Micafungin activity against Candida bloodstream isolates: effect of growth medium and susceptibility testing method

An excellent correlation between micafungin MICs were demonstrated against Candida bloodstream isolates (n = 200) by the Sensititre YeastOne and National Committee for Clinical Laboratory Standards M27-A2 methods. Use of antibiotic medium 3 (2%) dextrose improved micafungin activity and was not associated with paradoxical growth as noted with 3 Candida isolates tested using RPMI (2%) dextrose.     

Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

Efficacy of liposomal amphotericin B against four species of Candida biofilms in an experimental mouse model of intravascular catheter infection

The formation of Candida biofilms on implanted medical devices is crucial to the development of infections and an important clinical problem because of elevated resistance to antifungals. The aim of this study was to compare the in vitro activity of liposomal amphotericin B (L-AMB) and micafungin (MCFG) against four species of Candida biofilms, and the efficacy of systemic plus lock therapy with L-AMB and MCFG in a Candida biofilm-associated catheter infection model. An XTT-reduction assay was used to measure the metabolic activity of the biofilms to evaluation of in vitro antibiofilm activity. MCFG had better in vitro activity than L-AMB against Candida glabrata biofilms, whereas L-AMB had better activity than MCFG against Candida albicans and Candida tropicalis biofilms. L-AMB and MCFG had comparable efficacy against Candida parapsilosis biofilms. In an in vitro lock therapy model, 2 mg/ml L-AMB, unlike 2 mg/ml MCFG, significantly reduced the metabolic activity of all the strains of biofilms by >96%. Systemic and intraluminal lock treatment with L-AMB for 3-days resulted in more than about 2 log₁₀ reduction of Candida compared with that of systemic treatment and the control group in the C. albicans SP-20012, C. glabrata SP-20040, C. glabrata SP-20131, C. parapsilosis SP-20137, and C. tropicalis SP-20047 infection models. L-AMB was more effective at eradicating Candida biofilms in 3-day course of systemic and lock therapy than MCFG. L-AMB may be useful for the treatment of catheter-related Candida biofilm infections, but this finding will need to be confirmed by further studies including a long treatment duration.     

Risk assessment of micafungin-induced liver injury using spontaneous reporting system data and electronic medical records

IntroductionThere is limited information regarding antifungal-induced liver injuries, which have high mortality rates. Therefore, we used the Japanese Adverse Drug Event Report (JADER) database for signal detection associated with antifungal-induced liver injuries and medical records for risk assessment.MethodsReports of antifungal-induced liver injuries from JADER data were analyzed to calculate the reporting odds ratio (ROR) and 95% confidence interval (CI). A medical record-based study involving 109 adult patients treated with micafungin shows liver injury as the primary outcome in patients treated with micafungin. The albumin-bilirubin (ALBI) score was calculated based on albumin and total bilirubin levels. We selected five explanatory factors for multivariable logistic regression: alanine aminotransferase ≥20 IU/L, alkaline phosphatase ≥372 IU/L, aspartate aminotransferase ≥25 IU/L, ALBI score ≥ ?1.290, and age ≥65 years.ResultsSignal detection for micafungin was observed in both, hepatocellular and cholestatic injuries, as per data from JADER. Univariate analyses performed on medical records suggest that alanine aminotransferase (p = 0.008), aspartate aminotransferase (p = 0.036), alkaline phosphatase (p = 0.045), and ALBI score (p = 0.028) may be factors associated with micafungin-induced liver injury. Based on multivariable logistic regression, the adjusted odds ratio for micafungin-induced liver injury in patients with ALBI score ≥ ?1.290 was 2.78 (95% CI: 1.014–7.605, p = 0.047), suggesting that low hepatic functional reserve could be a risk factor for micafungin-induced liver injury.ConclusionsCareful monitoring of liver function may be necessary for micafungin administration in patients with low hepatic functional reserve.     

伏立康唑治疗侵袭性真菌感染有效性及安全性的Meta分析

目的系统评价伏立康唑治疗侵袭性真菌感染的有效性及安全性。方法检索PubMed、Co-chrane Library、EMbase、CNKI、CBM、VIP数据库,收集截至2011年12月已发表的伏立康唑治疗深部真菌感染的随机对照试验。由2名研究者按照纳入标准独立筛选文献、提取资料和评价质量后,采取RevMan 5.0软件进行Meta分析。结果共纳入研究7项,676例。Meta分析结果提示,伏立康唑、两性霉素B的治疗成功率比较,差异无统计学意义;伏立康唑、伊曲康唑的治疗成功率、不良反应发生率比较,差异均无统计学意义;伏立康唑治疗成功率略高于米卡芬净组(P=0.11),但差异无统计学意义,其不良反应发生率高于米卡芬净(P=0.000 6)。结论伏立康唑在治疗侵袭性真菌感染中表现出高效低毒的特点。随着其临床应用愈加广泛,其价值有待进一步检验。     

米卡芬净在儿童恶性血液病患者合并肺部真菌感染中的临床应用

目的 探讨米卡芬净治疗儿童恶性血液病并侵袭性肺部真菌感染的疗效及安全性.方法 选取柘城县人民医院血液/肿瘤病区治疗恶性血液病合并肺部真菌感染患儿51例,随机分为两组,分别给予米卡芬净与伏立康唑治疗,比较两组的治疗有效率、痊愈率和不良反应发生率.结果 两组患儿在有效率和痊愈率方面比较差异无统计学意义（P〉0.05）,但在不良反应发生率方面,米卡芬净组患儿低于伏立康唑组患儿,差异有统计学意义（P〈0.05）.结论 米卡芬净与伏立康唑对儿童恶性血液病侵袭性肺部真菌感染均具有良好的疗效,但米卡芬净具有更好的安全性.     

Evaluation of the safety and efficacy of micafungin in Japanese patients with deep mycosis: a post-marketing survey report

The safety and efficacy of micafungin were evaluated in a Japanese post-marketing survey involving 1,142 patients with deep mycosis caused by Candida or Aspergillus. The overall clinical response was 83.0%, and the respective responses for patients with candidiasis or aspergillosis were 86.3 and 70.8%. With regard to drug reactions, 562 adverse reactions were observed in 28.5% of patients. Among the 83 serious adverse drug reactions reported by 53 patients, a causal relationship with micafungin was assessed as definite or probable for 6 reactions in 5 patients. Age and baseline hepatic and renal function status did not affect the incidence of adverse reactions, although incidence increased significantly in proportion to the severity of mycosis and daily dose (p < 0.01). In multiple logistic regression analysis, neither baseline hepatic impairment nor increased daily dose of micafungin affected the incidence of hepatobiliary disorders, however, the severity of mycosis was found to correlate significantly with hepatobiliary disorders (p = 0.031). Taken together, our post-marketing findings show that micafungin is effective against deep mycosis caused by Candida or Aspergillus in patients across a range of backgrounds.     

Comparison of micafungin MICs as determined by the Clinical and Laboratory Standards Institute broth microdilution method (M27-A3 document) and Etest for Candida spp. isolates

Micafungin Etest and Clinical and Laboratory Standards Institute (CLSI) MICs were compared for 337 Candida spp. isolates. The performance of Etest for testing the susceptibilities of Candida spp. to micafungin was evaluated by the assessment of both categorical (CA) and essential (EA) agreements. The CA was evaluated 2 ways: (i) by the ability of Etest to separate resistant (nontreatable) from susceptible (treatable) isolates by using the newly adjusted species-specific micafungin clinical breakpoints (CBPs) that are available for most of the common species tested and (ii) by the ability to separate wild type (WT) from non-WT isolates or those harboring FKS mutations (with reduced echinocandin susceptibility) by using micafungin epidemiologic cutoff values (ECVs). Etest and CLSI MICs were in EA when the MICs were within 2 log(2) dilutions. Based on agreement percentages, our data indicated that Etest is suitable to test micafungin for most of the Candida species evaluated (overall EA 94.7%; overall CA according to CBPs 97.2% and according to ECVs 97.3%). However, the number of resistant isolates was small, so further evaluations are needed with a higher number of such isolates including more resistant or those with known mechanisms of resistance (non-WT).     

念珠菌对棘白菌素类药物体外药敏实验产生“矛盾现象”的动态研究

目的 观察念珠菌在卡泊芬净、米卡芬净低浓度时被抑制、高浓度时出现菌落生长的“矛盾现象”的动态变化.方法 在体外药敏实验中,采用CLSI公布的M-27A方案微量稀释法分别测定85株念珠菌对卡泊芬净、米卡芬净产生“矛盾现象”的发生率.连续观察7d.结果 48 h,白念珠菌、光滑念珠菌、近平滑念珠菌、热带念珠菌、都柏林念珠菌及其他念珠菌种产生“矛盾现象”的发生率在卡泊芬净组分别为90.0％、20.0％、41.7％、37.5％、33.3％、28.6％,各菌出现该现象的起始/终点药物浓度分别为4/16、8/32、8/32、2/8、2/8、8/32 μg/ml;48 h后,仅近平滑念珠菌、光滑念珠菌和其他念珠菌种该现象发生率仍升高.48 h,在米卡芬净组仅白念珠菌、热带念珠菌、都柏林念珠菌产生“矛盾现象”,发生率分别为5.0％、25.0％、33.3％,各菌出现该现象的起始/终点药物浓度分别为4/16、4/32、1/8 μg/ml;72 h,光滑念珠菌出现该现象.结论 “矛盾现象”的产生及出现的时间存在念珠菌种间差异性和棘白菌素类药物特异性.卡泊芬净出现“矛盾现象”的发生率高于米卡芬净.各菌株对卡泊芬净、米卡芬净产生“矛盾现象”的发生率与MIC的高低无明显相关性.