Sixteen thousand nine hundred and fiffteen clinical isolates of Klebsiella pneumoniae and 23, 568 clinical isolates of Escherichia coli were isolated during the period September 1994 through August 1995, and were subjected to susceptibility testing against ceftazidime (CAZ), aztreonam (AZT), latamoxef (LMOX), sulbactam/cefoperazone (SBT/CPZ), cefpirome (CPR), cefminox (CMNX), ceftizoxime (CZX), and piperacillin (PIPC). Forty one of the 16, 915 K. pneumoniae strains (0.24%) were found to be resistant to CAZ. Among the 41 CAZ-resistant strains, 30 were isolated from 5 hospitals in Kanagawa, 6 were from a hospital in Shizuoka, 6 were from 2 hospitals in Tokyo, and 1 strain was from a hospital in Yamaguchi. All 41 of these strains also demonstrated high-level resistances to both AZT and PIPC, and a portion of these strains showed additional moderate-to low-level resistances to the remaining 5 agents. Of the E. coli isolates tested, 25 strains demonstrating CAZ-resistance were identified from 8 hospitals throughout Japan. These isolates also demonstrated high-level resistance aginst AZT and PIPC. However, in contrast to the CAZ-resistant K. pneumoniae strains, CAZ-resistant E. coli strains exhibited higher-levels of resistance to the remaining 5 agents. Finally, a disturbing trend noted in this study was that in some hospitals, CAZ-resistant srrains were isolated repeatedly from patients who were hospitalized in the same ward, suggesting the presence of nosocomial outbreaks. Thus, the choice of appropriate antimicrobial agents based on timely and accurate antimicrobial suscepitibility testing is thought to be critical for the containment of CAZ-resistant strains.

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The efficacy of prophylactic oral administration of itraconazole (ITCZ) was studied in a rat model of invasive pulmonary aspergillosis (IPA). Immunosuppressed rats were infected by intratracheal inoculation of Aspergillusfumigatus conidia. Oral administration of various doses of ITCZ was started 7 days before infection (prophylactic treatment), or immediately after infection (postinfectious treatment), and both were continued for 7 days after infection. Prophylactic treatment with 40mg/kg/day of oral ITCZ (survival rate: 60% in 28 days) was more effective at prolonging survival than postinfectious treatment with 80mg/kg/day of oral ITCZ (survival rate: 20% in 28 days). Quantitative counts of aspergilli in the rat lung at 24 h after infection with 40mg/kg/day, 80mg/kg/day postinfectious treatment of oral ITCZ and no treatment controls exceeded 4.00 log₁₀CFU/g, but the number of aspergilli in the rat lung with 40mg/kg/day prophylactic treatment was 2.64± 0.23log₁₀ 0CFU/g (p<0.02). Pathology of the lungs, in rats were treated prophylactically with 40 mg/kg/day of oral ITCZ, at post-infection day 5, showed no invasive growth of aspergillus hyphae. However the lungs of rats treated post-infectiously with 40mg/kg/day of oral ITCZ, at the same time, showed invasive growth of aspergillus hyphae. Prophylactic treatment with oral ITCZ is useful for preventing IPA, because it inhibitsaspergilli in the early phase of infection of the lower respiratory tract.

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Previously we reported that photosensitivity reactions were observed in 6.6%(19 of 338) of patients treated with lomefloxacin hydrochloride (LFLX) for a relatively long period. Analysis of the therapeutic risk factors demonstrated that the incidence of the reactions was higher in patients treated for 30 days or more and with a total dose of 30g. On the basis of those results we investigated the records of patients administered LFLX 400mg or less daily for 14 days or less, and determined the incidence of photosensitivity reactions. At the reduced dosage photosensitivity reactions were observed in only one of 324 patients (0.3%), even though the backgrounds of the patients were almost the same as those in the previous study. In 175 cases evaluated for clinical efficacy, lomefloxacin at our dosage schedule was effective for treatment of urinary tract infections providing an efficacy rate of 77.1% and a bacteriological elimination rate of 84.3%. In conclusion, we need to instruct patients to avoid excessive exposure to sunlight during treatment with new quinolones including LFLX and we should refrain from administering the drugs for a long time.

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A clinical study on multi-drug resistant Streptococcus pneumoniae respiratory infectons in adult patients was performed. One hundred twenty strains of S. pneumoniae were isolated from different patients at the clinical microbiology laboratory of Kawasaki Medical School Hospital between November 1993 and February 1995. All of these patients' clinical records were reviewed to determine the backgrounds of patients such as age, diagnosis of infections, underlying disease, division where the patients were treated etc. Then, 78 adult patients with pneumococcal respiratory infections were selected as the study subjects. There were 32 patients with pneumonia, 18 with chronic respiratory tract infections and 28 with other respiratory infections. Fifty patients were treated in the division of internal medicine and 24 were treated in the emergency unit. The overall rate of resistant S. pneumoniae in these patients, was 46.7%; intermediately resistant (PISP) 25.8% and resistant (PRSP) 20.9%. In pneumonic cases, the resistant rate was only 15.4% in patients in the internal medicine division while a high resistant rate of 72.7% was observed in patients treated in the emergency unit, most of whom had severe underlying diseases and were treated by antibiotics selected by a different policy. The resistance rates were also higher in aged patients with pneumonia. A high resistance rate was also noted in patients with chronic respiratory tract infections who had many more opportunities to have frequent chemotherapy. The clinical effectiveness of penicillins and 1st generation injectable cephalosporins in the treatment of these resistant pneumococcal infections was not always satisfactory. However, in some patients with PISP pneumonia, high-dose penicillin G treatment was highly effective.These results suggest that consideration of the patient's condition and characteristics of drugs are important in the treatment of these resistant pneumococcal infections.

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