福地 貴彦

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.

Essential thrombocythaemia (ET) is characterised by elevated platelet count by a clonal stem cell disorder of megakaryocytes. Although thrombosis is a common complication of ET, splenic infarction (SI) is extremely rare. Here, we present the case of a 31-year-old Japanese man who presented with sudden-onset severe pain at the left hypochondrium on the day before admission. Enhanced abdominal CT revealed SI. The laboratory test results revealed a normal platelet count (439×109/L). Subsequently, the patient was diagnosed with ET because the platelet count gradually increased to 50.0×104/μL, and JAK2 V617F mutation was identified. Accordingly, low-dose aspirin was initiated, and no thrombotic episode occurred. Nevertheless, 6 months postdischarge, the platelet count gradually increased to >650 × 109/L, and anagrelide was initiated. This case demonstrates an unusual complication of acute SI due to ET under the rare situation of the normal platelet count.

Our case patient was a 38-year-old pregnant Japanese woman who underwent emergency Caesarean section because of massive vaginal bleeding due to a low-lying placenta. Immediately after delivery, she presented with rapidly progressive dyspnea. Contrast-enhanced computed tomography revealed bilateral pleural effusion, lung nodules, multiple liver tumors, and multiple osteolytic lesions. Accordingly, epidermal growth factor receptor-mutant advanced lung adenocarcinoma was diagnosed. This report highlights the occurrence of rapid progression of lung cancer following delivery that led to postpartum acute respiratory failure, rather than due to pulmonary thromboembolism associated with the existing deep venous thrombosis of the inferior vena cava.

Background: Brucellosis, an important zoonotic disease, is endemic in various parts of the world. Patients diagnosed with brucellosis in developed countries are often travelers and immigrants from endemic areas. This pathogen is listed as biosafety level 3, which means that it is highly contagious and therefore a risk to clinical laboratory technicians. Case presentation: A 43-year-old Chinese man, who could not understand Japanese, visited our hospital because of an intermittent fever that had persisted for 5 months. Associated symptoms included muscle pain whenever he had a fever. He reported currently working as a welder in Japan. However, his previous employment working in animal husbandry in Heilongjiang, mainland China was not determined at the initial visit owing to language barriers. Two sets of blood culture showed nonfermenting gram-negative bacilli, initially misidentified as Ochrobactrum anthropi and subsequently identified as Brucella abortus. Six-week doxycycline and rifampicin were administered, with intravenous gentamicin for the initial 1 week. The patient recovered without relapse, confirmed by the negative result of a Brucella agglutination test. The patient's wife and three laboratory technicians were required to undergo blood examinations, which revealed no evidence of infection; however, they received prophylaxis with 3 weeks' doxycycline and rifampicin. Conclusion: In nonendemic countries, immigrants with imported brucellosis can be treated, to prevent secondary brucellosis infection, an occupational hazard among laboratory technicians. Greater attention is needed for positive findings of blood cultures, which may initially be misidentified as O. anthropi. When providing medical care for immigrants with fever of unknown origin, it is especially important for primary care physicians to overcome language barriers so as to assess pertinent information regarding their home country, such as previous employment, to prevent the spread the imported zoonoses in the era of a dramatically increasing number of immigrants and foreign travelers.

We herein report a case of a 31-year-old Japanese man who simultaneously had a positive influenza A virus antigen test result and Vogt-Koyanagi-Harada disease (VKHD), demonstrated by both diffuse multiple early hyperfluorescent points on fluorescein fundus photography and serous retinal detachments on optical coherence tomography. He had meningitis. It was difficult to determine whether the main cause of meningitis was influenza A or VKHD. After initial treatment with peramivir for influenza A and then methylprednisolone pulse with subsequent corticosteroid therapy for VKHD, his symptoms improved gradually. These findings suggest that influenza A virus infection contributes to the onset or exacerbation of VKHD.

Common adverse effects of serotonin-norepinephrine reuptake inhibitors are nausea, dry mouth, dizziness and headache. We describe the case of a patient with dysosmia and subsequent dysgeusia associated with duloxetine. A 68-year-old Japanese woman with a history of type 1 diabetes mellitus, hypertension, insomnia and reflux esophagitis presented to a local hospital with bilateral leg pain; she was treated with duloxetine. However, after 4 weeks, she sensed rotten egg smell, experienced nausea and vomiting and was admitted to our hospital. We diagnosed dysosmia using the T&T olfactometer threshold test and dysgeusia using filter paper disk method. Taste was assessed using electrogustometry. We suspected that dysosmia and dysgeusia were adverse effects of duloxetine. After stopping duloxetine, her symptoms gradually subsided and the above test results improved, despite continuing the other ongoing medication. To the best of our knowledge, this is the first case report of dysosmia and dysgeusia associated with duloxetine.

Few studies have investigated the appropriateness of antibiotic use in postdisaster settings. We retrospectively evaluated clinical databases on health care delivered at clinics near shelters set up after the Great East Japan Earthquake, 2011. We defined appropriate, acceptable, and inappropriate antibiotic use for each diagnostic category, by applying and adopting precedent studies and clinical guidelines. From March to July, 2011, a total of 23,704 clinic visits occurred at 98 shelters with 7934 residents. Oral antibiotics were prescribed a total of 2253 times. The median age of the patients was 48.5 years old (range 0-97), and 43.7% were male. Of 2253 antibiotic prescriptions, 1944 were judged to be inappropriate (86.3% 95% CI 84.8%-87.7%). The most prescribed antibiotic was clarithromycin (646 times, 28.7%), followed by cefcapene pivoxil (644 times, 28.6%), levofloxacin (380, 16.9%), cefdinir (194, 8.6%), and cefditren pivoxil (98, 4.4%). The most frequent diagnosis for which antibiotics were prescribed was upper respiratory infection (URI, 1040 visits, 46.2%), followed by acute bronchitis (369, 16.4%), pharyngitis (298, 13.2%), traumatic injuries (194, 8.6%), acute gastroenteritis (136, 6.0%), urinary tract infections (UTIs, 123, 5.5%), and allergic rhinitis (5.1%). The majority of antibiotics prescribed at clinics after the Great East Japan Earthquake was inappropriate. Significant improvement of the use of antibiotics in postdisaster settings should be sought immediately in Japan.

BACKGROUND: ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms. METHODS: We performed a retrospective observational study on cases of bacteremia caused by ESBL-producers to investigate the efficacy of cefmetazole compared with carbapenems. We also evaluated whether the trend of antibiotic choice changed over years. RESULTS: Sixty-nine patients (male 34, age 69.2 ± 14.4), including two relapse cases, were reviewed for this analysis. The most common causative organisms were Escherichia coli (64, 93 %), followed by Klebsiella pneumoniae and K. oxytoca (2 each, 4 %). The group that received carbapenem therapy (43, 62 %) had increased severity in the Pittsburgh Bacteremic score than the group that received cefmetazole therapy, (1.5 ± 1.5 vs 2.5 ± 2.1, p = 0.048), while analysis of other factors didn't reveal any statistical differences. Five patients in the carbapenem group and one patient in the cefmetazole group died during the observation period (p = 0.24). CTX-M-9 were predominant in this series (59 %). Infectious disease physicians initially recommended carbapenems at the beginning of the current research period, which gradually changed over time favoring the use of cefmetazole instead (p = 0.002). CONCLUSION: Cefmetazole may be safely given to patients with bacteremia caused by ESBL-producers as a definitive therapy, if one can select out relatively stable patients.

BACKGROUND: Sushi is a traditional Japanese cuisine enjoyed worldwide. However, using raw fish to make sushi may pose risk of certain parasitic infections, such as anisakidosis, which is most reported in Japan. This risk of infection can be eliminated by freezing fish; however, Japanese people are hesitant to freeze fish because it is believed that freezing ruins sushi's taste. METHODS: A randomized double-blind trial with discrimination testing was conducted to examine the ability of Japanese individuals to distinguish between frozen and unfrozen sushi. A pair of mackerel and squid sushi, one once frozen and the other not, was provided to the participants, and they were asked to answer which one tasted better. RESULTS: Among 120 rounds of discrimination testing involving the consumption of 240 pieces of mackerel sushi, unfrozen sushi was believed to taste better in 42.5% (51 dishes) of cases, frozen sushi was thought to taste better in 49.2% (59 dishes), and the participants felt the taste was the same in 8.3% (10 dishes). The odds ratio for selecting unfrozen sushi as "tastes better" over frozen sushi was 0.86 (95% confidence interval [CI], .59-1.26; P = .45). For squid, unfrozen sushi was believed to be superior 48.3% of the time (58 dishes), and frozen sushi, 35.0% of the time (42 dishes). They were felt to be the same in 16.7% (20 dishes) (odds ratio, 1.38; 95% CI, .93-2.05; P = .11). CONCLUSIONS: Freezing raw fish did not ruin sushi's taste. These findings may encourage the practice of freezing fish before using it in sushi, helping to decrease the incidence of anisakidosis.

Infective endocarditis (IE) is a severe disease with high morbidity and mortality, and these can be exacerbated by delay in diagnosis. We investigated IE diagnosis in Japan with the emphasis on the delay in diagnosis and its cause and implications. We conducted a retrospective study on 82 definite IE patients at Kobe University Hospital from April 1, 2008, through March 31, 2013. We reviewed charts of the patients for data such as causative pathogens, prescription of inappropriate antibiotic use prior to the diagnosis, existence of risk factors of IE, previous doctor's subspecialty, or duration until the diagnosis, with the primary outcome of 180-day mortality. We also qualitatively, as well as quantitatively, analyzed those cases with delay in diagnosis, and hypothesized its causes and implications. Eighty-two patients were reviewed for this analysis. The average age was 61 ± 14.5-year-old. Fifty percent of patients had known underlying risk factors for IEs, such as prosthetic heart valve (10), valvular heart disease (21), congenital heart disease (3), or cardiomyopathy (2). The median days until the diagnosis was 14 days (range 2 days to 1 year). Sixty-five percent of patients received inappropriate antibiotic before the diagnosis (53). Forty percent of causative organisms were Staphylococcus aureus (MSSA 20, MRSA 13), 32% were viridans streptococci and Streptococcus bovis, 28% were others or unknown (CNS 5, Corynebacterium 3, Cardiobacterium 1, Candida 1). Subspecialties such as General Internal Medicine (15), and Orthopedics (13) were associated with delay in diagnosis. Ten patients (12%) died during follow up, and 8 of them had been received prior inappropriate antibiotics. Significant delay in the diagnosis of IE was observed in Japan. Inappropriate antibiotics were prescribed frequently and may be associated with poor prognosis. Further improvement for earlier diagnosis of IE is needed.

BACKGROUND: Although it has received a degree of notoriety as a cause for antibiotic-associated enterocolitis (AAE), the role of methicillin resistant Staphylococcus aureus (MRSA) in the pathogenesis of this disease remains enigmatic despite a multitude of efforts, and previous studies have failed to conclude whether MRSA can cause AAE. Numerous cases of AAE caused by MRSA have been reported from Japan; however, due to the fact that these reports were written in the Japanese language and a good portion lacked scientific rigor, many of these reports went unnoticed. METHODS: We conducted a systematic review of pertinent literatures to verify the existence of AAE caused by MRSA. We modified and applied methods in common use today and used a total of 9 criteria to prove the existence of AAE caused by Klebsiella oxytoca. MEDLINE/Pubmed, Excerpta Medica Database (EMBASE), the Cochrane Database of Systematic Reviews, and the Japan Medical Abstract Society database were searched for studies published prior to March 2013. RESULTS: A total of 1,999 articles were retrieved for evaluation. Forty-five case reports/series and 9 basic studies were reviewed in detail. We successfully identified articles reporting AAE with pathological and microscopic findings supporting MRSA as the etiological agent. We also found comparative studies involving the use of healthy subjects, and studies detecting probable toxins. In addition, we found animal models in which enteritis was induced by introducing MRSA from patients. Although we were unable to identify a single study that encompasses all of the defined criteria, we were able to fulfill all 9 elements of the criteria by collectively analyzing multiple studies. CONCLUSIONS: AAE caused by MRSA-although likely to be rarer than previous Japanese literatures have suggested-most likely does exist.

A 71-year-old man with myelodysplastic syndrome (MDS) receiving treatment with azacitidine developed extensive watery diarrhea for three consecutive days. As a result of high-grade dehydration, the patient was urgently admitted to the hospital and fluid replacement therapy was initiated. However, the patient's diarrhea did not improve. Vibrio cholerae non-O1/non-O139 was detected in a fecal culture. On the fourth day, the patient died due to circulatory collapse. An autopsy revealed extensive necrosis of the intestinal mucosa. Vibrio cholerae non-O1/non-O139-induced diarrheal disease often develops in patients with hepatic cirrhosis and has a serious clinical course. We herein report a fatal outcome of Vibrio cholerae O67 infection in an immunocompromised MDS patient.

Domestic animals are the main reservoirs of Pasteurella species for human zoonosis due to bites and scratches. Pasterurella multocida may cause serious soft-tissue infection and, less commonly, sepsis or septic shock, particularly in insufficient initial therapy and an immunocompromised host. We report a case of cat-scratch-induced P. multocida infection, presenting with disseminated intravascular coagulation and acute renal failure. A febrile 83-year-old woman with consciousness disturbance and a subcutaneous left-foot abscess due to a scratch from a pet cat. She was successfully treated with antibiotic piperacillin and clindamycin therapy and aggressive wound drainage.

Obsessive-compulsive disorder (OCD) is rare psychiatric disorder during pregnancy, and is often therapy-resistant. We report a 36-year-old pregnant woman with severe obsessive-compulsive disorder successfully treated by modified-electroconvulsive therapy. During the pregnancy, severe mysophobia and compulsive washing appeared, so severely that she was unable to lie down, endangering the life of the fetus. Since the pharmacotherapy was ineffective, modified electroconvulsive therapy (m-ECT) was performed in cooperation with the obstetrician and the anesthesiologist, along with monitored cardiotocography throughout the procedure. During the second therapy late deceleration on the fetal cardiotocogram occurred, but rapid intravenous administration of ritodrine led to the cessation of abnormal uterine contraction. Two courses of m-ECT markedly diminished her symptoms, and she delivered a healthy infant without complications. M-ECT can be an alternative treatment for pregnant patients with OCD.