Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration to lung cancer patients is common owing to the few options available. Impact of clinical factors on prognosis of EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKI readministration after first-line EGFR-TKI failure and a period of TKI holiday remains unclear. Through this retrospective study, we aimed to understand the impact of clinical factors in such patients. METHODS: Of 1386 cases diagnosed between December 2010 and December 2013, 80 EGFR-mutant NSCLC patients who were readministered TKIs after failure of first-line TKIs and intercalated with at least one cycle of cytotoxic agent were included. We evaluated clinical factors that may influence prognosis of TKI readministration as well as systemic inflammatory status in terms of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Baseline NLR and LMR were estimated at the beginning of TKI readministration and trends of NLR and LMR were change amount from patients receiving first-Line TKIs to TKIs readministration. RESULTS: Median survival time since TKI readministration was 7.0 months. In the univariable analysis, progression free survival (PFS) of first-line TKIs, baseline NLR and LMR, and trend of LMR were prognostic factors in patients receiving TKIs readministration. In the multivariate analysis, only PFS of first-line TKIs (p < 0.001), baseline NLR (p = 0.037), and trend of LMR (p = 0.004) were prognostic factors. CONCLUSION: Longer PFS of first-line TKIs, low baseline NLR, and high trend of LMR were good prognostic factors in EGFR-mutant NSCLC patients receiving TKI readministration.

Prognostic model to predict survival in patients with metastatic upper tract urothelial carcinoma treated with cisplatin-based chemotherapy.

OBJECTIVES: To create a novel prognostic model to predict survival in metastatic upper tract urothelial carcinoma patients treated with cisplatin-based chemotherapy. METHODS: After institutional review board approval, patients who had metastatic upper tract urothelial carcinoma and were treated with cisplatin based chemotherapy from 2000 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regress analyses. Kaplan-Meier curves were plotted to estimate overall survival. Several prognostic models were validated by using our cohort, and Harrell's c-index was calculated to evaluate their predicting performances. RESULTS: The present study consisted of 136 patients with a median age of 62 years and a median follow-up visit of 13.6 months. Multivariate analyses showed that renal function, performance status, liver metastasis and number of metastatic sites was independently related to survival. Based on these four variables, we constructed a prognostic model "renal function, performance status, liver metastasis, number of metastatic sites" with significantly different survival (P < 0.001). C-index results were renal function, performance status, liver metastasis, number of metastatic sites model 0.80 (0.69-0.90), Bajorin model 0.72 (0.61-0.83), Taguchi model 0.77 (0.67-0.87) and Tanaka model 0.78 (0.69-0.88). Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model achieved the highest c-index in this study. CONCLUSIONS: Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model could be useful for providing prognostic information on survival in patients with metastatic upper tract urothelial carcinoma.

Protective effects of resveratrol against UVA-induced damage in ARPE19 cells.

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

Mycelial Compatibility and Pathogenic Diversity Among Sclerotium rolfsii Isolates in the Southern United States.

Sclerotium rolfsii is a soilborne fungus that causes southern blight on a wide range of plants in tropical and subtropical regions of the world. Eighty-four isolates collected from Florida, Georgia, Louisiana, South Carolina, Texas, and Virginia were paired and assigned to 23 mycelial compatibility groups (MCGs), of which 11 MCGs consisted of a single isolate. Isolates within an MCG typically originated from different hosts and different geographical areas, with the exception of MCG 11. In all, 13 of the 15 isolates in MCG 11 originated from peanut in Georgia and Florida, while the other 2 isolates originated from potato in Virginia and from the ornamental Barlaeria cristata in Florida. Significant differences in the size and number of sclerotia produced in vitro existed between isolates from peanut and other hosts. Nineteen isolates representative of the most common MCGs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, and 18) were tested for pathogenicity on tomato, pepper, and peanut. All isolates were pathogenic on all hosts but virulence differed significantly among isolates. Isolates collected from peanut were the most virulent on all three hosts compared with isolates collected from tomato and pepper. 'Georgia Green' peanut was more susceptible to peanut isolates from Georgia than to the other tested isolates. Of the two tomato entries, the commercial tomato 'Tygress' was less susceptible than the previously reported resistant breeding line 5635M to many of the S. rolfsii isolates tested, with the exception of the peanut isolates collected from Georgia. These initial findings suggest that considerable variation exists among S. rolfsii isolates throughout the southern United States, with some indications of specialization for the isolates collected from peanut.

Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1-2 tumor and 1-3 axillary lymph node(s) metastasis.

BACKGROUND: To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-2 and N1 disease. PATIENTS AND METHODS: A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. RESULTS: With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn't prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. CONCLUSIONS: For patients with T1-2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.

A Novel Xanthomonas sp. Causes Bacterial Spot of Rose (Rosa spp.).

A bacterial spot of rose (Rosa spp.) caused by a xanthomonad was observed in Florida and Texas. Ten representative strains collected from the two states between 2004 and 2010 were used to determine the taxonomic position of this rose pathogen. Fatty acid methyl ester analysis was performed and a nearly 2-kb 16S-23S rRNA intergenic spacer along with flanking portions of the 16S and 23S rRNA genes were sequenced for selected strains, showing that they were members of the genus Xanthomonas. Multilocus sequence typing and analysis (MLST/MLSA) and pathogenicity tests were conducted to further characterize the Xanthomonas strains. The MLSA, based on six gene fragments-fusA, gapA, gltA, gyrB, lacF, and lepA-showed that the rose strains fell into Xanthomonas axonopodis subgroup 9.2 and shared the highest similarity values (98.8 to 99.7%) with X. alfalfae subsp. citrumelonis of the subgroup. However, principal coordinate analysis grouped the rose strains into a unique cluster distinct from other members of the subgroup according to virulence phenotypes on 11 plant species belonging to five plant families (Araceae, Euphorbiaceae, Rosaceae, Rutaceae, and Solanaceae). Moreover, the rose strains were aggressive on rose and Indian Hawthorn (Rhaphiolepsis indica). On the basis of the MLSA and virulence phenotypes, the pathovar epithet rosa is proposed.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 µg/ml), and only one MRSA isolate (MIC(90), 0.5 µg/ml) and three VRE isolates (MIC(90), 0.125 µg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 µg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 µg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 µg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

Effect of Application Frequency and Reduced Rates of Acibenzolar-S-Methyl on the Field Efficacy of Induced Resistance Against Bacterial Spot on Tomato.

Acibenzolar-S-methyl (ASM), a plant activator known to induce systemic acquired resistance, has demonstrated an ability to manage a number of plant diseases, including bacterial spot on tomato caused by four distinct Xanthomonas spp. The aim of this study was to evaluate application rate and frequency of ASM in order to optimize field efficacy against bacterial spot in Florida, while minimizing its impact on marketable yields. ASM was applied biweekly (once every 2 weeks) as a foliar spray at a constant concentration of 12.9, 64.5, and 129 µM throughout four field experiments during 2007-08. A standard copper program and an untreated control were also included. Overall, biweekly applications of ASM did not significantly reduce disease development or the final disease severity of bacterial spot compared with the copper-mancozeb standard or the untreated control. Only one experiment showed a significant reduction in the final disease severity on plants treated with ASM at 129 µM compared with the untreated control. Three additional field trials conducted during 2009-10 to evaluate the effects of weekly and biweekly applications of ASM at concentrations of 30.3 to 200 µM found that weekly applications provided significantly better disease control than biweekly applications. The tomato yields were not statistically improved with the use of ASM relative to the untreated control and standard copper program. Weekly ASM applications at rates as low as 75 µM (equivalent to 1.58 g a.i./ha in 100 liters of water or 0.21 oz. a.i./acre in 100 gallons of water) to 200 µM (equivalent to 4.20 g a.i./ha in 100 liters of water or 0.56 oz. a.i./acre in 100 gallons of water) were statistically equivalent in managing bacterial spot of tomato without significantly reducing yield compared with the untreated control.

Weekly paclitaxel combining with gemcitabine is an effective and safe treatment for advanced breast cancer patients.

OBJECTIVE: Patients with metastatic breast cancer usually accept several lines of chemotherapy. This retrospective study is to analyze the therapeutic effect and tolerance of weekly paclitaxel/gemcitabine combination on patients with metastatic breast cancer. METHODS: Paclitaxel 80 mg/m(2) and gemcitabine 800 mg/m(2) were administered sequentially on days 1, 8 and 15 every 28 days. Patients with measurable metastatic breast cancer or locally advanced breast cancer were included. RESULTS: From March 2005 to December 2006, 50 patients received this treatment at Chang Gung Memorial Hospital, Kaohsiung Medical Center. Thirteen (26%) patients accepted this regimen as their first-line treatment for metastatic breast cancer and 25 (50%) patients accepted this regimen after at least three lines of therapies for metastatic breast cancer. The overall response rate was 56% (95% confidence interval: 42.2-69.8%), 2 patients achieved complete response and 26 patients (52, 95% confidence interval: 38.2-65.9%) achieved partial response. The median progression free survival was 7.4 months (95% confidence interval: 5.5-9.3 months), and the median overall survival was 19.0 months (95% confidence interval: 9.7-28.3 months). Except alopecia, the most common Grade 3/4 toxicities were anemia and leucopenia; the incidences of both were fewer than 10%. CONCLUSIONS: The combination of weekly gemcitabine and paclitaxel in patients with advanced breast cancer showed acceptable outcome and excellent toxic profiles. This therapeutic benefit could be achieved in any linage of patients with good performance status; earlier usage of this regimen can provide better result.

Evaluation of Microbial Products for Management of Powdery Mildew on Summer Squash and Cantaloupe in Florida.

Powdery mildew, caused by Podosphaera xanthii (syn. Sphaerotheca fuliginea auct. p.p.), is a serious and frequently occurring disease of cucurbits worldwide. Efficacy of four microbial products (i.e., Actinovate AG, Companion, BU EXP 1216C, and BU EXP 1216S), which contain microbes as the active ingredient, were evaluated on summer squash and cantaloupe against powdery mildew when applied alone or in alternation with a half-rate of conventional fungicide under greenhouse and field conditions. In greenhouse experiments, the product BU EXP 1216S significantly (P < 0.05) reduced the disease severity by nearly 70% relative to the water control. The level of control achieved was not significantly different from that obtained with Procure 480SC (triflumizole), the half-rate of conventional fungicide treatment, in two of four greenhouse experiments. Compared with the untreated water control, BU EXP 1216C and BU EXP 1216S, when applied alternately with Procure 480SC, consistently promoted plant growth measured by plant height, stem caliper, total fresh weight, and chlorophyll content in the leaves. The degree of increase was 11.6 and 11.3% in plant height, 15.6 and 19.8% in stem caliper, 25 and 40.7% in chlorophyll content, and 164 and 250% in total fresh weight, respectively. Alternating applications of these products with Procure 480SC resulted in significantly less powdery mildew disease than in the water control. In the first field trial on summer squash, all products applied individually or in alternation with Procure 480SC significantly reduced the severity of powdery mildew at the early stage (60 days after planting [DAP]) of disease development. Moreover, these alternating treatments resulted in significantly better control than with Procure 480SC alone at the late assessment stage (88 DAP). The products in alternation with Procure 480SC had a level of disease reduction equivalent to Procure 480SC alone on cantaloupe and significantly reduced disease severity in comparison with the water control. Compared with applying the microbial products alone, alternating applications of these products with Procure 480SC significantly reduced disease severity on cantaloupe and improved the marketable fruit number and weight. The data from our studies suggest that these microbial products could be effectively incorporated into disease management programs. In particular, these microbial products could be integrated into the management of powdery mildew on summer squash and cantaloupe in Florida by alternating their application with low rates of conventional fungicides, potentially reducing the development of fungicide resistance in the pathogen population.

1-Aminocyclopropane-1-carboxylate (ACC) Deaminase Gene in Pseudomonas azotoformans Is Associated with the Amelioration of Salinity Stress in Tomato.

Although bacteria with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have been used to mitigate biotic and abiotic stresses in crops, it is not well known whether the ACC deaminase gene (acdS) in Pseudomonas azotoformans is related to the alleviation of salt stress by the bacterium. This study aimed to evaluate the effects of acdS in P. azotoformans strain CHB 1107 on the nutrient uptake and growth of tomato plants under salt stress. The acdS mutant (CHB 1107 M) of P. azotoformans CHB 1107 was obtained through bacterial conjugation. Wild-type (CHB 1107 WT) and CHB 1107 M were used to inoculate tomato plants grown in a soil or solution with an electrical conductivity of 6 dS/m adjusted by NaCl. CHB 1107 M completely lost the ability to produce ACC deaminase, whereas the complementation of acdS in CHB 1107 M preserved its ACC deaminase activity. CHB 1107 WT significantly reduced the production of ethylene and proline by tomato plants under salt stress, increasing the shoot and root dry weights of tomato plants compared with the noninoculated control and CHB 1107 M. In addition, tomato plants inoculated with CHB 1107 M showed a significant reduction in K (27.5%), Ca (23.0%), and Mn uptake (17.5%) compared with those inoculated with CHB 1107 WT. In contrast, CHB 1107 WT significantly reduced Na uptake by tomato plants in comparison to CHB 1107 M in saline soil conditions. In addition, the inoculation of tomato plants with CHB 1107 WT resulted in a higher K/Na ratio than in those inoculated with CHB 1107 M and the noninoculated control. These findings suggest that acdS in P. azotoformans is associated with the amelioration of salinity stress in tomato. Plant transformation with acdS and the field application of P. azotoformans may be used as potential management tools for crops under salt stress.

Tuberculosis with meningitis, myeloradiculitis, arachnoiditis and hydrocephalus: a case report.

PURPOSE: Involvement of the central nervous system (CNS) by tuberculosis is rare; it can affect either immunocompromised or immunocompetent people. CASE REPORT: Here, we report a case of tuberculosis with CNS involvement. We present the case of an immunocompetent young man who developed fever, subacute headache, disturbance of consciousness, paraparesis, sphincter dysfunction, and hypoesthesia. The final diagnosis was tuberculous meningitis, myeloradiculitis and arachnoiditis based on clinical signs, imaging studies, and cerebrospinal fluid culture. The patient received antituberculosis medication with adjunct intravenous steroid therapy. Although his clinical condition improved significantly, some neurological sequelae persisted. CONCLUSION: Methods for detection of CNS TB and treatment protocols should be constantly re-evaluated to improve treatment outcome and reduce likelihood and severity of neurological sequelae.

Synthesis and antitumor evaluation of novel bis-triaziquone derivatives.

Aziridine-containing compounds have been of interest as anticancer agents since late 1970s. The design, synthesis and study of triaziquone (TZQ) analogues with the aim of obtaining compounds with enhanced efficacy and reduced toxicity are an ongoing research effort in our group. A series of bis-type TZQ derivatives has been prepared and their cytotoxic activities were investigated. The cytotoxicity of these bis-type TZQ derivatives were tested on three cancer lines, including breast cancer (BC-M1), oral cancer (OEC-M1), larynx epidermal cancer (Hep2) and one normal skin fibroblast (SF). Most of these synthetic derivatives displayed significant cytotoxic activities against human carcinoma cell lines, but weak activities against SF. Among tested analogues the bis-type TZQ derivative 1a showed lethal effects on larynx epidermal carcinoma cells (Hep2), with an LC(50) value of 2.02 microM, and also weak cytotoxic activity against SF cells with an LC(50) value over 10 microM for 24 hr treatment. Comparing the viability of normal fibroblast cells treated with compound 1a and TZQ, the LC(50) value of the latter was 2.52 microM, indicating more toxicity than compound 1a. This significantly decreased cytotoxicity of compound 1a towards normal SF cells, while still maintaining the anticancer activity towards Hep2 cells is an interesting feature. Among the seven compounds synthesized, compound 1c has similar toxicity effects on the three cancer cell lines and SF normal cells as the TZQ monomer.

Nationwide surveillance in Taiwan of the in-vitro activity of tigecycline against clinical isolates of extended-spectrum beta-lactamase-producing Enterobacteriaceae.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria. This study compared the in-vitro activity of tigecycline against clinical isolates of resistant Gram-negative bacteria determined by the broth microdilution and Etest methods. A total of 622 isolates were collected from patients treated at 20 teaching hospitals. Tigecycline had excellent in-vitro activity against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (N = 275) with MIC(90) 0.5 microg/mL and a 99.6% susceptibility rate, and also against ESBL-producing Klebsiella pneumoniae (N = 324) with MIC(90) 2 microg/mL and a 98.5% susceptibility rate. For ESBL-producing Proteus mirabilis (N = 15) the MIC(90) was 4 microg/mL with a 73.3% susceptibility rate. For ESBL-producing Klebsiella oxytoca (N = 8) the MIC(50) and MIC(90) were 0.5 and 1 microg/mL, respectively, with a 100% susceptibility rate. Limited agreement (<80%) was found between the broth microdilution and the Etest methods when determining the in-vitro activity of tigecycline against ESBL- producing K. pneumoniae and K. oxytoca.

Nationwide surveillance in Taiwan of the in-vitro activity of tigecycline against clinical isolates of Gram-positive cocci.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria in Taiwan. This study, part of TIST-2006 study, aimed to compare the in-vitro activity of tigecycline against clinical isolates of Gram-positive bacteria. A total of 805 isolates of Gram-positive bacteria were collected from patients treated at 20 teaching hospitals. Minimum inhibitory concentrations (MICs) of tigecycline for these isolates were determined by the broth microdilution method according to the guidelines of the Clinical and Laboratory Standards Institute, and by the Etest as per the manufacturer's instructions. Susceptibility results were interpreted by the MIC criteria recommended by the US FDA. Agreement between the two methods was low: 80.7% for methicillin-resistant Staphylococcus aureus (MRSA), 27.2% for Streptococcus pneumoniae, 22.8% for other Streptococcus spp., and 30.8% for vancomycin-resistant E. faecium (VRE). There were no very major or major errors noted. Tigecycline exhibited excellent in-vitro activity against Gram-positive cocci, including MRSA, VRE, S. pneumoniae and other Streptococcus spp. isolates in Taiwan. Correlation between MIC values determined using the broth microdilution and Etest methods for these organisms was poor.

In-vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii in Taiwan.

We performed susceptibility testing using the microdilution method to determine the in-vitro activity of tigecycline against 393 Acinetobacter baumannii clinical isolates collected in 2006 from 19 hospitals in Taiwan. Significant proportions of the isolates were resistant to imipenem (44%), ciprofloxacin (75%), amikacin (69%), sulbactam (34%) and all four antibiotics (22%), and susceptibility to tigecycline among these different resistant phenotypes of A. baumannii varied from 71% to 82%. The minimum inhibitory concentration (MIC) of tigecycline ranged from 0.6 to 16 microg/mL (MIC(50) 2 microg/mL; MIC(90) 4 microg/mL). The cumulative curve of tigecycline MICs showed that when the MIC cut-offs were set at 2 microg/mL and 4 microg/mL, 80.9% and 93.1% of the isolates were susceptible, respectively. As tigecycline will be used in the future for infections caused by multidrug-resistant A. baumannii because of limited antibiotic choice, and as resistance to tigecycline in A. baumannii isolates may develop following antibiotic exposure, continuous monitoring of the susceptibility of A. baumannii isolates to tigecycline is warranted.

In-vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii in Taiwan determined by the broth microdilution and disk diffusion methods.

A total of 393 isolates of A. baumannii were collected from patients treated at 19 teaching hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibitory zone diameters for tigecycline were determined by the broth microdilution method and the disk diffusion method, respectively. The MIC results were interpreted using the US FDA tigecycline susceptibility breakpoints for Enterobacteriaceae (susceptible [S] or=8 microg/mL). The disk diffusion results were interpreted by criteria recommended by Jones et al. (S >or=16 mm; I 13-15 mm; R or=19 mm; I 15-18 mm; R