We studied the combined effects of fosfomycin (FOM) with other antimicrobial agents, such as sulbactam/cefoperazone (SBT/CPZ), ceftazidime (CAZ), aztreonam (AZT), ofloxacin (OFLX), panipenem/betamipron (PAPM/BP), imipenem/cilastatin (IPM/CS), dibekacin (DKB) and piperacillin (PIPC), in vitro against 20 strains of Pseudomonas aeruginosa isolated from sputa. Combined effects were observed in all agents tested in this study. The mean fractional inhibitory concentration indexes were 0.38 in SBT/CPZ, 0.42 in CAZ, 0.46 in AZT, 0.56 in OFLX, 0.64 in PAPM/BP, 0.65 in PIPC, 0.66 in IPM/CS and 0.77 in DKB. In combination therapy with FOM, the cumulative percentage of MIC under serum concentrations of agents at three hours after intravenous administration were 100% in SBT/CPZ, 95% in CAZ, 95% in AZT, 90% in DKB, 85% in PAPM/BP, 85% in IPM/CS, 85% in OFLX and 80% in PIPC. These results suggests that the most effective combination therapy was that of FOM with SBT/CPZ.

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The antigenicity of oral antimicrobial agents was studied in clinical examination and in a basic experiment. The clinical examinations were performed by calculating both the hypersensigenicity and the allergenicity. The hypersensigenicity was shown as (the number of patints with suspected hypersensitivity to the oral antimicrobial agents/the number of patients treated with the oral antimicrobial agents) ×100. The allergenicity was shown as (the number of patients of positive leucocyte migration inhibition test/the number of patients treated with the oral antimicrobial agents) ×100. A maximization test (MT) in guinea pigs was used in the basic experiment. The hypersensigenicity was 0.411 in all oral antimicrobial agents. Broken down into drug categories, results were as follows: 0.401 in β-lactams (0.632 in penicillins, 0.308 in cephems), 0.128 in quinolones, 0.353 in macrolides, 0.731 in tetracyclines, and 4.225 in other antibiotics. The allergenicity was 0.271 to all oral antimicrobial agents. By drug categories, results were as follows: 0.240 in β-lactams (0.486 in penicillins, 0.171 in cephems), 0.043 in quinolones, 0.136 in macrolides, 0.418 in tetracyclines and 1.408 in other antibiotics. A significantly higher hypersensigenicity (p<0.001, χ²-test) and allergenicity (p<0.005, χ²-test) was found in β-lactams than in quinolones. Then, the allergenicity showed a very high correlation with the hypersensigenicity (r=0.977, p<0.001).β-Lactams tested in the MT were positive for all four drugs, in contrast to quinolones which showed positive for one out of 4 drugs. Moreover the mean score of skin reaction was 20.8 for β-lactams, in contrast to 3.2 for quinolines. Therefore, β-lactams were found to have a significantly higher antigenicity than quinolones (P<0.01, Wilcoxon rank-sum test). Our findings indicate that β-lactams have a higher antigenicity (allergenicity) than quinolones.

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The difference in the results of urine microscopic analysis and urine cultures using the first voided, second voided, and catheterized urine specimens in the female patients was studied. We compared the urinalysis results of the first and second voided urine specimens in 80 female patients, who visited our clinic with or without urinary tract infections. Twenty eight of 80 patients showed normal levels of leukocytes in both the first and second voided urine specimens. On the other hand, 50 patients revealed an abnormal increase in levels of leukocytes in the first voided urine specimen, and 14 showed normal levels of leukocytes in the second voided urine specimen. The observation of urinary bacteriae in the first and second voided urine specimens was similar to that of urinary leukocytes. We compared the results of urine microscopic analysis and urine cultures using the second voided and the catheterized urine specimens in 35 female patients. Twenty six patients revealed abnormal levels of leukocytes in the second urine specimen, but 7 of them showed normal counts of leukocytes in the catheterized urine specimen. In the patients with acute urinary tract infections, no difference was found in the results of urine cultures using the second voided and the catheterized urine specimens. On the other hand, a majority of the patients, without obvious clinical signs of urinary tract infections, who revealed abnormal colony counts on urine cultures using the second voided urine specimen, presented negative results or colony counts of less than 10³CFU/ml by urine cultures using the catheterized urine specimens. In conclusion, the urinary examination for the diagnosis of urinary tract infection in female patients should be performed using catheterized urine specimens.

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Between January 1998 and June 1998, 32 children were treated with cefcapene-pivoxile (CFPN-PI). Ages of the patients ranged from 8 months to 7 years. CFPN-PI was administered orally in a daily dose of 8.8 to 10.1mg/kg 3 times a day after each meal for 3 to 10 days. The patients included 8 with pneumonia or bronchitis, 8 with otitis media, and 16 with pneumonia or bronchitis and otitis media, and were evaluated for clinical efficacy. The clinical efficacy rate was 78.1%. The efficacy rates were 88.9%, 73.3%, and 75.0% for Haemophilus, influenzae, Streptococcus pneumoniae, and H. influenzae and S. pneumoniae, respectively. The bacteriological eradication rate was 69.6%. Diarrhea was observed in an 8-month-old infant. Susceptibility of 30 H. influenzae and 40 S. pneumoniae to CFPN was measured. The MICs at which 90% of the strains were inhibited (MIC₉₀S) of CFPN were 0.06μg/ml and 1.0μg/ml for H. influenzae and S. pneumoniae, respectively.

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In 1996 Fujino et al. reported the cost-effectiveness analysis for the initial treatment of respiratory infections in Japanese hospitals, comparing the alternative regimens of antibiotics, imipenem/cilastatin (IPM/CS) versus the other β-lactams (β-LTM). Although they concluded IPM/CS could be more costeffective than β-LTM, this conclusion might be statistically confounded by some biases revealed during retrospective study. Therefore, we conducted a cost-effectiveness analysis of IPM/CS with a prospective view based on the original randomized-controlled clinical trial. Either IPM/CS or β-LTM was assigned at random to each regimen using the envelope method. The outcome of effectiveness was measured by the following two endpoints: 1) the number of days needed to cure a patient according to the subjective judgment of the physician in charge, and 2) the number of days needed for a patient to recover according to the objective criteria of diagnostic tests, which can eliminate physicians' subjective biases. These outcomes were compared and analyzed with the actual direct costs needed to treat patients. As a result, we could reconfirm that IPM/CS was more cost-effective than β-LTM, not only by entire crude analysis, but also by stratified analyses such as patients with underlying respiratory diseases and the patients with mild or moderate infections. Furthermore, the better cost-effectiveness of IPM/CS was found when comparing the sub-regimens in which ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ) were given as an initial antibiotic. In addition, the stratum of patients with secondary infections of chronic respiratory tract infections, who were treated with IPM/CS, indicated dominant cost-effectiveness, which is a new finding not known in the study by Fujino et al. Consequently, in evaluating both retrospective and prospective investigations, we could conclude IPM/CS is more cost-effective than β-LTM if IPM/CS is selected as an initial antibiotic to treat patient groups assuming certain conditions.

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