Multi-azole resistant Aspergillus fumigatus harboring Cyp51A TR46/Y121F/T289A isolated in Japan.

Multi-azole resistant Aspergillus fumigatus carrying TR46/Y121F/T289A was isolated from a patient in Japan in Dec 2013. This strain grouped into the same clade of the ones which were clinically isolated in France and Germany. A. fumigatus harboring this mutation could be rapidly diffused outside the Eurasian continent.

[Routine written intervention asserting the advantages of multiple blood cultures increases their order rate among doctors].

PURPOSE: Obtaining two or more blood culture sets is important for achieving good sensitivity and for detecting contamination. However, many doctors still only order one set for their laboratory testing. We wished to determine if routine written intervention to these doctors could increase the number of multiple blood cultures they ordered. MATERIALS AND METHODS: On November 11, 2011 at Tokyo Teishin Hospital, we began sending letters asserting the advantages of using multiple blood culture sets to doctors who only ordered solitary blood cultures. The effect of the intervention was determined by measuring the order rate of multiple blood culture sets at the hospital. We compared the order rate one year before intervention with that of one year after. We used a chi-square test (without Yates correction) to analyze the data, and p values less than 0.05 were considered to be statistically significant; all tests were two-tailed. RESULTS: Before written intervention, the order rate of multiple blood cultures was 41%. This increased significantly to 68% after intervention (p < 0.001). The latter figure was 1.7 times greater than the former (relative risk, 1.7; 95% confidence interval, 1.5-1.8). CONCLUSION: Routine written educational intervention asserting the advantage of multiple blood cultures led to an increase in their order rate by doctors. While this is a significant increase, it is still insufficient. Therefore, we propose the need for internal policies requiring at least two blood culture sets to ensure better sensitivity and detection of contamination. To enforce these policies, hospital personnel should be allowed to routinely intervene by either sending warning letters to the doctors or displaying this information on the patient's electronic chart.

Familial spread of a virulent clone of Klebsiella pneumoniae causing primary liver abscess.

Capsule-forming Klebsiella pneumoniae K1 caused primary liver abscess in two household members of a family. The causative isolates had identical pulsed-field gel electrophoresis patterns and were determined to be sequence type 23. An additional member of the family was found to carry the same strain without clinical manifestation.

Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007.

We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America.

[A case of disseminated nocardiosis followed by pneumocystis pneumonia in a patient prescribed corticosteroid and cyclosporin A and having elevated blood (1-->3)-beta-D-glucan].

A 78-year-old man administered prednisolone and cyclosporin A for bullous pemphigoid and found in computed tomography (CT) to have a left-lung nodule was suspected of having a fungal infection due to elevated blood (1-->3)-beta-D-glucan. Despite empirical antifungal therapy, however, the nodule grew, followed by new nodules in both lungs. Disseminated nocardiosis was eventually diagnosed based on sputum, blood, and skin cultures growing Nocardia sp. Antinocardial treatment with imipenem/cilastatin and amikacin was started. The patient then developed pneumocystis pneumonia for which pentamidine was added. He had recovered completely when antimicrobial therapy was completed. A wide variety of microorganisms may infect patients with impaired cellular immunity, simultaneously involving multiple organisms in some cases. Definitive microbiological diagnosis with culture or biopsy specimens is therefore crucial for appropriate management.

Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population.

Excessive immune response is believed to play a role in the development of severe acute respiratory syndrome (SARS). Inhomogeneous spread of SARS led one to think of an Asian genetic predisposition and contribution of human leukocyte antigen (HLA) to the disease susceptibility. However, past case-control studies showed inconsistent results. In Viet Nam, of 62 patients with SARS, 44 participated in the present study together with 103 individuals who had contact with SARS patients and 50 without contact history. HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.

Combined treatment with oral kanamycin and parenteral antibiotics for a case of persistent bacteremia and intestinal carriage with Campylobacter coli.

Campylobacter coli (C. coli) is a rare pathogen of bacteremia, but in immunocompromised hosts, C. coli occasionally causes bacteremia which can be refractory to antibiotic treatment. We report a case of C. coli bacteremia in a patient with X-linked agammaglobulinemia. Bacteremia relapsed repeatedly in spite of treatment with combined intravenous antibiotics. C. coli was observed in the biopsy specimens from the intestinal mucosa, suggesting intestinal carriage and reservoir of recurring infection. The addition of oral kamamycin with intravenous antibiotics was successful in eradicating C. coli from the blood and intestine.

Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population.

We analyzed genetic variations of angiotensin-converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) or development of SARS as a functional receptor. By cloning of the full-length cDNA of the ACE2 gene in the lung, where replication occurs on SARS-CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon-intron boundaries, and the corresponding 5'-flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non-synonymous substitution and three 3'-UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti-SARS-CoV antibody-positive contacts, 87 antibody-negative contacts, and 50 non-contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5'-untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future.

Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population.

We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2',5'-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p=0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position -88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p=0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.

ACE1 polymorphism and progression of SARS.

We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS.

Prevalence of measles, rubella, mumps, and varicella antibodies among healthcare workers in Japan.

OBJECTIVES: To evaluate the immune status of healthcare workers (HCWs) against measles, rubella, mumps, and varicella in Japan, and to promote an adequate vaccination program among HCWs. SETTING: University of Tokyo Hospital. PARTICIPANTS: Eight hundred seventy-seven HCWs. DESIGN: Serologic screening for measles, rubella, mumps, and varicella was performed on HCWs. Antibodies against measles, rubella, and mumps were detected using hemagglutination inhibition (HI) assay ($4.20 per test). If serum was negative by HI assay, enzyme-linked immunosorbent assay (EIA) was performed ($12.60 per test). Anti-varicella antibodies were detected by EIA only. RESULTS: Among tested HCWs, 98.5%, 90.4%, 85.8%, and 97.2% had immunity to measles, rubella, mumps, and varicella, respectively. All those born before 1970 were seropositive for measles. However, individuals susceptible to rubella, mumps, and varicella were present in all age groups. The sensitivities and negative predictive values of HI assay compared with EIA were 86.6% and 11.3% for measles, 99.1% and 92.2% for rubella, and 47.8% and 24.1% for mumps, respectively. For measles and mumps, prevaccination screening by HI assay in combination with EIA led to significant savings compared with EIA only. In contrast, it was estimated that prevaccination screening using only HI assay would be more economical for rubella. CONCLUSIONS: Aggressive screening and vaccination of susceptible HCWs was essential regardless of age. Prevaccination serologic screening using a combination of HI assay and EIA was more economical for measles and mumps.