Evaluation of Nosocomial Infection Control Measures to Minimize the Risk of Aspergillus Dispersion During Major Demolition Work: A Case Study of a Japanese University Hospital.

OBJECTIVES: To verify the effectiveness of our infection control measures based on the infection control risk assessment (ICRA) to minimize the risk of Aspergillus dispersion before, during, and after demolition work in a university hospital. BACKGROUND: It is widely accepted that invasive aspergillosis is associated with construction, renovation, and demolition activities within or close to hospital sites. However, the risk is underestimated, and only limited preventive measures are taken in Japanese hospitals. METHOD: The demolition process, carried out in July 2014, was supervised by our facility management in collaboration with the infection prevention team and followed an adapted ICRA tool. Dust containment measures were implemented to reduce the risk of airborne Aspergillus contamination. Air sampling was performed at four wards in the adjacent hospital buildings to assess the containment measures' effectiveness. RESULTS: A high, undetermined number of colonies of bacteria and molds were detected on all outside balconies before demolition. During demolition, Aspergillus spp. was detected only in the ward closest to the demolition site. However, no case of aspergillosis was reported. The difference-in-difference analysis revealed that the interaction between the demolition activity, height of the ward, and distance of the air intake to the demolition activities resulted in a significant increase in the numbers of Aspergillus spp. CONCLUSIONS: When large-scale demolition work occurs in hospital premises, Aspergillus spp. may increase in the ward where the vertical and horizontal distance of air intake from the demolition site is close, even though infection control measures based on the ICRA are implemented.

Molecular and Epidemiological Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates in Japan.

Carbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan.IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance.

Necessity to screen and treat latent tuberculosis before ruxolitinib treatment-Ruxolitinib-associated disseminated tuberculosis: A case report and literature review.

Ruxolitinib, a Janus kinase inhibitor, considerably improves symptoms of patients with polycythemia vera and primary or secondary myelofibrosis. However, its association with the development of infectious complications is a concern. Herein, we report the case of an 80-year-old man with primary myelofibrosis who developed disseminated tuberculosis during treatment with ruxolitinib at 15 mg twice daily and prednisone at 5 mg. We also reviewed the literature on patients who developed tuberculosis during treatment with ruxolitinib. There are 13 case reports of patients who developed tuberculosis during treatment with ruxolitinib, including our case. Disseminated tuberculosis manifestations were observed in 84.6 % of the patients and 50 % of them died. Although the interferon-gamma release assay was performed for seven of the patients with six positive results at the time of tuberculosis diagnosis, none were tested before the commencement of ruxolitinib. We suggest taking a history of tuberculosis and screening for and treating latent tuberculosis before administering ruxolitinib, especially in areas where the risk of tuberculosis is high.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 41.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.5% and 0.6%, respectively.

Impact of vaccination on measles, mumps, and rubella antibody titers in Japanese healthcare workers: An observational study.

Given the complicated history of Japan's National Immunization Program, a significant proportion of Japanese people including healthcare workers (HCWs) still lack adequate immunity against measles, mumps, and rubella (MMR), resulting in occasional outbreaks. In 2014, the Japanese Society of Infection Prevention and Control (JSIPC) published vaccination guidelines for HCWs. We evaluated antibody titers before and after MMR vaccination in HCWs at the Nara Medical University Hospital, the attainment rate of the target antibody titers defined by the JSIPC guidelines, and the safety of vaccines. We measured MMR antibody titers in HCWs, followed by inoculation with the respective monovalent vaccines and/or trivalent MMR (tMMR) vaccine according to the JSIPC guidelines. Among 467 HCWs evaluated, antibody titers against measles and mumps measured using the IgG-enzyme immunoassay increased from 11.0 [interquartile range (IQR): 8.0-13.6] to 13.7 (IQR: 11.3-16.9; P < 0.001) and from 2.8 (IQR: 2.1-3.5) to 4.8 (IQR: 3.7-5.7; P < 0.001), respectively. By evaluating a logarithmic value of log2(X + 1) converted from an antibody titer X, antibody titers against rubella measured using the hemagglutination assay increased from 3.2 (IQR: 0-4.1) to 6.0 (IQR: 4.6-8.0; P < 0.001). Antibody titer elevated following tMMR vaccination was lower than that following monovalent vaccination in a single dose of the measles-containing, a single dose of the mumps-containing, and two doses of rubella-containing vaccine groups (P = 0.01, 0.01, and <0.001, respectively). After vaccination, 20.0%, 61.5%, and 46.2% of HCWs attained target antibody titers specified by the JSIPC guidelines for measles, rubella, and mumps, respectively. The systemic response in female HCWs who underwent monovalent mumps vaccination was statistically higher than that in others. Although the vaccination program for HCWs according to the JSIPC guidelines caused increased MMR antibody titers, the rates of attaining the target criteria were low.

Filifactor alocis brain abscess identified by 16S ribosomal RNA gene sequencing: A case report.

We report a clinical case of Filifactor alocis brain abscess in an 85-year-old man who had decayed teeth 1 week prior. In this case, the abscess was surgically drained after empirical antibiotics had been initiated. Although the causative organism could not be identified by culture, F. alocis was detected via 16S ribosomal RNA (16S rRNA) gene sequencing of the pus isolated from the abscess. The patient recovered without serious sequelae after surgical drainage and prolonged antibiotic treatment, including metronidazole, ceftriaxone and meropenem for 8 weeks. The findings in this case emphasize that 16S rRNA gene sequencing allows bacterial diagnosis of brain abscess when phenotypic identification fails, such as in cases where patients are undergoing antimicrobial treatment at the time of sampling or where patients are infected with fastidious organisms.

Comparison of the inoculum size effects of antibiotics on IMP-6 ß-lactamase-producing Enterobacteriaceae co-harboring plasmid-mediated quinolone resistance genes.

Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened ß-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum ß-lactamases. All isolates carried one or more PMQRs; aac(6')-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-ß-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.

Case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma.

Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis.

Peritonitis due to Moraxella osloensis: A case report and literature review.

A-26-year-old man was admitted to our hospital with diffuse abdominal pain, nausea, and vomiting. He had a history of malignant nephrosclerosis, for which he had been receiving peritoneal dialysis (PD) for the past 14 months. His PD effluent was cloudy and turbid (white blood cell count, 10,528/µL; neutrophils 95.2%). A Gram-negative coccobacillus was isolated from peritoneal fluid culture. However, the organism could not be identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS, bioMérieux), but was identified as Moraxella osloensis by the 16S rRNA gene sequencing. He was successfully treated with intraperitoneal cefazolin therapy for 3 weeks without removing the intra-abdominal catheter. A literature review revealed three previous case reports all of which were diagnosed by MALDI Biotyper (Bruker Daltonics), suggesting that the identification of M. osloensis may vary depending on the type of MALDI-TOF MS system. In conclusion, we experienced a case of M. osloensis infection in a PD patient, which was successfully treated by antibiotic treatment, without removing the PD catheter.

Abrogated Caveolin-1 expression via histone modification enzyme Setdb2 regulates brain edema in a mouse model of influenza-associated encephalopathy.

Influenza-associated encephalopathy (IAE) is a serious complication that can follow influenza virus infection. Once a cytokine storm is induced during influenza virus infection, tight junction protein disruption occurs, which consequently leads to blood-brain barrier (BBB) breakdown. However, the details of IAE pathogenesis are not well understood. Here, we established a murine IAE model by administration of lipopolysaccharide following influenza virus infection. Brains from IAE model mice had significantly higher expression of type I interferons and inflammatory cytokines. In addition, the expression of Caveolin-1, one of the key proteins that correlate with protection of the BBB, was significantly lower in brains from the IAE group compared with the control group. We also found that, among 84 different histone modification enzymes, only SET domain bifurcated 2 (Setdb2), one of the histone methyltransferases that methylates the lysine 9 of histone H3, showed significantly higher expression in the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3 lysine 9 was correlated with repression of the Caveolin-1 promoter region. These studies identify Caveolin-1 as a key regulator of BBB permeability in IAE and reveal that it acts through histone modification induced by Setdb2.

Molecular epidemiology and clinical features of extended-spectrum beta-lactamase- or carbapenemase-producing Escherichia coli bacteremia in Japan.

OBJECTIVES: To identify risk factors and clinical outcomes in patients with bacteremia due to extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing Escherichia coli, as well as to determine the prevalence and genetic background of such isolates. METHODS: Case control study was performed with patients with E. coli bacteremia between January 2008 and May 2013 (n = 115) at a tertiary university hospital in Japan. Cases had ESBL-producing E. coli (ESBL-EC) whereas controls had non-ESBL-producing E. coli (non-ESBL-EC) isolates. A retrospective chart review was performed to identify risk factors and clinical outcomes. Isolates were characterized by antimicrobial susceptibility testing, polymerase chain reaction analysis for beta-lactamase genes, and multi-locus sequence typing. RESULTS: Of 115 unique cases of E. coli bacteremia, 30 (26.1%) were due to ESBL-EC and three (2.6%) were due to carbapenemase-producing E. coli. All three carbapenemase-producing E. coli isolates were IMP-6 and concurrently produced ESBL (ESBL/IMP-6-EC). ESBL-EC isolates showed multidrug resistance. Of the ESBL-EC isolates, CTX-M-27 was the most prevalent (33.3%), followed by CTX-M-14 (30%). Multi-locus sequence typing revealed that 19 (63.3%) isolates were ST131. The multivariate analysis identified nursing home-associated infections and antibiotic administration in the preceding 30 days as risk factors for ESBL-EC bacteremia. The 14-day mortality non-ESBL-EC, ESBL-EC, and ESBL/IMP-6-EC was 4.7% (4/85), 20% (6/30), and 66.7% (2/3), respectively. CONCLUSIONS: CTX-M-27, CTX-M-14, and ST131 were the most prevalent ESBL-EC isolates from bacteremic patients in a Japanese hospital. Further studies with larger sample sizes are warranted to investigate the clinical significance of ESBL-EC and ESBL/IMP-6-EC.

Rat-Bite Fever in Human with Streptobacillus notomytis Infection, Japan.

We report a case of rat-bite fever in a 94-year-old woman with Streptobacillus notomytis infection. We established an epidemiologic link between exposure to rats and human infection by performing nested PCRs that detected S. notomytis in the intraoral swab specimens obtained from rats captured in the patient's house.

Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.

BACKGROUND: Countries in the Southeast Asia region have a high prevalence of soil-transmitted helminth, such as roundworm, whipworm, and hookworms [Ancylostoma duodenale, Necator americanus, Ancylostoma ceylanicum]. Recent molecular-based surveys have revealed that A. ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in that part of the world, while others have noted that this infection is an emerging public health risk not only for indigenous people but also for visitors from other countries. CASE PRESENTATION: We recently encountered four cases of A. ceylanicum infection in Japanese individuals who returned from Southeast Asia and Papua New Guinea. Case 1 was a 25-year-old male who stayed in a rainforest in Malaysia for 4 weeks, where he developed abdominal pain and diarrhea in the third week. Eleven adult worms (five males, six females) were expelled after treatment with pyrantel pamoate and identified as A. ceylanicum based on morphological characteristics and DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Case 2 was a 26-year-old male who spent 2 years as an overseas cooperation volunteer for agriculture in Papua New Guinea. He did not note any symptoms at that time, though eggs were detected in feces samples at a medical check-up examination after returning. Although collection of adult worms was unsuccessful, DNA analysis of the eggs for cox1 and the ribosomal internal transcribed spacer (ITS)-1 and ITS-2 genes demonstrated that they were A. ceylanicum. Case 3 was a 47-year-old male who spent 1 month in a rural village in Lao People's Democratic Republic and began suffering from watery diarrhea from the third week. A total of nine adult worms (three males, six females) were collected by endoscopic procedures and following treatment with pyrantel pamoate. Morphological examination and molecular analyses of the cox1 gene showed that they were A. ceylanicum. Case 4 was a 27-year-old male who participated in group travel to India for 5 days. Three weeks after returning, he developed abdominal pain and diarrhea. Hookworm eggs were found in feces samples and developed into larvae in culture, which were identified as A. ceylanicum based on molecular analysis of the cox1 gene. Eosinophilia was observed in all of the cases prior to treatment. CONCLUSIONS: A. ceylanicum should be recognized as an important etiologic pathogen of hookworm diseases in travelers to countries in the Southeast Asia and West Pacific Ocean regions.

Characteristics of health problems in returned overseas travelers at a tertiary teaching hospital in a suburban area in Japan.

Few studies have analyzed the characteristics of patients who develop physical disorders after overseas travel. We retrospectively reviewed the medical records of 183 patients who visited Nara Medical University Hospital from 2008 to 2016 because of physical problems after traveling abroad. The main travel destinations were Southeast Asia (n = 100), Africa (n = 27), and South Asia (n = 23). The main reasons for the travel were leisure (n = 96), business (n = 51), and volunteer work (n = 19). The most common final diagnosis was gastrointestinal disease (n = 72), followed by febrile disease (n = 59) and respiratory disease (n = 19). There were eight malaria cases, including one patient who was infected after <14 days of overseas travel. Additionally, 61 of 71 cases of travelers' diarrhea and 15 of 21 cases of dengue fever occurred after <14 days travel. 26 cases of vaccine preventable diseases, such as hepatitis A, typhoid fever, and influenza, were observed. Consequently, healthcare providers should notify Japanese overseas travelers that there is a non-negligible health risk inherent to short-term travel, while stressing on the importance of pre-travel medical consultation.

Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations.

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54.

Pulmonary involvement of secondary syphilis.

Pulmonary involvement in secondary syphilis is considered a rare occurrence; however, the number of cases has increased in the 2000s. This is likely due to the increased use of computed tomography scans and molecular diagnostic testing. We report a case of an HIV-positive man with pleural chest pain and bilateral subpleural nodules on chest computed tomography. His rapid plasma reagin and Treponema pallidum hemagglutination tests were positive, and the specimen of one of the pulmonary nodules obtained by transthoracic biopsy was positive for the polA gene of Treponema pallidum. Since clinical manifestations of syphilis are highly variable, clinicians should bear in mind that pleural chest pain with bilateral subpleural nodules can be caused by pulmonary syphilis.

Infective Endocarditis Complicated by Intraventricular Abscesses, Pericarditis, and Mycotic Aneurysm Due to an Emerging Strain of Serotype VI Streptococcus agalactiae.

An increasing number of invasive infections due to Streptococcus agalactiae in non-pregnant adults have been reported. We report a case of infective endocarditis complicated by intraventricular abscesses, pericarditis, and mycotic aneurysm due to S. agalactiae belonging to ST681 with a capsular serotype VI in a woman with diabetes. The patient also had a myocardial infarction and was treated with percutaneous coronary intervention, pericardiocentesis, and 6 weeks of antibiotic treatment. Invasive infections due to serotype VI S. agalactiae are common in Asian countries such as Taiwan and Japan, so continuous monitoring of invasive S. agalactiae strains is warranted.

Mycobacterium wolinskyi Peritonitis after Peritoneal Catheter Embedment Surgery.

Mycobacterium wolinskyi belongs to the Mycobacterium smegmatis group, which comprises rapidly growing non-tuberculous mycobacteria. The number of case reports on M. wolinskyi infections associated with postoperative wounds has increased in recent years. We herein report a case of peritonitis due to M. wolinskyi after peritoneal catheter embedment surgery. Identification was achieved based on 16S ribosomal RNA and rpoB gene sequencing of the isolate. The patient recovered following catheter removal and treatment with levofloxacin and minocycline for one month.