Semen specimens from 678 oligozoospermic men who attended our male infertility clinic were checked for the presence of Ureaplasma unalyticum, and 239 out of 678 strains proved positive. The susceptibility of these strains to eight antimicrobial agents was determined by a broth dilution system. The median MIC of each drug was as follows: tetracycline 0.78 μg/ml; doxycycline 0.10μg/ml; minocycline 0.10μg/ml; lincomycin 3.13μg/ml; erythromycin 1.56μg/ml; rokitamycin 0.10μg/ml; enoxacin 12.5μg/ml and ofloxacin 3.13μg/ml. This result confirmed the effectiveness, in vitro, of tetracyclines and rokitamycin against genital U. urealyticum infections.

View full abstract

We determined the effects of several antimicrobial agents, alone or in combination, in vitro against methicillin-resistant Staphylococcus aureus (MRSA). One hundred strains of MRSA examined were clinically isolated from inpatients at seven hospitals in Yamaguchi Prefecture during March to August, 1990. The following MICs were defined as breakpoints of susceptibility for each agent: fosfomycin, ≤25 μg/ml; cefmetazole, ≤12.5 μg/ml; vancomycin, ≤6.25 μg/ml; rainocycline and imipenem, ≤3.13 μg/ml; ofloxacin and netilmicin, ≤1.56 μg/ml; rifampicin, ≤0.78 μg/ml. These values were decided on the basis of attainable concentrations in blood after the recommended dosage of each drug. All MRSA strains tested were susceptive to vancomycin. The susceptibility of MRSA was 97% for rifampicin, 90% for minocycline, and 36-45% for the other five agents. When cefmetazole was combined with 25 μg/ml of fosfomycin, it inhibited 72% of isolates at a concentration of ≤12.5 μg/ml. This two-drug combination was synergistic. Also, minocycline inhibited 95% of isolates at a concentration of ≤ 3.13 μg/ml, when the combination of minocycline+ fosfomycin (6.25 μg/ml) + cefmetazole (3.13 μg/ml) was tested. The excellent activity of the three-drug combination was due to the additive effect. In the combination minocycline with fosfomycin (6.25 or 25 μg/ml), the “skip phenomenon” was observed, namely, the bacterial growth was inhibited at a lower concentration and not inhibited at a higher concentration of minocycline, indicating the necessity of further study on the interaction of these two agents.

View full abstract

We quantitatively determined direct cytolysis of murine polymorphonuclear leukocytes (PMN) by various antibiotics measuring their release of prelabelled ⁵¹ Cr in vitro. The β-lactam antibiotics ampicillin, carbenicillin, piperacillin, ceftizoxime, cefotiam and latamoxef, the aminoglycoside gentamicin, the macrolide erythromycin, the lincomycin clindamycin, and the chloramphenicol chloramphenicol, were found to cause no cytolysis of PMN within the range of their usual blood concentrations. But the cytolytic concentrations of these drugs were 100 to 1, 000 times higher. Moreover, their cytolytic effects appeared suddenly at certain concentrations. In contrast, the cytolytic effects of the tetracycline minocycline, fosfomycin (fosfomycin), peptides (colistin, polymyxin B), and the polyene amphotericin B on PMN appeared gradually in a dose-dependent manner, and their cytolytic concentrations were over 50 times higher than their usual blood concentrations for antibacterial antibiotics and over 10 times higher for the antifungal antibiotic. The cytotoxic mechanisms of the above two groups also seemed to be different. Anti-neoplasmic antibiotics could be divided into two groups by their cytotoxic effects on PMN. The cytolytic effects mitomycin, bleomycin and pepleomycin were found to be low. In contrast, those of daunorubicin, actinomycin D, doxorubicin and aclarubicin were markedly high and especially the 50% cytolytic concentration of DNR on PMN (PMN ₅₀) was close to the usual blood cocentration. The PMN _5O was in good correlation with the LD ₅₀, one of the general toxicity indices. These results suggest that our PMN ₅₀ is a possible index of toxicity for these drugs.

View full abstract

We evaluated the protective effect of sulbactam/ampicillin (SBT/ABPC), ampicillin (ABPC), sulbactam (SBT) and piperacillin (PIPC) against experimental peritonitis in mice caused by intraperitoneal inoculation of Escherichia coli and Bacteroides fragilis.β-Lactamase activity, viable bacterial counts and drug concentrations in ascitic fluid of infected mice were determined in the time course of infection. The results obtained are summarized as follows,
1) The ED₅₀ values of SBT/ABPC and ABPC were 14.0 mg/kg and 23.0 mg/kg, but 50% of mice were not cured by 70 mg/kg administration of SBT or PIPC.
2) Without antimicrobial therapy, the β-lactamase activity of both penicillinase (PCase) and cephalosporinase (CSase) reached a plateau at 3 h after infection. SBT at a dose of 30 mg/kg demonstrated no reduction of the pathogens' viable bacterial counts, but showed a remarkable inhibition of β-lactamase activity, especially against CSase.
3) When each test drug was administered to infected mice, its concentration in ascitic fluid was ten times higher in infected than in normal mice.
4) Drug peak concentrations in ascitic fluid after the second administration of ABPC or PIPC proved to be almost half of the first peak level. On the other hand, in the case of SBT/ABPC, there was little difference in ABPC level after the first and second administrations. We conclude that the protective effect of SBT/ABPC mainly results from the inhibition of β-lactamases in ascitic fluid, and probably these β-lactamases parly cause the “indirect pathogenicity”

View full abstract

We performed a pharmacological study on the penetration of cefpimizole (CPIZ) into cerebrospinal fluid (CSF). The concentrations of CPIZ in serum and CSF were measured simultaneously at intervals from 30 min to 8 h after intravenous administration (drip infusion or one-shot injection) of 2g or 1g CPIZ in 13 neurosurgical patients. When the concentration in serum was more than 113.6 μ g/ml at 30 min, penetration of CPIZ into the CSF was detected in 7 cases in the 2 g CPIZ administration group and in 6 cases belonging to the 2 g drip infusion group. The mean concentrations of CPIZ in CSF were 1.44 μg/ml, 1.81 μg/ml, 3.60 μg/ml, 4.87 μg/ml and 2.63 μg/ml at 30 min and 1, 2, 4, 6 h after intravenous administration, respectively. As these levels of CPIZ in the CSF can directly stimulate neutrophils to produce superoxide anions, we anticipate that the antibacterial activity of CPIZ will be superior to that expected in terms of the minimum inhibitory concentration against the major organisms causing postoperative intracranial infection.

View full abstract

A total of 1, 320 cases who were enrolledin a prospective study of antibiotic prophylaxis for upper digestive, lower digestive or biliary tract surgery were analysed. The first cases of postoperative MRSA infection appeared in 1988. Although the isolation rate of MRSA was high in upper gastrointestinal surgery, there was no relationship with the prophylactic use of second-and third-generation cephems. Since 1988, the isolation rates of MRSA have bees high in other branches of surgery. We suggest, on the basis of our findings, that MRSA infection is mainly spread by hospital infection rather than by increased antibiotic resistance.

View full abstract

We carried out a clinical study of intramuscular imipenem/cilastatin sodium (IPM/CS) in the field of surgery and obtained the following results.
1. The antibacterial activity of IPM was satisfactory against clinical isolates obtained since 1988 from patients with surgical infections except for methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, which showed a tendency toward resistance to IPM.
2. Twelve patients with peritonitis, nine with biliary tract infections and one with a postoperative wound infection were treated with intramuscular IPM/CS, and the drug's clinical efficacy, safety and usefulness were evaluated. Clinical efficacy was excellent in 8 patients, good in 10, fair in 2 and poor in 2, with an overall efficacy rating of 81.8%. No adverse reactions were observed in any patients. Though abnormal laboratory findings were observed in 4 patients, they were mild and not clinically significant.
3. Our results suggest that intramuscular IPM/CS is useful in the treatment of surgical infections.

View full abstract

We investigated 32 infectious episodes of 30 hematologically malignant patients, measuring plasma β-D-glucan for its diagnostic significance andcomparing antifungal therapuetic effect. The value of β-D-glucan was calculated by the difference between Toxicolor (a broad-spectrum endotoxin) and endospecy (a bacteria-specific endotoxin).β-D-glucan was judged as positive when the value was over 10pg/ml.7 of 8 cases in whom fungus was detected were positive for β-D-glucan, and 5 of 24 cases of infection of unknown origin were positive.Miconazole had a good effect in 6 cases out of 8 with detected fungal infection.In 24 fungus-undetected cases, miconazole was effective in 4 of 5 β-D-glucan positive cases, but in only 8 out of 19 which were β-D-glucan negative. Miconazole was more effective when β-D-glucan decreased in value in the course of antifungal therapy, whereas all 3 cases with increased β-D-glucan had poor prognosis.β-D-glucan will be useful in the early diagnosis of fungal infection and as an indicator for antifungal therapy and its efficacy.

View full abstract

The antibacterial activities of 16 antistaphylococcal agents against 351 Staphylococcus aureus strains isolated from 1988-1989 were determined. The MIC distribution of methicillin against these strains divided into three groups: methicillin-susceptible S. aureus (MICs of methicillin, ≤6.25μg/ml), low-methicillin-resistant S.aureus (L-MRSA, MICs of methicillin, 12.5 to 100μg/ml) and high-methicillin-resistant S.aureus (H-MRSA: MICs of methicillin, ≥200μg/ml) The antibacterial activities of glycopeptides, tosufloxacin, arbekacin, and minocycline were superior to those of the other agents against methicillin-resistant S. aureus isolates. The isolation frequency of H-MRSA strains less-susceptible to β-lactams, fluoroquinolones and erythromycin were significantly higher than the corresponding values of L-MRSA strains. But the isolation frequency of strains less-susceptible to gentamicin, arbekacin and minocycline were almost the same for H-MRSA and L MRSA strains.

View full abstract