We studied changes in the drug resistance of 606 strains of Haemophilus influenzae (H. influenzae) and 502 strains of Streptococcus pneumoniae (S. pneumoniae) isolated from our patients between 1997 and 2006. The incidence of β-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) in 1997-1998 and 1999-2000 was 72.0 and 69.6％, respectively. In 2005-2006, the incidence of BLNAS decreased to 31.0％, while that of βlactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) and intermediate-resistant H. influenzae increased to 65.5％. Remarkably early development of BLNAR and intermediate-resistant H. influenzae was found in patients younger than 3 years, as compared to patients older than 3 years. The proportion of penicillin-susceptible S. pneumoniae (PSSP) in 1999-2000 was 18.4％. In 2005-2006, the proportions of penicillin resistant S. pneumoniae (PRSP) and penicillin-intermediate S. pneumoniae (PISP) were lower, while that of PSSP increased to 38.2％. An early increase in the proportion of PSSP was found in patients older than 3 years, as compared to patients younger than 3 years. The difference between age groups may be attributed to entrance into nursery school, frequent administration of antibiotics, and the immature immunological state of patients younger than 3 years. Therefore, changes in the drug resistance of H. influenzae and S. pneumoniae should be investigated separately, depending on the age of the patients. The minimum inhibitory concentrations of antibiotics, including cefditoren and cefcapene, against BLNAR and PRSP did not increase. The marked increase in intermediate-resistant H. influenzae and BLNAR mandates a re-evaluation of the directions for antibacterial agents.

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Haemophilus influenzae, a major respiratory tract pathogen, is becoming increasingly resistant to βlactam antibiotics. Studying annual trends in antibiotic susceptibility and genetic patterns of H.influenzae βlactam resistance, we isolated 122 strains from the adult respiratory tract in 2007, determined MIC for different antibiotics, and analyzed TEM-1 β-lactamase resistant genes and ftsI encoding PBP3 mutation compared to results in 2005 and 2007. We found that ABPC-susceptible strains with MIC ＜1µg/mL (BLNAS) accounted for 71.0％, ABPC-resistant strains with MIC exceeding 2µg/mL without β-lactamase activity (BLNAR) for 25.3％, and β-lactamase-positive strains (BLP) for 3.7％. The BLNAS ratio showed no significant change from 2002 and 2005. The BLP ratio decreased from those in 2002 and 2005. Genetic studies of resistant genes showed that gBLNAS with no resistant genes had increased in the last five years. The ratio of all strains with PBP3 mutation (gBLNAR and gLow-BLNAR) remained constant from 2002 to 2007. The proportion of gBLNAR with two PBP3 mutations had increased, however, while gLow-BLNAR with one mutation had decreased. LVFX showed constant strong antimicrobial potency for all mutation groups. Among β-lactam antibiotics, the lowest MIC₉₀ was observed in parenteral CTRX and oral CDTR-PI use. Although a new MIC peak generated by gBLNAR became obvious in the ABPC and CDTR-PI MIC distribution, the MIC of the new peak was still low enough to treat with high doses of those two antibiotics.

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We studied clinical manifestations, laboratory results, treatment, recurrence, and complications in 69 patients diagnosed with Kikuchiʼs disease by lymph node pathology from January 1, 1998, to December 31, 2007. Subjects were 34 men and 35 women (median age : 28 years, range : 12 to 58 years). Of the 69, 67 were Japanese and 2 were Korean. Major clinical symptoms and signs were fever＞37 degrees (71％) and lymphadenopathy (100％). Lymphadenopathy was cervical in 93％ and systemic in 3％. Some experienced night sweats and weight loss. The median white blood cell count was 3800µL (1,700-9,300µl), and 50.7％ of subjects had leukocytopenia (＜4,000µL). The median serum LDH concentration was 245U/L (129-923U/L). The median ferritin concentration, measured in 26 cases, was 769ng/mL (4.5-2,580ng/mL). The median concentration of soluble IL-2 receptor, measured in 27 cases, was 639U/mL (0.5-4,000U/ml). Having observed several cases with abnormally high ferritin and soluble IL2 receptor, we note the importance of carefully considering differential diagnosis from Stillʼs disease and malignant lymphoma. Treatment included no medication in 30％ of subjects, nonsteroidal anti-inflammatory drugs alone in 37.7％, steroids alone in 7％, and combined nonsteroidal anti-inflammatory drugs and steroids in 22％. Of the 29％ administered steroids, we mostly used prednisolone (0.5-1.0mg/kg), tapering the dose as clinical features improved. Two developed aseptic meningitis and 2 systemic lupus erythematosus. In total, 75％ improved in less than 3 months, whereas 6％ showed improvement only after at least 6 months of continued treatment. All were cured, but the condition recurred in 8％. Recurrence was not associated initial the disease duration. Recurrence cannot be predicted but can occur. In some cases, we could not distinguish lymphadenitis from malignant lymphoma or tuberculous lymphadenitis based on clinical features or laboratory data. Diagnosis must thus be based on lymph node pathology. We also must consider the possibility of recurrence or attacks of systemic lupus erythematosus.

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Itraconazole (ITCZ), a useful oral drug effective against Aspergillus, is reported to cause insufficient blood concentration through unstable enteral absorption. Hypoacidic gastic conditions have been reported to reduce absorption, whereas acidic drinks promote it. We present a case of pulmonary aspergillosis in a subject administered ITCZ with black vinegar, a popular health food in Japan. The 59-year-old man showed high blood concentrations of ITCZ, resulting in good Aspergillosis control. To confirm the efficacy in black vinegar on absorbing ITCZ, we administered ITCZ capsules with and without black vinegar to 10 healthy adults after preparation with a proton pump inhibitor to decrease gastric acidity, and measured blood concentrations of ITCZ and the metabolite OH-ITCZ. Administration of this combination increased ITCZ and OH-ITCZ Cmax significantly. For patients who produce too little gastric juice, black vinegar could thus serve to promote ITCZ capsule absorption.

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Travelerʼs vaccinations are recommended for preventing infectious disease among overseas travelers. Focusing on Japanese expatriate adults residing in developing countries, we report our results for 2002 and 2005 vaccination status. Positive responses to the statement “Had travelerʼs vaccination before leaving Japan” increased from 49.9％ in 2002 to 55.8％ in 2005. Regionally the vaccination rate was high among those traveling in South Asia and Tropical Africa, and vaccination rates high in all regions for hepatitis A and B and tetanus. Vaccinations rates for rabies, yellow fever, Japanese encephalitis, and polio, were high in regions where these are known to be specifically prevalent. A certain number of travelers in some regions had also been vaccinated against typhoid and meningococcal meningitis although these vaccinations are not authorized in Japan. Despite these positive developments, however, much work remains to be done to raise the awareness among Japanese expatriates in developing countries of the need for vaccinations.

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We report the finding for two food-poisonins outbreaks occurring in Tokyo and Chiba in September 2003. Patients in the Tokyo outbreak suffered from fever varying widely from 35.9℃ to 39.4℃. Throat pain was predominant, accompanied by headache, cough, and joint pain. Patients in the Chiba outbreak suffered from malaise in addition to the above symptoms. To clarify the relationship between pathology and virulence factors, we studied the properties of hemolysins and proteases produced by the causative bacteria,　Streptococcus pyogenes, specifically type T-28 in the Tokyo outbreak and type T-B3264 in the Chiba outbreak. 　The main S. pyogenes T serotypes isolated in 2003 were types T12, T1, T4, and T3, followed types T-28 and T-B3264. The hemolytic titer of hemolysins, which are metabolic, was 173HD50/mL for T-28 and 147HD50 /mL for T-B3264. Hemolysins produced by both strains did not depend on reducing agents and were not inhibited by γ-globulin or cholesterol, indicating the streptolysin S (SLS) rather than hemolysis inhibition by phospholipids. The fact that the titer increased slightly in the presence of reducing agents indicates that some amount of streptolysin O may also have been present. Protease production was four times greater for T-B3264 than for T-28. Proteases produced by both strains were similarly inhibited by sodium tetrathionate, iodoacetate, and normal serum. The outbreak infection was caused by infiltration of food-borne Streptococcus bacteria via the upper airway during eating. The primary cause of predominant throat pain was thought to be SLS cytotoxicity in the upper respiratory mucous membrane. This toxin was also thought to assist in Streptococcus bacteria infiltration and proliferation. Proteases produced by pathogenic bacteria were thought to have acted on the body as potent virulence factors.

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We analyzed rubella antibody data from hemagglutination-inhibition tests on 600,000 serum specimens from Japanese women 20-39 years old. Specimens had been sent by gynecology clinics nationwide to a commercial diagnostic laboratory from 1999 through 2007. Antibody-positive percentages in women in their 20s to mid 30s in 1999 to 2001 were 95％, while those in women in their early 20s from 2002 to 2007 were lower at 88％ among 20-year-olds in 2002 born in 1982 and 86％ among those in 2007 born in 1987. These lower percentages resulted from a change in rubella vaccination policy under which junior high school girls between 1977 and 1994-those born between 1962 and 1981-underwent mandatory rubella vaccination, while mandatory vaccination was administered to younger children, instead, from 1995. Due to this policy change,girls born between 1982 and 1987 were not subjected to mandatory vaccination. We believe that women in this group have a relatively higher risk of bearing children with congenital rubella syndrome (CRS). Additional campaigns for voluntary rubella vaccination should thus be addressed to this female cohort.

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A 73-year-old man with underlying chronic renal failure, angina pectoris, chronic heart failure, and respiratory failure reporting three-day appetite loss, fever, and drowsiness was admitted for lower right lung pneumonia. Despite antibiotic administration, infiltration progressed to the entire right lung and upper left lung after 12 hours, and he developed acute respiratory distress syndrome (ARDS) and multiple organ failure. Respirator ventilation and continuous hemodiafiltration (CHDF) failed to halt this progression and he died on hospital day 3. Acinetobacter baumannii was cultured from bronchoalveolar lavage fluid and the postmortem lung specimen, indicating that his severe community-acquired pneumonia was due to A. baumannii. Microscopically, the lung specimen showed prominent cellular alveolar exudate and partial hyaline membrane with suppurative pneumonia. Although A. baumannii is considered the causative agent in nosocomical pneumonia, community acquired pneumonia due to A. baumannii is very rare. This is, to our knowledge, the first report in Japan. In the subtropical zone, A. baumannii is recognized as an important cause of severe community-acquired pneumonia. Given the apparent progress of global warming, physicians in Japan would do well to familiarize themselves with subtropical disease causes such A. baumannii when managing severe community-acquired pneumonia.

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