We determined the susceptibility to antibiotics, producibility of penicillinase and coagulase typing of 75 strains of Staphylococcus aureus isolated during 1987 to 1988. Among the 75 strains, 58 were methicillin-resistant Staphylococcus aureus (MRSA) and 17 were methicillin-sensitive Staphylococcus aureus (MSSA). The effective concentration of antiseptics or disinfectants commonly used in hospitals against these strains was evaluated.
The minimum inhibitory concentrations (MICs) of methicillin (DMPPC) to MRSA were influenced by incubation temperature. The ratios of the resistant strains to which the MICs of DMPPC and cefazolin were more than 100 μg/ml at 37°C were 72% and 76%, respectively. The distribution of coagulase type of the MRSA was similar to recent investigations; the percentages of coagulase type II and IV strains were 64% and 9%.
No relationship between the lethal activity of benzalkonium chloride, chlorhexidine gluconate, povidone-iodine, glutaraldehyde and ethanol to the strains used and the susceptibility to DMPPC or coagulase type was observed. Staphylococcus aureus, even MRSA, can be killed by the antiseptics and the disinfectants mentioned above when they are used properly. Benzalkonium chloride, in combination with 0.01% sodium carbonate or 20% ethanol, showed synergy for all strains used; the lethal concentration of benzalkonium chloride, at a contact time of 30 sec, was less than 50μg/ml or 500μg/ml, respectively. Hence these combinations were effective for disinfection or sterilization to prevent nosocomial in ection by MRSA.

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One hundred and one clinically isolated strains of Pseudomonas aeruginosa obtained in six medical institutions were studied for susceptibility to norfloxacin, ciprofloxacin, cefotaxime, cefuzonam, ceftazidime, cefsulodin, imipenem and gentamicin. Most of the urine isolates were multiply-resistant.
Calculated from the MIC₅₀ and MIC₉₀ of the antimicrobial agents tested against the clinical isolates, the isolation frequency of ceftazidime, cefsulodin, norfloxacin, ciprofloxacin and gentamicin resistant strains was 21.8% 31.7% 19.8% 40% and 11.9%, respectively. While the activity of cefuzonam and cefotaxime against P.aeruginosa was weak, we found no imipenem resistance among the 101 strains of P.aeruginosa.

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The in vitro activity of imipenem in combination with fosfomycin against 17 clinical isolates of methicillin-resistant Staphylococcus aureus from hospitalized patients was investigated by checkerboard and time-kill studies. Of the 17 strains tested, checkerboard studies revealed synergy in 14 (82.3%) and indifference in 3 (17.6%): the time-kill studies also revealed synergy in 14 of 14 strains at both 24 and 48h. The combination of imipenem and fosfomycin may be useful for methicillin-resistant Staphylococcus aureus infections.

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We examined clinically the penetration of cefmetazole (CMZ) into wound exudate after Miles' operation. CMZ was administered to 6 patients, twice a day, in two different ways:(a) single-dose injection of 2 g intravenously (2 g i. v.) and (b) drip infusion of 2 g for 60 min (2 g d. i.). A drainage tube was inserted into the pelvic dead space and continuous suction was applied (-15cm H₂0). Wound exudate was collected daily, and every 30 or 60 min on the first post-operative day. The concentration of the drug was measured by thin layer cup method.
The volume of wound exudate and the concentration of hemoglobin in exudate on the day of operation were 305 ml and 3.40 g/dl, and decreased significantly after the first post-operative day. On the other hand, the concentration of albumin and CMZ in wound exudate showed little change in the five days after operation.
The daily concentration of CMZ in wound exudate was 12.7-15.3 μg/ml (average 14.0μg/ml). The maximum concentration and the area under the curve of CMZ in wound exudate were 23.0-54.5 μg/ml (average 33.5 μg/ml) and 112-246 μg·h/ml (average 168, μgh/ml).
The results of 2 g i. v. and 2 g d. i. were similar to each other.
The time-concentration curve of CMZ in wound exudate showed gentle change. About 3 h was needed to reach the peak. The peak time (during which the concentration of the drug is higher than half the peak level) of CMZ in wound exudate was 4.95 h. The level of CMZ in wound exudate remained higher than 12.5 μg/ml for 6.03 h, 6.25, μg/ml for 9.07 h and 3.13, μg/ml for 10.8 h.
These results were equal to those of our previous report in which penetration of CMZ into wound exudate after radical mastectomy was studied.

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We evaluated a combination therapy of aztreonam (AZT) and piperacillin (PIPC) in 41 febrileepisodes of 30 cases with malignant hematological diseases. The overall efficacy rate was 63.4% and in severe immuno-compromised cases with granulocyte counts less than 100/μl before and after administration it was 57.1%. The efficacy rate in cases with a serum Ig G level less than 900 mg/dl was 53.3%.
In sensitivity distribution of clinical isolates, AZT was active against Gram-negative bacteria, including Pseudomonas aeruginosa.
No significant side effects were observed, and clinical synergistic effect of AZT and PIPC combination therapy was expected.

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We studied the combined effect of tetracycline (Tc) and polymyxin B (PLB) against the mycelial growth of Cochliobolus miyabeanus, an Ascomycetes sp., and obtained the following results.
(1) The concentration of Tc and PLB required to inhibit 50% of mycelial growth (ED₅₀) was 140 μg/ml and 7.5 μg/ml.
(2) Compared with the addition of either Tc or PLB, simultaneous addition of both drugs showed 3-8 times stronger inhibition.(17.5 μg/ml Tc and 1.0 μg/ml PLB).
(3) The incorporation of ¹⁴C-Tc into cells increased about three-fold when Tc and PLB were added, compared to Tc alone, suggesting that PLB damages the cytoplasmic membrane.
(4) The protein content of growing mycelia was examined and was found to be lowest in the presence of both PLB and Tc, namely, about one-fourth of the control, while it was only about half of the control when either Tc or PLB was added.
These results suggest that the inhibition of mycelial growth is caused by the inhibition of protein synthesis by Tc in cells after PLB-induced damage to the cytoplasmic membrane.

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Since drugs for the treatment of AIDS are administered over long periods, and since it usually takes a considerable time before new compounds are approved by the health authorities, we screened for anti-HIV activity 58 already commercially avail able drugs for long-term administration without major side effects. Lorazepam, calcium hopantenate, prochlorperazine maleate, amantadine hydrochloride, perphenazine and nitrazepam were found to exhibit anti-HIV activity in MT-4 cells. But only perphenazine and nitrazepam did so without cytotoxicity. In peripheral blood mononuclear cells, perphenazine exhibited only weak anti-HIV activity, while nitrazepam showed none. These results stress the importance of selection of in vitro screening system.

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We tested the antiviral action of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (brovavir) on herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV) and human cytomegalovirus by a plaque reduction method on human embryo lung cells. Acyclovir, bromoviny1-2'-deoxyuridine, idoxuridine and vidarabine (are A) were used as control drugs. Brovavir exhibited extremely marked antiviral activity against all five strains of VZV and significant activity against all seven strains of HSV-1. Average ED₅₀ values of brovavir for VZV and HSV-1 were 0.4 and 22 ng/ml, respectively. Brovavir was most potent against VZV and HSV-1 of the antiviral drugs tested. Based on the ED₅₀ value, brovavir was over 2, 000 times more active than acyclovir, and about 4, 000 times more active than vidarabine against VZV. On the other hand, brovavir showed marginal or no effect on HSV-2 plaque formation and little effect on human cytomegalovirus. We consider brovavir a potential candidate for clinical application as a novel antiherpes drug in the treatment of HSV-1 and VZV infections, particularly herpes zoster.

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