Comparison of Four Carbapenems; Imipenem-Cilastatin, Panipenem-Betamipron, Meropenem, and Biapenem with Review of Clinical Trials in Japan

The development of carbapenem gives a revolutionary impact to the chemotherapy of infectious diseases. The bacteriological and clinical efficacies of carbapenems, including imipenem/cilastatin, panipenem/betamipron, meropenem and biapenem, were evaluated. All four carbapenems were potent against gram-positive and gram-negative bacteria except Stenotrophomonas maltophilia. The antimicrobial activities of meropenem against Enterobacteriaceae were slightly superior to other carbapenems. Imipenem and panipenem were slightly more active against gram-positive bacteria than meropenem and biapenem. Biapenem was the most potent against Acinetobacter anitratus. The in vitro activity of imipenem was compared between 1990 and 1992 in Nagasaki University Hospital. The resistance rate of S. aureus, whose MIC is higher than 25 mg/l, increased from 3% to 22%, S. pneumoniae, whose MIC is higher than 0.05 mg/l, increased from 9% to 30% and P. aeruginosa, whose MIC is higher than 5 mg/l, increased from 20% to 32%. The isolation rates of S. maltophilia from sputum increased gradually from 0.9% in 1984 to 3.5% in 1991. The clinical efficacy rates of imipenem/cilastatin and panipenem/betamipron were 79% and 77%, and the rates of meropenem and biapenem 100% and 96.2% for the treatment of respiratory infection in our department, respectively. The efficacy rates of imipenem/cilastatin decreased from 79% to 67.7% after being commercialized. This decline was due to administration to patients with severe underlying diseases and with infection caused by resistant strains such as P. aeruginosa and S. aureus. The phase II and III trials of carbapenems in internal medicine, which were performed separately in Japan, showed that the clinical efficacy rates were 73%, 79%, 86% and 89%, and the rates of adverse reaction were 4.7%, 3.3%, 1.8% and 2.2% in imipenem /cilastatin, panipenembetamipron, meropenem and biapenem, respectively. Newly develope

A Case of Paragonimus westermani Infection by Eating Imperfectly Cooked Wild Boar Flesh

A 19 year old woman was admitted because of abnormal chest X-ray showing smoothly outlined cystic lesion. The eggs of Paragonimus westermani was identified in the broncho-alveolar lavage fluid. Anti-Paragonimus westermani antibody was positive in the serum by the ELISA method. Six eggs were observed in one gram of feces before the administration of praziquantel. Praziquantel (75mg/kg) was administered for two day, the egg of Paragonimus westermani disappeared in the feces and the size of cystic lesion in the chest X-ray decreased

Whole Genome Sequencing of Influenza A and B Viruses With the MinION Sequencer in the Clinical Setting: A Pilot Study

Introduction: Whole genome sequencing (WGS) of influenza viruses is important for preparing vaccines and coping with newly emerging viruses. However, WGS is difficult to perform using conventional next-generation sequencers in developing countries, where facilities are often inadequate. In this study, we developed a high-throughput WGS method for influenza viruses in clinical specimens with the MinION portable sequencer.Methods: Whole genomes of influenza A and B viruses were amplified by multiplex RT-PCR from 13 clinical specimens collected in Tokyo, Japan. Barcode tags for multiplex MinION sequencing were added with each multiplex RT-PCR amplicon by nested PCR with custom barcoded primers. All barcoded amplicons were mixed and multiplex sequencing using the MinION sequencer with 1D2 sequencing kit. In addition, multiplex RT-PCR amplicons generated from each clinical specimen were sequenced using the Illumina MiSeq platform to validate the performance of MinION sequencer. The accuracy, recall, and precision rates of MinION sequencing were calculated by comparing the results of variant calling in the Illumina MiSeq platform and MinION sequencer.Results: Whole genomes of influenza A and B viruses were successfully amplified by multiplex RT-PCR from 13 clinical samples. We identified 6 samples as influenza type A virus H3N2 subtype and 7 as influenza B virus Yamagata lineage using the Illumina MiSeq platform. The overall accuracy, recall, and precision rates of the MinION sequencer were, respectively 99.95%, 89.41%, and 97.88% from 1D reads and 99.97%, 93.28%, and 99.86% from 1D2 reads.Conclusion: We developed a novel WGS method for influenza A and B viruses. It is necessary to improve read accuracy and analytical tools in order to better utilize the MinION sequencer for real-time monitoring of genetic rearrangements and for evaluation of newly emerging viruses

Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan

OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.METHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.RESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.CONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable

Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candida albicans strains

We investigated the drug efflux mechanism in azole-resistant strains of Candida albicans using rhodamine 6G (R6G). No significant differences in R6G uptake were observed between azole-sensitive B2630 (9.02 ± 0.02 nmol/108 cells) and azole-resistant B67081 (8.86 ± 0.03 nmol/108 cells) strains incubated in glucose-free phosphate buffered saline. A significantly higher R6G efflux (2.0 ± 0.21 nmol/108 cells) was noted in the azole-resistant strain (B67081) when glucose was added, compared with that in the sensitive strain B2630 (0.23 ± 0.14 nmol/108 cells). A fluconazole-resistant strain C40 that expressed the benomyl resistance gene (CaMDR) also showed a low R6G efflux (0.16 ± 0.06 nmol/108 cells) as did the sensitive strains. Accumulation of R6G in growing C. albicans cells was inversely correlated with the level of CDR1 mRNA expression. Our data also suggest that measurement of intracellular accumulation of R6G is a useful method for identification of azole-resistant strains due to CDR1-expressed drug efflux pum