Kenichiro Yaita

Epidemiology of extended-spectrum β-lactamase producing Escherichia coli in the stools of returning Japanese travelers, and the risk factors for colonization.

Objective Travel overseas has recently been considered a risk factor for colonization with drug-resistant bacteria. The purpose of this study was to establish the epidemiology and risk factors associated with the acquisition of drug-resistant bacteria by Japanese travelers. Methods Between October 2011 and September 2012, we screened the stools of 68 Japanese returning travelers for extended-spectrum β-lactamase (ESBL) producing Escherichia coli. All specimens were sampled for clinical reasons. Based on the results, the participants were divided into an ESBL-producing E. coli positive group (18 cases; 26%) and an ESBL-producing E. coli negative group (50 cases; 74%), and a case-control study was performed. Microbiological analyses of ESBL-producing strains, including susceptibility tests, screening tests for metallo-β-lactamase, polymerase chain reaction amplification and sequencing of bla CTX-M genes, multilocus sequence typing, and whole genome sequencing, were also conducted. Results In a univariate comparison, travel to India was a risk factor (Odds Ratio 13.6, 95% Confidence Interval 3.0–75.0, p<0.0001). There were no statistical differences in the characteristics of the travel, such as backpacking, purpose of travel, interval between travel return and sampling stool, and duration of travel. Although 10 of 13 analyzed strains (77%) produced CTX-M-15, no ST131 clone was detected. Conclusion We must be aware of the possibilities of acquiring ESBL-producing E. coli during travel in order to prevent the spread of these bacteria not only in Japan but globally.

Post-Travel Consultations in a Regional Hub City Hospital, Japan

OBJECTIVE To clarify the characteristics of post-travel consultation services in Japan, particularly in the provinces, we analyzed our post-travel patients in the travel clinic of Kurume University Hospital located in Kurume City (a regional hub City in southwestern Japan). METHODS Sixty post-travel patients visited our clinic between April 2008 and October 2014 and participated in this study: 55 were Japanese and five were foreign. We summarized and compared the characteristics of the patients after dividing the Japanese participants into long-term travelers (>14 days) and short-term travelers (≤14 days). The foreign travelers were described in a separate analysis. RESULTS Of the 55 Japanese travelers, the mean age (± standard deviation) was 37.3 ± 16.3 years, and 36 patients (65%) were men. Southeast Asia was the major destination (30/55, 55%), and business was stated as the major reason for travel (16/55, 29%). Post-exposure rabies prophylaxis (16/55, 29%) was the most common purpose for the consultations. There were 34 participants (62%) who were classified as short-term travelers. Fewer of the short-term travelers stated receiving pre-travel consultations compared with long-term travelers (11% vs. 79%, p=0.0002). The five foreign travelers included one dengue fever patient and two malaria patients. CONCLUSION Most post-travel Japanese patients visited our clinic were short-term travelers who had not received any pre-travel consultation. One of the most common complaints, post-exposure rabies prophylaxis, could have been avoided to some extent by appropriate pre-travel consultations. The results of this study suggest that pre-travel consultations should therefore be encouraged for both long- and short-term travelers.

A Retrospective Analysis of Drug Fever Diagnosed during Infectious Disease Consultation

OBJECTIVE To clarify the current situation concerning drug fever (DF) in Japan, we retrospectively analyzed patients undergoing infectious disease consultation at our institution. METHODS Between April 2014 and May 2015, we extracted the records of DF patients from among 388 patients who had obtained infectious disease consultations in Kurume University Hospital. We reviewed their medical charts and summarized the characteristics of DF. RESULTS This study included the records of 16 patients. Clinical signs (relative bradycardia, the duration of the drug administration before becoming febrile, and the interval between the discontinuation of a drug and the alleviation of a fever), and laboratory tests (varied white blood cell count, low level of C-reactive protein, and a mild elevation of transaminases) were compatible with those from previous reports. Among the drug-confirmed cases, five involved the use of glycopeptides (vancomycin: 3, teicoplanin: 2), which were considered to be uncommon causes, and the another five cases involved the use of β-lactams. In addition, the procalcitonin levels were either negative or low (≤0.25 ng/mL) in 10 of the 11 procalcitonin-measured cases. CONCLUSION Our findings demonstrated that glycopeptides, similar to β-lactams, may be the origin of DF. Furthermore, procalcitonin may be helpful in the diagnosis of DF, but only in combination with other detailed examinations.

Hepatitis B Vaccination Status among Japanese Travelers

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organizations payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

Typhoid Vaccination among Japanese Travelers to South Asia and the Factors Associated with Compliance

Objective In 2010, candid advice concerning the low rate of typhoid vaccination among Japanese travelers was received from Nepal. Recently, progressive Japanese travel clinics have encouraged Japanese travelers to be vaccinated against typhoid fever in conjunction with officially approved vaccines, such as hepatitis A vaccine. We herein report the status of typhoid vaccinations for Japanese travelers to the most endemic area (South Asia) and describe the factors associated with compliance. Methods In the travel clinic at Kurume University Hospital, we used the following criteria to retrospectively extract the records of new pre-travel Japanese clients between January 2011 and March 2015: hepatitis A vaccine administered, traveling to South Asian countries, and ≥2 years of age. We first summarized the participants and then divided them into typhoid-vaccinated and typhoid non-vaccinated groups for a comparative analysis. Results This study included 160 clients. A majority (70.0%) of these clients traveled for business. The duration of trips was long (≥1 month) (75.0%), and India was a popular destination (90.6%). A comparative study between the vaccinated group (n=122) and the non-vaccinated group (n=38) revealed that the two factors most positively associated with typhoid vaccination were business trips [adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 1.42-9.06] and coverage by a company/organization payment plan (aOR 7.14, 95% CI 2.67-20.3). Conclusion The trend toward typhoid vaccination among Japanese travelers to South Asia with pre-travel consultation is correlated with business trips and coverage by a company/organization payment plan. If problems concerning the cost of vaccines were resolved, more travelers would request typhoid vaccination.

Invasive meningococcal disease due to a non-capsulated Neisseria meningitidis strain in a patient with IgG4-related disease

BackgroundInvasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases).Case presentationWe report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed.ConclusionsOur IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient’s IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Integration of DPC and clinical microbiological data in Japan reveals importance of confirming a negative follow-up blood culture in patients with MRSA bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is one of the commonest and most life-threatening of all infectious diseases. The morbidity and mortality rates associated with MRSA bacteremia are higher than those associated with bacteremia caused by other pathogens. A common guideline in MRSA bacteremia treatment is to confirm bacteremia clearance through additional blood cultures 2-4 days after initial positive cultures and as needed thereafter. However, no study has presented statistical evidence of how and to what extent confirming a negative follow-up blood culture impacts clinical outcome. We present this evidence for the first time, by combining clinical microbiological data of blood cultures and the DPC administrative claims database; both had been systematically accumulated through routine medical care in hospitals. We used electronic medical records to investigate the clinical background and infection source in detail. By analyzing data from a university hospital, we revealed how survival curves change when a negative follow-up blood culture is confirmed. We also demonstrated confirmation of a negative culture is significantly associated with clinical outcomes: there was a more than three-fold increase in mortality risk (after adjusting for clinical background) if a negative blood culture was not confirmed within 14 days of the initial positive blood culture. Although we used data from only one university hospital, our novel approach and results will be a basis for future studies in several hospitals in Japan to provide statistical evidence of the clinical importance of confirming a negative follow-up blood culture in bacteremia patients, including those with MRSA infections.

Disseminated Mycobacterium intracellulare infection with multiple abscesses on extremities in a woman with chronic corticosteroid therapy

A 78‐year‐old Japanese woman with rheumatoid arthritis was admitted to our hospital due to fever. She had been prescribed prednisolone and bucillamine. Computed tomography revealed abscesses on extremities. M. intracellulare was cultured from her calcaneus osteomyelitis, and this result pointed to a disseminated mycobacterial infection. We drained the abscesses and found M. intracellulare. We started antimycobacterial agents, but the patient died finally. Disseminated mycobacterial infection is rare but critical, and the possibility of such an infection in an immunocompromised patient should be a prime consideration when choosing appropriate drugs and surgical approaches.

Typhoid fever: A rare cause of relative bradycardia in Japan

A 22yearold woman was referred to our hospital from a primary care clinic due to a fever (>38.5°C) that had persisted for 5 days with shaking chills and mild headache, but without diarrhea, rash, arthralgia, or myalgia. On the day of the onset of these symptoms, she had been prescribed levofloxacin tablets from her physician, but the fever persisted. She had returned travel to southern and southeastern Asia (a 3month backpacking trip to Thailand, India, Burma, Laos, and Nepal) 25 days before the onset of symptoms and had no history of pretravel consultation. In every country, she had enjoyed fruit juices at street stalls (Figure 1A). Upon first consultation, the general impression was not bad, instead of being febrile. A dry cough appeared on the day she visited our hospital. Her vital signs were as follows: blood pressure, 107/76 mm Hg; heart rate, 88 beats/min; body temperature, 37.3°C; and, Glasgow Coma Scale, E4V5M6. Her spleen was not palpable. The laboratory data showed a normal white blood cell count (4500/ μL [Eosinophils: 0.2%]), accompanied by mild elevations of Creactive protein (3.26 mg/dL), aspartate aminotransferase (33 IU/L), and lactate dehydrogenase (279 IU/L). A chest Xray examination was normal. A peripheral blood smear test and a malaria rapid diagnostic test (First Response Malaria Ag. (pLDH/HRP2) Combo Rapid Diagnostic Test, Premier Medical Corporation Ltd., US) were negative. On the day following our first consultation, a blood culture was positive for Gramnegative rod (GNR) (Figure 1B), and the relative bradycardia was shown (Day 1) (Figure 1C). Based on her travel history, examinations, and the relative bradycardia, we suspected a diagnosis of enteric fever. We also considered imported multidrugresistant GNR bloodstream infection. We initiated treatment with azithromycin 500 mg orally for 3 days and meropenem at a dose of 1 g intravenously every eight hours. Finally, GNR was identified as Salmonella typhi. On the 4th hospital day, we changed meropenem to ceftriaxone at a daily dose of 2 g administered intravenously according to the susceptibility tests for S. typhi (ceftriaxone: susceptible, levofloxacin: resistant). The patient was discharged after treatment that lasted 20 days. During an entire febrile period (days 15), relative bradycardia was documented (Figure 1C). Nevertheless our patient’s incubation period of enteric fever was longer than typical one (<21 days),1 our first diagnosis was enteric fever. A combination of the patient’s history and her nonspecific symptoms led us that we should draw blood cultures for possible enteric fever. A dry cough is a wellknown symptom of patients with typhoid fever (sensitivity: 40%).2 Relative bradycardia was also famous among typhoid fever patients,3 although the sensitivity was low (15%20%).4 Relative bradycardia is also seen in patients with drug fever, Legionella infection, lymphomas, and some tropical diseases (malaria, dengue fever, leptospirosis, and typhoid fever).5 Relative bradycardia caused by typhoid fever is rare in Japan; however, this symptom might be clinically relevant to a suspicion of typhoid fever, among partially treated culturenegative cases. In this era of globalization, general practitioners should know the typical characteristics of imported infectious

Mycobacterium conceptionense bloodstream infection in a patient with advanced gastric carcinoma

A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature.