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.

Field performance of clinical case definitions for influenza screening during the 2009 pandemic.

PURPOSE: The aim of this study was to assess the performance of 3 different influenza-like illness (ILI) case definitions, adopted by the European (European-CDC), USA (USA-CDC), and Taiwan Centers for Disease Prevention and Control (Taiwan-CDC), as screening tools for influenza during the 2009 H1N1 pandemic. METHODS: From August 15 to 30, 2009, all emergency department patients with clinical symptoms or at epidemiologic risk for influenza were enrolled in an observational cohort study. Influenza diagnosis was established by positive rapid influenza diagnostic test or virus isolation. Sensitivity, specificity, positive predictive value, and negative predictive value of the European-, USA, and Taiwan-CDC ILI case definitions for screening were determined. RESULTS: A total of 870 patients were screened during the study period. Rapid influenza diagnostic test was positive in 315 patients, 273 (85.6%) of whom had fever duration less than 72 hours. Virus isolation identified 4 more patients with influenza A initially negative by rapid influenza diagnostic test. The mean (SD) age of these 319 patients was 24.3 (18.1) years. Of the 870 screened patients, 670 (77.0%), 476 (54.7%), and 325 (37.4%) met the European-, USA-, and Taiwan-CDC ILI case definition, respectively. Screening sensitivity was 95%, 77.7%, and 57.7% and specificity was 33.4%, 58.6%, and 74.4%, respectively. Differences in sensitivity and specificity between any 2 of the 3 groups were statistically significant (P < .05). CONCLUSION: First-line physicians should recognize the advantage and limitation of different ILI case definitions in influenza screening, especially confronted by pandemic or highly pathogenic avian influenza in the future.

Human immunodeficiency virus testing among patients with tuberculosis at a university hospital in Taiwan, 2000 to 2006.

BACKGROUND/PURPOSE: Human immunodeficiency virus (HIV)-infected patients are more susceptible to tuberculosis (TB), which might be the initial presentation of HIV infection. This study assessed the frequency and results of HIV testing among patients diagnosed with TB at a university hospital from 2000 to 2006. METHODS: Surveillance data for all reported TB cases from 2000 to 2006 were reviewed to identify patients with unknown HIV serostatus who received HIV testing when TB was diagnosed. Trends in HIV testing among TB patients were examined, and factors associated with HIV infection were analyzed. RESULTS: From 2000 to 2006, 3643 patients were diagnosed with TB, and 49 with HIV infection prior to TB diagnosis were excluded. Of the 3594 patients with unknown HIV status before TB diagnosis, 1035 (28.8%) were offered HIV testing. There was an increasing trend of providing HIV testing to TB patients that ranged from 16.1% to 43.7% (p < 0.001), and the overall prevalence of HIV infection among TB patients was 5.6% (95% CI, 4.3-7.1%) of those tested. Compared with TB patients without HIV infection, those with HIV infection were more likely to be aged < 50 years [adjusted odds ratio (aOR), 8.0; 95% CI, 4.4-14.6), male (aOR, 7.1; 95% CI, 3.0-16.9), and present with extrapulmonary TB (aOR, 2.8; 95% CI, 1.7-4.6). CONCLUSION: The frequency of HIV testing among TB patients remained low at the university hospital providing TB and HIV care in Taiwan from 2000 to 2006. Among those tested for HIV infection, age < 50 years, male gender and presentation of extrapulmonary TB were associated with HIV infection.

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

2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan.

The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug-drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.

2016 guideline strategies for the use of antifungal agents in patients with hematological malignancies or hematopoietic stem cell transplantation recipients in Taiwan.

The Infectious Diseases Society of Taiwan (IDST), the Hematology Society of Taiwan, the Taiwan Society of Blood and Marrow Transplantation, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines cooperatively published this guideline for the use of antifungal agents in hematological patients with invasive fungal diseases (IFDs) in Taiwan. The guideline is the first one endorsed by IDST focusing on selection of antifungal strategies, including prophylaxis, empirical (or symptom-driven) and pre-emptive (or diagnostic-driven) strategy. We suggest a risk-adapted dynamic strategy and provide an algorithm to facilitate decision making in population level as well as for individual patient. Risk assessment and management accordingly is explicitly emphasized. In addition, we highlight the importance of diagnosis in each antifungal strategy among five elements of the antimicrobial stewardship (diagnosis, drug, dose, de-escalation and duration). The rationale, purpose, and key recommendations for the choice of antifungal strategy are summarized, with concise review of international guidelines or recommendation, key original articles and local epidemiology reports. We point out the interaction and influence between elements of recommendations and limitation of and gap between evidences and daily practice. The guideline balances the quality of evidence and feasibility of recommendation in clinical practice. Finally, this version introduces the concept of health economics and provides data translated from local disease burdens. All these contents hopefully facilitate transparency and accountability in medical decision-making, improvements in clinical care and health outcomes, and appropriateness of medical resource allocation.

Adult methicillin-resistant Staphylococcus aureus bacteremia in Taiwan: clinical significance of non-multi-resistant antibiogram and Panton-Valentine leukocidin gene.

It is poorly defined whether or not adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a non-multi-resistant antibiogram phenotype and Panton-Valentine leukocidin (PVL) gene carriage have different clinical syndromes. Clinical characteristics of 95 adult patients of MRSA bacteremia, with isolates that were non-multi-resistant to non-beta-lactam, were compared with a contemporaneous multiresistant group. Independent risk factors other than community-associated MRSA bacteremia patients associated with recovery of non-multi-resistant MRSA isolates by multivariate analysis included deep-seated infection and catheter insertion site infection. Older age, intensive care unit-onset bacteremia, and postoperative infection were negative independent risk factors associated with non-multi-resistant MRSA isolates. Most of the 60 recoverable non-multi-resistant MRSA isolates belonged to multilocus sequence type 59, and all isolates belonged to staphylococcal chromosomal cassette mec (SCCmec) element type IV or type V. Most PVL-positive MRSA isolates belonged to SCCmec V. PVL-positive CA-MRSA isolates could cause more deep-seated infections in patients presented with non-multi-resistant MRSA bacteremia.

Community-onset candidemia at a university hospital, 1995-2005.

BACKGROUND AND PURPOSE: Although not all candidemias are hospital-acquired, data on clinical epidemiology for the community-onset candidemia are limited. This retrospective study was conducted to describe predisposing factors and outcomes of community-onset candidemias. METHODS: Medical records of patients who were admitted to the National Taiwan University Hospital between January 1, 1995 and May 31, 2005 and had Candida isolated from their blood in the outpatient setting and/or within 48 h of hospitalization (community-onset) were reviewed. RESULTS: A total of 56 episodes of candidemia were reviewed, which included 8 episodes (14.3%) of true community-acquired candidemia occurring in patients with no record of hospitalization within the previous 30 days and without histories of invasive procedures either just before or at the time of admission, and 48 episodes (85.7%) that were health care-associated. The latter included 24 episodes (42.9%) in patients recently discharged from hospitals (within 2-30 days of current admission), 23 episodes (41.1%) associated with invasive procedures and/or central intravascular lines placed for outpatient therapy, and 1 episode (1.8%) in patients admitted from nursing homes. Gastrointestinal bleeding (46.4%), immunosuppressive therapy (42.9%) and previous antibiotics use (37.5%) were the most common predisposing factors. Diabetes was the single most important predisposing factor in true community-acquired candidemia (62.5%) and had a significantly higher prevalence among these patients than in those with health care-associated candidemias (p=0.035). Candida albicans was the most common isolate (39.7%), followed by Candida tropicalis (22.4%) and Candida glabrata (17.2%). The overall case fatality rate was 55.4% (31/56), and 58.1% (18/31) of this was attributable to candidemia. Multivariate analysis identified higher severity score and lack of antifungal therapy as having an independent and adverse influence on outcome. CONCLUSIONS: Up to 85.7% of community-onset candidemias are health care-associated. There is a conceptual and practical need for a new classification for the spectrum of acquisition of infection, wherein the new category of health care-associated infection will have implications for the selection of empirical therapy.

Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II, prospective, randomized, open-label trial.

BACKGROUND: We conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes. METHODS: Between April 7, 2015 and May 27, 2016, healthy adults aged 20-60years were enrolled sequentially in phase I (n=40) and phase II (n=160) from three hospitals in Taiwan and randomized to receive 2 doses of whole-virus H7N9 vaccine (15 or 30µg hemagglutinin antigen (HA) with or without an aluminum hydroxide adjuvant) at 21-day intervals. Safety up to 180days and changes in hemagglutinin inhibition (HI) titers at 21days after each vaccination were determined. RESULTS: Of the 200 randomized subjects, 193 (96.5%) received 2 doses of the study vaccine and were included in the intention-to-treat analysis for safety, and 190 (95%) were included in the per-protocol analysis for immunogenicity. Most adverse events were mild and transient; no death or vaccine-related serious adverse events were reported. Overall, higher immune responses were observed in the groups administered with 30µgHA formulation than in the other two groups administered with 15µgHA formulation. The highest immune response was observed in subjects who received 2 doses of the adjuvanted vaccine containing 30µgHA with HI titer, seroprotection rate, seroconversion rate, and seroconversion factor of 36.2, 64.6%, 64.6% and 5.7, respectively. CONCLUSIONS: Our study demonstrated that the H7N9 influenza vaccine containing 30µgHA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20-60years. CLINICALTRIALS.GOV identifier: NCT02436928.

High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan.

Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100-2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.

Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology-oncology patients: a retrospective cohort study.

In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100-day all-cause mortality.

Trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus causing invasive infections in Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST) study, 2006-2010.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

The Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: a phase I trial in Taiwan.

BACKGROUND: Avian H5N1 influenza has caused human infections globally and has a high mortality rate. Rapid production of effective vaccines is needed. METHODS: A phase 1, randomized, observer-blinded clinical trial was conducted to examine the safety and immunogenicity of an inactivated whole virion vaccine against the influenza A/H5N1 virus produced from the Madin-Darby canine kidney (MDCK) cell line. Participants were randomized to four groups and administered two intramuscular doses of vaccine containing 3 µg hemagglutinin (HA), 3 µg HA with 300 µg aluminum phosphate (AlPO4), 6 µg HA, and 6 µg HA with 300 µg AlPO4, respectively, at two visits, 21 days apart. Serum hemagglutination inhibition (HAI) and neutralizing antibody levels were determined at baseline and on Days 21 and 42. RESULTS: Sixty healthy individuals were enrolled. The neutralization assay showed a significant immune response in the 6 µg with ALPO4 group on Day 42 compared to pre-vaccination levels (11.32±9.77 vs. 4.00±0, p=0.02). The adjuvant effect in neutralization assay was also significant on Day 42 in the 6 µg group (4.52±1.94 without adjuvant vs. 11.32±9.77 with adjuvant, p=0.02). HAI assay also showed an aluminum adjuvant-induced increasing trend in HAI geometric mean titer on Day 42 in the 3 µg and 6 µg groups (6.02 versus 8.20, p=0.05 and 5.74 versus 8.21, p=0.14). The most frequent adverse event was local pain (20% to 60%). There were no vaccine-related severe adverse effects. CONCLUSION: MDCK cell line-derived H5N1 vaccine was well tolerated. It is necessary to investigate further the immunogenicity of higher antigen doses and the role of aluminum adjuvant in augmenting the effect of the vaccine.

Trends in the antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

Isolates of Streptococcus pneumoniae (n = 530) were collected from 20 hospitals in different parts of Taiwan from 2006 to 2010. MICs to 16 antimicrobial agents were determined by broth dilution method and serotypes were identified by latex agglutination. Based on meningitis (non-meningitis) criteria established by the CLSI, 11.7% (63.2%) of all isolates were susceptible to penicillin and 46.0% (83.8%) were susceptible to ceftriaxone. Of the isolates, 94.3% were non-susceptible to azithromycin and 5.8% and 7.2% were non-susceptible to moxifloxacin and levofloxacin, respectively. Susceptibility to penicillin by meningitis criteria increased significantly (P = 0.0012) with year, and that to clindamycin and amoxicillin/clavulanic acid declined significantly (P < 0.05). Six major serotypes were found, namely 19F (24.0%), 23F (18.5%), 14 (13.6%), 6B (12.5%), 19A (7.5%) and 3 (5.1%). Prevalence of serotypes 19F and 14 remained stationary, that of serotype 6B decreased significantly (P < 0.0001) and that of serotype 19A increased significantly (P < 0.0001) with year. The coverage rate of PCV-7 among the pneumococcal isolates declined from 80.5% in 2006 to 50% in 2010 (P < 0.0001) and that of PCV-13 declined from 91.5% in 2009 to 75% in 2010. The non-susceptibility rate to levofloxacin was highest among serotype 23F isolates (13.3%) and lowest among serotype 19A isolates (2.5%). Rates of resistance to the four agents penicillin, ceftriaxone, azithromycin and clindamycin were highest among serotype 19A isolates (70.0%) and 23F isolates (49.0%). All serotype 3 isolates were susceptible to four of the most commonly used antibiotics (penicillin, ceftriaxone, azithromycin and levofloxacin).

Changing trends in antimicrobial susceptibility of Streptococcus pneumoniae isolates in Taiwan, 2006-2007.

BACKGROUND: Multiple antibiotic-resistant clones of Streptococcus pneumoniae have spread throughout the world and continue to evolve under the selective pressure of antibiotics and vaccines. The aim of this study is to assess the susceptibility of S. pneumoniae isolates and to analyze the resistance trends in Taiwan. METHODS: Antimicrobial susceptibility tests were performed on 152 nonmeningeal isolates of S. pneumoniae that were collected from 13 different hospitals around Taiwan from 2006-2007. Tests were performed using the broth microdilution method according to recommendations of the Clinical and Laboratory Standards Institute. RESULTS: The minimal inhibitory concentrations (MIC(50)/MIC(90)) of penicillin, cefotaxime, vancomycin, and moxifloxacin were 0.5/1.0, 0.25/1.0, 0.25/0.5, and 0.06/0.12 µg/mL, respectively. The susceptibility rates of penicillin, cefotaxime, vancomycin, and moxifloxacin were 99.3%, 99.3%, 100%, and 98.7%, respectively. However, if the meningitis breakpoints were applied to these nonmeningeal isolates, the susceptibility rates of penicillin and cefotaxime were reduced to 18.4% and 76.3%, respectively. Compared with the findings from previous studies in Taiwan, our results show that the percentage of S. pneumoniae isolates with a penicillin MIC of 0.12-1.0 µg/mL increased from 43.3% in 1996-1997 to 73.7% in 2006-2007 (p < 0.001). The percentage of S. pneumoniae isolates with a cefotaxime MIC of 1.0 µg/mL increased from 11.3% in 1996-1997 to 23.0% in 2006-2007 (p < 0.001). Regarding the serial MIC intervals of the four antimicrobial agents, there was no significant difference between bacteremic and nonbacteremic isolates. CONCLUSION: Although nonmeningeal S. pneumoniae isolates remained susceptible to penicillin, the proportion of isolates with a penicillin MIC of 0.12-1.0 µg/mL or cefotaxime MIC of 1.0 µg/mL increased during the past decade in Taiwan. The ever-increasing resistance of S. pneumoniae has a great impact on the treatment of meningitis.