With stapylylococcus aureus isolated from various clinical materials in 4 months from Jan. to April 1984, and that isolated from blood cultures in 1 year of 1984 at the Central Clinical Laboratory, Teikyo University Hospital, we investigated resistant pattern to antibiotics and phage type of methicillinresistant staphylococci (MRSA) among them. The results obtained are as follows;
1. Of staphylococci isolated from inpatients, 13.4% were MRSA, which were most frequently isolated from blood culture, tip of IVH catheter and pus.
2. Of staphylococci isolated from outpatients, 17.5% were MRSA, which were most frequently isolated from otorrhea, pus and secretion.
3. Many strains of MRSA were simultaneously resistant to penicillin G (PCG), erythromycin (EM), kanamycin (KM) and gentamicin (GM). Strains having these resistant pattern were detected in 75 of 116 strains (64.7%) from inpatients and 30 of 37 strains (81.1%) from outpatients. The next most frequent pattern was the resistance to PCG, EM, KM and tobramycin (TOB), which was detected in 29 strains (25.0%) from inpatients and 3 strains (8.1%) from outpatients. The other resistant pattern were observed in less than 10% of MRSA.
4. The phage type of MRSA varied according to resistant pattern to antibiotics, with a particular phage type frequently observed in connection with a certain resistant pattern.In strains resistant to PCG, EM, KM and GM, roughly half of the strains fell into group I, while the remaining strains were untypable, group III and mixed groups.In strains resistant to PCG, EM, KM and TOB, on the other hand, about half of the strains fell into group III, and the remainder were untypable and mixed groups.
5. Of S. aureus 25 strains isolated from blood culture, 19 strains (76.0%) were resistant to multiple antibiotics including methicillin, and the phage type closely resembled to that of MRSA from inpatients.
6. From above findings, it was suggested that several strains of MRSA arising from a common source have already spread in our hospital, to cause infections in one after another of the patients depending on the patient condition and antibiotics used.

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The clinical efficacy and safety of GV-523, a newly developed normal human immunoglobulin preparation for intravenous use, were prospectively compared by the cross-over method with those of Venoglobulin-I in patients with severe infections complicating hematological disorders.Both test drugs were administrated at a dose of 100mg/kg/day.
The results were as follows:
1) 0f 76 patients studied, 46 were assessable for cross-over trials.An effective difference appeared between the drugs in 21 of 46 patients, in 12 GV-523 was most effective and in 9 Venoglobulin-I effective;this difference, however, was not statistically singnificant.Thus, the two drugs had essentially similar efficacy.
2) The clinical effectiveness of both drugs was evaluable in 55 cases: the effectiveness of GV-523 was excellent in 9 cases, good in 13, fair in 5, and poor in 28;the comparable groups for Venoglobulin-I were 11, 3, 8, and 33.The efficacy rate was 40.0% in the former and 25.5% in the latter.The difference was not statistically significant.
3) The efficacy of GV-523 on the first and second administration was 16.7% and 50.0%;this difference was statistically significant.The comparable efficacy of Venoglobulin-I was 9.1% and 25.0%; this difference was not statistically significant.
4) No subjective or objective clinical side effects were observed in any patients treated with either drug.
In conclusion, the clinical efficacy and safety of GV-523 were evaluated as similar to those of Venoglobulin-I.Thus, combination therapy with GV-523 and antibiotics was considered to be useful in patients with severe infections complicating hematological disorders.

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A retrospective study was carried out for the detection of hemorrhagic colitis associated with Escherichia coli 0157: H7, using stool specimens which were collected from 464 cases of diarrhea during a 9-month period in 1984 were kept in Cary-Blair medium. E. coli 0157: H7 which produced markedly vero-cytotoxin (VT) neutralized with anti-Shiga toxin was found in specimens from one child with grossly bloody diarrhea.His brother was also suffered from bloody diarrhea, and he developed thehemolytic-uremic syndrome 13 days after onset of illness.In the latter case, the retrospective examination of stool specimens kept in Cary-Blair medium did not reveal the presence of E. coli 0157: H7, but vero-cytotoxic activity was demonstrated in filtrate of his specimens.The presence of VT neutralising activity in patients serum at 21 days of illness was investigated, and was detected neutralising antibody titres of 1: 8 against 4 units of the appropriate cytotoxin preparation.
The results suggest that the incidence of hemorrhagic colitis caused by E. coli 0157: H7 occurs in Japan and that patients with diarrhea should be studied for E. coli O157: H7.MacConkey-sorbitol agar was discussed as an effective differential isolation medium for E. coli O157: H7.

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A seroepidemiological survey on hemagglutination-inhibition (HI) antibody titer to Japanese encephalitis (JE) virus in herds of swine in Tokyo metropolitan area during the past 21 years has disclosed a recent trend to dalay in period of antibody acquisition and decline in peak seropositivity rate.
Untill 1967 where human infections of JE virus were reported in the capital suburban areas, the HI antibody positivity rate of swine in those areas usually rose sharply late in July to early in August and remained thereafter virtually at a 100% level till October.Over the ensuing years, however, the sharp rise of HI antibody titer became delayed 1-2 months as compared to those before 1968 and the peak seropositivity rate lowered to as low as 20-40%.
This paper represents an attempt to numerically analyze the process of spread of an epidemic of JE virus infection with a view to theoretical delineation of the recent changes in mode of JE virus infiltration in herds of swine.
We postulated that it might be possible to proceed with the numerical analysis by a model set up on the following presumption. The incidence of swine that may newly contract JE virus infection in an arbitrary unit length of period (Y_i) can be expressed in terms of product of three factors;the rate of swine which may serve a potential source of infection in a given swine population (Y_i-1), that of susceptible swine in that population {100-(Y₀+Y₁+…+Y_i-1)} and the constant (K) representing the coefficient of swine JE transmission. Thus, we considered the following model for estimation of spread of JE virus infection:
Y_i=Y_i-1 ×{100-(Y₀+Y_i+…+Y_i-1)}× K. The cumulative incidence of swine estimated to newly contract the infection (Y_i) during consecutive unit lenghts of period being defined as “infection rate”. this theoretical value was found closely approximately to seropositivity rate determined for HI antibody to JE virus in swine populations studied.
Analysis of data with this model has revealed (1) that the rate of swine serving as a potential source of JE virus infection at the ontset of an epidemic of JE has diminished with a consequent delay in sharp rising of HI antibody seropositivity rate, and (2) that the recent decline in transmission coefficient relevant to spread of JE epidemics has led to depression of peak seropositivity rate for HI antibody to JE virus. Thus, these changes in epidemiologic features of outbreaks of JE observed in recent years in the Tokyo metropolitan area are explicable from those which have occurred in respect of the two factors, i. e. decreased subpopulation of swine that would serve as the source of infection and depressed coefficient of transmission of the infection.

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We examined about removal of antimicrobials in blood samples.
First, the Antimicrobial Removal Divice (ARD: Marion Laboratories, Inc., Kansas City, Mo.) and two kinds of charcoals (uncoated activated charcoal “yashigaratan” and cellulose coated activated charcoal “biizutan”) were evaluated in vitro with samples of 15 antimicrobials.
In addition, we checked both difference of ifs ability to remove by cell number in samples and adverse effect on organisms.
And the following results were obtained.
1. The ARD revealed much effectiveness in reducing the activity of all 15 antimicrobials, but it seems to suggest that effectiveness of ARD was not enough in the case that antibacterial activity of the drugs after ARD processing is higher than MIC of the organisms or cell number in samples are less.
2. Uncoated activated charcoal wass more effective than ARD on removal of antimicrobials except Aminoglycosides and PPA, but cellulose coated activated charcoal had no effect on all.
3. There was no adverse effect of the ARD on organisms, but cell number in samples decreased after treatment of charcoal especially uncoated activated charcoal.
These results seem to suggest that the ARD was the only system to actually use and improved use of charcoal can be useful in the clinical microbiology laboratory.

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The clinical efficacy and safety of Aztreonam (AZT), a new monobactam antibiotic, was objectively compared with that of Cefoperazone (CPZ) in patients with chronic respiratory tract infections, bacterial pneumonia or lung abscess by gram-negative pathogens in a well controlled study.Each drug was administered by intravenous drip infusion b. i. d.for 14 days at a daily dose of two grams.
The following results were obtained.
1. On the basis of committee judgement, the overall clinical efficacy rate was 71.2%(99/139) in the AZT group and 76.3%(100/131) in the CPZ group with no statistically significant difference between the two drug groups.
2. In the assessment by the physicians in charge, the overall clinical efficacy rate was 74.8%(98/131) in the AZT group and 77.5%(100/129) in the CPZ group with no significant difference between the two treatments. When reviewed for each diagnosis, there was no significant difference between the two drug groups with regard to clinical efficacy rate. For example, the rates were 78.4%(40/51) in the AZT group and 80.4%(37/46) in the CPZ group for those with bacterial pneumonia or lung abscess, and 72.2%(57/79) in the AZT group and 75.9%(60/79) in the CPZ group for those with chronic respiratory tract infections.
3. The bacteriological elimination rate judged by committee was 81.8%(72/88) for the AZT group and 79.2%(61/77) for the CPZ group with no significant difference between the two drug groups. In particular, H. influenzae, P. aeruginosa and K. pneumoniae were eliminated in a slightly higher rate in the AZT group than in the CPZ group, although there was no significant difference between the two treatments.
4. Some side effects were observed in 6 patients out of 162 in the AZT group and 6 out of 148 in the CPZ group, but there was no significant intergroup difference in the incidence of these side effects. Some abnormal laboratory findings were observed in 57 (36.8%) out of 155 patients in the AZT group and 28 (20.3%) out of 138 in the CPZ group, the difference between these two groups being significant (p<0.01). The observed laboratory abnormalities included GOT in 42 cases (27.6%) in the AZT group and 13 cases (9.6%) in the CPZ group, and GPT in 42 cases (27.6%) in the AZT group and 15 cases (11.0%) in the CPZ group. There was a significant difference in the incidence of GOT and GPT (p<0.01, respectively). However, there was no significant difference observed in other laboratory test findings. The GOT or GPT elevations in the AZT group were relatively mild and transient in every case and all the cases followed up thereafter (GOT elevation 25 cases, GPT 26 cases) reverted to pre-administration levels during or one week after completing or suspending the administration.
5. Clinical usefulness judged by the committee was 65.0%(91/140) in the AZT group and 74.8%(98/131) in the CPZ group with no significant difference between the two drug groups. The judgement by the physicians in charge also did not indicate any significant difference.
From all the above results, AZT was considered to be a useful drug for respiratory tract infections.

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We have assessed the clinical efficacy of AT III concentrate in infections complicated by DIC.
The total number of treated patients amounted to 45.11 patients had to be excluded from the efficacy evaluation.
20 out of the 34 cases that could be analyzed had bleeding symptoms and from these in 14 (70%) cases the bleeding resolved.
The clinical improvement rate was 69.7% and the hematological improvement rate was 81.8%.
If the patients were classified according to the presence or absence of a concomitant medication with Heparin or blood preparations, the following clinical, resp. hematological improvement rates were obtained:
For the group of exclusive administration of AT III: 71.4% resp.85.7% and for the group with concomitant medication: 70.0%, resp. 80.0%.
Side-effects or abnormal laboratory findings that could be attributed to AT III treatment were not observed in any of the 45 cases.
From these results, it can be concluded that AT III concentrate is useful for the treatment of DIC induced by infectious disease.

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Antibodies to Japanese encephalitis virus were assayed by the ELISA system using filter paper discs that contained human whole blood. A small quantity of blood was absorbed on a sheet of the blood sampling paper and brought to dryness. Paper discs were prepared by making holes in a blood infiltrated area of paper with a punch. Antibodies were eluted from paper discs which were placed in wells of ELISA plate containing the diluent solution, followed by the ordinary assay procedure after a removal of paper discs. The variation of measurement was minimized by vibrating the plate for 1 minute or at the time of the addition of paper discs and in the middle of the incubation period of 1 hr. Antibody titers were not reduced, when blood-absorbed filter paper was packed in a plastic bag and stored in a freezer. Antibody titers were reduced by 5 and 16% after 10 and 60 days, respectively, of storage in a refrigerator. When the specimens were stored at room temperature, the titers were decreased by 21 and 37% after 10 and 60 days, respectively, of storage.
Reproducibility of the ELISA system performed with paper discs was tested, showing the correlation coefficient of 0.98 between two trials. Furthermore, correlation coefficients were 0.91 to 0.94, when antibody titers were compared between this ELISA system, the ordinary ELISA system, and the hemagglutination inhibition test. Correlation coefficients between the neutralization and other tests were 0.81 to 0.87.

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We trapped wild rodents at a field near River Kiso in Sakahogi-town, Gifu Prefecture, Japan, to examine the possession of Rickettsia tsutsugamushi (Rt) and antibody in wild rodents and the possession of Rt in trombiculid mites parasitized in wild rodents, in November to December 1984.
Fifty percent of rodents trapped in Nobember and 62.5% in December had Rt.Antibody-positivities were 60.0% in Nobember and 62.5% in December, antibody or Rt positivities were 70.0% in Nobember and 75.0% in December.Specificities of antibody were prominent to Karp strain with cross-reactivities to Kato strain.
Rt-positivities were examined in trombiculid mites collected from 3 wild rodents.The positivities in Leptotrombidium fuji and in Gahrliepia saduski were both 0% out of 77 and 196, respectively. Two L. pallidum out of 234 in Exp. 1, and 3 out of 500 in Exp. 2, possessed Rt. The mean Rt-positivity was 0.73%. In the case of Exp. 2, analysis according to Poisson distribution showed that one more mite possessed Rt in the probabiliry of 24.6%. Therefore the mean positive rate was corrected to 0.83% in this case.On the contraly, the hypothesis that L.scutellare possessed Rt was negliglible in the analysis because the porobability was very low (<1%). In the conclusion, L. pallidum possessed Rt in the probability between 0.73 to 0.83%.The strain of Rt isolated from mites were resemble mainly to Karp strain and secondaly to Kato strain in the analysis of antibody.

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Positive Proteus OX2 agglutination in the Weil-Felix (WF) reaction performed as a clinical test for the diagnosis of a febrile exanthematous illness was examined by use of the antigens commercially available from different sources D and K. The sera of patients with similar clinical signs were also tested. The results were as follows. First, the sera agglutinating Proteus OX2 of the source D agglutinated the same antigen of the source K. However, the antigen of the source K had a tendency to show the prozone phenomenon of agglutination. Secondly, all sera tested did not agglutinate Proteus OX19 of the source D, though the OX19 agglutinin was absorbed by the antigen. Two out of three patients'sera agglutinated Proteus OX19 of the source K. Thirdly, all sera did not agglutinate Proteus OXK of either source. These results indicated that the WF test antigens commercially available in our country varied in the agglutinability. It was concluded that Proteus OX2 of the source D and Proteus OX19 of the source K employed were the reliable test antigens. Evaluation of the reliability of positive Proteus OX2 agglutination in the WF test of the first clinical case led to the presumption of a spotted fever group rickettsiosis, a novel illness in Japan.

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The case: 77-year-old male with multiple myeloma, who was admitted to our hospital. On the 6th hospital day, he complained high fever with chillness. By culture, Plesiomonas shigelloides was isolated twice from venous blood and once from fecal specimen.
His septicemic signs were relieved after combination chemotherapy with doxycycline and piperacillin.
Significant elevation of agglutinin titer against the isolated strain was demonstrated in his convalescent sera.
The minimal inhibitory concentration (μg/ml) of antibiotics against the isolate was as follows, ampicillin 6.25, carbenicillin 25, piperacillin 0.78, ticarcillin 12.5, cefazolin 3.13, ceftizoxime 0.05, latamoxef 0.05, gentamicin 1.56, amikacin 12.5 and doxycycline 0.39.

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A three-year-old boy suddenly developed high fever, pain in the extremities and flumminant purpura, and subsequently shock. The diagnosis was Neisseria meningitidis group Y meningitis complicated with disseminated intravascular coagulation (DIC). Intensive therapy with Ceftizoxime (CZX), heparin and steroid was performed immediatly. CZX was very effective with low MIC for this N. meningitidis and with good permiability to the cerebrospinal fluid when 38 mg/kg of this drug was administrated for 15 minutes d. i. 4 to 6 times a day. Heparin was administrated by continuous d. i. of 10 to 14 U/kg/hr;platlet count and FDP concentration were used as guides to count and FDP concentration were used as guides to adequate amount of the drug.To treat DIC, the most important point is the treatment for the primary illness;in this regard, DIC in this case ceased promptly accompanied with improvement of the meningitis.

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During the short period of summer, from the middle of May to July, 1984, there were three cases of an acute febrile disease with the characteristic exanthem successively at Aratono area in Anan city, Tokushima prefecture.The onset was abrupt, with headache and witha sudden shaking rigor and the fever was 39°Cto 40°Cor more. The rash was not tender or didn't itch, and it appeared on extremities, face and trunk, relatively in great numbers on extremities. The erythematous lesions were macular and nonfixed and then became macropapular and hemorrhagic. A tick bite was noticed in one case and in two cases out of three, eschars were observed: the erythematous induration covered by a scab in one case and the ulcerated lesion located in a center of the indurated area in the others.
The generalized lymphadenopathy was not detected, and the liver and spleen were not palpable. Agglutinins against Proteus OX2 with a significant rise were found in the sera of the patients by Weil-Felix test. It was proved by indirect immunoperoxidase reaction that the sera of all cases contained no antibody against any three strain of Rickettsia tsutsugamushi. After the treatment with doxycycline the patients became afebrile promptly and the response was dramatic.
The clinical observations and serologic examinations were led to consider these cases to be the rickettsial infection of spotted fever group, the novel disease in our country. The diagnosis was confirmed by the complement fixation test using group specific rickettsial antigens of spotted fever group.

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