[in Japanese]

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We examined the antibacterial activity of CMX in comparisonwith those of other CEPs, using aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria, 870 strains in total, all isolated from clinical specimens, in 1979 and 1980.
Against Streptococcus, CMX showed superior antibacterial activity than those of CFX, CMZ, CXM and CTM. Against H. influenzae, CMX also showed superior antibacterial activity than those of CFX, CMZ, CXM, CTM and CEZ. ABPC-and PIPC-resistant strains weresensitive to CMX. CTX, CPZ and CZX also showed antibacterial activities equivalent to thatof CMX.
Against enteric bacteria, E. coli, Klebsiella, E. cloacae, Serratia, C. freundii and Proteus, CMX showed superior antibacterial activity than those of CFX, CMZ, CXM, CTM and CEZ. Especially, against E. coli, Klebsiella, P. mirabilis, P. rettgeri and P. inconstans, CMX showed strong antibacterial activity.
As to non-fermentation bacteria, CMX's antibacterial activity was relatively weak except P. putrefaciens, Alcaligenes and Comamonas. However, it was superior than that of CEZ. In comparison with other CEPs, the strength of CMX varied according to the kinds of bacteria.
As to anaerobic bacteria, CMX showed strong antibacterial activity against Peptococcus, Peptostreptococcus, Lactobacillus, Propionibacterium, C. perfringens, Veillonella and Fusobacterium.However, its antibacterial activity against Bacteroides was similar to those of other CEPs.

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In the field of orthopedic surgery, the formerly common hematogenous osteomyelitis is on the decline and severe osteomyelitis accompanying open fractures as well as hard-to-cure osteomyelitis which is accompanied by a reduction in the host's immunological functions due to treatment with antitumor agents are on the increase. Various types of antibiotic-resistant bacteria causing inflammation are also increasing. On this occasion we administered fosfomycin to 8 cases of hard-to-cure osteomyelitis. Due to the nature of osteomyelitis judgment of therapeutic effectiveness is extremely difficult and there is no sure method. We used as our indications the increase or decrease in bacteria thought to be due to the action of antibiotics, improvement in clinical symptoms, and improvement in test results. Based on these original judgment criteria we evaluated the clinical effectiveness. Since for these patients who underwent a surgical procedure it is uncertain whether only antibiotics effected a cure under our evaluation criteria we judged cured cases not as excellent. Thus during this course of treatment there are no cases evaluated as excellent but 4 cases were rated ‘good’ and 4 rated ‘fair’. If it is kept in mind that these were ‘hard-to-cure’ cases than the evaluations of ‘good’ and ‘fair’ must be clinically regarded as quite satisfactory results.
The blood circulation in the bone tissue in comparison with other organs is quite poor. Especially, when an infection has become chronic, it is observed that circulation of blood at the disease focus declines. For this reason, in treating osteomyelitis it is necessary that the antibiotics achieve a high blood concentration and at the same time they must be able to penetrate into the bone tissue. Fosfomycin is not metabolized by the liver or the kidneys and since the burden on both these organs is slight, it can be administered in massive doses. When we studied the results of administering intravenously drip infusion 4 g on the blood dynamics, we achieved a value after 1 hour of 217±161 μg/ml and we found that there was sufficient concentration even in areas with little blood flow. YANAGINUMA et al. during their experiment with fosfomycin on rats found that it was well absorbed by the bone tissue and thus it is thought to be an effective and useful antibiotic for treating osteomyelitis. Many investigators point out that the inflammatory bacteria involved in osteomyelitis undergo a change. These changes accompany the development of antibiotics and increased dosages. Among representative types of problem bacteria, resistant staphylococci and Gram negative bacilli such as Pseudomonas, Proteus, Serratia and Bacteroides are typical of the anaerobic bacteria which cause mixed infections and are becoming problematic. Cases resistant to cephalosporins and penicillins antibiotics have become quite common. The inflammatory bacteria in our cases exhibited similar tendencies but fosfomycin exhibited in these cases a relatively good susceptibility.
Many clinicians point out that it is difficult to completely eradicate this problem not only because of the antibiotics but also because of the problem of poor blood circulation. Especially, in chronic cases it is often necessary to perform curettage of the disease focus and as in case 5 administration only into the blood stream was not sufficient but fosfomycin in a local perfusion fluid was administered to the affected area in order to maintain sufficient concentrations. In the future we are considering not only just using intravenous drip infusions of fosfomycin but we will administer fosfomycin in local perfusion fluids with the purpose of maintaining high local concentrations of fosfomycin.

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Amoxicillin (AMPC), a synthetic penicillin for oral use, was studied in the aspect of in vitro antibacterial efficiencies brought about by different schedules of AMPC-treatment. Using Proteus mirabilis IID-994 and Escherichia coli NIHJ JC-2 as test strains.
The results were obtained as follows.
1. The antibacterial effects of AMPC against P. mirabilis IID-994 and E. coli NIHJ JC-2 were shown to be bactericidal rather than bacteriostatic and the numbers of viable cells were decreased in proportion to the length of exposing time to AMPC.
2. The decrease of viable cells was independent on the drug at which level concentration we tested, namely, it was not much changed by the level of AMPC at least among 1 to 4 times of minimal inhibitory concentration.
3. The length of time retaining growth-inhibitory ability was longer in the case of treating continuously for 4 hours than that of contacting twice for 2 hours at intervals of 6 hours, although the levels of viable cells after 12 hours incubation were almost same in both cases.
4. The level of bactericidal effect and the length of growth-inhibitory time were proportional to the length of exposing time to AMPC.

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Piperacillin, a new injectable synthetic penicillin, was evaluated against biliary tract infections.
1. Two grams of piperacillin was intravenously administered to patients received cholecystectomy. The mean level in gallbladder bile of PIPC was 795.6μg/ml except for 3 cases with obstruction of the cystic duct.The mean gallbladder tissue level was 31.2μg/g. The gallbladder tissue level in the cases with obstruction of the cystic duct was such high levels as 71.3μg/g and 79.5μg/g.
2. The excretion of PIPC into bile was compared with TIPC and APPC using crossover method. When administered 2g of PIPC, the peak biliary levels were 950μg/ml to 2,120μg/mi at 2 hours and 20 minutes to 2 hours and 40 minutes after the administration, and biliary recoveries during 6 hours were 2.84% to 11.6%. The peak levels and biliary recoveries were lower after administration of TIPC 2g. Mn and Zn were excreted enormously together with APPC into human bile.
3. The influence on clinical laboratory findings was negligible. Therefore, PIPC may be expected to show excellent effects on biliary tract infections except rare occurrence of drug eruption.

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Cefamandole (CMD) was intravenously drip infusion administered at daily dose of 400mg/kg to the neonate with purulent meningitis caused by E. coli which was resistant to ABPC.
In clinical application, CMD was evaluated as effective, although 6mg/kg/day of GM given concomitantly.
No adverse effect and abnormal laboratory findings were observed.
This study would support the clinical usefulness of CMD in severe neonatal infection especially like meningitis.

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Laboratory and clinical studies on cefsulodin (CFS), a new antipseudomonal cephalosporin antibiotic, were carried out and the following results were obtained.
1. The MIC of CFS against P. aeruginosa showed the peak of susceptibility at 3.13mcg/ml in the inoculum size of 10⁸cells/ml and at 1.56mcg/ml in the inoculum size of 10⁶cells/ml. It has a higher superiority as compared with gentamicin or piperacillin and gentamicin-resistant strains of P. aeruginosa were sensitive to CFS.
2. CFS was given to 3 patients with acute pneumonia and 5 patients with chronic cystitis which were all due to P. aeruginosa. Clinical effects were good in 2 patients and poor in a patient with acute pneumonia, and those were good in 3 patients and poor in 2 patients with chronic cystitis. Side effects were not recognized at all.

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