Molecular Epidemiology and Antifungal Susceptibility of Candida glabrata in China (August 2009 to July 2014): A Multi-Center Study.

Candida glabrata is an increasingly important cause of invasive candidiasis. In China, relatively little is known of the molecular epidemiology of C. glabrata and of its antifungal susceptibility patterns. Here we studied 411 non-duplicate C. glabrata isolates from 411 patients at 11 hospitals participating in the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET; 2010-2014). Genotyping was performed using multilocus sequence typing (MLST) employing six genetic loci and by microsatellite analysis. Antifungal susceptibility testing was performed using Sensititre YeastOne™ YO10 methodology. Of 411 isolates, 35 sequence types (ST) were identified by MLST and 79 different genotypes by microsatellite typing; the latter had higher discriminatory power than MLST in the molecular typing of C. glabrata. Using MLST, ST7 and ST3 were the most common STs (66.4 and 9.5% of all isolates, respectively) with 24 novel STs identified; the most common microsatellite types were T25 (30.4% of all isolates) and T31 (12.4%). Resistance to fluconazole (MIC > 32 µg/mL) was seen in 16.5% (68/411) of isolates whilst MICs of >0.5 µg/mL for voriconazole, >2 µg/mL for itraconazole and >2 µg/mL for posaconazole were seen for 28.7, 6.8, and 7.3% of isolates, respectively; 14.8% of all isolates cross-resistant/non-wide-type to fluconazole and voriconazole. Fluconazole resistant rates increased 3-fold over the 5-year period whilst that of isolates with non-WT MICs to voriconazole, 7-fold. All echinocandins exhibited >99% susceptibility rates against all isolates but notably one isolate exhibited multi-drug resistance to the azoles and echinocandins. The study has provided a global picture of the molecular epidemiology and drug resistance rates of C. glabrata in China during the period of the study.

Antifungal susceptibilities of Candida glabrata species complex, Candida krusei, Candida parapsilosis species complex and Candida tropicalis causing invasive candidiasis in China: 3 year national surveillance.

OBJECTIVES: To define the antifungal susceptibility patterns of the most common non-albicans Candida spp. in China. METHODS: We evaluated the susceptibilities to nine antifungal drugs of Candida parapsilosis species complex, Candida tropicalis, Candida glabrata species complex and Candida krusei isolates from patients with invasive candidiasis at 11 hospitals over 3 years. Isolates were identified by MALDI-TOF MS supplemented by DNA sequencing. MICs were determined by Sensititre YeastOne(TM) using current clinical breakpoints/epidemiological cut-off values to assign susceptibility (or WT), and by CLSI M44-A2 disc diffusion for fluconazole and voriconazole. RESULTS: Of 1072 isolates, 392 (36.6%) were C. parapsilosis species complex. C. tropicalis, C. glabrata species complex and C. krusei comprised 35.4%, 24.3% and 3.7% of the isolates, respectively. Over 99.3% of the isolates were of WT phenotype to amphotericin B and 5-flucytosine. Susceptibility/WT rates to azoles among C. parapsilosis species complex were ≥97.5%. However, 11.6% and 9.5% of C. tropicalis isolates were non-susceptible to fluconazole and voriconazole, respectively (7.1% were resistant to both). Approximately 14.3% of C. glabrata sensu stricto isolates (n = 258) were fluconazole resistant, and 11.6% of C. glabrata sensu stricto isolates were cross-resistant to fluconazole and voriconazole. All C. krusei isolates were susceptible/WT to voriconazole, posaconazole and itraconazole. Overall, 97.7%-100% of isolates were susceptible to caspofungin, micafungin and anidulafungin, but 2.3% of C. glabrata were non-susceptible to anidulafungin. There was no azole/echinocandin co-resistance. Disc diffusion and Sensititre YeastOne(TM) methods showed >95% categorical agreement for fluconazole and voriconazole. CONCLUSIONS: In summary, reduced azole susceptibility was seen among C. tropicalis. Resistance to echinocandins was uncommon.

In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study.

We conducted active, laboratory-based surveillance for isolates from patients with invasive infections across China from August 2009 to July 2010. DNA sequencing methods were used to define species, and susceptibility to fluconazole and voriconazole was determined by the Clinical and Laboratory Standards Institute M44-A2 disk diffusion method but using up-to-date clinical breakpoints or epidemiological cutoff values. Candida spp. made up 90.5% of the 814 yeast strains isolated, followed by Cryptococcus neoformans (7.7%) and other non-Candida yeast strains (1.7%). Bloodstream isolates made up 42.9% of the strains, isolates from ascitic fluid made up 22.1%, but pus/tissue specimens yielded yeast strains in <5% of the cases. Among the Candida isolates, Candida albicans was the most common species from specimens other than blood (50.1%) but made up only 23% of the bloodstream isolates (P < 0.001). C. parapsilosis complex species were the most common Candida isolates from blood (33.2%). Uncommon bloodstream yeast strains included Trichosporon spp., C. pelliculosa, and the novel species C. quercitrusa, reported for the first time as a cause of candidemia. Most (>94%) of the isolates of C. albicans, C. tropicalis, and the C. parapsilosis complex were susceptible to fluconazole and voriconazole, as were all of the Trichosporon strains; however, 12.2% of the C. glabrata sensu stricto isolates were fluconazole resistant and 17.8% had non-wild-type susceptibility to voriconazole. Seven C. tropicalis strains were cross-resistant to fluconazole and voriconazole; six were from patients in the same institution. Resistance to fluconazole and voriconazole was seen in 31.9% and 13.3% of the uncommon Candida and non-Candida yeast strains, respectively. Causative species and azole susceptibility varied with the geographic region. This study provided clinically useful data on yeast strains and their antifungal susceptibilities in China.

The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).

PURPOSE: To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). METHODS: 70 patients with AMI were allocated to two groups, one was PBSCs transplantation group (n=35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group (n=35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 microg) with the dose of 300-600 microg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up. RESULTS: 35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0+/-8.2% to 57.1+/-7.8% (P<0.0001), wall motion score index (WMSI) from 1.219+/-0.190 to 1.101+/-0.118 (P<0.0001), left end-systolic volume (ESV) from 63.8+/-23.9 ml to 52.6+/-20.3 ml (P=0.01) and left end-diastolic volume (EDV) from 134.2+/-36.7 ml to 119.2+/-30.3 ml (P=0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV (P=0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1+/-7.8 to 52.6+/-5.7 (P=0.041) and WISM from 1.101+/-0.118 to 1.184+/-0.138 (P=0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed. CONCLUSION: Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up.

[Safety and efficacy of intracoronary transplantation of G-CSF mobilized autologous peripheral blood stem cells in patients with acute myocardial infarction].

OBJECTIVE: To investigate the safety and efficacy of intracoronary transplantation of G-CSF mobilized autologous peripheral blood stem cells in patients with acute myocardial infarction (AMI). METHODS: Patients with AMI were randomly assigned to receive intracoronary PBSCs transplantation following bone marrow cells mobilization by granulocyte colony-stimulating factor (300-600 microg/day subcutaneously for 5 days) in addition to standard therapy (standard drug therapy and PCI, PBSCs transplantation group, n = 35) or standard therapy (standard drug therapy and PCI, n = 35). One day after G-CSF treatment was finished the patient's mononuclear cells were harvested by Baxter CS 3000 blood cell separator in a volume of 57 ml and then transferred into the infarct related artery by occluding the over the wire balloon and infusing artery through balloon center lumen. Complications during intervention and left ventricular function at baseline and 6 months thereafter were monitored. RESULTS: No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. Left ventricular function was significantly improved 6 months after G-CSF mobilized autologous peripheral blood stem cell transplantation compared to baseline (global left ventricular function ejection fraction: 57.1 +/- 7.8 vs. 50.0 +/- 8.2%, P < 0.0001; WMSI: 1.101 +/- 0.118 vs. 1.219 +/- 0.190, P < 0.0001; left end-systolic volume: 52.6 +/- 20.3 vs. 63.8 +/- 23.9 ml, P = 0.01 and left end-diastolic volume: 119.2 +/- 30.3 vs. 134.2 +/- 36.7 ml, P = 0.07) while these parameters remained unchanged in the control group. CONCLUSION: The present study demonstrates that G-CSF mobilized autologous intracoronary PBSCs transplantation is a safe and feasible treatment for patients with AMI and global left ventricular function is improved and left ventricular remodeling attenuated at six-month follow-up.