Antitumor polyoxomolybdates have been recognized in the course of study on the medical utilization of polyoxometalates, inorganic polymers of metal oxide. [NH₃Pr¹]₆ [Mo₇O₂₄] ·3H₂0 (PM-8) was found as a representative of antitumor polyoxomolybdates. The growth suppressions of PM-8 against Co-4, human colon cancer, xenografted under the renal capsule in cd-1 mice were equal or superior to that of 5-FU, MMC, ACNU, ADM and CDDP. Potent antitumor activity of PM-8 was also established against MX-1, human breast cancer, and OAT, human lung cancer, xenografted in athymic nude mice. Polymolybdate is a new type of antitumor substance.

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Antibacterial substances were examined in amniotic fluid samples obtained from 10 uninfected women and 12 women with intraamnionitis between 26 and 38 gestational weeks
1) There was no association between the amniotic phosphate level and amniotic infection.
2) The amniotic transferrin level increased in intraamnionitis.
3) The amniotic IgG level increased in intraamnionitis. Amniotic IgM increased in two cases inan early stage of intraamnionitis. Amniotic IgA had no changes in the infection.
4) The amniotic C₃ level increased in some infected cases, but the amniotic C₄ level did notchange.
These findings suggest that some substances may play a major role in the prevention of infections.

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Rat granuloma pouches were infected with Enterobacter cloacae H-27 possessing an inducible β-lactamase, and then cefmetazole (CMZ), a good inducer of, β-lactamase or cefoperazone (CPZ), a poor one, was administered to the rats. Subsequently, tosufloxacin (TFLX) was administered to the rats in order to reduce the number of the surviving cells in the pouches. At four days postinfection, the pouches were secondarily infected with Escherichia coil TK-353 R, and we studied the influence of the, β-lactamase remaining in the pouches on the antibacterial effect of ceftizoxime (CZX) or cefbuperazone (CBPZ). When CZX was administered to the CMZ-pretreated group, the number of E. coli TK-353 R began to regrow at 4 h after the administration of CZX, and increased significantly in comparison with those in the other CZX-treated groups (CPZ-pretreated and control groups). At this time, the pouch exudate levels of CZX in the CMZ-pretreated group were lower than those in the CPZ-pretreated and the control groups. On the other hand, CBPZ showed bactericidal action till 24 h after the administration and the pouch exudate levels of CBPZ were similar in any groups (CMZ-pretreated, CPZ-pretreated, and control groups). The β-lactamase (cephalosporinase: CEPase) activity detected in pouch exudate was 0.1 unit/ml in the CMZ-pretreated group directly before the pouches were secondarily infected, while the, β-lactamase activity was <0.02 unit/ml in the CPZ-pretreated and the control groups. Therefore, the decline in the exudate levels and the bactericidal effect of CZX in the CMZ-pretreated group seemed to be due to the inactivation of CZX by the CEPase from E. cloacae reraining in the pouches. Further, CBPZ seemed to be uninfluenced by the CEPase from E. cloacae, because CBPZ was more stable against this enzyme than CZX. We suggest, in conclusion, that the inducibly produced, β-lactamase, which leaked from previously infected bacterial cells due to β-lactam-treatment and remained at the infection site long after the disappearance of previously infected β-lactamase-producing bacteria, will influence the effect of β-lactam therapy on the second infection.

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Microbial contamination of used eyedrop preparations collected from outpatients was investigated and the proper use and storage methods to avoid contamination are discussed. At Yamaguchi University Hospital, 214 used eyedrop samples were collected from outpatients. Twelve samples (5.6%) were found to be contaminated at concentrations of 10¹-10⁴ viable organisms per container. The major contaminants were glucose nonfermentative gram-negative bacilli, such an Pseudomonas spp. and Flavobacterium spp., and yeast-like fungi, such as Candida albicans. Contamination was observed in eyedrop preparations containing any of three preservatives (benzalkonium chloride, p-hydroxybenzoate esters, and chlorobutanol). On the other hand, no growth occurred when contaminants of used eyedrop samples were inoculated into the same kinds of eyedrops that had not been used. Microbial contamination of ophthalmic preparations during use could not be avoided, because the amounts of antimicrobial substances are limited by eye irritation. Insufficient selfsterilizing capacity was demonstrated for all three preservatives. However, those preservatives prevented prolification of the contaminants.

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Rokitamycin (RKM) is a new oral macrolide antibiotic developed by Toyo Jozo Co., Ltd. It has superior antibacterial activity to existing 16-membered ring macrolides such as josamycin (JM) and midecamycin (MDM). It also gives characteristically high blood levels. In our study, RKM was administered to 24 children with Campylobacter enteritis. The results obtained are summarized as follows.
1. Blood was no longer present in stools in any of the cases one day after the initiation of RKM administration.
2. Stool textures showed complete improvement in 2 days after the start of RKM administration in 15 of 18 evaluable cases, and in 4 days in all cases.
3. All cases showed good or better clinical response.
4. Bacteriological eradication was obtained in all the cases.
5. The MICs of RKM were determined against 23 isolates of Campylobacter jejuni, and were found to be at or below 0.2μg/ml for all of the isolates. These values were one or two dilutions lower than those of MDM and JM, but one or two dilutions higher than those of erythromycin.
6. No side effects were observed in any of the cases.
From the above results, RKM appears to be a useful agent in the treatment of Campylobacter enteritis.

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In vitro antibacterial activitiy of ciprofloxacin (CPFX), in combination with the β-lactams aztreonam, imipenem, ceftazidime, cefsulodin and piperacillin, against Pseudomonas aeruginosa isolated from patients with LRTIs was investigated by the checker board titration method. The clinical efficacy of monotherapy with CPFX or combination therapy with CPFX and β-lactams for LRTIs was studied in a multicenter trial. In vitro CPFX synergy with β-lactams was demonstrated in 50.0% to 88.5% of the strains tested, and no antagonism was observed. The clinical efficacy rate and the bacteriologic eradication rate for CPFX monotherapy were 90.1% and 82.1%, respectively. CPFX and β-lactam combination therapy was effective in all patients, although P. aeruginosa was isolated from 7 of 8 patients.

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We studied the safety and pharmacokinetics of vancomycin hydrochloride, which was intravenously administered to healthy male volunteers. A single-administration study (SAS) of its 0.5g and 1.0 g doses and a multiple-administration study (MAS) of a 1.0 g dose administered twice a day for 5 days (total, 9 times) were done on two volunteer populations. In terms of subjective and objective signs, physiological and clinical examinations revealed no marked abnormalities or changes, except in two cases of facial flushing and a slight, transient elevation of heart rate when the 1.0 g dose was administered. No marked changes were observed in serum histamine concentration and intestinal bacterial flora. In the SAS (0.5 g and 1.0 g dose), the C_max of average plasma levels was 23.4 and 49.5 μg/ml, respectively. The average elimination half life in β-phase was 4.3 h (0.5 g) and 5.2h (1.0 g). Urinary recovery up to 72 h in the SAS for the 0.5g dose was 90.7% and 90.9% for the 1.0 g dose. In the MAS, plasma levels observed in the first and ninth doses showed no significant difference and remained linear. Twenty-four hours' urinary recovery of this drug, compared to the daily dosage, was slightly under 72% for the first dose but almost 90% after the second dose and overall recovery was about 90%. Renal clearance was 114 ml/min for the initial administration and 121 ml/min for the final administration, which was not a substantial difference. Multiple administration had no influence on excretion from the kidney. The serum protein binding ratio was 34.3±3.6%.

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We compared the safety and efficacy of cefmetazole (CMZ), a second-generation cephalosporin, to those of ceftizoxime (CZX), a third-generation cephalosporin, for prophylaxis in patients undergoing elective upper gastro-intestinal surgery. Eighty-seven patients were randomized for therapy with CMZ 2 gm IV started in the operating room before the surgical procedure and 1 gm 8-hourly for 4 days or CZX 2 gm IV before the surgical procedure and 1 gm 8-hourly for 4 days. Fourty-six patients were given CMZ and 41 patients were given CZX. The groups were comparable in age, sex, type of intervention and diagnosis. Eight patients (17.4%) developed surgery-related infection (including 1 case of wound sepsis and 7 of intra-abdominal abscess) in the CMZ group. Eight patients (19.5%) developed postoperative infections (2 cases of wound sepsis and 6 of intraabdominal abscess) in the CZX group. The rate of postoperative infection was not significantly different between the groups. There were no side effects in either group. In the early postoperative period, abnormal liver function was noted in 9 patients (4 in the CMZ group and 5 in the CZX group), The rate of abnormal laboratory findings was not significantly different between the groups.

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