Hirotoshi Iihara

Mycobacterium kumamotonense Sp. Nov. recovered from clinical specimen and the first isolation report of Mycobacterium arupense in Japan: Novel slowly growing, nonchromogenic clinical isolates related to Mycobacterium terrae complex.

Three mycobacterium strains isolated from clinical specimens in Japan were provisionally assigned to the genus Mycobacterium based on their phenotypical characteristics. These isolates were further investigated to determine their specific taxonomic statuses. Mycolic acid analysis and 16S rRNA gene, rpoB, and hsp65 sequence data for the isolates showed that they are most similar to M. terrae complex. DNA‐DNA hybridization studies indicated that the three strains were of two species and were distinguishable from M. terrae, M. nonchromogenicum, and M. hiberniae. Therefore, these strains represent two novel species within the genus Mycobacterium. However, one potential new species should have been considered as M. arupense with the 16S rRNA gene and hsp65 sequences similarities of 99.8% and 100% respectively; it was isolated from human specimens in the United States and was proposed in June 2006 as a new species. This report describes the first isolation of M. arupense in Japan, suggesting that the organism is clinically relevant. In addition, we propose the novel species designation Mycobacterium kumamotonense sp. nov. The type strain is CST 7247T (=GTC 2729T, =JCM 13453T, =CCUG 51961T).

Corynebacterium resistens sp. nov., a New Multidrug-Resistant Coryneform Bacterium Isolated from Human Infections

ABSTRACT Five strains of an unknown, multidrug-resistant coryneform, gram-positive rod were isolated from blood, bronchial aspirate, and abscess specimens. Four of the five strains isolated were highly resistant to antimicrobial agents, including β-lactams, aminoglycosides, macrolides, quinolones, and tetracyclines, except for glycopeptides. In immunocompromised patients, bacteremia associated with this organism was rapidly fatal. This coryneform bacterium was nonmotile, lipophilic, and nonsaccharolytic. Lack of pyrazinamidase activity differentiated this organism from other lipophilic corynebacteria. Chemotaxonomic studies indicated that this multidrug-resistant coryneform bacterium belongs to the genus Corynebacterium. Comparative 16S rRNA gene sequencing and DNA-DNA hybridization analyses revealed that the five isolates were genetically identical and that they represent a new subline within the genus Corynebacterium, for which we propose the designation Corynebacterium resistens sp. nov. The type strain of Corynebacterium resistens is GTC 2026T (SICGH 158T, JCM 12819T, CCUG 50093T).

Suture-Related Keratitis Caused by Corynebacterium macginleyi

ABSTRACT We report two cases of suture-related keratitis following penetrating keratoplasty. In both cases, Corynebacterium macginleyi was isolated from corneal specimens. Scanning electron microscopy revealed that corynebacteria could aggregate and form a biofilm. The MICs of sulbenicillin and fluoroquinolones were high for both isolates. Our findings show that C. macginleyi can cause keratitis with biofilm formation.

Pharmacists contribute to the improved efficiency of medical practices in the outpatient cancer chemotherapy clinic

RATIONALE, AIMS AND OBJECTIVES Outpatient cancer chemotherapy is increasing with the development of anticancer agents, and roles of medical staff are becoming more and more important in cancer chemotherapy. We showed here roles of pharmacists with experience in oncology and evaluated outcomes of their activities in medical practices in cancer chemotherapy clinic. METHODS Two pharmacists were newly assigned to the outpatient cancer chemotherapy clinic, where they were in charge of verification of prescription orders, mixing of anticancer injections, monitoring adverse drug reactions, implementation of supportive care and provision of information about cancer chemotherapy to medical staff and patients. The number of patients, amounts of mixing of anticancer injections and hospital revenue were compared before and after assignment of pharmacists. Management of chemotherapy-induced nausea and vomiting in breast cancer patients receiving the combination chemotherapy with anthracycline and cyclophosphamide were also compared. RESULTS Pharmacists spent 75 hours per month in patient education and adverse drug reactions monitoring, which led to the reduction of the workload of physicians. As a consequence, the number of outpatients and the resultant hospital revenue markedly increased. In addition, facilitation of proper use of anti-emetic drugs led to the improved control of chemotherapy-induced nausea with reducing the cost for anti-emesis by 16%. CONCLUSIONS Pharmacists contributed to the improved efficiency of medical practices.

Pharmaceutical interventions facilitate premedication and prevent opioid-induced constipation and emesis in cancer patients

BackgroundOpioid analgesics possess a number of side effects, among which constipation and nausea/vomiting occur most frequently. Although pretreatment with laxatives and antiemetics for the prophylaxis of opioid-induced constipation and nausea/vomiting, respectively, is recommended, such side effects are still a matter of concern in clinical setting.MethodsWe first surveyed the prevalence of premedication in 83 cancer patients who took opioid analgesics and the incidence of such side effects. Subsequently, intervention was carried out to promote premedication, and the effectiveness of the intervention was evaluated in 107 patients.ResultsProphylactic treatment with laxatives and antiemetics were conducted in 57% and 52%, respectively. The most frequently prescribed laxatives and antiemetics were magnesium oxide in combination with pantethine, a mild stimulant laxative, and prochlorperazine, respectively. The lack of premedication increased the risk of constipation (odds ratio, 5.25; 95% confidence intervals, 1.93–14.31; p = 0.001) and vomiting (4.67, 1.04–21.04; p = 0.045). Intervention such as provision of drug information to physicians, verification of prescription orders, and instructions to patients increased the rates of prophylactic medications to 93% (p < 0.001) for laxatives and 81% (p < 0.001) for antiemetics. The incidence of side effects was lowered from 36% to 9% (p < 0.001) for constipation, from 28% to 17% for nausea (p = 0.077), and from 16% to 4% for vomiting (p = 0.0085).ConclusionIntervention to promote prophylactic medication was highly effective in reducing the risk of opioid-induced constipation and nausea/vomiting.

Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non-small-cell lung cancer.

A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 μL samples of human blood plasma. Diluted plasma samples were extracted using a liquid-phase extraction procedure with tert-butyl methyl ether. The three drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05-100 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall-cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC-MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Leptomeningeal metastases occur in 1% of patients with non-small-cell lung cancer. There have been several reports on the treatment of leptomeningeal metastases with afatinib. Our patient was a 41-year-old woman who had never smoked and was diagnosed with stage IV adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation. She was treated with afatinib for the recurrence of leptomeningeal metastases. After the treatment with afatinib was initiated, the neurological symptoms dramatically regressed, and she achieved progression-free survival for 7 months. The concentration of afatinib in the cerebrospinal fluid (CSF) ranged from 0.05 to 0.14 ng/mL, and the penetration rate of afatinib from the plasma to the CSF ranged from 0.28 to 0.40%. This concentration might be sufficient to achieve a clinical effect for leptomeningeal carcinomatosis. Therefore, afatinib administered at the usual doses may be an effective treatment for leptomeningeal carcinomatosis of EGFR-mutated or EGFR-tyrosine kinase inhibitor-sensitive lung adenocarcinoma.

Comparison of the Control of Nausea and Vomiting among Several Moderately Emetic-Risk Chemotherapy Regimens

Background: Different antiemetic medications with or without aprepitant are recommended for moderately emetic-risk chemotherapy (MEC) depending on the emetic potential of chemotherapy agents, although the criterion for the use of aprepitant is still unclear. The present study was designed to compare the control of chemotherapy-induced nausea and vomiting (CINV) among several MEC regimens used in the outpatient chemotherapy setting. Materials and Methods: A single center prospective observational study was carried out in 326 patients who received 2,061 chemotherapy cycles from January 2013 to December 2014. Antiemetic medication consisting of two-drug combination of granisetron (day 1) and dexamethasone (days 1-3) was carried out in 87.6% of patients receiving the first chemotherapy cycle. The checklist for CINV was provided to all patients, and the control of CINV was evaluated on the next visit based on the checklist. Complete inhibition of nausea and vomiting during acute and delayed periods were compared among MEC regimens. Results: Two hundred and one patients received the first cycle of chemotherapy, in which the rates of complete inhibition of nausea and vomiting were 87.6% and 95.5%, respectively, during acute period, and 68.2% and 92.0%, respectively, during delayed period. There were no significant differences in the control of CINV among oxaliplatin, carboplatin and irinotecan, except for the cyclophosphamide-base regimen. Conclusions: Two-drug antiemetic medication of 5-HT3 receptor antagonist and dexamethasone was sufficiently effective for prevention of CINV in most MEC regimens.