Studies on combination of antibiotics (II)

Seiichi Aonuma, Kikuo Onuma, Akira Watanabe, Masako Sasaki, Kotaro Oizumi, Kiyoshi Konno, Izumi Hayashi, Hiroaki Okamoto

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    In vitro combined activity of cefsulodin (CFS) and dibekacin (DKB) against 45 clinical isolates of Pseudomonas aeruginosa was investigated by use of Dynatech MIC 2000. CFS, at 6. 25 µg/ml, inhibited 65% of the test strains and killed 55% of them. On the other hand, DKB, at 0. 39 Ag/ml, inhibited 24% and killed 9% of the test strains. In combination of CFS and DKB, at concentrations of 6. 25 µg/ml and 0. 39 µg/ml, 84% of the test strains were inhibited and 82% of them were killed. A potentiation of inhibitory and killing activities was demonstrated in combination of CFS and DKB at various concentrations. CFS, in single use at 1. 56µg/ml and below, inhibited only 9% of the test strains. But in the presence of 0.1 or 0. 39µg/ml of DKB, CFS, at the same range of concentrations as mentioned above, inhibited 44% or 73% of the test strains. Similarly, CFS killed only 7% of the test strains, at 1. 56µg/ml and below, but when combined with 0.1 or 0. 39 µg/ml of DKB, it killed 27% or 67% of the test strains at the same concentration range. If the concentrations of both drugs in combination were raised, the more evident potentiation of inhibitory and killing activities was observed. Namely, when CFS and DKB were combined at 6. 25 µg/ml and 0. 39 µg/ml, 84% of the test strains were inhibited and 82% of them were killed. As evidence by 0.5 and below of fractional inhibitory concentration(FIC)- and fractional bactericidal concentration(FBC)-indices, a synergism between CFS and DKB for inhibition and killing was demonstrated in 67% of the test strains of Pseudomonas aeruginosa. To clarify clinical significance of this in vitro synergism, the following observation was made. The test strains were divided into two groups according to their susceptibilities to CFS;group I, consisting of the strains against which MICs or MBCs of CFS were 6.25(µg/ml and below and group II, consisting of the strains against which those of CFS were 12. 5µg/ml and above. The strains in group I and II were treated with CFS and DKB in combination and an average FIC- and FBC-index for each group was calculated from the results of checker board dilutions. Both indices were smaller in group II than those in group I. This result, showing the more distinct combined effect with DKB on the less sensitive strains to CFS, indicated a clinical significance of the combination. Then therapeutic effects of CFS combined with DKB or tobramycin (TOB) on 5 episodes of Pseudomonas infection in 5 patients with chronic obstructive pulmonary diseases were evaluated. The patients were treated by intravenous drip infusion of 2 grams of CFS combined with intramuscular injection of 100 miligrams of DKB in 3 cases or 60 miligrams of TOB in 2 cases, twice a day for 14 days in all cases. Clinical response was good in all cases and Pseudomonas aeruginosa was eradicated from the sputum of all patients. No adverse symptom developed; eosinophilia, elevation of GPT, elevation of GOT and GPT were detected in each one patient at the end of administration.

    Original languageEnglish
    Pages (from-to)770-775
    Number of pages6
    JournalChemotherapy
    Volume30
    Issue number7
    DOIs
    Publication statusPublished - 1982 Jan 1

    ASJC Scopus subject areas

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

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