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Peter C Appelbaum - One of the best experts on this subject based on the ideXlab platform.
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time kill studies of the antianaerobe activity of garenoxacin compared with those of nine other agents
Antimicrobial Agents and Chemotherapy, 2003Co-Authors: Kim Credito, Michael R. Jacobs, Peter C AppelbaumAbstract:The activities of garenoxacin, ciprofloxacin, levofloxacin, moxifloxacin, Trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 20 anaerobes were tested. At two times the MIC, garenoxacin was bactericidal against 19 of 20 strains after 48 h and against 17 of 20 after 24 h. Other drugs, except clindamycin (which gave lower killing rates), gave killing rates similar to those for garenoxacin.
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single and multi step resistance selection study of gemifloxacin compared with Trovafloxacin ciprofloxacin gatifloxacin and moxifloxacin in streptococcus pneumoniae
Journal of Antimicrobial Chemotherapy, 2001Co-Authors: Kensuke Nagai, Michael R. Jacobs, Todd A Davies, Bonifacio Dewasse, Peter C AppelbaumAbstract:The ability of sequential subcultures in subinhibitory concentrations of gemifloxacin, Trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to select resistant mutants was studied in 16 pneumococci [eight with ciprofloxacin MICs (mg/L) 0.25‐1; four with 8‐16; four with 16‐32]. Subculturing was done 50 times, or until mutants with elevated MICs ( 4 � ) to the selecting drug emerged. Subculturing in gemifloxacin selected six resistant mutants (gemifloxacin MICs 2 mg/L); Trovafloxacin selected nine (Trovafloxacin MICs 2‐4 mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8‐128 mg/L); gatifloxacin selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2‐16 mg/L). DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE or GyrB. Some new mutations were found in ParE or GyrB that have not yet been reported; GyrB mutation might be associated with moxifloxacin resistance. Both DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin; gemifloxacin also selected mutants with single modifications in gyrA, parC or parE alone among derived mutants by repeated exposure to subinhibitory concentrations of fluoroquinolones. In the presence of reserpine, most mutants had lower MICs of ciprofloxacin and gemifloxacin (4‐32 � ), and gatifloxacin (4‐8 � ), suggesting an efflux mechanism; none had lower Trovafloxacin and moxifloxacin MICs. All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones.
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in vitro selection of resistance to clinafloxacin ciprofloxacin and Trovafloxacin in streptococcus pneumoniae
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Kensuke Nagai, Michael R. Jacobs, Todd A Davies, Glenn A Pankuch, Bonifacio Dewasse, Peter C AppelbaumAbstract:Ability of daily sequential subcultures in subinhibitory concentrations of clinafloxacin, ciprofloxacin, and Trovafloxacin to select resistant mutants was studied in 10 pneumococci (ciprofloxacin MICs, 1 to 4 microg/ml, and clinafloxacin and Trovafloxacin MICs, 0.06 to 0.125 microg/ml [n = 9]; ciprofloxacin, clinafloxacin, and Trovafloxacin MICs, 32, 0.5, and 2 microg/ml, respectively [n = 1]). Subculturing was done 50 times, or until MICs increased fourfold or more. Mutants for which MICs were fourfold (or more) higher than those for parent strains were selected in five strains by clinafloxacin, in six strains by Trovafloxacin, and nine strains by ciprofloxacin. Sequence analysis of type II topoisomerase showed that most mutants had mutations in ParC at Ser79 or Asp83 and in GyrA at Ser81, while a few mutants had mutations in ParE or GyrB. In the presence of reserpine, the MICs of ciprofloxacin and clinafloxacin for most mutants were lower (four to eight times lower), but for none of the mutants were Trovafloxacin MICs lower, suggesting an efflux mechanism affecting the first two agents but not Trovafloxacin. Single-step mutation rates were also determined for eight strains for which the MICs were as follows: 0.06 microg/ml (clinafloxacin), 0.06 to 0.125 microg/ml (Trovafloxacin), and 1 microg/ml (ciprofloxacin). Single-step mutation rates with drugs at the MIC were 2.0x10(-9) to <1.1x10(-11), 5.0x10(-4) to 3.6x10(-9), and 4.8x10(-4) to 6.7x10(-9), respectively. For two strains with clinafloxacin MICs of 0.125 to 0.5 microg/ml Trovafloxacin MICs of 0. 125 to 2 microg/ml, ciprofloxacin MICs of 4 to 32 microg/ml mutation rates with drugs at the MIC were 1.1x10(-8)-9.6x10(-8), 3.3x10(-6)-6. 7x10(-8), and 2.3x10(-5)-2.4x10(-7), respectively. Clinafloxacin was bactericidal at four times the MIC after 24 h against three parent and nine mutant strains by time-kill study. This study showed that single and multistep clinafloxacin exposure selected for resistant mutants less frequently than similar exposures to other drugs studied.
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in vitro development of resistance to five quinolones and amoxicillin clavulanate in streptococcus pneumoniae
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Todd A Davies, Michael R. Jacobs, Glenn A Pankuch, Bonifacio Dewasse, Peter C AppelbaumAbstract:The ability of 50 sequential subcultures in subinhibitory concentrations of ciprofloxacin, levofloxacin, grepafloxacin, sparfloxacin, Trovafloxacin, and amoxicillin-clavulanate to select for resistance was studied for six penicillin-susceptible and four penicillin-intermediate pneumococci. Subculturing in ciprofloxacin, grepafloxacin, levofloxacin, and sparfloxacin led to selection of mutants requiring increased MICs for all 10 strains, with MICs rising from (i) 0.5 to 4.0 to (ii) 4.0 to 32.0 μg/ml after 7 to 12 passages for ciprofloxacin, from (i) 0.06 to 0.25 to (ii) 0.5 to 8.0 μg/ml after 5 to 23 passages for grepafloxacin, from (i) 0.5 to 1.0 to (ii) 4.0 to 64 μg/ml after 14 to 49 passages for levofloxacin, and from (i) 0.125 to 0.25 to (ii) 1.0 to 16.0 μg/ml after 8 to 26 passages for sparfloxacin. Subculturing in Trovafloxacin led to increased MICs for eight strains, with MICs rising from (i) 0.06 to 0.125 to (ii) 0.5 to 8.0 μg/ml after 6 to 28 passages. Subculturing in amoxicillin-clavulanate led to raised MICs for only one strain, with the MIC rising from 0.015 to 0.125 μg/ml after 24 passages. Double mutations in both ParC and GyrA led to high-level quinolone resistance when ParC mutations were at S79. Trovafloxacin MICs were 1 to 2 μg/ml in double mutants with ParC mutations at positions other than S79 (e.g., D83). Mutations in ParE (at D435, R447, and E474) and GyrB (at S405, D406, and D435) were found in four and six mutants, respectively. In the presence of reserpine, 29 mutants had lower ciprofloxacin MICs (2 to 16 times lower), 8 mutants had lower levofloxacin MICs (2 times), and one mutant had a lower Trovafloxacin MIC (2 times), suggesting the involvement of an efflux mechanism. In contrast to the case for quinolones, subculturing in the presence of amoxicillin-clavulanate did not select for resistance to this drug.
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activities of gatifloxacin compared to those of seven other agents against anaerobic organisms
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Lois M Ednie, Michael R. Jacobs, Peter C AppelbaumAbstract:The agar dilution MIC was used to compare activities of gatifloxacin with those of ciprofloxacin, sparfloxacin, Trovafloxacin, ampicillin, ampicillin-sulbactam, clindamycin, and metronidazole against 351 anaerobes. Overall MICs at which 50% of the isolates are inhibited and MICs at which 90% of the isolates are inhibited (in micrograms per milliliter) were as follows: gatifloxacin, 0.5 and 4; ciprofloxacin, 2 and 32; sparfloxacin, 2 and 8; Trovafloxacin, 1 and 4; ampicillin, 1 and 64; ampicillin-sulbactam, 0.5 and 4; clindamycin, 0.125 and 8; and metronidazole, 1 and >16, respectively. Gatifloxacin MICs were similar to those of Trovafloxacin in all organism groups.
Gary V Doern - One of the best experts on this subject based on the ideXlab platform.
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comparative bactericidal activities of ciprofloxacin clinafloxacin grepafloxacin levofloxacin moxifloxacin and Trovafloxacin against streptococcus pneumoniae in a dynamic in vitro model
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Michael E Klepser, Erika J Ernst, Rosemarie C Petzold, Paul R Rhomberg, Gary V DoernAbstract:Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed. Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and Trovafloxacin against three isolates of quinolone-susceptible S. pneumoniae. Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve [AUC]). Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent. Ciprofloxacin was the least active agent against all three isolates. With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum. At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates. The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC. At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, Trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h. All six agents produced cidal activity at 10 times the AUC. In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S. pneumoniae. The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) grepafloxacin, moxifloxacin, and Trovafloxacin > levofloxacin > clinafloxacin.
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antimicrobial activity of gatifloxacin tested against 1676 strains of ciprofloxacin resistant gram positive cocci isolated from patient infections in north and south america
Diagnostic Microbiology and Infectious Disease, 1998Co-Authors: Ronald N Jones, Mondell L Beach, Michael A Pfaller, Gary V DoernAbstract:Abstract Gatifloxacin (formerly AM-115) is a new 8-methoxy fluoroquinolone with an expanded spectrum against Gram-positive cocci and some anaerobes. To assess this new agent's activity, a collection of 1,676 Gram-positive cocci were selected for resistance to ciprofloxacin (≥4 μg/mL) and tested against gatifloxacin and 18 other compounds by reference broth microdilution methods. The strains (approximately 23,000 total isolates from the SENTRY Antimicrobial Surveillance Program) were from significant blood stream, respiratory tract, wound, and urinary tract infections in patients in North (38 hospitals) and South (10 hospitals) America. Against Enterococcus faecalis and E. faecium , gatifloxacin inhibited only 16% and 10% of strains compared with 12% and 5% for recently released Trovafloxacin, respectively. Among Staphylococcus aureus (90% oxacillin-resistant) strains, gatifloxacin was more active (67% susceptible at ≤4 μg/mL) than Trovafloxacin (59%) or sparfloxacin (4%). Gatifloxacin had a wider spectrum than Trovafloxacin against coagulase-negative staphylococci especially S. epidermidis, 2% versus 58% resistance. The glycopeptides, chloramphenicol and rifampin were most active. Against all genus/species groups with more than 100 sample strains (1,566), high-level resistance to gatifloxacin and Trovafloxacin (>4 μg/mL) was not significantly different (41.7% versus 39.1%; p > 0.05). Emerging resistance to the fluoroquinolones remains a clinical problem among Gram-positive species, and gatifloxacin seems to be active in vitro against many of these contemporary strains isolated in the Americas.
Michael R. Jacobs - One of the best experts on this subject based on the ideXlab platform.
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time kill studies of the antianaerobe activity of garenoxacin compared with those of nine other agents
Antimicrobial Agents and Chemotherapy, 2003Co-Authors: Kim Credito, Michael R. Jacobs, Peter C AppelbaumAbstract:The activities of garenoxacin, ciprofloxacin, levofloxacin, moxifloxacin, Trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 20 anaerobes were tested. At two times the MIC, garenoxacin was bactericidal against 19 of 20 strains after 48 h and against 17 of 20 after 24 h. Other drugs, except clindamycin (which gave lower killing rates), gave killing rates similar to those for garenoxacin.
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single and multi step resistance selection study of gemifloxacin compared with Trovafloxacin ciprofloxacin gatifloxacin and moxifloxacin in streptococcus pneumoniae
Journal of Antimicrobial Chemotherapy, 2001Co-Authors: Kensuke Nagai, Michael R. Jacobs, Todd A Davies, Bonifacio Dewasse, Peter C AppelbaumAbstract:The ability of sequential subcultures in subinhibitory concentrations of gemifloxacin, Trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to select resistant mutants was studied in 16 pneumococci [eight with ciprofloxacin MICs (mg/L) 0.25‐1; four with 8‐16; four with 16‐32]. Subculturing was done 50 times, or until mutants with elevated MICs ( 4 � ) to the selecting drug emerged. Subculturing in gemifloxacin selected six resistant mutants (gemifloxacin MICs 2 mg/L); Trovafloxacin selected nine (Trovafloxacin MICs 2‐4 mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8‐128 mg/L); gatifloxacin selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2‐16 mg/L). DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE or GyrB. Some new mutations were found in ParE or GyrB that have not yet been reported; GyrB mutation might be associated with moxifloxacin resistance. Both DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin; gemifloxacin also selected mutants with single modifications in gyrA, parC or parE alone among derived mutants by repeated exposure to subinhibitory concentrations of fluoroquinolones. In the presence of reserpine, most mutants had lower MICs of ciprofloxacin and gemifloxacin (4‐32 � ), and gatifloxacin (4‐8 � ), suggesting an efflux mechanism; none had lower Trovafloxacin and moxifloxacin MICs. All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones.
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in vitro selection of resistance to clinafloxacin ciprofloxacin and Trovafloxacin in streptococcus pneumoniae
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Kensuke Nagai, Michael R. Jacobs, Todd A Davies, Glenn A Pankuch, Bonifacio Dewasse, Peter C AppelbaumAbstract:Ability of daily sequential subcultures in subinhibitory concentrations of clinafloxacin, ciprofloxacin, and Trovafloxacin to select resistant mutants was studied in 10 pneumococci (ciprofloxacin MICs, 1 to 4 microg/ml, and clinafloxacin and Trovafloxacin MICs, 0.06 to 0.125 microg/ml [n = 9]; ciprofloxacin, clinafloxacin, and Trovafloxacin MICs, 32, 0.5, and 2 microg/ml, respectively [n = 1]). Subculturing was done 50 times, or until MICs increased fourfold or more. Mutants for which MICs were fourfold (or more) higher than those for parent strains were selected in five strains by clinafloxacin, in six strains by Trovafloxacin, and nine strains by ciprofloxacin. Sequence analysis of type II topoisomerase showed that most mutants had mutations in ParC at Ser79 or Asp83 and in GyrA at Ser81, while a few mutants had mutations in ParE or GyrB. In the presence of reserpine, the MICs of ciprofloxacin and clinafloxacin for most mutants were lower (four to eight times lower), but for none of the mutants were Trovafloxacin MICs lower, suggesting an efflux mechanism affecting the first two agents but not Trovafloxacin. Single-step mutation rates were also determined for eight strains for which the MICs were as follows: 0.06 microg/ml (clinafloxacin), 0.06 to 0.125 microg/ml (Trovafloxacin), and 1 microg/ml (ciprofloxacin). Single-step mutation rates with drugs at the MIC were 2.0x10(-9) to <1.1x10(-11), 5.0x10(-4) to 3.6x10(-9), and 4.8x10(-4) to 6.7x10(-9), respectively. For two strains with clinafloxacin MICs of 0.125 to 0.5 microg/ml Trovafloxacin MICs of 0. 125 to 2 microg/ml, ciprofloxacin MICs of 4 to 32 microg/ml mutation rates with drugs at the MIC were 1.1x10(-8)-9.6x10(-8), 3.3x10(-6)-6. 7x10(-8), and 2.3x10(-5)-2.4x10(-7), respectively. Clinafloxacin was bactericidal at four times the MIC after 24 h against three parent and nine mutant strains by time-kill study. This study showed that single and multistep clinafloxacin exposure selected for resistant mutants less frequently than similar exposures to other drugs studied.
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in vitro development of resistance to five quinolones and amoxicillin clavulanate in streptococcus pneumoniae
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Todd A Davies, Michael R. Jacobs, Glenn A Pankuch, Bonifacio Dewasse, Peter C AppelbaumAbstract:The ability of 50 sequential subcultures in subinhibitory concentrations of ciprofloxacin, levofloxacin, grepafloxacin, sparfloxacin, Trovafloxacin, and amoxicillin-clavulanate to select for resistance was studied for six penicillin-susceptible and four penicillin-intermediate pneumococci. Subculturing in ciprofloxacin, grepafloxacin, levofloxacin, and sparfloxacin led to selection of mutants requiring increased MICs for all 10 strains, with MICs rising from (i) 0.5 to 4.0 to (ii) 4.0 to 32.0 μg/ml after 7 to 12 passages for ciprofloxacin, from (i) 0.06 to 0.25 to (ii) 0.5 to 8.0 μg/ml after 5 to 23 passages for grepafloxacin, from (i) 0.5 to 1.0 to (ii) 4.0 to 64 μg/ml after 14 to 49 passages for levofloxacin, and from (i) 0.125 to 0.25 to (ii) 1.0 to 16.0 μg/ml after 8 to 26 passages for sparfloxacin. Subculturing in Trovafloxacin led to increased MICs for eight strains, with MICs rising from (i) 0.06 to 0.125 to (ii) 0.5 to 8.0 μg/ml after 6 to 28 passages. Subculturing in amoxicillin-clavulanate led to raised MICs for only one strain, with the MIC rising from 0.015 to 0.125 μg/ml after 24 passages. Double mutations in both ParC and GyrA led to high-level quinolone resistance when ParC mutations were at S79. Trovafloxacin MICs were 1 to 2 μg/ml in double mutants with ParC mutations at positions other than S79 (e.g., D83). Mutations in ParE (at D435, R447, and E474) and GyrB (at S405, D406, and D435) were found in four and six mutants, respectively. In the presence of reserpine, 29 mutants had lower ciprofloxacin MICs (2 to 16 times lower), 8 mutants had lower levofloxacin MICs (2 times), and one mutant had a lower Trovafloxacin MIC (2 times), suggesting the involvement of an efflux mechanism. In contrast to the case for quinolones, subculturing in the presence of amoxicillin-clavulanate did not select for resistance to this drug.
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activities of gatifloxacin compared to those of seven other agents against anaerobic organisms
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Lois M Ednie, Michael R. Jacobs, Peter C AppelbaumAbstract:The agar dilution MIC was used to compare activities of gatifloxacin with those of ciprofloxacin, sparfloxacin, Trovafloxacin, ampicillin, ampicillin-sulbactam, clindamycin, and metronidazole against 351 anaerobes. Overall MICs at which 50% of the isolates are inhibited and MICs at which 90% of the isolates are inhibited (in micrograms per milliliter) were as follows: gatifloxacin, 0.5 and 4; ciprofloxacin, 2 and 32; sparfloxacin, 2 and 8; Trovafloxacin, 1 and 4; ampicillin, 1 and 64; ampicillin-sulbactam, 0.5 and 4; clindamycin, 0.125 and 8; and metronidazole, 1 and >16, respectively. Gatifloxacin MICs were similar to those of Trovafloxacin in all organism groups.
Franz-josef Schmitz - One of the best experts on this subject based on the ideXlab platform.
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Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and Trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with al
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Sylvain Brisse, Dana Milatovic, Jan Verhoef, Nele Martin, Sybille Scheuring, Karl Köhrer, Franz-josef SchmitzAbstract:The in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and Trovafloxacin were tested against 72 ciprofloxacin-resistant and 28 ciprofloxacin-susceptible isolates of Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes. Irrespective of the alterations in GyrA and ParC proteins, clinafloxacin exhibited greater activity than all other fluoroquinolones tested against K. pneumoniae and E. aerogenes.
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Comparative Activities of Clinafloxacin, Grepafloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin, and Trovafloxacin and Nonquinolones Linozelid, Quinupristin-Dalfopristin, Gentamicin, and Vancomycin against Clinical Isolates of Ciprofloxac
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Mark E. Jones, Jan Verhoef, Maarten R. Visser, Miriam Klootwijk, Peter Heisig, Franz-josef SchmitzAbstract:The activities of eight fluoroquinolones and linezolid, quinupristin-dalfopristin (Synercid), gentamicin, and vancomycin were tested against 96 ciprofloxacin-susceptible and 205 ciprofloxacin-resistant Staphylococcus aureus strains. Overall, clinafloxacin, followed by moxifloxacin and Trovafloxacin, was the most active quinolone tested. For all isolates, linezolid and quinupristin-dalfopristin showed activities that were at least comparable to vancomycin, with no cross-resistance to any other test compound.
Helen Giamarellou - One of the best experts on this subject based on the ideXlab platform.
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sitafloxacin du 6859a and Trovafloxacin postantibiotic effect and in vitro interactions with rifampin on methicillin resistant staphylococcus aureus
Diagnostic Microbiology and Infectious Disease, 1999Co-Authors: Evangelos J Giamarelloubourboulis, Helen Sambatakou, P Grecka, Zoi Chryssouli, Helen GiamarellouAbstract:Abstract Sitafloxacin (DU-6859a) and Trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug–resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1×, 4×, and 10× MIC and the killing effect after exposure to 1× and 4× MIC. Rifampin was applied for interactive studies at a concentration of 2 μg/mL, which is equal to its mean serum level. Median PAEs produced by 1×, 4×, and 10× MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1×, 4×, and 10× MIC of Trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by Trovafloxacin; PAEs achieved by a concentration of 10× MIC of each quinolone did not differ significantly from those achieved by a concentration of 4× MIC. Both the 4× and 10× MIC concentrations produced a more prolonged PAE than the 1× MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and Trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug–resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.
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sitafloxacin du 6859a and Trovafloxacin postantibiotic effect and in vitro interactions with rifampin on methicillin resistant staphylococcus aureus
Diagnostic Microbiology and Infectious Disease, 1999Co-Authors: Evangelos J Giamarelloubourboulis, Helen Sambatakou, P Grecka, Zoi Chryssouli, Helen GiamarellouAbstract:Abstract Sitafloxacin (DU-6859a) and Trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug–resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1×, 4×, and 10× MIC and the killing effect after exposure to 1× and 4× MIC. Rifampin was applied for interactive studies at a concentration of 2 μg/mL, which is equal to its mean serum level. Median PAEs produced by 1×, 4×, and 10× MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1×, 4×, and 10× MIC of Trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by Trovafloxacin; PAEs achieved by a concentration of 10× MIC of each quinolone did not differ significantly from those achieved by a concentration of 4× MIC. Both the 4× and 10× MIC concentrations produced a more prolonged PAE than the 1× MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and Trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug–resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.
