of this substance were relatively week against gram positive cocci such as S. pneumoniae, S. pyogenes and S. aureus as compared with those of cefazolin (CEZ). In contrast, against some species of gram negative bacilli 6059-S showed remarkably potent antimicrobial activities. Namely, the peak in MICs distribution against clinical isolates of H. influenzae was found at the range of 0.025 to 0.05 μg/ml and these concentrations were lower than thoise of aminobenzylpenicillin by 2~3 hold dilutions. Similar potent activities of the drug against patient strains of gram negative bacilli, such as E. coli and K. pneumoniae, were evident when susceptibilites of these strains to CEZ were determined and compared with those of 6059-S. This substance was also found to be highly active against patient strains of E, clqacae, i. e. 6 out of 7 patient strains were inhibited at O.1 or 0.2 μg/ml of the drug and these concentrations were one eighth of those of aminoglycosides required for growth inhibition. MICs of sulbenicillin (SBPC) against these strains of E. cloacae ranged from 3.13 to 25 /ug/ml and those of CEZ were over 50 jig/mL MICs of 6059-S against 5. marcescens distributed widely, ranging from 0.78 to>200jig/ ml, though over 60 per cent of the strains were inhibited at concentrations less than 25 #ig/ml of the drug. Thus, 6059-S was shown to be apparently superior to CEZ and SBPC and slightly more active than aminoglycosides in antimicrobial activities against S. marcescens. Of 9 patient strains of A calcoaceticus, only 1 of them was inhibited at 0.78 g/ml of 6059-S and MICs against the remaining strains were over 50 /ig/ml. Among antibiotics tested, dibekacin was most active against the strains of A calcoaceticus and MICs of it ranged from 3.13 to 25 g/ml. While MICs of CEZ against all 26 patient strains tested of P. aeruginosa were over 200 fig/ml 6059-S inhibited the growth of 70 per cent of them at concentrations less than 25/ig/ ml. One to three grams of 6059-S were given twice a day by intravenous drip infusion and efficacy of the drug in the treatment of respiratory tract infections was evaluated. Thirty patients, on whom evaluation was made, consisted of 11 patients with pneumonia, 4 with lung abscess, 1 with chronic bronchiolitis, 4 with secondary infection to interstitial pneumonitis, 2 with mixed infection with pulmonary tuberculosis, 7 with secondary infection to lung cancer and 1 with sepsis complicated with pneumonia and meningitis. Excellent and good responses were obtained in 7 and 15 patients respectively by treatment with the drug. Fairly good therapeutic effects was observed in.7 of the patients treated, In 2 patients responses were poor and other 2 patients were excluded from evaluation because of simultaneous administration of the other antibiotic in combination. Twenty-three strains of potentially pathogenic organisms were cultured from the specimens of the patients before the treatment and 21 of them were eradicated from the sputum by use of 6059-S. The eradicated pathogens consisted of 9 strains of H. influenzae, 5 strains of 5. pneumoniae, 3 of K. pneumoniae and each 1 of E. cloacae, 5. marcescens, P. cepacia and E. coli. As adverse effects which emerged during the course of 6059-S administration, elevation of 8-GOT and s-GPT values was noted in 3 patients and elevation of s-GPT value alone in 2 patients. Eosinophilia was seen in 2 patients. But these abnormal laboratory findings were not serious and they returned to normal levels and values soon after the withdrawal of the drug.

    Original languageEnglish
    Pages (from-to)304-321
    Number of pages18
    JournalChemotherapy
    Volume28
    DOIs
    Publication statusPublished - 1980

    ASJC Scopus subject areas

    • Oncology
    • Pharmacology
    • Drug Discovery
    • Pharmacology (medical)
    • Infectious Diseases

    Fingerprint Dive into the research topics of '6059-S, A'new oxa cephalosporin; its antimicrobial activity and efficapy on respiratory tract infections'. Together they form a unique fingerprint.

    Cite this