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Jeronimo Pachon - One of the best experts on this subject based on the ideXlab platform.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent Poirel, Jeronimo PachonAbstract:New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae. The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. Pneumoniae NDM) and 37 (K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating Pneumonia due to NDM-1-producing K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae.
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efficacy of rifampin and its combinations with imipenem sulbactam and colistin in Experimental models of infection caused by imipenem resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, A Garciacuriel, Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, M E Jimenezmejias, Luis Jimenez, Jeronimo PachonAbstract:There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in Experimental Pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine Pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the Pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in Experimental models of Pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
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activity of ciprofloxacin and levofloxacin in Experimental Pneumonia caused by klebsiella Pneumoniae deficient in porins expressing active efflux and producing qnra1
Clinical Microbiology and Infection, 2008Co-Authors: Josemanuel Rodriguezmartinez, C Pichardo, Jeronimo Pachon, Maria Eugenia Pachonibanez, Fernando Docoboperez, Alvaro Pascual, Isabel Garcia, Luis MartinezmartinezAbstract:ABSTRACT The objective of this study was to evaluate the activities of ciprofloxacin and levofloxacin in a murine model of Pneumonia caused by Klebsiella Pneumoniae C2 (with altered GyrA, deficient in porins and expressing active efflux of quinolones) and the transconjugant C2pMG252 derived from it and expressing the q nrA1 determinant. MICs and MBCs of the two quinolones were determined according to CLSI guidelines. Time-kill curves (at 1× and 4× MIC) were also performed to assess bactericidal activity. An Experimental model of Pneumonia in mice was evaluated. Groups of 15 mice were infected with either strain and treated with ciprofloxacin (80 mg/kg/day) or levofloxacin (100 mg/kg/day). Control non-treated animals were also evaluated. In the case of strain C2, log 10 CFU/g of lung in non-treated animals was 9.16 ± 2.16. This value was reduced to 3.53 ± 1.04 (p 10 CFU/g) in lungs of animals infected with strain C2pMG252 were 9.65 ± 2.49 in non-treated animals and 7.74 ± 2.67 and 7.57 ± 3.84 for those treated with ciprofloxacin or levofloxacin, respectively (p >0.05 vs. control group). Of non-treated animals infected with strain C2pMG252, 14.3% survived. Ciprofloxacin and levofloxacin improved the survival in these mice (53.3% for both antimicrobials, p 0.03). In conclusion, the expression of qnrA1 in K. Pneumoniae with additional mechanisms of resistance causes decreased efficacy of fluoroquinolones in a Pneumonia model in mice.
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prevention of rifampicin resistance in acinetobacter baumannii in an Experimental Pneumonia murine model using rifampicin associated with imipenem or sulbactam
Journal of Antimicrobial Chemotherapy, 2006Co-Authors: Maria Eugenia Pachonibanez, Jeronimo Pachon, Fernando Docoboperez, Felipe Fernandezcuenca, Alvaro PascualAbstract:OBJECTIVES: To examine the development of rifampicin resistance in multidrug-resistant Acinetobacter baumannii exposed to rifampicin and the prevention of the appearance of rifampicin-resistant mutants when rifampicin is used in association with imipenem or sulbactam. METHODS: A clinical strain of multidrug-resistant A. baumannii was used to examine the frequency of resistance to rifampicin in vivo, in a Pneumonia model in immunocompetent C57BL/6 mice. The in vitro and in vivo prevention of the development of resistance to rifampicin was analysed using rifampicin alone or in association with imipenem or sulbactam, in time-kill studies and in the Experimental murine Pneumonia, respectively. RESULTS: Rifampicin-resistant mutants were found at 48 and 72 h, both in vitro and in vivo, when rifampicin was used alone, with the MIC increasing from 4 to > or =128 mg/L. The in vivo frequency of rifampicin-resistant mutants was 3 x 10(-6). On the contrary, no resistant mutants appeared after 72 h, in vitro or in vivo, when rifampicin was employed in association with imipenem or sulbactam. After six daily passages in rifampicin-free agar plates the resistant mutants maintained the high resistance to rifampicin (> or =128 mg/L). CONCLUSIONS: These results suggest that rifampicin must not be used alone in the treatment of infections caused by multidrug-resistant A. baumannii. In these cases, rifampicin may be used in combination with imipenem or sulbactam, which prevent the development of resistance to rifampicin.
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sulbactam efficacy in Experimental models caused by susceptible and intermediate acinetobacter baumannii strains
Journal of Antimicrobial Chemotherapy, 2001Co-Authors: Mariajesus Rodriguezhernandez, L Cuberos, C Pichardo, F J Caballero, Enrique M Jimenezmejias, A Garciacuriel, Ignacio Moreno, Jeronimo PachonAbstract:Sulbactam and imipenem were compared in an Experimental Pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an Experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.
Fernando Docoboperez - One of the best experts on this subject based on the ideXlab platform.
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impact of qnra1 qnrb1 and qnrs1 on the efficacy of ciprofloxacin and levofloxacin in an Experimental Pneumonia model caused by escherichia coli with or without the gyra mutation ser83leu
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Juan Dominguezherrera, C Pichardo, Fernando Docoboperez, Rafael Lopezrojas, C Velasco, Josemanuel Rodriguezmartinez, Alejandra Briales, Paula Diazdealba, Jesus Rodriguezbano, Alvaro PascualAbstract:Objectives: The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an Experimental model of Pneumonia caused by Escherichia coli. Methods: Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an Experimental Pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated. Results: For the Pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P,0.05) reduced the bacterial lung concentration by .7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P,0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P,0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes. Conclusions: The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine Pneumonia model.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent PoirelAbstract:Abstract New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae . The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration–time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 ( K. Pneumoniae NDM) and 37 ( K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 log CFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 log CFU/g and 4.62 log CFU/g ( P E. coli NDM by 2.27 log CFU/g and 4.15 log CFU/g ( P P K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli . A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae .
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent Poirel, Jeronimo PachonAbstract:New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae. The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. Pneumoniae NDM) and 37 (K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating Pneumonia due to NDM-1-producing K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae.
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efficacy of rifampin and its combinations with imipenem sulbactam and colistin in Experimental models of infection caused by imipenem resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, A Garciacuriel, Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, M E Jimenezmejias, Luis Jimenez, Jeronimo PachonAbstract:There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in Experimental Pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine Pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the Pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in Experimental models of Pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
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activity of ciprofloxacin and levofloxacin in Experimental Pneumonia caused by klebsiella Pneumoniae deficient in porins expressing active efflux and producing qnra1
Clinical Microbiology and Infection, 2008Co-Authors: Josemanuel Rodriguezmartinez, C Pichardo, Jeronimo Pachon, Maria Eugenia Pachonibanez, Fernando Docoboperez, Alvaro Pascual, Isabel Garcia, Luis MartinezmartinezAbstract:ABSTRACT The objective of this study was to evaluate the activities of ciprofloxacin and levofloxacin in a murine model of Pneumonia caused by Klebsiella Pneumoniae C2 (with altered GyrA, deficient in porins and expressing active efflux of quinolones) and the transconjugant C2pMG252 derived from it and expressing the q nrA1 determinant. MICs and MBCs of the two quinolones were determined according to CLSI guidelines. Time-kill curves (at 1× and 4× MIC) were also performed to assess bactericidal activity. An Experimental model of Pneumonia in mice was evaluated. Groups of 15 mice were infected with either strain and treated with ciprofloxacin (80 mg/kg/day) or levofloxacin (100 mg/kg/day). Control non-treated animals were also evaluated. In the case of strain C2, log 10 CFU/g of lung in non-treated animals was 9.16 ± 2.16. This value was reduced to 3.53 ± 1.04 (p 10 CFU/g) in lungs of animals infected with strain C2pMG252 were 9.65 ± 2.49 in non-treated animals and 7.74 ± 2.67 and 7.57 ± 3.84 for those treated with ciprofloxacin or levofloxacin, respectively (p >0.05 vs. control group). Of non-treated animals infected with strain C2pMG252, 14.3% survived. Ciprofloxacin and levofloxacin improved the survival in these mice (53.3% for both antimicrobials, p 0.03). In conclusion, the expression of qnrA1 in K. Pneumoniae with additional mechanisms of resistance causes decreased efficacy of fluoroquinolones in a Pneumonia model in mice.
Juan Dominguezherrera - One of the best experts on this subject based on the ideXlab platform.
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impact of qnra1 qnrb1 and qnrs1 on the efficacy of ciprofloxacin and levofloxacin in an Experimental Pneumonia model caused by escherichia coli with or without the gyra mutation ser83leu
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Juan Dominguezherrera, C Pichardo, Fernando Docoboperez, Rafael Lopezrojas, C Velasco, Josemanuel Rodriguezmartinez, Alejandra Briales, Paula Diazdealba, Jesus Rodriguezbano, Alvaro PascualAbstract:Objectives: The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an Experimental model of Pneumonia caused by Escherichia coli. Methods: Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an Experimental Pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated. Results: For the Pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P,0.05) reduced the bacterial lung concentration by .7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P,0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P,0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes. Conclusions: The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine Pneumonia model.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent Poirel, Jeronimo PachonAbstract:New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae. The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. Pneumoniae NDM) and 37 (K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating Pneumonia due to NDM-1-producing K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent PoirelAbstract:Abstract New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae . The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration–time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 ( K. Pneumoniae NDM) and 37 ( K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 log CFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 log CFU/g and 4.62 log CFU/g ( P E. coli NDM by 2.27 log CFU/g and 4.15 log CFU/g ( P P K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli . A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae .
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efficacy of rifampin and its combinations with imipenem sulbactam and colistin in Experimental models of infection caused by imipenem resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, A Garciacuriel, Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, M E Jimenezmejias, Luis Jimenez, Jeronimo PachonAbstract:There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in Experimental Pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine Pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the Pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in Experimental models of Pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
Rafael Lopezrojas - One of the best experts on this subject based on the ideXlab platform.
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impact of qnra1 qnrb1 and qnrs1 on the efficacy of ciprofloxacin and levofloxacin in an Experimental Pneumonia model caused by escherichia coli with or without the gyra mutation ser83leu
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Juan Dominguezherrera, C Pichardo, Fernando Docoboperez, Rafael Lopezrojas, C Velasco, Josemanuel Rodriguezmartinez, Alejandra Briales, Paula Diazdealba, Jesus Rodriguezbano, Alvaro PascualAbstract:Objectives: The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an Experimental model of Pneumonia caused by Escherichia coli. Methods: Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an Experimental Pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated. Results: For the Pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P,0.05) reduced the bacterial lung concentration by .7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P,0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P,0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes. Conclusions: The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine Pneumonia model.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent Poirel, Jeronimo PachonAbstract:New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae. The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. Pneumoniae NDM) and 37 (K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating Pneumonia due to NDM-1-producing K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent PoirelAbstract:Abstract New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae . The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration–time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 ( K. Pneumoniae NDM) and 37 ( K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 log CFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 log CFU/g and 4.62 log CFU/g ( P E. coli NDM by 2.27 log CFU/g and 4.15 log CFU/g ( P P K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli . A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae .
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efficacy of rifampin and its combinations with imipenem sulbactam and colistin in Experimental models of infection caused by imipenem resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, A Garciacuriel, Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, M E Jimenezmejias, Luis Jimenez, Jeronimo PachonAbstract:There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in Experimental Pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine Pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the Pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in Experimental models of Pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent PoirelAbstract:Abstract New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae . The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration–time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 ( K. Pneumoniae NDM) and 37 ( K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 log CFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 log CFU/g and 4.62 log CFU/g ( P E. coli NDM by 2.27 log CFU/g and 4.15 log CFU/g ( P P K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli . A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae .
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efficacies of colistin and tigecycline in mice with Experimental Pneumonia due to ndm 1 producing strains of klebsiella Pneumoniae and escherichia coli
International Journal of Antimicrobial Agents, 2012Co-Authors: Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, Patrice Nordmann, Younes Smani, Laurent Poirel, Jeronimo PachonAbstract:New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an Experimental model of Pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella Pneumoniae. The susceptibilities of K. Pneumoniae NDM, E. coli NDM and K. Pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an Experimental model of Pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. Pneumoniae NDM) and 37 (K. Pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. Pneumoniae NDM and K. Pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating Pneumonia due to NDM-1-producing K. Pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating Experimental Pneumonia due to NDM-1-producing E. coli and K. Pneumoniae.
