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G. Siami - One of the best experts on this subject based on the ideXlab platform.
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Clinafloxacin versus piperacillin tazobactam in the treatment of severe skin and soft tissue infections in adults at a veterans affairs medical center
Clinical Therapeutics, 2002Co-Authors: Flora S. Siami, Bonnie Lafleur, G. SiamiAbstract:Abstract Background: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. Objective: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was 1 site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of Clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. Methods: Over an 18-month period, patients aged ≥18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either Clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with Clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. Results: The center enrolled 84 patients (42 in each group), all but 1 of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36–80 years) in the Clinafloxacin group and 65 years (range, 35–87) in the piperacillin/tazobactam group; the latter group was significantly older ( P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean (±SD) duration of treatment was 10.69 ± 5.34 days in the Clinafloxacin group and 12.07 ± 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 ± 10.28 days and 14.95 ± 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the Clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa , and Enterobacter cloacae . Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/tazobactam arm experienced more all-cause adverse events than the Clinafloxacin arm, although the difference was not statistically significant. The Clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related ( P = 0.034). Conclusions: In this study population of hospitalized adults, Clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving Clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the fluoroquinolones can be limited.
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Clinafloxacin versus piperacillin/tazobactam in the treatment of severe skin and soft-tissue infections in adults at a Veterans Affairs medical center.
Clinical Therapeutics, 2002Co-Authors: Flora S. Siami, Bonnie Lafleur, G. SiamiAbstract:Abstract Background: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. Objective: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was 1 site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of Clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. Methods: Over an 18-month period, patients aged ≥18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either Clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with Clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. Results: The center enrolled 84 patients (42 in each group), all but 1 of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36–80 years) in the Clinafloxacin group and 65 years (range, 35–87) in the piperacillin/tazobactam group; the latter group was significantly older ( P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean (±SD) duration of treatment was 10.69 ± 5.34 days in the Clinafloxacin group and 12.07 ± 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 ± 10.28 days and 14.95 ± 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the Clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa , and Enterobacter cloacae . Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/tazobactam arm experienced more all-cause adverse events than the Clinafloxacin arm, although the difference was not statistically significant. The Clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related ( P = 0.034). Conclusions: In this study population of hospitalized adults, Clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving Clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the fluoroquinolones can be limited.
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Clinafloxacin versus piperacillin-tazobactam in treatment of patients with severe skin and soft tissue infections
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: G. Siami, I. Eiseman, L. Parish, J. F.k. Boulevard, Nicolas Christou, M. Zervos, Kenneth J Tack, L. Nicolle, S Wilson, J. CaldwellAbstract:Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive Clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to Clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P = 0.001). The Clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P = 0.577) in the two treatment groups. Drug-associated adverse events (P = 0.050) and treatment discontinuations (P = 0.052) were marginally more frequent in the Clinafloxacin group, primarily due to phototoxicity in outpatients receiving Clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, Clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs
Kenneth J Tack - One of the best experts on this subject based on the ideXlab platform.
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Clinafloxacin for the treatment of bacterial endocarditis.
Clinical Infectious Diseases, 2004Co-Authors: Donald P. Levine, Irene A. Eiseman, P. A. Willcox, H. Preston Holley, Kenneth J TackAbstract:We report the results of a prospective, multicenter trial assessing intravenous and oral Clinafloxacin treatment for infective endocarditis. Sixty-six patients constituted the final study population. Among the 53 patients with native valve infection, Staphylococcus aureus and Streptococcus viridans were the most common pathogens. Twelve patients with native valve infection required surgery, at which time all valve tissue culture results were negative. The overall success rate for native valve infection was 87%. Single valves were involved in 11 of 13 patients with prosthetic valve endocarditis (PVE), and multiple valves were involved in 2 cases. Enterococcus faecalis was the most common pathogen, causing 4 of the PVE cases. The overall success rate for treatment of PVE was 69%. Patients with PVE who did not respond to treatment presented with complications that predict poor prognosis. Clinafloxacin may be effective for both native and PVE, but further studies are indicated.
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Clinafloxacin versus piperacillin-tazobactam in treatment of patients with severe skin and soft tissue infections
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: G. Siami, I. Eiseman, L. Parish, J. F.k. Boulevard, Nicolas Christou, M. Zervos, Kenneth J Tack, L. Nicolle, S Wilson, J. CaldwellAbstract:Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive Clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to Clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P = 0.001). The Clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P = 0.577) in the two treatment groups. Drug-associated adverse events (P = 0.050) and treatment discontinuations (P = 0.052) were marginally more frequent in the Clinafloxacin group, primarily due to phototoxicity in outpatients receiving Clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, Clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs
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Results of a clinical trial of Clinafloxacin versus imipenem/cilastatin for intraabdominal infections.
Annals of Surgery, 2001Co-Authors: Joseph S. Solomkin, Samuel E. Wilson, Nicholas V. Christou, Ori D. Rotstein, E. Patchen Dellinger, Robert S. Bennion, Raphael Pak, Kenneth J TackAbstract:OBJECTIVE Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy. SUMMARY BACKGROUND DATA Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity. METHODS This prospective, randomized, double-blind trial was conducted to compare Clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections. RESULTS Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with Clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with Clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin. CONCLUSIONS The results of this study clearly demonstrate the safety and efficacy of Clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances.
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results of a clinical trial of Clinafloxacin versus imipenem cilastatin for intraabdominal infections
Annals of Surgery, 2001Co-Authors: Joseph S. Solomkin, Samuel E. Wilson, Nicholas V. Christou, Ori D. Rotstein, Robert S. Bennion, Raphael Pak, Patchen E Dellinger, Kenneth J TackAbstract:OBJECTIVE Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy. SUMMARY BACKGROUND DATA Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity. METHODS This prospective, randomized, double-blind trial was conducted to compare Clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections. RESULTS Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with Clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with Clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin. CONCLUSIONS The results of this study clearly demonstrate the safety and efficacy of Clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances.
J. Caldwell - One of the best experts on this subject based on the ideXlab platform.
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Clinafloxacin versus piperacillin-tazobactam in treatment of patients with severe skin and soft tissue infections
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: G. Siami, I. Eiseman, L. Parish, J. F.k. Boulevard, Nicolas Christou, M. Zervos, Kenneth J Tack, L. Nicolle, S Wilson, J. CaldwellAbstract:Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive Clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to Clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P = 0.001). The Clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P = 0.577) in the two treatment groups. Drug-associated adverse events (P = 0.050) and treatment discontinuations (P = 0.052) were marginally more frequent in the Clinafloxacin group, primarily due to phototoxicity in outpatients receiving Clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, Clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs
Flora S. Siami - One of the best experts on this subject based on the ideXlab platform.
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Clinafloxacin versus piperacillin/tazobactam in the treatment of severe skin and soft-tissue infections in adults at a Veterans Affairs medical center.
Clinical Therapeutics, 2002Co-Authors: Flora S. Siami, Bonnie Lafleur, G. SiamiAbstract:Abstract Background: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. Objective: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was 1 site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of Clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. Methods: Over an 18-month period, patients aged ≥18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either Clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with Clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. Results: The center enrolled 84 patients (42 in each group), all but 1 of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36–80 years) in the Clinafloxacin group and 65 years (range, 35–87) in the piperacillin/tazobactam group; the latter group was significantly older ( P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean (±SD) duration of treatment was 10.69 ± 5.34 days in the Clinafloxacin group and 12.07 ± 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 ± 10.28 days and 14.95 ± 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the Clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa , and Enterobacter cloacae . Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/tazobactam arm experienced more all-cause adverse events than the Clinafloxacin arm, although the difference was not statistically significant. The Clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related ( P = 0.034). Conclusions: In this study population of hospitalized adults, Clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving Clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the fluoroquinolones can be limited.
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Clinafloxacin versus piperacillin tazobactam in the treatment of severe skin and soft tissue infections in adults at a veterans affairs medical center
Clinical Therapeutics, 2002Co-Authors: Flora S. Siami, Bonnie Lafleur, G. SiamiAbstract:Abstract Background: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. Objective: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was 1 site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of Clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. Methods: Over an 18-month period, patients aged ≥18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either Clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with Clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. Results: The center enrolled 84 patients (42 in each group), all but 1 of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36–80 years) in the Clinafloxacin group and 65 years (range, 35–87) in the piperacillin/tazobactam group; the latter group was significantly older ( P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean (±SD) duration of treatment was 10.69 ± 5.34 days in the Clinafloxacin group and 12.07 ± 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 ± 10.28 days and 14.95 ± 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the Clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa , and Enterobacter cloacae . Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/tazobactam arm experienced more all-cause adverse events than the Clinafloxacin arm, although the difference was not statistically significant. The Clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related ( P = 0.034). Conclusions: In this study population of hospitalized adults, Clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving Clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the fluoroquinolones can be limited.
Peter C Appelbaum - One of the best experts on this subject based on the ideXlab platform.
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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, Todd A Davies, Glenn A Pankuch, Bonifacio Dewasse, Michael R Jacobs, 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 selection of resistance to Clinafloxacin, ciprofloxacin, and trovafloxacin in Streptococcus pneumoniae.
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Kensuke Nagai, Todd A Davies, Glenn A Pankuch, Bonifacio Dewasse, Michael R Jacobs, 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
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Activities of Clinafloxacin, Alone and in Combination with Other Compounds, against 45 Gram-Positive and -Negative Organisms for Which Clinafloxacin MICs Are High
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Catherine Clark, Michael R Jacobs, Peter C AppelbaumAbstract:Time-kill studies indicated that Clinafloxacin showed synergy after 24 h with ceftazidime, amikacin, and imipenem against 12, 8, and 10 of 33 gram-negative rods, respectively; with vancomycin, teicoplanin, cefotaxime, and amikacin against 3, 3, 1, and 1 of 9 staphylococci and enterococci, respectively; and with vancomycin, penicillin, and cefotaxime against 0, 2, and 2 of 3 pneumococci, respectively. The MICs of Clinafloxacin alone for most strains were ≥1 μg/ml.
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Comparative Activities of Clinafloxacin against Gram-Positive and -Negative Bacteria
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Lois M. Ednie, Michael R Jacobs, Peter C AppelbaumAbstract:Activities of Clinafloxacin, ciprofloxacin, levofloxacin, sparfloxacin, trovafloxacin, piperacillin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, ceftazidime, and imipenem against 354 ciprofloxacin-susceptible and -intermediate-resistant organisms were tested by agar dilution. Clinafloxacin yielded the lowest quinolone MICs (≤0.5 μg/ml against ciprofloxacin-susceptible organisms and ≤16.0 μg/ml against ciprofloxacin-intermediate-resistant organisms) compared to those of levofloxacin, trovafloxacin, and sparfloxacin. Ceftazidime, piperacillin alone or combined with tazobactam, trimethoprim-sulfamethoxazole, and imipenem usually yielded higher MICs against ciprofloxacin-resistant strains.
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Activity of CP 99,219 (trovafloxacin) compared with ciprofloxacin, sparfloxacin, Clinafloxacin, lomefloxacin and cefuroxime against ten penicillin-susceptible and pencillin-resistant pneumococci by time-kill methodology
Journal of Antimicrobial Chemotherapy, 1996Co-Authors: M. A. Visalli, Michael R Jacobs, Peter C AppelbaumAbstract:Activity of CP 99,219 (trovafloxacin), Clinafloxacin, ciprofloxacin, sparfloxacin, lomefloxacin and cefuroxime against 4 penicillin-susceptible, 2 penicillin-intermediate and 4 penicillin-resistant pneumococci was tested by MIC and time-kill methodology. Bacteriostatic values for all three groups did not differ significantly with all compounds tested except cefuroxime, and were lowest for trovafloxacin and Clinafloxacin, followed by sparfloxacin, ciprofloxacin and lomefloxacin; cefuroxime yielded values which increased in line with those of penicillin G. The test compounds were bactericidal (i.e. they reduced original counts by > or = 3 log10 cfu/mL at one dilution above bacteriostatic levels) in most cases, though some strains showed slightly greater discrepancies between bacteriostatic and bactericidal levels of all compounds tested. Trovafloxacin, Clinafloxacin and sparfloxacin yielded MIC and time-kill results which point to possible efficacy in treatment of penicillin-susceptible and -resistant pneumococcal infections.