Search

Background Spread of vancomycin-resistant Enterococcus (VRE) is a global concern as a significant cause of healthcare-associated infections. A series of VRE faecium (VREf) outbreaks caused by clonal propagation due to interhospital transmission occurred in six general hospitals in Aomori prefecture, Japan. Methods The number of patients with VREf was obtained from thirty seven hospitals participating in the local network of Aomori prefecture. Thirteen hospitals performed active screening tests for VRE. Whole genome sequencing analysis was performed. Results The total number of cases with VREf amounted to 500 in fourteen hospitals in Aomori from Jan 2018 to April 2021. It took more than three years for the frequency of detection of VRE to return to pre-outbreak levels. The duration and size of outbreaks differed between hospitals according to the countermeasures available at each hospital. Whole genome sequencing analysis indicated vanA-type VREf ST1421 for most samples from six hospitals. Conclusions This was the first multi-jurisdictional outbreak of VREf sequence type 1421 in Japan. In addition to strict infection control measures, continuous monitoring of VRE detection in local medical regions and smooth and immediate communication among hospitals are required to prevent VREf outbreaks.

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.

Patients supported by mechanical circulatory support have to wait for longer periods for heart transplantation in Japan. Infective events are a major complication and influence survival. Here, we present the case of a patient with an implantable left ventricular assist device for 6 months who had the complication of ruptured infective common iliac aneurysm. Graft placement with an omental flap was successfully performed via the alternative surgical approach to avoid percutaneous driveline injury. In samples of aortic specimens, 16S ribosomal DNA gene analysis identified Helicobacter cinaedi. Complete removal of the infected tissue and correct pathogen identification may have been relevant to the good clinical course.

To the Editor: Infected abdominal aortic aneurysm (IAAA) is uncommon, but life-threatening; the mortality rate ranges from 25% to30% (1,2). Identification of the pathogen is essential for diagnosis and treatment. Previous studies have shown that species of the genera Salmonella, Staphylococcus, and Streptococcus are the most common pathogens associated with IAAA, but a causative organism is not identified in 14%–40% of patients (1,2). Helicobacter cinaedi has mainly been isolated from immunocompromised patients with bacteremia, cellulitis, and septic arthritis (3,4). Here, we report 3 cases of IAAA caused by H. cinaedi detected by 16S ribosomal RNA (16S rRNA) gene analysis. The 3 patients (case-patients 1–3) were referred to Tohoku University Hospital, Sendai, Japan, for surgical treatment of IAAA in 2013. None had a history of disease known to cause immunodeficiency. Because their abdominal aneurysms enlarged rapidly, all 3 patients underwent resection of the aneurysm and extensive local debridement and irrigation. Histopathologic examination of the surgical specimens revealed severe atherosclerosis and inflammation, consistent with a diagnosis of IAAA. For each case-patient, blood culture (BacT/ALERT; bioMerieux Industry, Tokyo, Japan) was negative, as was culture of surgically removed tissue on HK semisolid agar (Kyokuto Pharmaceutical Industrial Co., Ltd., Tokyo, Japan) at 35°C under aerobic conditions for 7 days for enrichment of microorganisms, and on chocolate agar at 35°C under 5% CO2 for 48 h. We then used 16S rRNA gene analysis to identify a pathogen. We extracted DNA from resected tissues using a QIAamp DNA Mini kit (QIAGEN K.K., Tokyo, Japan), amplified it using PCR, and sequenced it using universal primers for 16S rRNA (5). We used the EzTaxon-e Database for sequence analysis (http://eztaxon-e.ezbiocloud.net/), which revealed that the 16S rRNA gene sequence of bacteria in the aneurysmal tissues was identical to that of H. cinaedi. For case-patient 3, we cultured microaerophilic tissue at 35°C using Trypticase Soy Agar II with 5% sheep blood (Kyokuto Pharmaceutical Industrial Co.) and an Anaero Pouch-MicroAero (Mitsubishi Gas Chemical Co., Inc., Tokyo, Japan) to detect H. cinaedi. We observed bacterial colonies, after Gram staining, which showed gram-negative spiral rods. By 16S rRNA gene analysis, we confirmed that the isolate was H. cinaedi. For each of the 3 case-patients, species identification was further confirmed by sequence analysis of 23S ribosomal RNA (23S rRNA) (DNA Data Bank of Japan: http://blast.ddbj.nig.ac.jp/blastn?lang = ja) and amplification of the gyrB gene region that is specific to H. cinaedi (6,7). In samples from the 3 patients, there were mutations of the 23S rRNA gene and amino acid substitutions in GyrA related to macrolide and fluoroquinolone resistance, respectively (6,8). After identifying the pathogen, we selected antimicrobial agents based on the reported drug susceptibility profile of H. cinaedi (6,8). The patients survived and are being followed up as outpatients. Clinical and molecular characteristics of the 3 cases of IAAA with H. cinaedi infection are shown in the Table. Table Clinical characteristics of 3 patients with Helicobacter cinaedi–infected abdominal aortic aneurysms and molecular characteristics of isolates, Japan * Although the high negative culture rate for pathogens causing IAAA had been explained by prolonged preoperative antimicrobial drug therapy (2), another possibility is that H. cinaedi may be a causative organism. Earlier research has suggested that H. cinaedi infections can remain undiagnosed or be incorrectly diagnosed because of difficulty in isolating this microorganism (9). H. cinaedi grows slowly under microaerophilic conditions, but no current standard laboratory methods result in a diagnosis of this pathogen (6,7,9). We isolated H. cinaedi from surgically removed tissue from case-patient 3 by microaerophilic culture after taking this pathogen into consideration. For diagnosis of H. cinaedi infections, methods leading to accurate identification by clinical microbiological laboratories are needed. Currently, H. cinaedi is identified by molecular analysis of the 16S rRNA gene (6,7,10). In addition, matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) (10), may become a useful tool for this purpose. Standard breakpoints of antimicrobial drugs for H. cinaedi have not been defined, but all isolates in this study had mutations that indicated resistance to macrolides and fluoroquinolones. For adequate treatment for H. cinaedi infections, guidelines for selection of antimicrobial drugs and surveillance of its antimicrobial susceptibility profile are required. During November 2012–November 2013, 8 patients underwent their first operation for IAAA at the university hospital. We used 16S rRNA gene analysis of surgical tissues and culture of blood and tissue specimens to detect pathogens (data not shown). Identification of H. cinaedi in 3 of 8 patients suggests that it could be a prevalent pathogen related to IAAA. Taking such information into consideration could affect the prognosis of many patients. Accordingly, tissue should be cultured while considering H. cinaedi infection in patients with IAAA. H. cinaedi colonizes the gastrointestinal tract, and bacterial translocation may lead to bacteremia associated with mucosal damage (4). However, the route of transmission and reason most H. cinaedi infections have been reported in Japan are unclear. To clarify the relationship between H. cinaedi and IAAA, further clinical and epidemiologic studies are needed. Meanwhile, we recommend clinical consideration of H. cinaedi infection, use of appropriate laboratory procedures to identify cases, and development of treatment guidelines.

Acinetobacter baumannii is generally the most frequently isolated Acinetobacter species. Sequence analysis techniques allow reliable identification of Acinetobacter isolates at the species level. Forty-eight clinical isolates of Acinetobacter spp. were obtained from blood cultures at Tohoku University Hospital. These isolates were identified at the species level by partial sequencing of the RNA polymerase β-subunit ( rpoB ), 16S rRNA, and gyrB genes. Then further characterization was done by using the PCR for detection of OXA-type β-lactamase gene clusters, metallo-β-lactamases, and carO genes. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing were also performed. The most frequent isolate was Acinetobacter soli (27.1%). Six of the 13 A. soli isolates were carbapenem nonsusceptible, and all of these isolates produced IMP-1. PFGE revealed that the 13 A. soli isolates were divided into 8 clusters. This study demonstrated that A. soli accounted for a high proportion of Acinetobacter isolates causing bacteremia at a Japanese tertiary hospital. Non- A. baumannii species were identified more frequently than A. baumannii and carbapenem-nonsusceptible isolates were found among the non- A. baumannii strains. These results emphasize the importance of performing epidemiological investigations of Acinetobacter species.

Culture-negative endocarditis remains a diagnostic and therapeutic challenge despite recent medical advances. Streptococcus tigurinus, a novel member of the Streptococcus mitis group, was first identified in Zurich. S. tigurinus possesses virulence determinants and causes invasive infections. We report a case of culture-negative endocarditis with serious complications due to S. tigurinus, which was identified by 16S ribosomal RNA gene sequence analysis of excised valve tissue specimens. This technique is useful for identification of the causative microorganism in patients with culture-negative endocarditis and may facilitate early diagnosis and appropriate antimicrobial treatment.

Background Natural catastrophes increase infectious disease morbidity rates. On March 11, 2011, a 9.0-magnitude earthquake and associated Pacific coast tsunami struck East Japan. The aim of this study was to investigate the characteristics of patients with infectious diseases who needed hospitalization after this disaster. Methods We searched the medical records of 1,577 patients admitted to Tohoku University Hospital in the Sendai area within 1 month (March 11, 2011-April 11, 2011) after the disaster. We examined (1) changes in the rates of hospitalizations for infectious diseases over time and (2) the variety of infectious diseases. Results The number of hospitalized patients with infectious diseases increased after the first week to double that during the same period in 2010. Pneumonia comprised 43% of cases, and 12% consisted of skin and subcutaneous tissue infection, including tetanus. Pneumonia was prevalent in elderly patients (median age, 78 years) with low levels of serum albumin and comorbid conditions, including brain and nervous system disorders. Sputum cultures contained Streptococcus pneumoniae, Moraxella catarrhalis , and Haemophilus influenzae , known pathogens of community-acquired pneumonia in Japan. In addition, 20.5% of patients had positive results for urinary pneumococcal antigen. Conclusions Among hospitalized patients, infectious diseases were significantly increased after the disaster compared with the same period in 2010, with pneumonia being prominent. The analyses suggest that taking appropriate measures for infectious diseases, including pneumonia, may be useful for disaster preparedness and medical response in the future.

Background Klebsiella pneumonia is a well-known human pathogen, and recently, a distinct invasive syndrome caused by K. pneumoniae serotypes K1 and K2 has been recognized in Southeast Asia. This syndrome is characterized by primary liver abscess and extrahepatic complications resulting from bacteremic dissemination. We report the first adult case of primary liver abscess caused by the definite K2 serotyped pathogen, with endogenous endophthalmitis in Japan. Case presentation A 64-year-old woman was admitted to a nearby hospital for a high fever and diarrhea. She had visual loss of her right eye, renal dysfunction, and thrombocytopenia within 24 h from admission. She was transferred to our institution. On admission, she had no alteration of mental status and normal vital signs; however, she had almost complete ablepsia of the right eye. Laboratory data showed severe inflammation, liver dysfunction, thrombocytopenia, an increased serum creatinine level, and coagulopathy. Computed tomography showed a low density area in the right lobe of the liver. Invasive liver abscess syndrome probably caused by K. pneumonia was highly suspected and immediately administered broad-spectrum antibiotics for severe sepsis. Concurrently, endogenous endophthalmitis was diagnosed, and we performed vitrectomy on the day of admission. The blood culture showed K. pneumoniae infection. Percutaneous drainage of the liver abscess was also performed. Although she was discharged in a good general condition on day 22, she had complete ablepsia of the right eye. The K2A gene was detected by polymerase chain reaction (PCR), which is consistent with the K2 serotype. PCR was also positive for the virulence-associated gene rmpA. Final diagnosis was invasive liver abscess syndrome caused by K2 serotype K. pneumonia. Conclusions Although the primary liver abscess caused by K. pneumoniae with a hypermucoviscous phenotype is infrequently reported outside Southeast Asia, physicians should recognize this syndrome, and appropriate diagnosis and treatment is essential for saving patients’ lives and preserving organ function, especially for visual acuity.

Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused byToxocara canisorToxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA againstToxocaraexcretory-secretory antigen. Only a corticosteroid was used in Case 1, whereas a corticosteroid and albendazole were used in Case 2 as induction therapy. Both patients recovered. Albendazole was also used in Case 1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole.

Cryptococcal lung disease is usually diagnosed by chest X-ray abnormalities. Although no treatment exists for asymptomatically immunocompetent patients, a case with central nervous system (CNS) involvement as cryptococcus dissemination had a new chest X-ray abnormality during marked eosinophilia diagnosed as pulmonary cryptococcosis by lung biopsy. Eosinophilia may thus be associated with pulmonary cryptococcosis. We had seen reports of disseminated cryptococcosis with eosinophilia, so we conducted lumbar puncture and blood culture, but found no disseminated lesion or CNS involvement. Eosinophilia association with disseminated cryptococcosis has been reported, but not pulmonary cryptococcosis with solitary localized lung lesion with marked eosinophilia, making our case the first, in so far as we know reported of pulmonary cryptococcosis with a solitary localized lung lesion with marked eosinophilia.

Tuberculosis was diagnosed in a person who had stayed in a shelter after the 2011 Great East Japan Earthquake. A contact investigation showed that the prevalence of latent tuberculosis infection among other evacuees at the shelter was 20%. Our report underscores the importance of tuberculosis prevention and control after natural disasters.

Over-expression of alpha-phenol-soluble modulins (PSMs) results in high virulence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). The psm-mec gene, located in the mobile genetic element SCCmec-II, suppresses PSMαs production. Fifty-two patients with MRSA bacteraemia were enrolled. MRSA isolates were evaluated with regard to the psm-mec gene sequence, bacterial virulence, and the minimum inhibitory concentration (MIC) of vancomycin and teicoplanin. Fifty-one MRSA isolates were classified as SCCmec-II, and 10 had one point mutation in the psm-mec promoter. We compared clinical characteristics and outcomes between mutant MRSA and wild-type MRSA. Production of PSMα3 in mutant MRSA was significantly increased, but biofilm formation was suppressed. Wild-type MRSA caused more catheter-related bloodstream infections (30/41 vs. 3/10, p 0.0028), whereas mutant MRSA formed more deep abscesses (4/10 vs. 3/41, p 0.035). Bacteraemia caused by mutant MRSA was associated with reduced 30-day mortality (1/10 vs. 13/41, p 0.25), although this difference was not significant. The MIC90 of teicoplanin was higher for wild-type MRSA (1.5 mg/L vs. 1 mg/L), but the MIC of vancomycin was not different between the two groups. The 30-day mortality of MRSA with a high MIC of teicoplanin (≥1.5 mg/L) was higher than that of strains with a lower MIC (≤0.75 mg/L) (6/10 vs. 6/33, p 0.017). Mutation of the psm-mec promoter contributes to virulence of SCCmec-II MRSA, and the product of psm-mec may determine the clinical characteristics of bacteraemia caused by SCCmec-II MRSA, but it does not affect mortality.

The characteristics of active tuberculosis in cancer patients in Japan and the effects of this infection on cancer treatment have not yet been clarified. The records of all consecutive patients with microbiologically documented Mycobacterium tuberculosis infection diagnosed between September 2002 and March 2008 at Shizuoka cancer center (a 557-bed tertiary care cancer center in Japan) were reviewed. There were 24 cancer patients with active tuberculosis during the study period. Of these, 23 had solid-organ tumors, and the most common site of the underlying malignancy was the lung. Most of the patients had pulmonary tuberculosis. Among 15 patients followed up for more than 2 months prior to the diagnosis of pulmonary tuberculosis, 12 had healed scars suggestive of old tuberculosis lesions, as shown by chest imaging obtained at the time of the initial evaluation. Discontinuation of cancer therapy or more than a month's delay in surgery occurred in 10 patients with pulmonary tuberculosis. Development of active tuberculosis can delay cancer treatment in Japanese centers. Cancer patients with scars suggestive of old tuberculosis disease lesions as shown by chest imaging should be screened for active tuberculosis and carefully followed up. In some cases, prophylactic treatment should be considered.

The prevalence of ESBL has been increasing worldwide. In this study, we investigated the molecular characteristics of ESBL among clinical isolates of Escherichia coli from a Japanese tertiary hospital. A total of 71 consecutive and nonduplicate clinical isolates of ESBL-positive E. coli collected at Tohoku University Hospital between January 2008 and March 2011 were studied. The antimicrobial susceptibility profile of these strains was determined. PCR and sequencing were performed to identify genes for β-lactamase (bla(TEM), bla(SHV), bla(OXA-1-like), and bla(CTX-M)) and plasmid-mediated quinolone resistance determinants (PMQR). The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Of the 71 strains, 68 were positive for CTX-M, 28 were positive for TEM, four were positive for OXA-1, and one was positive for SHV. Sequencing revealed that CTX-M-14 was the most prevalent (31/71), followed by CTX-M-27 (21/71) and then CTX-M-15 (9/71). Of the 28 TEM-positive strains, one was TEM-10 and the rest were TEM-1. One SHV-positive strain was SHV-12. The 21 CTX-M-27-producing isolates were divided into 14 unique PFGE types, while the 9 CTX-M-15 producers were divided into 8 types. Based on MLST, 9 CTX-M-14 procedures, 19 CTX-M-27 procedures, and 8 CTX-M-15 producers belonged to ST131. Thirty-five (94.6%) of the 37 ST131 E. coli strains showed resistance to levofloxacin, which was a higher rate than among non-ST131 strains (63.6%). Among ESBL-producing isolates, one, two, and six possessed qnrB, qnrS, qepA, and aac(6')-Ib-cr, respectively. Of the 6 isolates with aac(6')-Ib-cr, 4 carried the CTX-M-15 gene. Our data suggest that CTX-M-15-producing E. coli ST131 has emerged as a worldwide pandemic clone, while CTX-M-27 (a variant of CTX-M-14) is also spreading among E. coli ST131 in Japan.

The public health community is faced with the global challenge posed by antimicrobial-resistant bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum b-lactamases (ESBLs)-producing enterobacteriaceae. The need to address this issue prompted the focus of World Health Day 2011, which was entitled “Antimicrobial resistance: no action today, no cure tomorrow.”In today’s world of international travel, the globalization of drug-resistant bacteria is a pressing issue for public health professionals. In the World Health Organization (WHO) Western Pacific Region, as well as other regions in the world, more and more new types of antimicrobial-resistant bacteria have come to the forefront. An important example is New Delhi Metallo-b-lactamase 1 (NDM-1)-carrying enterobacteriaceae, which attracted attention in Europe in 2010 as imported cases associated with health care contact in India and Bangladesh. Although some NDM-1 cases were reported from Australia and Japan,2 no outbreaks were reported in the Western Pacific Region.In this perspective article, we consider four focus areas for countries in the Western Pacific Region to consider when strategizing their response to antimicrobial resistant bacteria.

Carbapenems are the most potent agents for treating infections by Gram-negative bacteria due to their stability with respect to the majority of β-lactamases and their high rate of penetration through the bacterial outer membranes. However, there have been increasing reports of Gram-negative

Acinetobacter sp. has emerged as a major hospital pathogen ([8][1]). The greatest concern has been the emergence of carbapenem resistance in Acinetobacter baumannii by the acquisition of OXA-type carbapenemase or metallo-β-lactamases, since few effective antimicrobial agents exist. Several

Influenza-associated encephalopathy (IAE) is a serious complication of influenza and is reported most frequently in Japan. This paper presents an assessment of the epidemiological characteristics of influenza A (H1N1) 2009-associated encephalopathy in comparison to seasonal IAE, based on Japanese national surveillance data of influenza-like illness (ILI) and IAE during flu seasons from 2004-2005 through 2009-2010. In each season before the pandemic, 34-55 IAE cases (mean 47.8; 95% confidence interval: 36.1-59.4) were reported, and these cases increased drastically to 331 during the 2009 pandemic (6.9-fold the previous seasons). Of the 331 IAE cases, 322 cases were reported as influenza A (H1N1) 2009-associated encephalopathy. The peaks of IAE were consistent with the peaks of the influenza epidemics and pandemics. A total of 570 cases of IAE (seasonal A, 170; seasonal B, 50; influenza A (H1N1) 2009, 322; unknown, 28) were reported over six seasons. The case fatality rate (CFR) ranged from 4.8 to 18.2% before the pandemic seasons and 3.6% in the 2009 pandemic season. The CFR of pandemic-IAE was 3.7%, which is lower than that of influenza A-/B-associated encephalopathy (12.9%, p

The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing bla(CTX-M), bla(SHV), or bla(TEM) were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan.