The Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) was formed in 1999 in response to international concerns about the impact of antimicrobial resistance on public health. The aim of the present investigation was to provide insight into the occurrence of antimicrobial resistance among bacterial strains isolated from cattle, swine and poultry on farms across Japan. In this paper, we summarize a nationwide investigation (1999-2003) on antimicrobial susceptibility of the targeted bacterial species for the JVARM, namely Salmonella, Campylobacter, Enterococcus and Escherichia coli, isolated from the feces of healthy domestic animals. Minimum inhibitory concentrations (MICs) of 10-18 antimicrobial agents including the major generic groups were determined using an agar dilution method according to the international NCCLS guideline in principle.
The outline of present results is as follows (1)A total of 307 Salmonella, 3, 225 Escherichia coli, 2, 822 Enterococcus and 1, 122 Campylobacter were isolated from healthy domestic animals and examined for antimicrobial susceptibility.(2)The isolates of all targeted bacterial species represent high rates of antimicrobial resistance to both oxytetracycline (OTC) and dihydrostreptomycin (DSM).(3)Among the isolates of Campylobacter and E. coli, the frequency of isolation of resistance to fluoroquinolones ranged from 14 to 24% and 2 to 3%, respectively.(4)Resistance to fluoroquinolones was not observed among the isolates of Salmonella or Enterococcus.
Continious investigation at the nation level of antimicrobial resistance among the isolates from healthy domestic animals remains a high priority for the JVARM program. Furthermore, appropriate and prudent use of antimicrobials for diseased animals should be considered essential.

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Deep-seated trichosporonosis is a lethal opportunistic infection occasionally found in immunocompromised patients, particularly those who are neutropenic due to cytotoxic therapy for hematological malignancies. Trichosporon asahii is considered the principal etiologic agent of non-Candida fungemia and disseminated trichosporonosis in Japan. This infection may disseminate to multiple organs and difficult to diagnosis and treat. Because clinical findings and courses of trichosporonosis are similar to disseminated candidasis, it is impossible to distinguish these infections without fungal isolation. Monotherapy of amphotericin B is thought to be unsuccessful for this infection, and new antifungal agents echinocandins are also not active against Trichosporon species. Some clinical reports and animal models suggest that triazoles and combination therapies are most effective drugs against trichosporonosis. Recently, T. asahii isolates with reduced susceptibility in vitro to multi-antifungal agents are reported. T. asahii is the allergen of summer-type hypersensitivity pneumonitis and sometimes isolated from the houses environments, but it is not clear that the environmental strains directly infect to human. There is no clinical evidence that Trichosporon is the common outbreak pathogen in the hospital. However, it is necessary for a clinician to pay enough care as the lethal infections in immunocompromised patients.

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After official acceptance of eradication therapy for Helicobacter pylori infected peptic ulcer disease in 2000, this treatment has been generalized as ulcer therapy in Japan. In 2003 the consensus statement of the Japanese Society for Helicobacter Research (JSHR) for Helicobacter pylori infection was presented. According this statement MALT lymphoma was recommended to treat H. pylori infection because of the efficacy of its out come. Atrophic gastritis was also advised to treat H. pylori infection for the purpose of preventing gastric cancer development. The extra alimentary disease such as idiopathic thrombocytopenic purpura wasstill under evaluation.
In diagnostic method the importance of drug susceptibility test is rising because of the increase of drug resistant H. pylori strain in Japan. The false positive case of urea breath test, the accuracy of new Japaneseoriginal serology tests and the stool antigen test are also under investigation.
The standard regimen of H. pylori eradication therapy in Japan is proton pomp inhibitor (PPI) + amoxicilin (AMPC) + clarithromycin (CAM). The problem of this regimen is the decrease of eradication rate. The reason of this trend might be increase of CAM resistant strain. JSHR recommended a rescue regimen as PPI + AMPC + metronidazole for the patient whose first eradication therapy was unsuccessful result. The eradication of this second line regimen was reported as about 90%.

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Objective: Immunization for varicella is not currently included in routine immunizations in Japan. Thisstudy was conducted to assess test its cost-effectiveness when it becomes a routine.
Methods: We surveyed and collected information for the year beginning 15th June 2004 in one area.Almost all 11 pediatric clinics or hospitals in the area cooperated in this survey. There was a questionnaireform for families and for doctors. Absent days from routine tasks, i.e., job, housekeeping or study, for familynursing and others were asked on family form. Medical costs and other costs were asked on doctor form.Neither form included the patient's name or name of the medical institution. Doctors explained this surveyto patients' family on their first visiting day and asked to cooperate. If they refused the doctor form was also discarded. Since family form was written after recovery and mailed, cooperation in this survey was voluntary.Opportunity cost for family nursing is estimated as opportunity cost based on the 2002 Basic Surveillance of Wage Structure. The burden of sequel cases was estimated assuming six million yen per Quality-adjusted Life Years (QALY). Total number of patients was estimated to be 0.84 million, which includes unvaccinated people in a birth cohort. We adopted incremental benefit cost ratios form societal viewpointas a measure.
Results: We collected 402 data from the doctor form and 265 from the family form. Total disease burden in all of Japan is estimated to be 52.2 billion yen, but opportunity cost accounted for 80%. The incremental benefit cost rations averaged more than 4 when vaccination cost is assumed to be five to twelve thousand yen. The lower limit of the confidence intervals is about 1.5.
Discussion and Conclusion: The disease burden of varicella was greater than measles in 2000, when there were measles 0.2 million patients. The incremental benefit cost ratio showed that there will almost surely be an additional benefit due to routine immunization is greater than the additional cost. Therefore, we found strong evidence for routine immunization for varicella.

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We studied distribution of Vibrio vulnificus in sea water, sediment, and shellfish along the coast and contamination of retail fish and shellfish with V vulnificus in Shimane Prefecture, Japan between 2001 and 2004. V. vulnificus was isolated from 77 (68.1%) of 113 sea water samples with≤10⁵MPN/L, 88 (70.4%) of 125 sediment samples with≤10⁷MPN/100g, 8 (17.2%) of 46 fish samples with≤10⁶CFU/10g and 68 (43.8%) of 156 shellfish samples with≤10⁶ MPN/10g. This organism was isolated from 64 (70.3%) of 91 shellfish samples, (short-necked clam, clam, hen clam, oyster and scallop, etc) with≤10⁶MPN/10g and from 7 (43.7%) of 16 prawn samples with<10² MPN/10g. These isolates were divided into 11 serotypes with the most prevalent serotype being O4 followed by O1, O3 and O6. Serotype O12 strain (isolated from a patient from interior Shimane Prefecture in August 2004) was isolated from sea water and a sediment sample and from 3 samples of short-necked clam produced in Kumamoto Prefecture. These findings suggested potential transmission of V. vulnificus through the water environment along the coast of the Japan Sea, that V. vulnificus is easily spread by coldtransport of fresh marine product, and that the occurrence of V. vulnificus infection is possible regardless of one's nearness to coastal areas where V. vulnificus is prevalent.

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We studied 247 strains of Proteus mirabilis collected during the 6 months from November 2003 to April 2004 from 12 clinical laboratories in the Kinki region of Japan for the production of extended-spectrum β-lactamase (ESBL).Eighteen strains (7.3%) showed MICs for cefpodoxime of≥2μg/mL and 13 strains (5.2%) were positive for the double-disk synergy test. Susceptibility depended on genotype. MICs for cefepime, cefozopran, and cefpirome were high (≥8μg/mL), and that for ceftazidime was low (0.12-0.5μg/mL). Meropenem showed the lowest MIC (≤0.03-0.25μg/mL) of the calbapenems, while other calbapenems showed somewhat higher values (0.5-2μg/mL). The MIC of tazobactam/piperacillin was also relatively low (≤0.25-1μg/mL). Analysis of the ESBL genotype by the polymerase chain reaction showed that 12 of 13 strains were CTX-M2 types. CTX-M9 was detected in a single laboratory. The clinical background showed 5 strains in urine samples. Twelve of 13 strains were detected in patients with minimal devices use. No symptoms were found in most cases of established syndrome. Analysis of PCR fingerprint profiles of random amplified polymorphic DNA patterns showed that 6 of 7 strains from hospital 1 showed the same pattern, and 5 of 5 strains from hospital 13 showed the same pattern, suggesting the nosocomial spread of P. mirabilis in each hospital.

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In May 2004, 65 people from 18 groups of visitors to guesthouse (a traditional Japanese guesthouse) in the Nagano Prefecture, Japan developed acute gastroenteritis. Although these cases originally attributed to food poisoning, based on epidemiological and dietary surveys, there was nothing that is associated as a cause food. The same wall water was used throughout the guesthouse except in the kitchen, so testing was conducted on this water. Lordsdale variant strain of Norovirus was detected from both of the well water and the feces of patients and staff. The well supplying to the guesthouse was only 10 meters deep and fecal coliform group was also detected in the well water from the guesthouse. This suggested that the water source was contaminated by human feces.

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The concomitant use of low concentration β-lactam antibiotics antagonizes the activity of vancomycin against some strains of MRSA. These strains, called β-lactam antibioticinduced vancomycin resistant MRSA (BIVR), have been increasing for a number of years. We previously reported that the combination of VCM and ceftizoxime displayed this antagonism not only in vitro, but also in vivo, in a systemic infection caused by BIVR in mice.
In the present study, we validated the antagonism in combinations of VCM with other β-lactams, i.e., flomoxef (FMOX), ampicillin (AMPC), azthreonam (AZT) and imipenem/cilastatin (IPM/CS), in systemic infections and pneumoniain in mice. The survival rate of the mice with systemic infections caused by BIVR treated with combinations of FMOX, AMPC, AZT, and IPM/CS with VCM were significantly lower than with VCM monotherapy, and the number of residual viable cells in the kidneys of mice treated with combinations of FMOX and IPM/CS with VCM were significantly higher than with VCM monotherapy The number of residual viable cells in the lungs of mice with pneumonia caused by BIVR treated with the combination of IPM/CS and VCM was significantly higher than with VCM monotherapy.
On the other hand, the survival rate with combination therapy consistings IPM/CS plus teicoplanin (TEIC) was significantly higher, and the number of residual viable cells in the kidney was significantly lower, than with TEIC monotherapy alone. In the mice with pneumonia, the number of residual viable cells in the lung after combination therapy with IPM/CS and TEIC was significantly lower than with TEIC monotherapy.
Combination therapy with P-lactams plus VCM showed antagonistic in models of systemic infection and pulmonary infection caused by BIVR, whereas combination therapy consisting of a β-lactam plus TEIC had a synergistic effect in the same models, even though VCM and TEIC are member of the same glycopeptide antibiotic class.

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The performance of a real-time DNA amplification assay, BD ProbeTec ET System (BDPT, BD Diagnostic Systems), to detect Chlamydia trachomatis and Neisseria gonorrhoeae on endocervical and oropharyngeal samples was evaluated. After obtaining informed consent, 364 endocervical, 363 urine and 247 oropharyngeal specimens were collected from 307 cases. The overall agreement rate of the BDPT and Amplicor (AMP, Roche) assays for the detection of C. trachomatis and N. gonorrhoeae in endocervical samples was 99.2 % (361/364) for C. trachomatis and 99.5 % (362/364) for N. gonorrhoeae. Assay of oropharyngeal swabs by the BDPT yielded 21 C.trachomatis positives, and 19 of them were C. trachomatis negative by the DNA probe assay (Gen-Probe PACE). The AMP assay showed that 16/19 (84.2%) of the BDPT+ /DNA probe-samples were positive. The BDPT also yielded 21 N. gonorrhoeae positives, 15 of which were negative with the DNA probe. Additional testing showed that all 15 BDPT+/DNA probe-samples were positive by the established nested PCR method. Our data suggest that the performance of the BDPT is comparable to that of AMP for detection of C. trachomatis and N. gonorrhoeae in endocervical swab samples and that it may be a useful method for detecting of C. trachomatis and N. gonorrhoeae in oropharyngeal samples clinically.

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A 75-year-old woman was admitted with fever of unknown origin and liver damage, and treated withprednisolone. Hypercalcemia appeared when of the dose of prednisolone was reduced, and human T-celllymphotropic virus type-I (HTLV-I) proviral DNA was detected in the leukemic cells by Southern blot analysis, and a diagnosis of acute adult T-cell lymphoma (ATL) was made. After chemotherapy with sobuzoxanewas started, she went into septic shock caused by multiple resistant Serratia marcesense, and was treatedwith PMX-DHP and antibiotics. Although ner general condition and her serum cytokine leyels improved, theseptic shock became more severe, and the patient died.
Serratia marcesense expreses lipopolysaccharide (LPS), a biologically active substance that is present ingram-negative bacteria.Exposure to LPS leads to activation of cytoklnes, including TNF-α, IL-1β, IL-6, andIFN-γ.After treatment withPMX-DHP, the patien, s general condition improved, but she died of septicshock. Bacterial infection may be a life-threatening complication in the immunocompromised hosts and elderlypatients, particularly when granulocytopenia has been induced by chemotherapy, and thus such thesepatients require careful management.

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We report a case of blood stream infection due to Mycobacterium goodii in a patient who had an implanting pacemaker. The patient injured left thorax where the pacemaker was implanted several days before septicemia. The microorganism was isolated from both blood cultures and leads of the pacemaker. The serial isolates were identified as M. goodii by conventional biochemical methods, tobramycin susceptibility test and 16Sr-RNA sequencing.
This is the first reported case of M. goodii septicemia in Japan. M. goodii is regarded as an environmental bacterium and its pathogenicity has been recognized recently. The present case suggests that its ability as a primary invader should not be underestimated, especially in a patient with indwelling devices.

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Endogenous endophthalmitis (EBE) is intraocular infection usually associated by bcteremia. Although, EBE is an uncommon disease, visually prognosis is very poor.
Immune suppressive disease, such as diabetes or malignancy is a predisposing factor of EBE. Although, in east Asia, including Japan, gram negative organisms reported as common pathogen causing EBE, we here repot a case of group B streptococcus EBE.
A 53-year old man, who has history of diabetes mellitus, was admitted to our hospital with compliant of sudden visual loss and pain at his right eye. His visual acuity was no hand perception in the right. In auscultation, there were coarse crackles at his left lung. Axial magnetic resonance imaging of eye showed exophthalmos of right eye and cellulites. Chest radiography revealed infiltration at the left middle lung field.
EBE and pneumonia due to GBS were diagnosed and he was treated with intravenous cefotaxim. Despite of administration of antibiotics and vitreous surgery, deterioration of his visual activity was observed. Therefore antibiotics were changed to intravenous vancomicin and topical levofloxacin and amykacin were added also. But he finally lost his visual acuity of right eye.

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Salmonella Enteritidis often causes food poisoning. In this study, an extremely rare case of cervical abscess caused by S. Enteritidis is reported. In January 2003, a 44-year-old man visited our hospital with swelling of the left submandibular region. He had been suffering from a severe diabetic condition but had neglected to seek medical attention. An incision was made at the abscess to drain the pus from which only S. Enteritidis was isolated. This finding led to the discovery that he had suffered from an episode of food poisoning 6 months earlier. However, the organism was not isolated from the stool. The patient recovered with the administration of panipenem/betamipron and gatifloxacin. The S. Enteritidis strain isolated from the pus obtained from this case and that detected from the samples originating from the other patients during the episode of food poisoning 6 months earlier were examined by using pulse-field gel electrophoresis (PFGE). The PFGE patterns of the strains were almost identical. The molecular epidemiological analysis by PFGE was useful in estimating the infection route. In an immuno-compromised host such as those suffering from diabetes mellitus, one must be reminded that unusual bacteria (including S. Enteritidis) may cause a cervical abscess.

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