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Michael J Dowzicky - One of the best experts on this subject based on the ideXlab platform.
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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
MDPI AG, 2013Co-Authors: Michael J Dowzicky, Stefania StefaniAbstract: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
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prevalence and regional variation in meticillin resistant staphylococcus aureus mrsa in the usa and comparative in vitro activity of tigecycline a Glycylcycline antimicrobial
Journal of Medical Microbiology, 2007Co-Authors: Debra A Goff, Michael J DowzickyAbstract:The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a surveillance study established in 2004 to monitor the activity of tigecycline, the first Glycylcycline, and comparator agents [β-lactams (including penicillins, cephalosporins and carbapenems), glycopeptides, tetracyclines, fluoroquinolones and oxazolidinones] against Gram-positive and Gram-negative pathogens worldwide. This report examines 1692 isolates of Staphylococcus aureus collected in the continental United States between January 2004 and September 2005. Meticillin-resistant S. aureus (MRSA) accounted for 52.0 % of isolates. Prevalence of MRSA by state ranged from 12.5 % in New Hampshire to 100 % in Kentucky. All isolates were susceptible to tigecycline, linezolid and vancomycin. In vitro, tigecycline was potent against both meticillin-susceptible S. aureus (MSSA) (MIC50 and MIC90=0.12 μg ml−1) and MRSA (MIC50=0.12 μg ml−1; MIC90=0.25 μg ml−1). Only a single isolate was resistant to three or more antimicrobial classes. Ninety-six isolates (5.7 %) were susceptible to the complete antimicrobial panel.
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tigecycline gar 936 activity against streptococcus gallolyticus bovis and viridans group streptococci
Diagnostic Microbiology and Infectious Disease, 2007Co-Authors: Gary J Moet, Michael J Dowzicky, Ronald N JonesAbstract:Abstract Viridans group streptococci including Streptococcus gallolyticus (formerly S. bovis) represent serious invasive pathogens often associated with endocarditis or sepsis among immunocompromised or cancer patients. Tigecycline (GAR-936), the first clinically studied Glycylcycline, has a potent Gram-positive activity with a potential treatment option for these streptococcal infections. The studied collection (848 strains) included 100 isolates each of Streptococcus anginosus , Streptococcus constellatus , Streptococcus intermedius , Streptococcus mitis , Streptococcus oralis , Streptococcus salivarius , Streptococcus sanguis , and fewer strains of S. gallolyticus (98 strains) and Streptococcus mutans (50 strains). These strains were isolated from patients on 3 continents in the SENTRY Antimicrobial Surveillance Program and tested for susceptibility and interpreted by Clinical and Laboratory Standards Institute broth microdilution methods and criteria (≤0.25 μg/mL for tigecycline per US Food and Drug Administration). Penicillin susceptibility rates for the entire collection varied from 61% ( S. sanguis ) to 98% ( S. constellatus ), and macrolide susceptibility was also compromised (49–88%; average, 69%). Tigecycline was active against all isolates tested, in contrast to tetracycline resistance rates of 8–66%, and highest for S. gallolyticus . In conclusion tigecycline was quite active against bacteremic isolates of viridans group streptococci species and S. gallolyticus with an overall MIC 90 at ≤0.06 μg/mL; the highest MIC was only 0.25 μg/mL.
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in vitro activity of tigecycline against 6792 gram negative and gram positive clinical isolates from the global tigecycline evaluation and surveillance trial test program 2004
Diagnostic Microbiology and Infectious Disease, 2005Co-Authors: Daryl J Hoban, S Bouchillon, B Johnson, J Johnson, Michael J DowzickyAbstract:Tigecycline, a new Glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrugresistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (Ag/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 Ag/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 Ag/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 Ag/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new Glycylcycline agent for the treatment of many types of
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in vitro activity of tigecycline against 6792 gram negative and gram positive clinical isolates from the global tigecycline evaluation and surveillance trial test program 2004
Diagnostic Microbiology and Infectious Disease, 2005Co-Authors: Daryl J Hoban, S Bouchillon, B Johnson, J Johnson, Michael J DowzickyAbstract:Tigecycline, a new Glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new Glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.
Andrew M. Wier - One of the best experts on this subject based on the ideXlab platform.
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destruction of spirochete borrelia burgdorferi round body propagules rbs by the antibiotic tigecycline
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Oystein Brorson, James Macallister, Sverrehenning Brorson, John Scythes, Andrew M. WierAbstract:Persistence of tissue spirochetes of Borrelia burgdorferi as helices and round bodies (RBs) explains many erythema-Lyme disease symptoms. Spirochete RBs (reproductive propagules also called coccoid bodies, globular bodies, spherical bodies, granules, cysts, L-forms, sphaeroplasts, or vesicles) are induced by environmental conditions unfavorable for growth. Viable, they grow, move and reversibly convert into motile helices. Reversible pleiomorphy was recorded in at least six spirochete genera (>12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second “Great Imitator” (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = “cysts”) by the antibiotic Tigecycline (TG; Wyeth), a Glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged.
Daryl J Hoban - One of the best experts on this subject based on the ideXlab platform.
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tigecycline a novel Glycylcycline antibiotic
Expert Review of Anti-infective Therapy, 2006Co-Authors: George G Zhanel, Ethan Rubinstein, James A Karlowsky, Daryl J HobanAbstract:Tigecycline, the first-in-class Glycylcycline, was developed to recapture the broad spectrum of activity of the tetracycline class and to treat patients with difficult-to-treat bacterial infections. Tigecycline's in vitro spectrum of activity encompasses aerobic, facultative and anaerobic Gram-positive and -negative bacteria, including antimicrobial-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Clinical trials involving patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, including patients infected with methicillin-resistant S. aureus, demonstrated that tigecycline was bacteriologically and clinically effective with mild-to-moderate gastrointestinal adverse events (i.e., nausea, vomiting and diarrhea) the most commonly reported. Tigecycline is a promising new broad-spectrum parenteral monotherapy for the treatment of patients with Gram-positive and -negative bacterial infections.
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in vitro activity of tigecycline against 6792 gram negative and gram positive clinical isolates from the global tigecycline evaluation and surveillance trial test program 2004
Diagnostic Microbiology and Infectious Disease, 2005Co-Authors: Daryl J Hoban, S Bouchillon, B Johnson, J Johnson, Michael J DowzickyAbstract:Tigecycline, a new Glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrugresistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (Ag/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 Ag/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 Ag/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 Ag/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new Glycylcycline agent for the treatment of many types of
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in vitro activity of tigecycline against 6792 gram negative and gram positive clinical isolates from the global tigecycline evaluation and surveillance trial test program 2004
Diagnostic Microbiology and Infectious Disease, 2005Co-Authors: Daryl J Hoban, S Bouchillon, B Johnson, J Johnson, Michael J DowzickyAbstract:Tigecycline, a new Glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new Glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.
Ronald N Jones - One of the best experts on this subject based on the ideXlab platform.
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tigecycline gar 936 activity against streptococcus gallolyticus bovis and viridans group streptococci
Diagnostic Microbiology and Infectious Disease, 2007Co-Authors: Gary J Moet, Michael J Dowzicky, Ronald N JonesAbstract:Abstract Viridans group streptococci including Streptococcus gallolyticus (formerly S. bovis) represent serious invasive pathogens often associated with endocarditis or sepsis among immunocompromised or cancer patients. Tigecycline (GAR-936), the first clinically studied Glycylcycline, has a potent Gram-positive activity with a potential treatment option for these streptococcal infections. The studied collection (848 strains) included 100 isolates each of Streptococcus anginosus , Streptococcus constellatus , Streptococcus intermedius , Streptococcus mitis , Streptococcus oralis , Streptococcus salivarius , Streptococcus sanguis , and fewer strains of S. gallolyticus (98 strains) and Streptococcus mutans (50 strains). These strains were isolated from patients on 3 continents in the SENTRY Antimicrobial Surveillance Program and tested for susceptibility and interpreted by Clinical and Laboratory Standards Institute broth microdilution methods and criteria (≤0.25 μg/mL for tigecycline per US Food and Drug Administration). Penicillin susceptibility rates for the entire collection varied from 61% ( S. sanguis ) to 98% ( S. constellatus ), and macrolide susceptibility was also compromised (49–88%; average, 69%). Tigecycline was active against all isolates tested, in contrast to tetracycline resistance rates of 8–66%, and highest for S. gallolyticus . In conclusion tigecycline was quite active against bacteremic isolates of viridans group streptococci species and S. gallolyticus with an overall MIC 90 at ≤0.06 μg/mL; the highest MIC was only 0.25 μg/mL.
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antimicrobial activity and spectrum of the new Glycylcycline gar 936 tested against 1 203 recent clinical bacterial isolates
Diagnostic Microbiology and Infectious Disease, 2000Co-Authors: Ana C Gales, Ronald N JonesAbstract:Abstract The in vitro activity of GAR-936, a new semisynthetic Glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1, 203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two- to four-fold more active than minocycline, and two- to 16-fold more active than tetracycline. All enteric bacilli MIC 90 results were ≤ 4 μg/mL; the exception being Proteus mirabilis and indole-positive Proteae (≥ 8 μg/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 μg/ml, while the same isolates had a MIC 90 of 8 and > 8 μg/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 μg/mL of GAR-936 (MIC 90 , 0.12 or 0.25 μg/mL). Although GAR-936 (MIC 50 , 0.25 μg/mL) was two-fold less active than minocycline (MIC 50 , 0.12 μg/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at ≤ 0.25 μg/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC 90 , 2 μg/ml) and Stenotrophomonas maltophilia (MIC 90 , 4 μg/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC 50 , 8 μg/mL). Haemophilus influenzae (MIC 90 , 1–2 μg/mL), Moraxella catarrhalis (MIC 90 , 0.12 μg/mL), and various Neisseria spp. (MIC 90 , 0.12–0.5 μg/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several Gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest Glycylcycline candidate for clinical use.
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Disk diffusion susceptibility test development for the new Glycylcycline, GAR-936.
Diagnostic microbiology and infectious disease, 1999Co-Authors: Ronald N JonesAbstract:The in vitro activity of GAR-936, a new semisynthetic Glycylcycline, was evaluated in comparison with two tetracyclines and the disk diffusion susceptibility test was assessed. Nearly 700 recent clinical isolates were tested by reference broth microdilution and disk diffusion (two disk contents) methods. Among the Enterobacteriaceae, GAR-936 was generally two- to 16-fold more active than other tetracyclines. All enteric bacilli MIC90 results were or = 8 micrograms/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with Enterococcus spp. (including vancomycin-resistant isolates) inhibited at 0.25 microgram/mL (GAR-936 MIC90, 0.12 or 0.25 microgram/mL) and the oxacillin-resistant Staphylococcus aureus strains were inhibited at < or = 0.25 microgram/mL. GAR-936 demonstrated good potency against several non-fermentative bacteria, but possessed limited activity against Pseudomonas aeruginosa (MIC50, 8 micrograms/mL). In vitro susceptibility test methods were developed (disk diffusion versus reference MIC results) and tentative breakpoints were proposed. Using susceptibility criteria of either < or = 2 or < or = 4 micrograms/mL, GAR-936 in vitro susceptibility tests demonstrated rare significant serious inter-method discords (< or = 1.2%) and an absolute agreement between test results of 92.3 to 96.2%. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important rapidly growing pathogenic bacteria, and that this novel Glycylcycline candidate for clinical use should be further developed.
Oystein Brorson - One of the best experts on this subject based on the ideXlab platform.
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destruction of spirochete borrelia burgdorferi round body propagules rbs by the antibiotic tigecycline
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Oystein Brorson, James Macallister, Sverrehenning Brorson, John Scythes, Andrew M. WierAbstract:Persistence of tissue spirochetes of Borrelia burgdorferi as helices and round bodies (RBs) explains many erythema-Lyme disease symptoms. Spirochete RBs (reproductive propagules also called coccoid bodies, globular bodies, spherical bodies, granules, cysts, L-forms, sphaeroplasts, or vesicles) are induced by environmental conditions unfavorable for growth. Viable, they grow, move and reversibly convert into motile helices. Reversible pleiomorphy was recorded in at least six spirochete genera (>12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second “Great Imitator” (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = “cysts”) by the antibiotic Tigecycline (TG; Wyeth), a Glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged.