We examined in vitro the synergistic effect of fosfomycin (FOM) and other antibiotics against Pseudomonas aeruginosa under various conditions. The results were as follows.
1) In combination with FOM and other antibiotics, the bactericidal activities against P. aeruginosa pretreated with sub MIC of FOM were greater than those of non-pretreated bacteria, and these synegistic effects increased with increasing concentrations of sub-MIC of FOM.
2) In FOM and other antibiotic combinations, good synergism was found when an antibiotic was added for less than 1 hours after the removal of FOM for the pretreatment of cells. No apparent synergism was observed when the antibiotic was added for more than 1 hour later after FOM was removed.
3) We did not observe a correlation between these synergistic bactericidal effects and the antipseudomonal susceptibilities of each antibiotic.
4) In the test strains that revealed synergistic effects the cell surface of P. aeruginosa became more hydrophobic than without FOM treatment.
5) The combination of FOM and ofloxacin (OFLX) induced lysis at higher frequencies than that either FOM or OFLX alone according to morphorogical observation by scanning electron microscope.

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Five hundred and two patients sheduled for transurethral resection of the prostate were treated with either a single dose or 6 doses of β-lactam antibiotic for 4 postoperative days. Among them, 193 patients had preoperative bacteriuria. The incidences of both postoperative fever and bacteriuria were less in the group given 6 doses, but the differences were not statistically significant. The comparison with pre-operative prophylaxis also failed to show an advantage over postoperative administration.

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A double-blind two-dose comparative clinical study of azithromycin (AZM), a new oral antibiotic, in the treatment of pneumonia was conducted to determine the optimal clinical dose. AZM at a dose of 250mg (Group L) or 500mg (Group H), was administered once daily postprandially for three days. The following results were obtained:
1. Clinical efficacy:
The efficacy rates were 95.8%, 23 of 24 evaluable cases, and 96.4%, 27 of 28 evaluable cases, for Group L and Group H, respectively. The proportion of cases rated as “Excellent” in the efficacy assessment was 25% of the Group L and 46.4% of the Group H population. Though the difference is not statistically significant, the proportion of cases evaluated as “Excellent” for Group H was approximately twice as high as that for Group L.
2. Bacteriological efficacy:
The eradication rate for Group L was 92.3%, 12 of 13 cases, while that for Group H was 85.7%, 6 of 7 cases.
3. Adverse reactions:
Two of 29 patients, 6.9% of Group L, experienced adverse reactions. However, the symptoms were allergic and of a minor or moderate degree. None of the subjects in Group H experienced adverse reactions.
4. Abnormal changes in clinical laboratory data:
Ten of 29, 34.5%, Group L subjects had abnormal changes in clinical laboratory findings, whereas 3.2%, one of 31, of Group H subjects showed an abnormality. However, these abnormalities were all mild.
5. Clinical usefulness:
The usefulness rates were 91.7%, 22 of 24 Group L cases, and 96. 4%, 27 of 28, Group H cases. While the rating of “Very useful” was given to 12.5% of the Group L cases (3 of 24), the same rating was given to 42.9% of the Group H cases (12 of 28). The proportion with the rating “Very useful” was higher, with a statistical significance of p=0.020, for Groups H and L.
Group H had a higher proportion of cases with the rating of “Excellent” for efficacy, though the ratio was not statistically significant as compared with Group L. Furthermore, no dose-dependent occurrence of adverse reactions or laboratory abnormalities was found. Therefore, it was concluded that a daily dose of AZM, at a level of 500 mg/day, is the optimal clinical dose for treatment of pneumonia.

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The efficacy, safety and usefulness of a newly developed oral macrolide antibiotic, azithromycin (AZM), for treatment of pneumonia were investigated using a randomized double blind trial with clarithromycin (CAM) as the control drug. AZM was administered at a dose of 500mg (titer) once a day for 3 days, and CAM was administered at a dose of 200 mg (titer) twice a day for 14 days. The following results were obtained:
1. The efficacy rate (proportion of patients in whom clinical efficacy was excellent or good) was determined in a total of 122 patients in whom clinical efficacy could be analyzed, out of a total of 163 patients to whom the drug had been administered. The rate was 98. 3%(58/59) in the AZM group, and 90.5%(57/63) in the CAM group. There was no significant difference between the two groups, and the clinical equivalency of AZM to CAM was demonstrated (Δ=10%, p<0.001).
2. The elimination rate of isolated bacteria was 86.7%(13/15) in the AZM group, and 88.2%(15/17) in the CAM group (no significant difference).
3. The incidences of adverse reactions were 4.1%(3/74), in the AZM group, and 6.7%(5/75), in the CAM group (no significant difference).
4. The incidences of abnormal changes in clinical laboratory test values were 20.8%(15/72). in the AZM group, and 21.4%(15/70), in the CAM group (no significant difference).
5. The rate of safety (proportion of patients in whom the drug was not problematic) was determined in 144 patients in whom the degree of general safety could be analyzed. The rate was 77.8%(56/72) in the AZM group, and 73.6%(53/72) in the CAM group (no significant difference).
6. The rate of usefulness (proportion of patients in whom the drug was extremely useful or useful) was determined in 121 patients in whom usefulness could be analyzed. The rate was 94.9%(56/59) in the AZM group, and 87.1%(54/62) in the CAM group (no significant difference).
These results suggest that AZM is a very useful drug, comparable to CAM, for the treatment of pneumonia.

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The efficacy, safety and usefulness of a newly developed oral macrolide antibiotic, azithromycin (AZM). for treatment of chronic respiratory infection were investigated using a randomized double blind trial with clarithromycin (CAM) as the control drug. AZM wasa dministered at a dose of 500mg (titer) once a day for 3 days, and CAM was administered at a dose of 200mg (titer) twice a day for 14days. The following results were obtained:
1. The efficacy rate (proportion of patients in whom the clinical efficacy was excellent or good) was determined in a total of 144 patients in whom clinical efficacy could be analyzed, out of a total of 171 patients to whom the drug had been administered. The rate was 94.5%(69/73) in the AZM group, and 83.1%(59/71) in the CAM group. There was no significant difference between the two groups, and the clinical equivalency of AZM to CAM was demonstrated (Δ=10%, p<0.001).
2. The elimination rate of isolated bacteria was 75.8%(25/33) in the AZM group, and 68.2%(15/22) in the CAM group (no significant difference).
3. The incidences of adverse reactions were 7.6%(6/79), in the AZM group, and 5.1%(4/78), in the CAM group (no significant difference).
4. The incidences of abnormal changes in clinical laboratory test values were 13.5%(10/74), in the AZM group, and 9.3%(7/75), in the CAM group (no significant difference).
5. The rate of safety (proportion of patients in whom the drug was not problematic) was determined in 149 patients in whom the degree of general safety could be analyzed. The rate was79.7%(59/74) in the AZM group, and 86.7%(65/75) in the CAM group (no significant difference).
6. The rate of usefulness (proportion of patients in whom the drug was very useful or useful) was determined in 138 patients in whom the degree of usefulness could be analyzed. The rate was 92.9%(65/70), in the AZM group, and 79.4%(54/68), in the CAM group (no significant difference).
These results suggest that AZM is very useful for chronic respiratory infection and iscomparable to CAM.

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