In considering the status of post-marketing surveillance (PMS) in Japan, it is important to disseminate the collection, assessment, and transmission of drug and safety information to gain an understanding of proper-use information on drugs and the mechanism of transmitting such information for seeking cooperation in drug safety measures. It is especially important to ensure that physicians, pharmacists, nurses and other health care professionals are well-informed about adverse events.It is also essential for patients to have an appropriate understanding of adverse events. It is thus hoped that explaining PMS will help pharmaceutical companies and those engaged in medical care take rational measures against adverse events. Internationally shared information on appropriate drug use is necessary for taking full mutual advantage of drug information to benefit patients worldwide, especially for promoting drug safety given the globe's growing borderlessness. An agreement must thus be reached on globally applicable information exchange and standardization of electronic transmission abreast of the times. Accordingly, such are also discussed. To detect and announce new adverse events is crucial for the physician or patient to have valid suspicion about the use of drugs and changes in symptoms caused by drugs.

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We tested 100 strains of Mycoplasma pneumoniae for susceptibility to moxifloxacin, a new quinolone compound, using sparfloxacin, levofloxacin, ciprofloxacin, and clarithromycin as references. Among the 100 strains of M. pneumoniae isolated from throat swabs of patients with respiratory infectious disease, 39 strains were isolated prior to 1986, 24 strains between 1986-1990, and 37 strains between 1991-1995. The susceptibility of these strains to the above antimicrobial agents was determined by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Of the new quinolones, moxifloxacin was the most active against these organisms, with MIC₅₀ of the drug 0.08μg/mL and MBC₆₀ 0.08μg/mL. The MIC, os of sparfloxacin, levofloxacin, and ciprofloxacin were 0.15μg/mL, 0.6μmL, and 2.5μg/mL. The MBC₅₀s of these drugs were 0.3μg/mL, 1.25μg/mL, and 2.5μg/mL. The MIC₅₀ of clarithromycin was 0.008μg/mL, and the MBC₆₀ was 0.015μg/mL. These results indicate that moxifloxacin possesses a high potentiality of anti-M. pneumoniae activity and is a promising antibiotic in thetreatment of mycoplasmal infections.

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The emergence of β-lactam resistant mutants of Pseudomonas aeruginosa S-1278, a clinical isolat susceptible to β-lactams, was investigated in a rat pouch infection model using 4 β-lactam antibiotics: piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), and imipenem (IPM). After intravenous administration of 20 and 100mg/kg of each drug in the rat pouch infection model, the frequency of mutants resistant to PIPC and TAZ/PIPC were <1.0×10^-5 to 3.7×10^-8: lower than those of CAZ and IPM (2.4×10^-5 to 7.5×10^-5). The frequency of mutants resistant to CAZ increased drastically after 3 administrations, and its frequency (4.7×10^-2 to 2.17times;10^-1) was the highest. No significant difference of frequency of resistant mutants was seen among the 4 β-lactam antibiotics in vitro, but CAZ selected resistant mutants in a wider concentration than in other antibiotics. In conclusion, the frequency of mutants resistant to PIPC was comparable to that of TAZ/PIPC, and was lower than for CAZ and IPM in the rat pouch infection model.

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The antibacterial activity of cefepime, cefozopran, cefpirome, ceftazidime, cefotaxime, piperacillin, and imipenem/cilastatin against clinical isolates in 1996-98 were tested (a total of 523 strains from 19 organism groups, i.e., methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Serratia marcescens Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter spp. and Bacteroides spp.) and compared to those against clinical isolates in 1985-87, prior to cefepime use. Staphylococci were uniformly susceptible (MIC₉₀, ≤0.025-3.13μg/mL) to all drugs except ceftazidime (MIC₉₀, 12.5μg/mL). This did not change in 1985-87. Among E. coli and K pneumoniae, the ranking of antibacterial activity was cefepime>cefpirome=cefozopran>imipenem/cilastatin>ceftazidime>piperacillin. Isolates of 13.3% of C. freundii and 16.7%of E. cloacae resistant to ceftazidime (13.3, 16.7% resistance respectibility) remained susceptible to cefepime and imipenem/cilastatin. Imipenem and fourth-generation cephalosporin were stable to β-lactamase produced from these species. P. aeruginosa isolates were susceptible to cefepime, cefozopran, ceftazidime and imipenem/cilastatin. Metalloenzyme was identified in 1 strain of S. marcescense. No difference in the antibacterial activity of cefepime to most species of bacteria was seen between this study and that 10 years ago. Cefepime thus has a low rate of selection in drug resistance because it has potent antibacterial activity and is stable to β-lactamase. Our results suggest that cefepime is useful in the treatment of bacterial infections. An extended-spectrum β-lactamase was identified in 2 strains from 82E. coli strains isolated from the same clinical center and showed the same pulsed-field gel electrophoresis (PFGE) pattern. It was surmised that the same clone had spread throughout the hospital.

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We evaluated the mechanism behind the efficacy of roxithromycin (RXM) in chronic infection to determine the influence of RXM on mucociliary epithelization by the outgrowth of mucociliary epithelial culture. We focused on the degree of epithelization by measuring the outgrowth of explant culture and on the degree of differentiation by counting the number of beating ciliary cells in the outgrowth epithelial sheet. The area of outgrowth cells with 1.0×10^-5mol/L and 10^-6mol/L of RXM was higher than that of controls, 10^-4mol/L and 10^-7mol/L of RXM. The number of ciliary cells with 1.0×10^-6mol/L of RXM was significantly higher than in other groups. Based on the above data, we concluded that nasal epithelial cells were sensitive to RXM in growth and differentiation but in some optimal concentration.

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We studied the bacteriological effect and resistances to cefpirome (CPR) in the treatment of complicated urinary tract infection caused by Enterococcus faecalis over the 5 years from 1994 to 1998. E. faecalis was isolated in 68 of 129 subjects (52.7%) in whom clinical efficacy was analyzable. Monomicrobial infection accounted for 33.8%(23/68) and polymicrobial infection for 66.2%(45/68). In terms of clinical efficacy in E. faecalis-isolated subjects, cefpirome was markedly effective in 21 subjects, effective in 36, and no response or ineffective in 11. Efficacy was 83.8%. Efficacy in monomicrobial infection was 87.0% and that in polymicrobial infection was 82.2%. Efficacy related catheter was 73.7% with use and 87.8% without, indicating a favorable outcome in either case. The efficacy of CPR in subjects in whom E. faecalis was not detected was 82.0%, comparable to E. faecalis-isolated subjects. No particular problem was seen in adverse subjective or objective adverse effects. In the MIC distribution of CPR against E. faecalis by isolation chronology, MIC₅₀was 6.25 or 12.5μg/mL whereas MIC₉₀ was 25 or 50μg/mL findings similar to those for strains isolated during from 1985 to 1988. For MIC₁₀₀, 200μg/mL was the highest recorded before 1990, indicating no trend toward resistance. CPR is the first cephem medicinal product approval for use against E. faecalis, which has thus far shown no problem such as decreased efficacy or the development of resistance, demonstrating its usefulness.

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The patient was a 68-year-old woman. At age 61, she was diagnosed with breast cancer that was cured by surgery, chemotherapy, and radiotherapy. On February 3, 1998, she consulted a local physician for malaise. She had a leukocyte count of 1, 950/mm³ with 28% myeloblasts containing Auer bodies, suggesting a diagnosis of acute leukemia. On February 3, 1998, she was referred to our department and was admitted on the same day. A diagnosis of acute myelocytic leukemia was made by bone marrow aspiration, and the patient received remission induction therapy with idarubicin and cytarabine from February 9 to 15. Filgrastim (granulocyte-colony stimulating factor) was administered intravenously (300mg/day) beginning on February 10 for neutropenia. On February 24, myelosuppression occurred and fever with chills developed. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA), indicating a diagnosis of MRSA sepsis. On February 26, the patient noted tenderness in her lower left jaw, that was following by the appearance of a subcutaneous mass the size of a walnut. An intramuscular mass the size of the tip of the little finger was also observed on the extensor aspect of the right leg. Aspiration biopsy of the cervical mass was performed on March 9, and culture revealed MRSA, indicating a diagnosis of subcutaneous and intramuscular MRSA abscess. Since abscesses are prone to hemorrhage and fistula formation in patients with thrombocytopenia, and they are difficult to resect or drain, healing is often delayed, and the risk of disseminated infection is increased. Accordingly, intravenous antibiotic therapy with panipenem/betamipron (PAPM/BP) 2g/day and vancomycin (VCM) 2g/day was given until March 21, but the patient's condition failed to improve. Treatment was changed to intravenous arbekacin (ABK) 200 mg/day and oral minocycline (MINO) 200mg/day, and the masses resolved on April 20. Although the organism was sensitive (MIC:≤4μg/mL) to both VCM and ABK, combined therapy with ABK and MINO proved to be superior.

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