Sulbactam/cefoperazone plus amikacin versus sulbactam/cefoperazone plus doxycycline: A microbiological study and well-controlled comparative clinical study on infection in association with lung cancer

Akira Watanabe, Yushi Nakai, Jun ichi Saito, Yoshihiro Honda, Yutaka Tokue, Mitsunobu Honma, Tsukasa Yoshida, Kenichi Takeuchi, Izumi Hayashi, Shigeo Takizawa, Kenji Yanase, Kotaro Oizumi, Yoichiro Ichikawa, Kazuma Fujino, Ken Araki, Masao Kawahara, Hiroshi Minami, Fumio Tanaka, Yoshiyuki Mitsutake, Toshihiro Higashi

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    Abstract

    In vitro combined effects of sulbactam/cefoperazone (SBT/CPZ) plus amikacin (AMK) and SBT/CPZ plus doxycycline (DOXY) against 13 strains each of clinical isolates of methicillinsusceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) and 27 strains of clinical isolates of Pseudomonas aeruginosa were evaluated. Against MSSA and MRSA, the combination of SBT/CPZ plus DOXY showed more synergistic combined effects than those of SBT/CPZ plus AMK. On the other hand, the combination of SBT/CPZ plus AMK showed more synergistic combined effects than those of SBT/CPZ plus DOXY against P. aeruginosa. A well-controlled study of two different combined regimens, SBT/CPZ plus AMK (Regimen A) and SBT/CPZ plus DOXY (Regimen B), was undertaken to compare the efficacy of the two regimens on infections associated with lung cancer. A daily dose of 2 g of sulbactam/cefoperazone plus 200 mg of amikacin or doxycycline was administered intravenously for 12.4 days (mean) in 46 patients (AlB=20/26) consisting of 27 with pneumonia (17/20), two with lung abscess (2/0), five with chronic respiratory infection (3/2) and three with sepsis (1/2). Clinical efficacy could be evaluated in 37 cases (17/20) and safety in 42 cases (17/25). Clinical efficacy was 65%(11/17) in Regimen A and 80%(16/20) in Regimen B, not a statistically significant difference. Regimen B was effective even in patients with “progressive disease” of lung cancer or with marked bronchial stenosis. Bacteriological effects could be evaluated in nine cases of both regimens. Six strains in Regimen Aand eight in Regimen B were eradicated by the therapy. One case each of drug-induced fever and transient diarrhea were observed in Regimen B. These adverse effects disappeared after the cessation of therapy. Three cases of elevated GOT/GPT values were found in Regimen B and one case of elevated BUN value was found in Regimen A during therapy. The above abnormalities of blood chemistry disappeared after therapy. We conclude from the results that the efficacy of the combined chemotherapy of sulbactam/cefoperazone plus doxycycline exceeds that of sulbactam/cefoperazone plus amikacin. More exact observation is required regarding adverse effects.

    Original languageEnglish
    Pages (from-to)177-191
    Number of pages15
    JournalChemotherapy
    Volume42
    Issue number2
    DOIs
    Publication statusPublished - 1994 Jan 1

    ASJC Scopus subject areas

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

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