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

  • Comparative in vivo activity of Gemifloxacin in a rat model of respiratory tract infection
    Journal of Antimicrobial Chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    The in vivo efficacy of the novel quinolone Gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral Gemifloxacin, amoxycillin‐clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, Gemifloxacin produced a 3‐5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin‐ clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than Gemifloxacin: these agents reduced bacterial numbers by 3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than Gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of Gemifloxacin against these organisms. This indicates that Gemifloxacin may be of significant benefit in the treatment of RTI.

  • Comparative efficacy of Gemifloxacin in experimental models of pyelonephritis and wound infection.
    Journal of Antimicrobial Chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of Gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), Gemifloxacin reduced bacterial numbers significantly (P 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than Gemifloxacin (P < 0.01). No comparator agent had greater activity than Gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of Gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

  • Comparative efficacy of Gemifloxacin in experimental models of pyelonephritis and wound infection.
    The Journal of antimicrobial chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of Gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), Gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than Gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than Gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, Gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than Gemifloxacin (P < 0.01). No comparator agent had greater activity than Gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of Gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

  • In vitro activity of Gemifloxacin (SB 265805; LB20304a) against human mycoplasmas
    The Journal of antimicrobial chemotherapy, 2000
    Co-Authors: Peter C. T. Hannan, G Woodnutt
    Abstract:

    The in vitro activity of Gemifloxacin, a new broad-spectrum fluoroquinolone, was compared with those of ciprofloxacin, erythromycin, azithromycin and doxycycline against 29 human respiratory or urogenital tract mycoplasmas. Gemifloxacin was highly active against all of the mycoplasma and ureaplasma species tested (MIC range 0.001-0.25 mg/L) and was 5- to 100-fold more active than ciprofloxacin. Doxycycline was less active than Gemifloxacin against the mycoplasmas (MIC range 0.01-1 mg/L) but had similar activity against Ureaplasma urealyticum (MIC ranges 0.025-0.25 mg/L and 0.1-0. 25 mg/L, respectively). The macrolides, particularly azithromycin, were more active than Gemifloxacin against Mycoplasma pneumoniae (MIC range 0.001-0.0025 mg/L) and Mycoplasma genitalium (0.0005-0. 001 mg/L) isolates but were less active against Mycoplasma fermentans and U. urealyticum and inactive against Mycoplasma hominis. Gemifloxacin may therefore be useful in the treatment of respiratory, urogenital or systemic mycoplasma infections in humans.

Michael J. Rybak - One of the best experts on this subject based on the ideXlab platform.

  • synergy between Gemifloxacin and trimethoprim sulfamethoxazole against community associated methicillin resistant staphylococcus aureus
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.

  • Synergy between Gemifloxacin and trimethoprim/sulfamethoxazole against community-associated methicillin-resistant Staphylococcus aureus
    The Journal of antimicrobial chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.

Steven N. Leonard - One of the best experts on this subject based on the ideXlab platform.

  • synergy between Gemifloxacin and trimethoprim sulfamethoxazole against community associated methicillin resistant staphylococcus aureus
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.

  • Synergy between Gemifloxacin and trimethoprim/sulfamethoxazole against community-associated methicillin-resistant Staphylococcus aureus
    The Journal of antimicrobial chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.

V Berry - One of the best experts on this subject based on the ideXlab platform.

  • Comparative in vivo activity of Gemifloxacin in a rat model of respiratory tract infection
    Journal of Antimicrobial Chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    The in vivo efficacy of the novel quinolone Gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral Gemifloxacin, amoxycillin‐clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, Gemifloxacin produced a 3‐5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin‐ clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than Gemifloxacin: these agents reduced bacterial numbers by 3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than Gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of Gemifloxacin against these organisms. This indicates that Gemifloxacin may be of significant benefit in the treatment of RTI.

  • Comparative efficacy of Gemifloxacin in experimental models of pyelonephritis and wound infection.
    Journal of Antimicrobial Chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of Gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), Gemifloxacin reduced bacterial numbers significantly (P 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than Gemifloxacin (P < 0.01). No comparator agent had greater activity than Gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of Gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

  • Comparative efficacy of Gemifloxacin in experimental models of pyelonephritis and wound infection.
    The Journal of antimicrobial chemotherapy, 2000
    Co-Authors: V Berry, R Page, J Satterfield, C Singley, R Straub, G Woodnutt
    Abstract:

    Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of Gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), Gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than Gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than Gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, Gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than Gemifloxacin (P < 0.01). No comparator agent had greater activity than Gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of Gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

Glenn W. Kaatz - One of the best experts on this subject based on the ideXlab platform.

  • synergy between Gemifloxacin and trimethoprim sulfamethoxazole against community associated methicillin resistant staphylococcus aureus
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.

  • Synergy between Gemifloxacin and trimethoprim/sulfamethoxazole against community-associated methicillin-resistant Staphylococcus aureus
    The Journal of antimicrobial chemotherapy, 2008
    Co-Authors: Steven N. Leonard, Glenn W. Kaatz, Latoyia R. Rucker, Michael J. Rybak
    Abstract:

    Objectives: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with Gemifloxacin would enhance Gemifloxacin activity against CA-MRSA. Methods: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to Gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between Gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/ pharmacodynamic (PK/PD) model. Results: In time-kill analyses, Gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to Gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of Gemifloxacin and rifampicin. In the PK/PD model, combining Gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log 10 cfu/mL by 48 h; Gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to Gemifloxacin at 96 h with Gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. Conclusions: Synergy or additivity was demonstrated by time-kill analysis between Gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimetho-prim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of Gemifloxacin against CA-MRSA and suppressed the emergence of resistance to Gemifloxacin.