Antimicrobial susceptibility of Gram-negative and Gram-positive bacteria collected from Eastern Europe: Results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), 2011-2016.

OBJECTIVES: The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance programme monitoring the in vitro activity of a panel of antimicrobial agents against clinically important bacterial isolates. Data for Gram-positive and Gram-negative isolates collected in Eastern Europe between 2011 and 2016 are presented here. METHODS: Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method using CLSI guidelines. Antimicrobial susceptibility was assessed using EUCAST breakpoints. RESULTS: Nine Eastern European countries submitted 4289 isolates. Among Acinetobacter baumannii, resistance to levofloxacin, amikacin and meropenem was 77.5%, 63.4% and 62.2%, respectively. Multidrug resistance among A. baumannii was higher in 2015 than in previous years (44.1% in 2011 and 71.0% in 2015), decreasing to 51.7% in 2016. The multidrug resistance percentage for Pseudomonas aeruginosa was 26.9% and was relatively stable over time. The percentage of extended-spectrum ß-lactamase (ESBL)-positive isolates among Escherichia coli and Klebsiella pneumoniae was 20.1% and 55.7%, respectively. Resistance to amikacin, meropenem and tigecycline was low among E. coli and K. pneumoniae and the ESBL-producing subset (≤5.9%). Among Staphylococcus aureus isolates, 36.7% were methicillin-resistant (MRSA); percentages varied year-on-year. No S. aureus isolates, including MRSA, were resistant to linezolid, vancomycin or tigecycline. Among Enterococcus faecium isolates, resistance was 22.6% to vancomycin and 2.3% to linezolid; no isolates were resistant to tigecycline. CONCLUSION: This study shows low resistance to meropenem and tigecycline among Enterobacteriaceae isolates and continued activity of linezolid, vancomycin and tigecycline against Gram-positive organisms. However, antimicrobial resistance continues to be problematic in Eastern Europe and requires continued surveillance.

In vitro activity of tigecycline and comparators (2014-2016) among key WHO 'priority pathogens' and longitudinal assessment (2004-2016) of antimicrobial resistance: a report from the T.E.S.T. study.

We report contemporary (2014-2016) Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) global data on activity of tigecycline and comparators against WHO 'priority pathogens', and global trends (2004-2016) in antimicrobial resistance. MICs were determined using CLSI broth microdilution methodology. Antimicrobial resistance was determined using CLSI breakpoints (FDA breakpoints for tigecycline). Data are reported for Africa, Asia, Europe, North America and South America. From 2014-2016, Africa, Asia and South America reported highest resistance rates among Acinetobacter baumannii; North America lowest (all antimicrobials tested). The tigecycline MIC90 against A. baumannii was 2 mg/L in all regions except South America (1 mg/L). Among Enterobacteriaceae, meropenem resistance was low and tigecycline resistance was ≤1.3% in all regions (Escherichia coli, 0.0-0.3%; Klebsiella pneumoniae 0.0-1.3%; Enterobacter spp. 0.5-1.1%; Serratia marcescens 0.0-1.3%). Ceftriaxone resistance among E. coli ranged from 14.5% (North America) to 54.7% (Asia), and among K. pneumoniae from 9.1% (North America) to 54.0% (South America). North America reported highest rates of vancomycin-resistant Enterococcus faecium (64.6%); Europe lowest (17.7%). The tigecycline MIC90 against methicillin-resistant Staphylococcus aureus (MRSA) ranged from 0.12 mg/L (Africa and North America) to 0.5 mg/L (Asia). From 2004-2016, carbapenem resistance increased among A. baumannii (all regions), reaching 92.3% in Africa and 85.7% in South America (2016). Rates of ceftriaxone-resistant E. coli increased in all regions except Asia. Ceftriaxone resistance in K. pneumoniae increased in Europe. Rates of vancomycin-resistant E. faecium and MRSA were highest in North America and South America (and Asia for MRSA); lowest in Europe.

The tigecycline evaluation and surveillance trial; assessment of the activity of tigecycline and other selected antibiotics against gram-positive and gram-negative pathogens from France collected between 2004 and 2016.

Background: A high level of antibiotic consumption in France means antimicrobial resistance requires rigorous monitoring. The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study that monitors the in vitro activities of tigecycline and a panel of marketed antimicrobials against clinically important Gram-positive and Gram-negative isolates. Methods: Annually clinically relevant strains were prospectively included in the survey through a national network of hospital-based laboratories. MICs were determined locally by broth microdilution using CLSI guidelines. Antimicrobial susceptibility was assessed using European Committee on Antimicrobial Susceptibility Testing breakpoints. Results: Thirty-three centres in France collected 26,486 isolates between 2004 and 2016. Enterococcus species were highly susceptible (≥94.4%) to linezolid, tigecycline and vancomycin. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), were susceptible (≥99.9%) to tigecycline, vancomycin and linezolid. Between 2004 and 2016, 27.7% of S. aureus isolates were MRSA, decreasing from 28.0% in 2013 to 23.5% in 2016. Susceptibility of Streptococcus pneumoniae isolates was 100% to vancomycin, and > 99.0% to levofloxacin, linezolid and meropenem; 3.0% were penicillin-resistant S. pneumoniae (100% susceptibility to vancomycin and linezolid). Escherichia coli isolates were highly susceptible (> 98.0%) to meropenem, tigecycline and amikacin. The rate of extended-spectrum ß-lactamase (ESBL) positive E. coli increased from 2004 (3.0%), but was stable from 2012 (23.1%) to 2016 (19.8%). Susceptibility of Klebsiella pneumoniae isolates was 99.4% to meropenem and 96.5% to amikacin. The proportion of ESBL-positive K. pneumoniae isolates increased from 2004 (7.5%) to 2012 (33.3%) and was highest in 2016 (43.6%). A. baumannii was susceptible to meropenem (81.0%) and amikacin (74.9%); none of the 6.2% of isolates identified as multidrug-resistant (MDR) was susceptible to any agents with breakpoints. P. aeruginosa isolates were most susceptible to amikacin (88.5%), and MDR rates were 13.6% in 2013 to 4.0% in 2016; susceptibility of MDR isolates was no higher than 31.4% to amikacin. Conclusions: Rates of MRSA decreased slowly, while rates of ESBL-positive E. coli and K. pneumoniae increased from 2004 to 2016. Susceptibility of Gram-positive isolates to vancomycin, tigecycline, meropenem and linezolid was well conserved, as was susceptibility of Gram-negative isolates to tigecycline and meropenem. The spread of MDR non-fermentative isolates must be carefully monitored.

In vitro activity of tigecycline and comparators against a European collection of anaerobes collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2010-2016.

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global program that aims to monitor the in vitro antimicrobial activities of current therapeutic agents against clinical isolates. This study presents surveillance data for Gram-positive and Gram-negative anaerobic isolates (N = 7008) collected from nine European countries between 2010 and 2016. Presented in this study are antimicrobial susceptibility data, according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST) breakpoints, and minimum inhibitory concentration (MIC) distributions. The antimicrobial agents tested were cefoxitin (Gram-negative isolates only), clindamycin, meropenem, metronidazole, penicillin (Gram-positive isolates only), piperacillin-tazobactam and tigecycline. Among all Gram-positive and Gram-negative anaerobes, the lowest rates of resistance were to meropenem and metronidazole (0.0%-1.7% and 0.0%-1.9%, respectively). High rates of resistance were reported to clindamycin, in particular among isolates of the Bacteroides fragilis group (22.1%-48.1%) and Prevotella spp. (10.9%-32.2%). The majority of MIC distributions were unimodal, with the exception of clindamycin, which were mostly bimodal. Fifty percent of Gram-negative isolates gave tigecycline MICs between 0.06 and 1 mg/L, and 50% of Gram-positive isolates exhibited tigecycline MICs between 0.06 and 0.25 mg/L. The findings of this study suggest that the majority of anaerobic isolates were susceptible to meropenem and metronidazole, and that tigecycline remained active, but clindamycin resistance is a cause for concern in Europe. Surveillance studies, such as T.E.S.T., provide information on changes in the susceptibility of clinically important pathogens to commonly prescribed antimicrobial agents, and can highlight problems of antimicrobial resistance that need to be addressed.

Antimicrobial activity among gram-positive and gram-negative organisms collected from the Asia-Pacific region as part of the Tigecycline Evaluation and Surveillance Trial: Comparison of 2015 results with previous years.

We report the in vitro activity of tigecycline and comparators against Gram-negative and Gram-positive organisms collected from Asia-Pacific during 2004-2010 and 2015. MICs were determined by broth microdilution using CLSI guidelines. Antimicrobial susceptibility was assessed using CLSI breakpoints, except for tigecycline FDA breakpoints. For Acinetobacter baumannii, multidrug-resistant (MDR) rates were 81.8% in 2015 and 48.5% during 2004-2010. Among Escherichia coli and Klebsiella pneumoniae respectively, rates of extended-spectrum ß-lactamase-producers in 2015 were 24.6% and 15.8%, and during 2004-2010, 21.6% and 23.8%. Pseudomonas aeruginosa MDR rates were 12.7% in 2015 and 18.5% during 2004-2010. For Staphylococcus aureus, 57.1% were methicillin-resistant in 2015 and 46.3% between 2004 and 2010. For Streptococcus pneumoniae, 32.1% were penicillin-resistant in 2015 and 29.9% between 2004 and 2010. Tigecycline MIC90 values were ≤2mg/L against all species except P. aeruginosa, against which tigecycline is inactive. Antimicrobial resistance in Asia-Pacific is widespread, including a concerning increase in MDR A. baumannii.

Antimicrobial susceptibility among Gram-positive and Gram-negative organisms collected from the Latin American region between 2004 and 2015 as part of the Tigecycline Evaluation and Surveillance Trial.

BACKGROUND: The in vitro activity of tigecycline and comparator agents was evaluated against Gram-positive and Gram-negative isolates collected in Latin American centers between 2004 and 2015 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) global surveillance study. METHODS: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution methodology according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Antimicrobial susceptibility was determined using CLSI breakpoints, except for tigecycline for which the US Food and Drugs Administration breakpoints were used. RESULTS: A total of 48.3% (2202/4563) of Staphylococcus aureus isolates were methicillin-resistant S. aureus (MRSA). All MRSA isolates were susceptible to linezolid and vancomycin, and 99.9% (2199/2202) were susceptible to tigecycline. Among Streptococcus pneumoniae isolates, 13.8% (198/1436) were penicillin-resistant; all were susceptible to linezolid and vancomycin, and 98.0% (194/198) were susceptible to tigecycline. Susceptibility was >99.0% for linezolid and tigecycline against Enterococcus faecium and Enterococcus faecalis isolates. A total of 40.8% (235/576) E. faecium and 1.6% (33/2004) E. faecalis isolates were vancomycin-resistant. Among the Enterobacteriaceae, 36.3% (1465/4032) of Klebsiella pneumoniae isolates, 16.4% (67/409) of Klebsiella oxytoca isolates and 25.4% (1246/4912) of Escherichia coli isolates were extended-spectrum ß-lactamase (ESBL) producers. Of the ESBL-producing K. pneumoniae and E. coli isolates, susceptibility was highest to tigecycline [93.4% (1369/1465) and 99.8% (1244/1246), respectively] and meropenem [86.9% (1103/1270) and 97.0% (1070/1103), respectively]. A total of 26.7% (966/3613) of Pseudomonas aeruginosa isolates were multidrug-resistant (MDR). Among all P. aeruginosa isolates, susceptibility was highest to amikacin [72.8% (2632/3613)]. A total of 70.3% (1654/2354) of Acinetobacter baumannii isolates were MDR, and susceptibility was highest to minocycline [88.3% (2079/2354) for all isolates, 86.2% (1426/1654) for MDR isolates]. Tigecycline had the lowest MIC90 (2 mg/L) among A. baumannii isolates, including MDR isolates. CONCLUSIONS: This study of isolates from Latin America shows that linezolid, vancomycin and tigecycline continue to be active in vitro against important Gram-positive organisms such as MRSA, and that susceptibility rates to meropenem and tigecycline against members of the Enterobacteriaceae, including ESBL-producers, were high. However, we report that Latin America has high rates of MRSA, MDR A. baumannii and ESBL-producing Enterobacteriaceae which require continued monitoring.

Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial.

Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing global study designed to monitor the in vitro activities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study, in vitro data are presented for MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, and Enterobacter cloacae isolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded among A. baumannii (overall rate, 44% [8,294/18,741], increasing from 23% [309/1,323] in 2004 to 63% [447/712] in 2014). Other multidrug resistance rates ranged from 2.5% for K. oxytoca (203/8,000) to 12% for P. aeruginosa and K. pneumoniae (3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDR E. coli, Klebsiella spp., and E. aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90 value against A. baumannii was observed for tigecycline (2 mg/liter; MIC range, ≤0.008 to ≥32 mg/liter). The only significant change in resistance to tigecycline during the study period was for MDR E. coli (P < 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A. baumannii highlight the need for the continued monitoring of global multidrug resistance. IMPORTANCE Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.

Antimicrobial Susceptibility among European Gram-Negative and Gram-Positive Isolates Collected as Part of the Tigecycline Evaluation and Surveillance Trial (2004-2014).

BACKGROUND: European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates. METHODS: Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints. RESULTS: The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum ß-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus. CONCLUSIONS: The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.

Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.).

As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) we report the in vitro activity of tigecycline and its comparators against Gram-negative and Gram-positive organisms collected from Italian centers between 2012 and 2014. Minimum inhibitory concentrations were determined according to the broth microdilution methodology of the Clinical and Laboratory Standards Institute, and antimicrobial resistance was determined using the European Committee on Antimicrobial Susceptibility Testing interpretive criteria. Among the Enterobacteriaceae, 31% of Escherichia coli isolates, 22% of Klebsiella pneumoniae, and 1% of Klebsiella oxytoca were extended-spectrum ß-lactamase producers (ESBLs). Resistance rates among ESBL-K. pneumoniae and ESBL-E. coli to meropenem were 24% and <1%, respectively. Thirty-seven percent of K. pneumoniae were multidrug resistant (MDR) strains. Resistance rates among isolates of Acinetobacter baumannii to amikacin, levofloxacin and meropenem were between 84% and 94%. Eighty percent of A. baumannii isolates were MDR strains. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 38% of S. aureus isolates. No isolates of MRSA were resistant to linezolid, tigecycline or vancomycin. Antimicrobial resistance remains a problem in Italy with increasing numbers of MDR organisms. Despite high levels, MRSA rates appear to be stabilising. Tigecycline retains its in vitro activity against the majority of organisms, including those with multidrug resistance.

Antimicrobial susceptibility among important pathogens collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) in Spain, 2004-2014.

Here we report in vitro activity data from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) for tigecycline and comparators against Gram-positive and Gram-negative organisms collected from 27 medical centres in Spain between 2004 and 2014. Minimum inhibitory concentrations (MICs) were determined according to the broth microdilution methodology of the Clinical and Laboratory Standards Institute (CLSI) and susceptibility were determined according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretive criteria. Susceptibility was >97% for all antimicrobials tested against Enterococcus faecalis, and >98% of Enterococcus faecium tested were susceptible to tigecycline, linezolid and vancomycin. A total of 34.1% (1071/3143) of Staphylococcus aureus were meticillin-resistant S. aureus (MRSA), and all MRSA were susceptible to tigecycline and vancomycin. Among the Streptococcus pneumoniae, 5.2% (74/1430) were penicillin-resistant and all isolates were susceptible to linezolid and vancomycin. Among the Enterobacteriaceae, 17.1% (542/3167) of Escherichia coli, 2.8% (19/682) of Klebsiella oxytoca and 19.0% (441/2327) of Klebsiella pneumoniae isolates produced extend-spectrum ß-lactamases (ESBLs). Against ESBL-producing E. coli and K. pneumoniae, susceptibility was highest for meropenem, amikacin and tigecycline with rates of >92% and >80%, respectively. Among the Acinetobacter baumannii, susceptibility ranged between 23.5% for levofloxacin and 51.4% for amikacin, and an MIC90 of 2mg/L was observed for tigecycline. In conclusion, monitoring of antimicrobial susceptibility among organisms such as S. aureus, Enterobacteriaceae and A. baumannii is of continuing importance as a guide to clinicians. Depending on the organism to be treated, carbapenems, linezolid, vancomycin and tigecycline continue to be active in Spain.

Antimicrobial activity against a global collection of skin and skin structure pathogens: results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), 2010-2014.

BACKGROUND: As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) we report antimicrobial resistance among Gram-positive and Gram-negative isolates collected globally from integumentary sources between 2010 and 2014. METHODS: Minimum inhibitory concentrations and antimicrobial resistance were determined according to Clinical and Laboratory Standards Institute guidelines (US Food and Drug Administration breakpoints against tigecycline). The Cochran-Armitage trend test was used to identify statistically significant changes in resistance. RESULTS: Global rates of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii were 38% and 43%, respectively. No S. aureus isolates were resistant to linezolid or vancomycin; all isolates were susceptible to tigecycline. Two percent of Enterococcus faecalis and 28% of Enterococcus faecium were vancomycin-resistant. Extended-spectrum ß-lactamase (ESBL) producers accounted for 22% of Klebsiella pneumoniae and 16% of Escherichia coli. Resistance to minocycline among E. faecalis, E. faecium, K. pneumoniae, and E. coli decreased significantly (p<0.0001). There were significant increases (p<0.0001) in A. baumannii resistance to cefepime, ceftazidime, ceftriaxone, levofloxacin, meropenem, and piperacillin-tazobactam. CONCLUSIONS: Among isolates from integumentary sources, rates of MRSA and ESBL-producing Enterobacteriaceae are stabilizing. Carbapenems and tigecycline have retained their in vitro activity against Gram-positive and Gram-negative organisms. Few agents were active against A. baumannii; its increasing resistance is cause for concern.

Antimicrobial susceptibility trends among gram-positive and -negative clinical isolates collected between 2005 and 2012 in Mexico: results from the Tigecycline Evaluation and Surveillance Trial.

BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (T.E.S.T) is a global antimicrobial surveillance study of both gram-positive and gram-negative organisms. This report presents data on antimicrobial susceptibility among organisms collected in Mexico between 2005 and 2012 as part of T.E.S.T., and compares rates between 2005-2007 and 2008-2012. METHOD: Each center in Mexico submitted at least 200 isolates per collection year; including 65 gram-positive isolates and 135 gram-negative isolates. Minimum inhibitory concentrations (MICs) were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution methodology and antimicrobial susceptibility was established using the 2013 CLSI-approved breakpoints. For tigecycline US Food and Drug Administration (FDA) breakpoints were applied. Isolates of E. coli and K. pneumoniae with a MIC for ceftriaxone of >1 mg/L were screened for ESBL production using the phenotypic confirmatory disk test according to CLSI guidelines. RESULTS: The rates of some key resistant phenotypes changed during this study: vancomycin resistance among Enterococcus faecium decreased from 28.6 % in 2005-2007 to 19.1 % in 2008-2012, while ß-lactamase production among Haemophilus influenzae decreased from 37.6 to 18.9 %. Conversely, methicillin-resistant Staphylococcus aureus increased from 38.1 to 47.9 %, meropenem-resistant Acinetobacter spp. increased from 17.7 to 33.0 % and multidrug-resistant Acinetobacter spp. increased from 25.6 to 49.7 %. The prevalence of other resistant pathogens was stable over the study period, including extended-spectrum ß-lactamase-positive Escherichia coli (39.0 %) and Klebsiella pneumoniae (25.0 %). The activity of tigecycline was maintained across the study years with MIC90s of ≤2 mg/L against Enterococcus spp., S. aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Enterobacter spp., E. coli, K. pneumoniae, Klebsiella oxytoca, Serratia marcescens, H. influenzae, and Acinetobacter spp. All gram-positive organisms were susceptible to tigecycline and susceptibility among gram-negatives ranged from 95.0 % for K. pneumoniae to 99.7 % for E. coli. CONCLUSION: Antimicrobial resistance continues to be high in Mexico. Tigecycline was active against gram-positive and gram-negative organisms, including resistant phenotypes, collected during the study.

Global in vitro activity of tigecycline and comparator agents: Tigecycline Evaluation and Surveillance Trial 2004-2013.

BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TEST) is a global antimicrobial susceptibility surveillance study which has been ongoing since 2004. This report examines the in vitro activity of tigecycline and comparators against clinically important pathogens collected globally between 2004 and 2013. METHODS: Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute. The Cochran Armitage Trend Test was used to identify statistically significant changes in susceptibility between 2004 and 2013. RESULTS: Among the Enterobacteriaceae susceptibility was highest to the carbapenems [imipenem 97.1% (24,655/25,381), meropenem 97.0% (90,714/93,518)], tigecycline (97.0%, 115,361/118,899) and amikacin (96.9%, 115,200/118,899). Against Acinetobacter baumannii the highest rates of susceptibility were for minocycline (84.5%, 14,178/16,778) and imipenem (80.0%, 3,037/3,795). The MIC90 for tigecycline was 2 mg/L. 40% (6,743/16,778) of A. baumannii isolates were multidrug-resistant. Enterococci were highly susceptible to tigecycline and linezolid (>99%); vancomycin resistance was observed among 2% of Enterococcus faecalis (325/14,615) and 35% of Enterococcus faecium (2,136/6,167) globally. 40% (14,647/36,448) of Staphylococcus aureus were methicillin-resistant while 15% (2,152/14,562) of Streptococcus pneumoniae were penicillin-resistant. Against S. aureus and S. pneumoniae susceptibility to linezolid, vancomycin, and tigecycline was ≥99.9%. Globally, 81% (331/410) of statistically significant susceptibility changes during the study period were decreases in susceptibility. CONCLUSIONS: Amikacin, the carbapenems, and tigecycline were active against most gram-negative pathogens while linezolid, tigecycline, and vancomycin retained activity against most gram-positive pathogens collected in TEST during 2004-2013.

Global assessment of antimicrobial susceptibility among Gram-negative organisms collected from pediatric patients between 2004 and 2012: results from the Tigecycline Evaluation and Surveillance Trial.

The Tigecycline Evaluation and Surveillance Trial (TEST) was designed to monitor susceptibility to commonly used antimicrobial agents among important pathogens. We report here on susceptibility among Gram-negative pathogens collected globally from pediatric patients between 2004 and 2012. Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute (CLSI). Most Enterobacteriaceae showed high rates of susceptibility (>95%) to amikacin, tigecycline, and the carbapenems (imipenem and meropenem); 90.8% of Acinetobacter baumannii isolates were susceptible to minocycline, and susceptibility rates were highest in North America, Europe, and Asia/Pacific Rim. Amikacin was the most active agent against Pseudomonas aeruginosa (90.4% susceptibility), with susceptibility rates being highest in North America. Extended-spectrum ß-lactamases (ESBLs) were reported for 11.0% of Escherichia coli isolates and 24.2% of Klebsiella pneumoniae isolates globally, with rates reaching as high as 25.7% in the Middle East and >43% in Africa and Latin America, respectively. Statistically significant (P<0.01) differences in susceptibility rates were noted between pediatric age groups (1 to 5 years, 6 to 12 years, or 13 to 17 years of age), globally and in some regions, for all pathogens except Haemophilus influenzae. Significant (P<0.01) differences were reported for all pathogens globally and in most regions, considerably more frequently, when pediatric and adult susceptibility results were compared. Amikacin, tigecycline, and the carbapenems were active in vitro against most Gram-negative pathogens collected from pediatric patients; A. baumannii and P. aeruginosa were susceptible to fewer antimicrobial agents. Susceptibility rates among isolates from pediatric patients were frequently different from those among isolates collected from adults.

Regional and global antimicrobial susceptibility among isolates of Streptococcus pneumoniae and Haemophilus influenzae collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from 2009 to 2012 and comparison with previous years of T.E.S.T. (2004-2008).

BACKGROUND: We report here on 14438 Streptococcus pneumoniae and 14770 Haemophilus influenzae isolates collected from 560 centres globally between 2004 and 2012 as a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). METHODS: MIC testing was performed using broth microdilution methods as described by the Clinical and Laboratory Standards Institute (CLSI) using CLSI-approved breakpoints; US Food and Drug Administration breakpoints were used for tigecycline as CLSI breakpoints are not available. RESULTS: At least 99% of S. pneumoniae isolates globally were susceptible to levofloxacin, linezolid, tigecycline or vancomycin. Penicillin resistance was observed among 14.8% of S. pneumoniae and was highest in Asia/Pacific Rim (30.1%) and Africa (27.6%); 23.4% of S. pneumoniae isolates were penicillin-intermediate, which were most common in Africa (37.6%). Minocycline susceptibility among S. pneumoniae decreased by 20% between 2004-2008 and 2009-2012. High (>98.5%) susceptibility was reported among H. influenzae to all antimicrobial agents on the T.E.S.T. panel excluding ampicillin, to which only 78.3% were susceptible. ß-lactamase production was observed among 20.2% of H. influenzae isolates; 1.5% of isolates were ß-lactamase negative, ampicillin-resistant. CONCLUSIONS: S. pneumoniae remained highly susceptible to levofloxacin, linezolid, tigecycline and vancomycin while H. influenzae was susceptible to most antimicrobial agents in the testing panel (excluding ampicillin).

A longitudinal assessment of antimicrobial susceptibility among important pathogens collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) in France between 2004 and 2012.

BACKGROUND: Clinically important Gram-positive and -negative isolates were collected from patients in France between 2004 and 2012 as a part of the Tigecycline Evaluation and Surveillance Trial. METHODS: MICs were determined using methodology described by the Clinical and Laboratory Standards Institute. RESULTS: In total, 17,135 isolates were contributed by 29 medical centres; respiratory (25.1%) and cardiovascular (20.3%) sources predominated. High susceptibility was observed among Enterococcus spp. and Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]) to linezolid (100%), tigecycline (≥99.8%) and vancomycin (≥94.6%). The percentage of MRSA decreased from 34.3% in 2004 to 20.0% in 2009 before increasing to 34.7% in 2012. Vancomycin, linezolid, levofloxacin and carbapenems were highly active (≥99.6%) against Streptococcus pneumoniae; 3.2% were PRSP. Escherichia coli showed peak susceptibility to the carbapenems (≥99.9%), tigecycline (99.3%) and amikacin (97.9%); significant (p < 0.01) decreases in susceptibility were observed for ampicillin, cefepime and ceftriaxone between 2004 and 2012. ESBL production among E. coli increased from 3.0% (2004) to 14.9% (2012). High susceptibility was noted among Haemophilus influenzae to levofloxacin (100%), amoxicillin-clavulanate (99.2%), carbapenems (≥98.7%) and ceftriaxone (98.5%); ß-lactamase production fluctuated with no notable trend between 18.1% (2007) and 27.7% (2011). Klebsiella spp. were highly susceptible to carbapenems (≥99.6%) and amikacin (≥96.4%); significant (p < 0.01) decreases in amoxicillin-clavulanate, cefepime, ceftriaxone, levofloxacin, piperacillin-tazobactam and tigecycline susceptibility were observed among K. pneumoniae between 2004 and 2012. Only imipenem was highly active (96.5% susceptible) against Acinetobacter baumannii. Imipenem and amikacin (87.7% and 87.1% susceptible) were the most active agents against P. aeruginosa; 10.2% of isolates were categorized as multidrug resistant. CONCLUSIONS: Carbapenems, linezolid, tigecycline and vancomycin conserved good in vitro activity against most pathogens (according to their spectrum of activity) in France between 2004 and 2012.

In vitro activity of tigecycline and comparators against Gram-positive and Gram-negative isolates collected from the Middle East and Africa between 2004 and 2011.

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum ß-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC90 (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.

Antimicrobial susceptibility among Gram-positive and Gram-negative isolates collected in Europe between 2004 and 2010.

Here we report on the in vitro activity of a suite of antimicrobial agents against Gram-negative and Gram-positive pathogens collected in Europe between 2004 and 2010 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodologies were used to determine minimum inhibitory concentrations. CLSI interpretive criteria were applied for all antimicrobial agents to establish susceptibility; European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used for tigecycline. In total, 46,921 Gram-negative and 19,174 Gram-positive isolates were included in this study. Extended-spectrum ß-lactamases increased in proportion from 15.7% to 21.1% among Klebsiella pneumoniae and from 9.7% to 16.1% among Escherichia coli isolates between 2004-2007 and 2010. E. coli susceptibility decreased to most antimicrobials but it remained highly susceptible (>98%) to tigecycline and meropenem. Acinetobacter baumannii susceptibility also decreased to most agents. The proportion of meticillin-resistant Staphylococcus aureus (MRSA) decreased from 25.7% to 19.4% over the study period. Antimicrobial susceptibility has decreased among many of the pathogens observed in the T.E.S.T. surveillance study between 2004-2007 and 2010.

Longitudinal Assessment of Antimicrobial Susceptibility among Gram-Negative and Gram-Positive Organisms Collected from Italy as Part of the Tigecycline Evaluation and Surveillance Trial between 2004 and 2011.

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was initiated in 2004 to longitudinally monitor the activity of the broad-spectrum glycylcycline antimicrobial tigecycline, and a suite of comparator agents, against an array of clinically important bacterial pathogens worldwide. In this report, we examine the activity of tigecycline and comparators against a collection of 13,245 clinical isolates, both Gram-positive (n = 4,078 and Gram-negative (n = 9,167), collected from 27 centres in Italy between 2004 and 2011. Susceptibility was established according to Clinical Laboratory Standards Institute guidelines. Tigecycline and linezolid exhibited very good activity against Gram-positive pathogens, with MIC90s ranging from 0.06 to 0.25 mg/L and 1-4 mg/L, respectively; vancomycin and the carbapenems also showed good activity against select Gram-positive pathogens. Tigecycline was the most active agent against Gram-negative pathogens (except P. aeruginosa), with MIC90s ranging from 0.25-2 mg/L (16 mg/L for P. aeruginosa). Amikacin and the carbapenems also possessed good activity against many Gram-negative pathogens here. ESBL-positive E. coli increased in prevalence from 2004 to 2011, while ESBL-positive Klebsiella spp., vancomycin-resistant enterococci and MRSA decreased in prevalence. Linezolid, tigecycline and vancomycin susceptibility were very stable over the course of this study, while susceptibility to ampicillin, piperacillin-tazobactam, ceftriaxone and levofloxacin varied over time according to pathogen; minocycline and cefepime susceptibility among several pathogens decreased during this study.