To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows:
The total number of patients enrol led in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy.
1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated.
2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups.
3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference.
4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups.
Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infCctions.

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A clinical study on sulbactam/cefoperazone was performed and the following results were obtained.
Sulbactam/cefoperazone was administered intravenously to 30 elderly patients with urinary tract infections. Those patients were treated with 1g of sulbactam/cefoperazone 2 times daily.
1. Clinical efficacies in 24 cases of complicated urinary tract infections were excellent in 8, moderate in 11 and poor in 5, with an overall efficacy rate of 79.2%. As to bacteriological responses, 20 of 25 strains identified in the complicated urinary tract infections were eradicated, with an eradication rate of 80%.
2. Clinical efficacie s in two cases of acute uncomplicated pyelonephritis were excellent in 1 and moderate in 1, with an overall efficacy rate of 100%. Bacteriologically, two of the strains in the acute uncomplicated pyelonephritis was eradicated, with an eradication rate of 100%.
3. SafCty evaluation was made in all 30 patients received sulbactam/cefoperazone.
No adverse reactions were observed in any cases. As to laboratory test results, slight elevation of GPT was noted in 1 patient.
In conclusion, sulbactam/cefoperazone is considered as a clinically useful antibiotics in the treatment of urinary tract infections with elderly patients.

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Assessment was made on the serum protein binding of clarithromycin (CAM), a representative oral macrolide, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF) applying equilibrium dialysis in vitro. The protein binding of CAM was 81.9±1.9%, 85.9±3.6%, 82.9±3.3% and 86.8±3.3% for sera from HS, from patients in conservative treatment (ND), from those receiving hemodialysis (HD) and from those with continuous ambulatory peritoneal dialysis (CAPD), respectively. There was no significant difference among these values. The protein binding of CAM was 82.9±3.3% and 68.8±3.5% for sera before and after HD, respectively. There was significant difference between these values.
In the study of the protein bindin g in patients on HD at an albumin concentration of 0.5mM, the protein binding of CAM for sera was found to be significantly decreased following HD as compared to that prior to HD. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS, the protein binding of CAM showed no change.
These findings suggest that changes in the protein bindi ng of CAM with HD have been possibly caused by an increase in a drug binding inhibiter other than NEFA (PA) or by an allosteric effect on the albumin binding capacity.
At therapy using CAM, the possibility of enhanced pharmacological effects and increased adverse reactions of CAM due to decreased protein binding in patients on HD should be considered.

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FD501 is a newly synthesized quinolone derivative with aminoazepine group at the C-7 position. The in vitro and in vivo antibacterial activities of FD501 were investigated comparing with those of norfloxacin, ofloxacin, ciprofloxacin and sparfloxacin.
The in vitro antibacterial activities of FD501 against Gram-positive bacteria including methicillinresistant Staphylococcus aureus, were equal to or higher than those of other quinolones. But its activities against Gram-negative bacteria were equal to or lower than those of other quinolones.
Minimum inhibitory concentrations of FD501 against Gram-positive bacteria were similar to that of sparfloxacin. The bactericidal activity may be due to the inhibition of the DNA supercoiling activity of DNA gyrase.
The area under the serum concentration-time curve of FD501 in rats following oral administration was larger than norfloxacin and ciprofloxacin and smaller than those of ofloxacin and sparnoxacin.

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The morphological response of urinary Gram-negative bacteria to ceftibuten (CETB) was investigated in four patients with urinary tract infections (one patient: acute uncomplicated cystitis, three patients: chronic complicated urinary tract infection).
The daily dose of CETB was 400 mg administ ered orally and the durations were 3 days for the acute uncomplicated cystitis case and 5 days for the chronic complicated urinary tract infection cases.
In the four patients, changes in urinary CETB concentrations, viable bacterial counts, and morphology of the bacteria were studied after the initial administration. The urinary concentrations of CETB were 7.38-60.3μg/ml at one hour after the first administration. The urinary viable cell counts were 1-5×10⁷ cells/ml before administration, but they were reduced to 1-3×10³ cells/ml at one hour after the first oral administration.
Morphological changes of ba cteria: Under phase contrast microscopy, filamentous debris and spherical bacteria with severe body damage were observed at 30 minutes after the first administration. By transmission electron microscopy, the cell wall of the filamentous bacteria showed a number of projections with formation of vacuolar structures in the space between the cell wall and the irregularly-shaped cytoplasm.
According to the Japanese UTI criteria, the efficacy rate was 100% in the 4 patients. Neither side effect nor abnormal laboratory result was observed in any patient.
Conclusiton: The morphological changes of the bacteria sugges ted that CETB, in vivo, bounds not only penicillin-bindipnrgo tein(PBP)-3 but also PBP-1.

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We investigated antibacterial activities of combination uses of isepamicin (ISP) and β-lactams in vitro against Klebsiella pneumoniae and Enterobacter cloacae, and the following conclusions were obtained.
1. ISP+cefazolin, ISP+cefotiam and ISP+flomoxef against K. pneumoniae and ISP+piperacillin, ISP+ceftazidime, ISP+aztreonam, ISP+imipenem and ISP+panipenem against E. cloacae showed strong combined effects.
2. The minimum inhibitory concentrations (MICs) of these combinations were low due to the dependence of ISP concentrations. Strong antibacterial activities were observed at sub-MIC levels of ISP. These combined effects were stronger than those against Staphylococcus aureus described in the first report at sub-MIC levels of ISP. 1/4 MIC-1/8 MIC of ISP showed enhanced activities of β-lactams.
Similarly strong combined effects were observed against both β-lactam-sensitive and -resistant stralns.

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To examine the antimicrobial activity of clarithromycin (CAM) against strains clinically isolated from outpatients in 1994, minimum inhibitory concentrations (MICs) were determined for CAM and the control drugs.
The results were as follows;
1. MIC₅₀ and MIC₉₀ of CAM were similar to those investigated in 1980's against many bacterial species.
2. C AM showed strong antimicrobial activities against β-lactamase producing Moraxella subgenus Branhamella catarrhalis, Bordetella pertussis, Campylobacter jejuni subsp. jejuni and Peptostreptococcus spp.
3. It appears that resistance to MLs including CAM is increasing among Streptococcus pneumomae.

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