Garenoxacin

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Ronald N Jones - One of the best experts on this subject based on the ideXlab platform.

  • activity of Garenoxacin an investigational des f 6 quinolone tested against pathogens from community acquired respiratory tract infections including those with elevated or resistant level fluoroquinolone mic values
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Thomas R Fritsche, Helio S Sader, Matthew G Stilwell
    Abstract:

    Abstract Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999–2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for Garenoxacin and 19 comparison agents. The Garenoxacin MIC 90 and percentage (%) of strains inhibited at ≤1 μg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 μg/mL, >99.9% susceptible), H. influenzae (≤0.03 μg/mL, >99.9%), and M. catarrhalis (≤0.03 μg/mL, 100.0%). The Garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC 90 , 0.12 μg/mL). Resistances to other classes of antimicrobials did not adversely influence Garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, ≥4 μg/mL) S. pneumoniae had higher Garenoxacin MIC 90 values (1 μg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher Garenoxacin MIC results, with ≥3 to 4 QRDR mutations required to elevate Garenoxacin MIC values to ≥2 μg/mL. In conclusion, Garenoxacin possesses a potent activity against pneumococci, H. influenzae , and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae , respectively, had a Garenoxacin MIC at ≥2 μg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).

  • Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Helio S Sader, Matthew G Stilwell, Thomas R Fritsche
    Abstract:

    Abstract Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens ( Streptococcus pneumoniae and Haemophilus influenzae ) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC 90 , 0.06 μg/mL) and H. influenzae (MIC 90 , ≤0.03 μg/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and >99.9% of strains were inhibited at ≤1 μg/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the β-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against >99.9% (MIC, ≤1 μg/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at ≤1 μg/mL) to Garenoxacin (MIC 90 , 0.06 μg/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for the emerging MDR pneumococci strains.

  • potency and spectrum of Garenoxacin tested against an international collection of skin and soft tissue infection pathogens report from the sentry antimicrobial surveillance program 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Thomas R Fritsche, Helio S Sader, Ronald N Jones
    Abstract:

    Abstract The spectrum and potency of Garenoxacin, a novel des-F(6)-quinolone, against a large international collection (11723 strains) of Gram-positive and Gram-negative bacterial pathogens that cause skin and soft tissue infections (SSTIs) were evaluated for the years 1999 to 2004. Consecutive nonduplicate bacterial isolates were collected from patients with documented community-acquired or nosocomial SSTI in >70 medical centers participating in the SENTRY Antimicrobial Surveillance Program in North America (37.4%), Europe (26.7%), Latin America (16.7%), and the Asia-Pacific region (19.2%). All isolates were tested using the reference broth microdilution methods against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and representative comparator agents used for the empiric or directed therapy for SSTI. Ranking pathogens producing SSTI during these years included Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), β-hemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%), and Acinetobacter spp. (2.1%). Garenoxacin was the most potent agent tested against S. aureus and was at least 2-fold more active than gatifloxacin (MIC 50 , 0.06 mg/L) and 8-fold more active than levofloxacin (MIC 50 , 0.25 mg/L). Furthermore, Garenoxacin was 2- to 8-fold more potent than the fluoroquinolones against β-hemolytic and viridans group streptococci, as well as up to 4-fold more active against enterococci. Garenoxacin was largely comparable with the comparator fluoroquinolones against E. coli , Klebsiella spp., and Acinetobacter spp., but it is less active than these agents against P. aeruginosa . In summary, Garenoxacin was documented to be the most potent quinolone when tested against key Gram-positive pathogens ( S. aureus , β-hemolytic streptococci, viridans group streptococci, and enterococci) and was similar in activity to these agents against other species (Enterobacteriaceae and Acinetobacter spp.). These in vitro data suggest that Garenoxacin warrants further clinical studies in SSTI, especially against staphylococci and streptococcal pathogens.

  • in vitro activity of Garenoxacin tested against a worldwide collection of ciprofloxacin susceptible and ciprofloxacin resistant enterobacteriaceae strains 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Helio S Sader, Thomas R Fritsche, Ronald N Jones
    Abstract:

    Abstract Garenoxacin is a novel des-F(6)-quinolone with a chemical structure that lacks the C6 position fluorine and has a unique difluoromethoxy substitution at position C8. This study evaluated the in vitro activity of Garenoxacin tested against a large collection of Enterobacteriaceae collected worldwide. The bacterial isolates were consecutively collected from more than 70 medical centers from bloodstream, respiratory, urinary tract, and skin and soft tissue infections. The isolates were tested against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and many other oral and parenteral antimicrobial agents. All isolates were susceptibility tested by broth microdilution methods according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and interpretative criteria. A Garenoxacin-susceptible breakpoint of ≤2 μg/mL was applied for comparison purposes only. The fluoroquinolones were the most active oral compounds with overall susceptibility rates of 87.5% to 90.0%. Garenoxacin showed in vitro activity comparable with that of ciprofloxacin and the other fluoroquinolones against Escherichia coli (MIC 50 , ≤0.03 μg/mL; 87.3% susceptible), Klebsiella spp. (MIC 50 , 0.12 μg/mL; 90.4–94.5% susceptible), Enterobacter spp. (MIC 50 , 0.12 μg/mL; 85.6–86.5% susceptible), Salmonella spp. (MIC 50 , 0.06 μg/mL; 99.7% susceptible), and Shigella spp. (MIC 50 , ≤0.03 μg/mL; 99.9% susceptible), which accounted for 87.0% of the Enterobacteriaceae strains tested. Garenoxacin was highly active against ciprofloxacin-susceptible strains (98.1% susceptibility), whereas ciprofloxacin-resistant strains were generally resistant to all other fluoroquinolones and also showed high rates of resistance to other orally administered antimicrobials. In conclusion, Garenoxacin in vitro activity was similar to that of currently marketed fluoroquinolones and superior to other orally administered antimicrobial agents (cephalosporins, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole) when tested against more than 45000 globally collected Enterobacteriaceae.

  • symposium section Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    2007
    Co-Authors: Ronald N Jones, Matthew G Stilwell, H S Sader, Thomas R Fritsche
    Abstract:

    Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens (Streptococcus pneumoniae and Haemophilus influenzae) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC90, 0.06 Ag/mL) and H. influenzae (MIC90, V0.03 Ag/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and N99.9% of strains were inhibited at V1 Ag/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the h-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against N99.9% (MIC, V1 Ag/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at V1 Ag/mL) to Garenoxacin (MIC90, 0.06 Ag/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for

Thomas R Fritsche - One of the best experts on this subject based on the ideXlab platform.

  • activity of Garenoxacin an investigational des f 6 quinolone tested against pathogens from community acquired respiratory tract infections including those with elevated or resistant level fluoroquinolone mic values
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Thomas R Fritsche, Helio S Sader, Matthew G Stilwell
    Abstract:

    Abstract Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999–2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for Garenoxacin and 19 comparison agents. The Garenoxacin MIC 90 and percentage (%) of strains inhibited at ≤1 μg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 μg/mL, >99.9% susceptible), H. influenzae (≤0.03 μg/mL, >99.9%), and M. catarrhalis (≤0.03 μg/mL, 100.0%). The Garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC 90 , 0.12 μg/mL). Resistances to other classes of antimicrobials did not adversely influence Garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, ≥4 μg/mL) S. pneumoniae had higher Garenoxacin MIC 90 values (1 μg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher Garenoxacin MIC results, with ≥3 to 4 QRDR mutations required to elevate Garenoxacin MIC values to ≥2 μg/mL. In conclusion, Garenoxacin possesses a potent activity against pneumococci, H. influenzae , and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae , respectively, had a Garenoxacin MIC at ≥2 μg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).

  • Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Helio S Sader, Matthew G Stilwell, Thomas R Fritsche
    Abstract:

    Abstract Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens ( Streptococcus pneumoniae and Haemophilus influenzae ) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC 90 , 0.06 μg/mL) and H. influenzae (MIC 90 , ≤0.03 μg/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and >99.9% of strains were inhibited at ≤1 μg/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the β-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against >99.9% (MIC, ≤1 μg/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at ≤1 μg/mL) to Garenoxacin (MIC 90 , 0.06 μg/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for the emerging MDR pneumococci strains.

  • potency and spectrum of Garenoxacin tested against an international collection of skin and soft tissue infection pathogens report from the sentry antimicrobial surveillance program 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Thomas R Fritsche, Helio S Sader, Ronald N Jones
    Abstract:

    Abstract The spectrum and potency of Garenoxacin, a novel des-F(6)-quinolone, against a large international collection (11723 strains) of Gram-positive and Gram-negative bacterial pathogens that cause skin and soft tissue infections (SSTIs) were evaluated for the years 1999 to 2004. Consecutive nonduplicate bacterial isolates were collected from patients with documented community-acquired or nosocomial SSTI in >70 medical centers participating in the SENTRY Antimicrobial Surveillance Program in North America (37.4%), Europe (26.7%), Latin America (16.7%), and the Asia-Pacific region (19.2%). All isolates were tested using the reference broth microdilution methods against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and representative comparator agents used for the empiric or directed therapy for SSTI. Ranking pathogens producing SSTI during these years included Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), β-hemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%), and Acinetobacter spp. (2.1%). Garenoxacin was the most potent agent tested against S. aureus and was at least 2-fold more active than gatifloxacin (MIC 50 , 0.06 mg/L) and 8-fold more active than levofloxacin (MIC 50 , 0.25 mg/L). Furthermore, Garenoxacin was 2- to 8-fold more potent than the fluoroquinolones against β-hemolytic and viridans group streptococci, as well as up to 4-fold more active against enterococci. Garenoxacin was largely comparable with the comparator fluoroquinolones against E. coli , Klebsiella spp., and Acinetobacter spp., but it is less active than these agents against P. aeruginosa . In summary, Garenoxacin was documented to be the most potent quinolone when tested against key Gram-positive pathogens ( S. aureus , β-hemolytic streptococci, viridans group streptococci, and enterococci) and was similar in activity to these agents against other species (Enterobacteriaceae and Acinetobacter spp.). These in vitro data suggest that Garenoxacin warrants further clinical studies in SSTI, especially against staphylococci and streptococcal pathogens.

  • in vitro activity of Garenoxacin tested against a worldwide collection of ciprofloxacin susceptible and ciprofloxacin resistant enterobacteriaceae strains 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Helio S Sader, Thomas R Fritsche, Ronald N Jones
    Abstract:

    Abstract Garenoxacin is a novel des-F(6)-quinolone with a chemical structure that lacks the C6 position fluorine and has a unique difluoromethoxy substitution at position C8. This study evaluated the in vitro activity of Garenoxacin tested against a large collection of Enterobacteriaceae collected worldwide. The bacterial isolates were consecutively collected from more than 70 medical centers from bloodstream, respiratory, urinary tract, and skin and soft tissue infections. The isolates were tested against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and many other oral and parenteral antimicrobial agents. All isolates were susceptibility tested by broth microdilution methods according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and interpretative criteria. A Garenoxacin-susceptible breakpoint of ≤2 μg/mL was applied for comparison purposes only. The fluoroquinolones were the most active oral compounds with overall susceptibility rates of 87.5% to 90.0%. Garenoxacin showed in vitro activity comparable with that of ciprofloxacin and the other fluoroquinolones against Escherichia coli (MIC 50 , ≤0.03 μg/mL; 87.3% susceptible), Klebsiella spp. (MIC 50 , 0.12 μg/mL; 90.4–94.5% susceptible), Enterobacter spp. (MIC 50 , 0.12 μg/mL; 85.6–86.5% susceptible), Salmonella spp. (MIC 50 , 0.06 μg/mL; 99.7% susceptible), and Shigella spp. (MIC 50 , ≤0.03 μg/mL; 99.9% susceptible), which accounted for 87.0% of the Enterobacteriaceae strains tested. Garenoxacin was highly active against ciprofloxacin-susceptible strains (98.1% susceptibility), whereas ciprofloxacin-resistant strains were generally resistant to all other fluoroquinolones and also showed high rates of resistance to other orally administered antimicrobials. In conclusion, Garenoxacin in vitro activity was similar to that of currently marketed fluoroquinolones and superior to other orally administered antimicrobial agents (cephalosporins, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole) when tested against more than 45000 globally collected Enterobacteriaceae.

  • symposium section Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    2007
    Co-Authors: Ronald N Jones, Matthew G Stilwell, H S Sader, Thomas R Fritsche
    Abstract:

    Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens (Streptococcus pneumoniae and Haemophilus influenzae) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC90, 0.06 Ag/mL) and H. influenzae (MIC90, V0.03 Ag/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and N99.9% of strains were inhibited at V1 Ag/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the h-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against N99.9% (MIC, V1 Ag/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at V1 Ag/mL) to Garenoxacin (MIC90, 0.06 Ag/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for

Helio S Sader - One of the best experts on this subject based on the ideXlab platform.

  • activity of Garenoxacin an investigational des f 6 quinolone tested against pathogens from community acquired respiratory tract infections including those with elevated or resistant level fluoroquinolone mic values
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Thomas R Fritsche, Helio S Sader, Matthew G Stilwell
    Abstract:

    Abstract Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999–2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for Garenoxacin and 19 comparison agents. The Garenoxacin MIC 90 and percentage (%) of strains inhibited at ≤1 μg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 μg/mL, >99.9% susceptible), H. influenzae (≤0.03 μg/mL, >99.9%), and M. catarrhalis (≤0.03 μg/mL, 100.0%). The Garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC 90 , 0.12 μg/mL). Resistances to other classes of antimicrobials did not adversely influence Garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, ≥4 μg/mL) S. pneumoniae had higher Garenoxacin MIC 90 values (1 μg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher Garenoxacin MIC results, with ≥3 to 4 QRDR mutations required to elevate Garenoxacin MIC values to ≥2 μg/mL. In conclusion, Garenoxacin possesses a potent activity against pneumococci, H. influenzae , and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae , respectively, had a Garenoxacin MIC at ≥2 μg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).

  • Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Helio S Sader, Matthew G Stilwell, Thomas R Fritsche
    Abstract:

    Abstract Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens ( Streptococcus pneumoniae and Haemophilus influenzae ) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC 90 , 0.06 μg/mL) and H. influenzae (MIC 90 , ≤0.03 μg/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and >99.9% of strains were inhibited at ≤1 μg/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the β-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against >99.9% (MIC, ≤1 μg/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at ≤1 μg/mL) to Garenoxacin (MIC 90 , 0.06 μg/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for the emerging MDR pneumococci strains.

  • potency and spectrum of Garenoxacin tested against an international collection of skin and soft tissue infection pathogens report from the sentry antimicrobial surveillance program 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Thomas R Fritsche, Helio S Sader, Ronald N Jones
    Abstract:

    Abstract The spectrum and potency of Garenoxacin, a novel des-F(6)-quinolone, against a large international collection (11723 strains) of Gram-positive and Gram-negative bacterial pathogens that cause skin and soft tissue infections (SSTIs) were evaluated for the years 1999 to 2004. Consecutive nonduplicate bacterial isolates were collected from patients with documented community-acquired or nosocomial SSTI in >70 medical centers participating in the SENTRY Antimicrobial Surveillance Program in North America (37.4%), Europe (26.7%), Latin America (16.7%), and the Asia-Pacific region (19.2%). All isolates were tested using the reference broth microdilution methods against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and representative comparator agents used for the empiric or directed therapy for SSTI. Ranking pathogens producing SSTI during these years included Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), β-hemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%), and Acinetobacter spp. (2.1%). Garenoxacin was the most potent agent tested against S. aureus and was at least 2-fold more active than gatifloxacin (MIC 50 , 0.06 mg/L) and 8-fold more active than levofloxacin (MIC 50 , 0.25 mg/L). Furthermore, Garenoxacin was 2- to 8-fold more potent than the fluoroquinolones against β-hemolytic and viridans group streptococci, as well as up to 4-fold more active against enterococci. Garenoxacin was largely comparable with the comparator fluoroquinolones against E. coli , Klebsiella spp., and Acinetobacter spp., but it is less active than these agents against P. aeruginosa . In summary, Garenoxacin was documented to be the most potent quinolone when tested against key Gram-positive pathogens ( S. aureus , β-hemolytic streptococci, viridans group streptococci, and enterococci) and was similar in activity to these agents against other species (Enterobacteriaceae and Acinetobacter spp.). These in vitro data suggest that Garenoxacin warrants further clinical studies in SSTI, especially against staphylococci and streptococcal pathogens.

  • in vitro activity of Garenoxacin tested against a worldwide collection of ciprofloxacin susceptible and ciprofloxacin resistant enterobacteriaceae strains 1999 2004
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Helio S Sader, Thomas R Fritsche, Ronald N Jones
    Abstract:

    Abstract Garenoxacin is a novel des-F(6)-quinolone with a chemical structure that lacks the C6 position fluorine and has a unique difluoromethoxy substitution at position C8. This study evaluated the in vitro activity of Garenoxacin tested against a large collection of Enterobacteriaceae collected worldwide. The bacterial isolates were consecutively collected from more than 70 medical centers from bloodstream, respiratory, urinary tract, and skin and soft tissue infections. The isolates were tested against Garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and many other oral and parenteral antimicrobial agents. All isolates were susceptibility tested by broth microdilution methods according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and interpretative criteria. A Garenoxacin-susceptible breakpoint of ≤2 μg/mL was applied for comparison purposes only. The fluoroquinolones were the most active oral compounds with overall susceptibility rates of 87.5% to 90.0%. Garenoxacin showed in vitro activity comparable with that of ciprofloxacin and the other fluoroquinolones against Escherichia coli (MIC 50 , ≤0.03 μg/mL; 87.3% susceptible), Klebsiella spp. (MIC 50 , 0.12 μg/mL; 90.4–94.5% susceptible), Enterobacter spp. (MIC 50 , 0.12 μg/mL; 85.6–86.5% susceptible), Salmonella spp. (MIC 50 , 0.06 μg/mL; 99.7% susceptible), and Shigella spp. (MIC 50 , ≤0.03 μg/mL; 99.9% susceptible), which accounted for 87.0% of the Enterobacteriaceae strains tested. Garenoxacin was highly active against ciprofloxacin-susceptible strains (98.1% susceptibility), whereas ciprofloxacin-resistant strains were generally resistant to all other fluoroquinolones and also showed high rates of resistance to other orally administered antimicrobials. In conclusion, Garenoxacin in vitro activity was similar to that of currently marketed fluoroquinolones and superior to other orally administered antimicrobial agents (cephalosporins, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole) when tested against more than 45000 globally collected Enterobacteriaceae.

Douglas J Biedenbach - One of the best experts on this subject based on the ideXlab platform.

  • comparative activity of Garenoxacin bms 284756 a novel desfluoroquinolone tested against 8 331 isolates from community acquired respiratory tract infections north american results from the sentry antimicrobial surveillance program 1999 2001
    Diagnostic Microbiology and Infectious Disease, 2003
    Co-Authors: Ronald N Jones, Douglas J Biedenbach
    Abstract:

    Abstract Emerging resistances to orally administered antimicrobials have escalated among bacteria causing community-acquired respiratory infections (CARTI). The spectrum and potency of Garenoxacin, (formerly BMS 284756) was assessed against a collection of CARTI isolates from North American medical centers during a longitudinal surveillance study, the SENTRY Antimicrobial Surveillance Program (1999-2001). A total of 8,331 strains of Hemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were tested by reference methods and compared to numerous other marketed antimicrobials. Nearly all (95.1%) M. catarrhalis were penicillin-resistant, 27.9% of H. influenzae were ampicillin-resistant and 35.0% of S. pneumoniae had MICs at ≥ 0.12 μg/ml for penicillin. Garenoxacin was very active against the three monitored species with MIC 90 values of ≤0.06 μg/ml. Garenoxacin and other quinolones were equally active against the Gram-negative pathogens (except moxifloxacin which was at least twofold less potent versus M. catarrhalis ). However, against pneumococci the rank order of potency (MIC 50 in μg/ml) was: gemifloxacin (0.015) > Garenoxacin (0.06) > trovafloxacin=moxifloxacin (0.12) > gatifloxacin (0.25) > levofloxacin=ciprofloxacin (1). A trend toward greater resistance worldwide was observed for ciprofloxacin (MIC, ≥ 4 μg/ml), increasing from 1.5% in 1999 to 6.8% in 2001. The highest quinolone resistance rate was observed in North America. Garenoxacin, a new desfluoro(6)quinolone, was documented to be very active in vitro (MIC, ≤2 μg/ml) against > 99.9% of all CARTI isolates in the SENTRY Program. Evolving resistances to other antimicrobial classes or among currently used quinolones appear to position this investigational desfluoro(6)quinolone as a potential treatment option for future clinical use in ambulatory patients.

  • geographic variations in Garenoxacin bms284756 activity tested against pathogens associated with skin and soft tissue infections report from the sentry antimicrobial surveillance program 2000
    Diagnostic Microbiology and Infectious Disease, 2002
    Co-Authors: Jeffrey T Kirby, Ronald N Jones, Alan H Mutnick, Douglas J Biedenbach, Michael A Pfaller
    Abstract:

    Abstract The antimicrobial activity of Garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC 90 , 0.06 μg/ml) compared to levofloxacin (MIC 90 , 0.25 μg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to Garenoxacin (≥90.5%) at ≤4 μg/ml than ciprofloxacin or levofloxacin. Enterococcus spp. were more susceptible to Garenoxacin and gatifloxacin (MIC 50 , 0.5 μg/ml) than ciprofloxacin or levofloxacin (MIC 50 , 2 μg/ml). All tested quinolones inhibited 64.7 to 69.7% of P. aeruginosa isolates, and the rank order of potency slightly favored ciprofloxacin (MIC 50 , ≤0.25 μg/ml). Similar susceptibility rates for the four quinolones were observed against E. coli (85.8–87.0%), Enterobacter spp. (90.8–94.3%) and Klebsiella spp. (89.8–95.2%) with the greatest levels of resistance recorded in Latin America for E. coli and Enterobacter spp. The occurrence of extended spectrum β-lactamase-producing isolates (predominantly K. pneumoniae ) was documented in all three monitored regions (Latin America > Europe > North America). Continued development of Garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.

Matthew G Stilwell - One of the best experts on this subject based on the ideXlab platform.

  • activity of Garenoxacin an investigational des f 6 quinolone tested against pathogens from community acquired respiratory tract infections including those with elevated or resistant level fluoroquinolone mic values
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Thomas R Fritsche, Helio S Sader, Matthew G Stilwell
    Abstract:

    Abstract Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999–2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for Garenoxacin and 19 comparison agents. The Garenoxacin MIC 90 and percentage (%) of strains inhibited at ≤1 μg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 μg/mL, >99.9% susceptible), H. influenzae (≤0.03 μg/mL, >99.9%), and M. catarrhalis (≤0.03 μg/mL, 100.0%). The Garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC 90 , 0.12 μg/mL). Resistances to other classes of antimicrobials did not adversely influence Garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, ≥4 μg/mL) S. pneumoniae had higher Garenoxacin MIC 90 values (1 μg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher Garenoxacin MIC results, with ≥3 to 4 QRDR mutations required to elevate Garenoxacin MIC values to ≥2 μg/mL. In conclusion, Garenoxacin possesses a potent activity against pneumococci, H. influenzae , and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae , respectively, had a Garenoxacin MIC at ≥2 μg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).

  • Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    Diagnostic Microbiology and Infectious Disease, 2007
    Co-Authors: Ronald N Jones, Helio S Sader, Matthew G Stilwell, Thomas R Fritsche
    Abstract:

    Abstract Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens ( Streptococcus pneumoniae and Haemophilus influenzae ) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC 90 , 0.06 μg/mL) and H. influenzae (MIC 90 , ≤0.03 μg/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and >99.9% of strains were inhibited at ≤1 μg/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the β-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against >99.9% (MIC, ≤1 μg/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at ≤1 μg/mL) to Garenoxacin (MIC 90 , 0.06 μg/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for the emerging MDR pneumococci strains.

  • symposium section Garenoxacin activity against isolates form patients hospitalized with community acquired pneumonia and multidrug resistant streptococcus pneumoniae
    2007
    Co-Authors: Ronald N Jones, Matthew G Stilwell, H S Sader, Thomas R Fritsche
    Abstract:

    Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens (Streptococcus pneumoniae and Haemophilus influenzae) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999–2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, Garenoxacin. Results indicated that Garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC90, 0.06 Ag/mL) and H. influenzae (MIC90, V0.03 Ag/mL). This Garenoxacin potency was 8- to 32-fold greater than gatifloxacin, levofloxacin, and ciprofloxacin against the pneumococci and N99.9% of strains were inhibited at V1 Ag/mL (proposed susceptible breakpoint). Garenoxacin MIC values were not affected by resistances among S. pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the h-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that Garenoxacin was active against N99.9% (MIC, V1 Ag/mL) of strains, and the most resistant pneumococci (6-drug resistance, 1051 strains or 7.2% of all isolates) were completely susceptible (100.0% at V1 Ag/mL) to Garenoxacin (MIC90, 0.06 Ag/mL). These results illustrate the high activity of Garenoxacin against contemporary CAP isolates and especially against multidrug-resistant (MDR) S. pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for

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