Tsrang Neng Jang

Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the Tigecycline In Vitro Surveillance in Taiwan Study, 2006 to 2010

ABSTRACT 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 β-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 (MIC90, 0.03 μg/ml), and only one MRSA isolate (MIC90, 0.5 μg/ml) and three VRE isolates (MIC90, 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 (MIC90, 0.5 μg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC90, 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 (MIC90, 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.

Establishing a clinical decision rule of severe acute respiratory syndrome at the emergency department

Abstract Study objective In the absence of reliable rapid confirmatory tests during severe acute respiratory syndrome (SARS) endemics, we designed a 2-phase cohort study to establish a scoring system for SARS and to evaluate whether it could improve the sensitivity and specificity of the World Health Organization (WHO) criteria. Methods According to the clinical characteristics and initial laboratory findings of 175 suspected cases defined by the WHO criteria (20 confirmed as cases of SARS) in 3 university teaching hospitals in Taipei between March 1 and April 20, 2003, the scoring system for SARS was designed by multivariate analysis and stepwise logistic regression as the simple arithmetic sum of point values assigned to 7 parameters. We thereafter applied the scoring system for SARS to the consecutive 232 patients (the validation group) who met the WHO criteria of suspected cases from April 21 to May 22, 2003. Final diagnosis of SARS was determined by the results of real-time polymerase chain reaction and paired serum. Results The scoring system for SARS was defined as radiographic findings of multilobar or bilateral infiltrates (3 points), sputum monocyte predominance (3 points), lymphocytopenia (2 points), history of exposure (1 point), lactate dehydrogenase more than 450 U/L (1 point), C-reactive protein more than 5.0 mg/dL (1 point), and activated partial prothrombin time more than 40 seconds (1 point). Of the validation group, 60 patients (group A) were confirmed as having cases of SARS, and the other 172 (group B) patients tested negative for SARS. The total points of the scoring system for SARS at initial presentation were significantly higher in the SARS group (median 9; range 6 to 11) than in the non-SARS group (median 4; range 3 to 7; P<.001). At the cutoff value of 6 points, the sensitivity and specificity of the scoring system for SARS in diagnosing SARS were 100% and 93%, respectively. The positive and negative predictive values of the scoring system for SARS were 83% and 100%, respectively. Conclusion The scoring system for SARS can provide a rapid and reliable clinical decision to help emergency physicians detect cases of SARS more accurately in the endemic area.

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=2 microg/mL; intermediate [I] 4 microg/mL; resistant [R] >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=12 mm) and also by those recommended by the US FDA for Enterobacteriaceae (S >or=19 mm; I 15-18 mm; R <or=14 mm). The percentages of susceptible, intermediate and resistant isolates determined by the broth microdilution method were 80.9%, 12.2%, and 6.9%, respectively. The rates of susceptible, intermediate and resistant isolates by the disk diffusion method using the criteria of Jones et al. were 88.3%, 9.9% and 1.8% and using the US FDA criteria were 44.0%, 51.7% and 4.3%. Using the criteria recommended by Jones et al., the total error rate of the disk diffusion method in comparison with the broth microdilution method was 14.2% (56/393). For routine susceptibility testing of tigecycline against A. baumannii the broth microdilution method, not the disk diffusion method, should be used due to the poor correlation of results between these two methods interpreted either by the Jones et al. or US FDA criteria.

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

ABSTRACT 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 β-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 MIC90 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

ABSTRACT 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 (MIC90s) from 2006-2007 (0.06 μg/ml) to 2008–2010 (0.12 μg/ml). The MIC90s 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.

Nationwide surveillance in Taiwan of the in-vitro activity of tigecycline against clinical isolates of extended-spectrum β-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.

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.

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 manufacturers 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.