Harushige Kanno

Life-threatening Clostridium difficile-associated diarrhea induced by paclitaxel-carboplatin combination chemotherapy.

Diarrhea has been reported in 10% of patients undergoing antineoplastic chemotherapy (1). Infectious colitis contributes to diarrhea in some chemotherapy-induced cases, and the most common etiologic agent is Clostridium difficile. Prior antibiotic use is considered the most important risk factor in the development of C. difficile-associated diarrhea (CDAD). However, CDAD can occur in the absence of antibiotic use and the association between antineoplastic therapy and CDAD has recently become evident. Meanwhile, the risk of paclitaxel in CDAD is not well defined.

Interaction of Beta-Lactam Antibiotics with the Penicillin-Binding Proteins of Penicillin-Resistant Streptococcus pneumoniae

The binding of five structurally diverse beta-lactam antibiotics to penicillin-binding proteins (PBPs) of two clinical isolates of Streptococcus pneumoniae resistant to penicillin G was compared with that of a susceptible strain. A common feature of the PBP patterns of the resistant strains was the absence of PBP 1a detected in the susceptible strain. For each beta-lactam antibiotic tested, there appeared to be significant decreases in the affinity for BPB 1b, 2a and 2b of the resistant strains. We attempted to evaluate a quantitative correlation between the antibacterial activity of the drugs for three strains and their affinity for the various PBPs. A close correlation was found between the minimum inhibitory concentrations and the affinity for PBP 2a, but not for any of the other PBPs.

Characterization of an Extended-Spectrum β-Lactamase from Escherichia coli Mediated by a Plasmid

The β-lactamase fromEscherichia coli ML 4953 pKU56 was purified about 190-fold from the crude cell-free extract with an overall recovery of 17%. The molecular weight mediated by pKU56 was about 28,000, and the isoelectric point was about 9.4. This enzyme hydrolyzed cephaloridine, cephalothin, cefamandole, cefuroxime, and cefsulodin at high rate, but ampicillin, piperacillin, and carbenicillin moderately. Antisera against pKU56 enzyme showed partly cross-reaction with β-lactamase fromKlebsiella oxytoca andProteus vulgaris.

[Studies on 145 cases of septicemia in infancy and childhood--especially on septicemic patients with malignant and hematological diseases].

Clinical and bacteriological data of 145 inpatients with septicemia, treated at the hospital of Chiba University School of Medicine from 1972 to 1987, were reviewed by dividing them into three stages. (stages I: 1972-76, stage II: 1978-82, stage III: 1983-87) Patients with underlying diseases have been increasing: 91.8% of the total patients in stage III. Among the patients with underlying diseases, malignant and hematological diseases occupied about 60%, and in the other diseases, congenital heart diseases have been increasing in number. As to the organisms isolated, gram positive bacteria have increased, while gram negative bacteria have decreased. In stage III, the rate of gram positive organisms and gram negative ones accounted for 43.1% and 41.2% of all the isolates from the septic patients with malignant & hematological diseases, respectively. In patients with malignant & hematological diseases, alpha-streptococcus, coagulase-negative staphylococcus, and Fusobacterium sp. have been increasing, whereas, Escherichia coli, Enterobacter sp., Klebsiella sp., and Pseudomonas aeruginosa decreasing. In patients with other underlying diseases, S. aureus, CNS, and non Fermenters have been increasing. Among the patients without underlying diseases, gram positive bacteria accounted for the major part. The decrease of gram negative organisms in patients with malignant and hematological diseases may partially depend on the introduction of polymixin B as the drug of gut decontamination. The outcome of septicemia in the patients with malignant & hematological diseases has been markedly improving through all the three stages. During stage III, episode mortality and case mortality rate proved to be 23% and 31%, respectively. The introduction of the third generation cephems has decreased the mortality rate for gram negative organisms and contributed to the improvement of the total prognosis. The prognosis was worst in the case of P. aeruginosa, showing a mortality rate of 50% during stage III. Coincidence rate of blood and other cultures have been largest in the case of P. aeruginosa, so, the drug sensitivity of the strain cultured from other sites is sometimes useful in the choice of antibiotics.

Synergistic Activities of Combinations of Antibiotics against Methicillin-Resistant Staphylococcus Aureus

The effect of an antibiotic combination against methicillin-resistant Staphylococcus aureus which is frequently found in hospitalized patients were investigated. By means of the microtiter checkerboard method, combinations of vancomycin-minocycline, vancomycin-cefamandole, vancomycin-fosfomycin, cefamandole-minocycline and cefamandole-fosfomycin were found to be synergistic against 6.4, 84.0, 20.9, 19.3 and 100.0% of the sixty-two strains tested, respectively. The means of the fractional inhibitory concentration (FIC) indices of vancomycin-minocycline, vancomycin-cefamandole, vancomycin-fosfmycin, cefamandole-minocycline and cefamandole-fosfomycin were 1.50, 0.39, 0.64, 0.85 and 0.25, respectively. Thus, the effect of the combination of cefamandole-fosfomycin was superior to other combinations.