Methicillin-resistant Staphylococcus aureus (MRSA) is frequently isolated from skin lesions, such as decubitus ulcers and burns. There is the possibility that MRSA spreads widely throughout a hospital via such lesions. However, local treatment with most antibiotics and antiseptics does not eradicate MRSA from infected wounds. We studied the bactericidal effects of 4 different dye series, including 6 dye preparations, against 3 different bacterial species. The dye preparations of the triphenylmethane series were more effective against S. aureus than those of the other series. Gentian violet, a member of the triphenylmethane series, possessed a significant bactericidal effect on MRSA isolated from clinical specimens. The minimum bactericidal concentration (MBC) of gentian violet on MRSA was between 0.0025% and 0.08%. The minimum inhibitory concentration (MIC) of gentian violet on MRSA was between 0.00032% and 0.00064%, and the MIC was uninfluenced by the addition of whole human serum (5 %) to the medium. Inhibitory activity was not destroyed even by incubating gentian violet for 54 h at 37 °C in medium containing serum (5%). This suggests that gentian violet may be a useful drug in the treatment of skin lesions infected with MRSA.

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A reproducible in vitro method for the determination of IC₅₀ values of antifungals for filamentous fungi is described. A paper disk in which conidium of the test fungi was immersed was placed on a susceptibility agar plate and then incubated under appropriate conditions. The fungal conidium developed radial mycelium around the disk. Fungal growth was monitored by a growth zone radius around the disk. The effects of inoculum size and temperature on the mycelium growth of Aspergillus fumigatus were examined using four media. During the test period, the daily radius extention was linear and was little affected by the inoculum size. The inhibiotory effects of four antifungals, amphotericin B, miconazole, fluconazole and flucytosine, against Aspergillus fumigatus were examined. Dose-response regression of the radius was observed, and the IC₅₀ value was obtained. The inhibitory effect of fluconazole could be detected sensitively even at 10 μg/ml or less. These data were closer to those obtained by the turbidmetric method than those obtained by the dry weight method.

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We investigated the synergistic effects of an aminoglycoside and various antimicrobials againstPseudomonas aeruginosa ATCC 27853 from the stand point of antimicrobial actions on the aminoglycoside- induced postantibiotic effect phase bacteria. Bacterial growth at 1/16 to 1/2 of the MIC of piperacillin, ampicillin, ceftazidime, imipenem, ciprofloxacin, and rifampicin wan examined after removal of 8 X MIC gentamicin exposure for 0.5 hour (postantibiotic effect phase: PAE phase) and in the absence of previous exposure to antimicrobials (non-PAE phase).β-lactams at sub-MICs suppressed the growth All of the PAE-phase bacteria longer than non-PAE phase bacteria, and piperacillin at sub-MICs enhanced bactericidal activity during the PAE phase. We termed these effects the “postantibiotic sub-MIC effect” and defined the enhancement of growth suppression at sub-MICs during the PAE phase as “postantibiotic sub-MIC enhancement: PASE”, Rifampicin and ciprofloxacin did not display any postantibiotic sub-MIC effects. These suggest that the postantibiotic sub-MIC effects influenced the synergy of aminoglycosides with β-lactams.

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Some antimicrobial drugs, such as the new quinolones and macrolides, reportedly become highly concentrated in the neutrophils. The effects of ofloxacin (OFLX) and roxithromycin (RXM) against Staphylococcus aureus phagocytosed by human neutrophils were examined in this experiment. An S. aureus strain isolated from an impetigo and ATCC 29213 strain were studied. Neutrophils separated from human peripheral blood were incubated with S. aureus cells at 37°C in the presence of human serum. Non-phagocytosed extracellular bacteria were killed using lysostaphin, and the neutrophils with phagocytosed S. aureus were obtained. These were then incubated with 0, 0.2, 0.25, 1, 2, 4, 8, 16, or 32 mg/l of OFLX, or either 2 or 16 mg/l of RXM for 6 h. The neutrophils were then sonicated and the viable bacteria were counted by culturing on plate agar. After incubating with low concentrations of OFLX for 6 h, the viable bacterial counts were not significantly different from those of the control group, which had been incubated for 6 h without antimicrobial agents. A slight decrease in the number of viable bacteria was observed with higher concentrations of OFLX. RXM showed a little effect against S. aureus in the neutrophils. The results indicate that S. aureus in neutrophils can survive in the presence of OFLX and RXM.

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A comparative study has been conducted to determine the clinical efficacy, safety and utility of a new injectable cephem antibiotic cefozopran (CZOP) versus a control drug, ceftazidime (CAZ), for bacterial pneumonia. CZOP and CAZ were administered, in principle, by intravenous drip infusion at a dose of 1.0 g (potency), twice daily for 14 days, and the following results were obtained:
1. The efficacy rates for the total number of cases evaluated were 90.5%(95/105) in the CZOP group and 96.0%(97/101) in the CAZ group.
2. Bacteriological eradication rates were 94.3%(50/53) in the CZOP group and 97.6%(41/42) in the CAZ group.
3. Adverse reaction rates were 6.2%(7/113) in the CZOP group and 3.4%(4/117) in the CAZ group. Abnormal laboratory finding rates were 27.0%(30/111) in the CZOP group and 31.6%(37/117) in the CAZ group.
4. Usefulness rates were 87.6%(92/105) in the CZOP group and 91.2%(93/102) in the CAZ group.
These results indicate that CZOP is useful for the treatment of bacterial pneumonia.

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The clinical efficacy, safety and utility of cefozopran (CZOP), a new cephem antibiotic, were evaluated in chronic respiratory infections in a comparative study versus ceftazidime (CAZ), Each drug was administered by intravenous drip infusion at a dose of 1.0 g (potency), twice daily for 14 days, and the forllowing results were obtained:
1. A total of 264 patients were enrolled in this study. Efficacy rates (“good” or better responses) were 91.0%(101/111) in the CZOP group and 88.3%(106/120) in the CAZ group, with no significant difference between the two groups.
2. Bacteriologically, eradication rates were 91.5%(65/71) in the CZOP group and 85.3%(64/75) in the CAZ group, with no significant difference between the two groups.
3. Adverse reactions occurred in 8 of the 122 patients in the CZOP group and in 3 of the 126 patients in the CAZ group. There was no significant difference between the two groups. The incidence of abnormal laboratory findings was 27.7%(33/119) in the CZOP group and 19.8%(25/126) in the CAZ group with no significant difference between the two groups.
4. The usefulness rates (“useful” or better evaluations) were 87.6%(99/113) in the CZOP group and 86.0%(104/121) in the CAZ group, with no significant difference between the two groups.
No significant differences were observed between the two groups with respect to any of the above parameters. These results indicate that CZOP is useful for the treatment of chronic respiratory tract infections.

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Clinical studies of the effectiveness sultamicillin fine granules (SBTPC FG) on acute suppurative otitis media in children were performed.
1. SBTPC FG was administered to 127 children with acute suppurative otitis media and its clinical efficacy was 97.6%. This ratio was similar to the Expected Efficacy Index (EEI) of sultamicillin.
2. Clinical efficacy for the 167 strains of bacteria isolated was 98.8%.
3. Major pathogens were Streptococcus pneumoniae and Haemophilus influenzae.
4.24% of the S. pneumoniae strains isolated were PCG insensitive S. pneumoniae (PISP) and were the primary infections agent (11% of all patients).
5. 52 (31.1%) of the 167 strains isolated from middle ear discharge and 93 (46.0%) of the 202 strains isolated from nasopharyngeal swabs were β-lactamase producers.
6. Side effects occurred in 25 of the 128 patients assessed, an incidence of 19.5%. Diarrhea developed in 23 patients (18.8%). The incidence of diarrhea was higher in those under three years of age.
7. SBTPC FG was concluded to be very effective for the treatment of acute suppurative otitis media in children.

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The efficacy of fluconazole in treating deep mycosis was evaluated in 18 episodes of fungal infections that developed in 14 patients with hematological malignancies. The breakdown of the episodes was as follows: two episodes (one, initial; the other, relapsed) of hepatosplenic abscess that developed in one patient with Candida albicans sepsis; one episode of multiple microabscess of the liver that was probably of fungal origin; and two episodes of pneumonia and 13 febrile episodes that were unresolved with ordinary broad-spectrum antibiotics. Determination of plasma (1→3)-β-D-glucan was used as an aid for diagnosing mycosis. The concentration was calculated from the difference between the results of Toxicolor (Seikagaku Corporation, Tokyo), which is sensitive to endotoxin and (1→3)-β-D-glucan, and Endospecy (Seikagaku Corporation), which is sensitive only to endotoxin. CAND-TEC (Ramco Laboratories, Inc.) was also used in several patients. The efficacy rate of intravenous fluconazole was 61.1%(11/18). Of 6 episodes with high plasma (1→3)-β-D-glucan concentration (≥10pg/ml), fluconazole was effective in 5 (83.3%), while of 12 episodes with low plasma (→3)-, β-D-glucan concentration (<10 pg/ml), it was effective in only 6 (50.0%). Granulocyte-colony stimulating factor was also administered in one patient with a high plasma (1→ 3)-β-D-glucan concentration and 4 with a low plasma (1→3)-β-D-glucan concentration. The former and 2 of the latter responded to fluconazole (3 of 5, 60.0%). No side effects of fluconazole were seen in this study. Determination of the plasma (1→3)-β-D-glucan concentration is a useful guide for the early diagnosis of deep mycosis. We conclude that fluconazole is an effective drug in patients with deep mycosis complicating hematological malignancies.

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We evaluated the efficacy of combining aztreonam with clindamycin or piperacillin in severe infections complicating hematologic disorders. Ninety-seven infectious episodes were treated, : 57 underwent aztreonam/clindamycin therapy and 40 aztreonam/piperacillin therapy. In the aztreonam/clindamycin group, complicating infections consisted of suspected sepsis in 41, sepsis in 3, pneumonia in 11, urinary tract infection in one, and perianal abscess in one case, while the aztreonam/piperacillin group included suspected sepsis in 29, sepsis in 5, pneumonia in 4, tonsillitis in one, and subcutaneous abscess in one case. The clinical efficacy of aztreonam/clindamycin therapy was 52.6%(59% in suspected sepsis, 33% in sepsis, 46% in pneumonia), and in the aztreonam/piperacillin therapy group it was 60.0%(65% in suspected sepsis, 20% in sepsis, 75% in pneumonia). No statistically significant difference was found between the two groups. The number of organisms detected was too small to draw a conclusion, but neither of these two therapies were satisfactory for methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa infections. During the neutropenic period (neutrophil count less than 500/μl), the efficacy of aztreonam/clindamycin and aztreonam/piperacillin therapy was 48%(n=27) and 41%(n=17), respectively. With neutrophil counts severely depressed under 100/μl, atreonam/clindamycin therapy showed better efficacy (32%) than aztreonam/piperacillin therapy (10%). Thus, both aztreonam/clindamycin and aztreonam/piperacillin therapy appear to be useful as empirical therapy for infections associated with hematologic disorders, and aztreonam/clindamycin proved to be more potent against the infections during the neutropenic period.

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