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M Wootton - One of the best experts on this subject based on the ideXlab platform.
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Ticarcillin Hypersusceptibility in Pseudomonas Aeruginosa in Cystic Fibrosis
2017Co-Authors: I. T. Hettiarachchi, T O’sullivan, M Wootton, A Smith, J Duckers, R. DhillonAbstract:Background: A subpopulation of Pseudomonas aeruginosa (PsA) exists in cystic fi brosis (CF) patients that is hypersusceptible to ticarcillin, a Carboxypenicillin, in vitro (Tichs strain) defi ned as a minimum inhibitory concentration (MIC) ≤4μg/ml.
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P276 The Prevalence of Ticarcillin Hyper-susceptible Pseudmonoas aeruginosa isolates from Non Cystic Fibrosis Bronchiectasis patients compared to patients with Cystic Fibrosis and controls
Thorax, 2015Co-Authors: I. T. Hettiarachchi, T O’sullivan, M Wootton, J Duckers, R.p. DhillonAbstract:Background and aims Pseudomonas aeruginosa (PsA) is associated with considerable morbidity and mortality in Non-Cystic Fibrosis bronchiectasis (NCFB) and Cystic Fibrosis (CF) patients. Ticarcillin, a Carboxypenicillin, is occasionally used in NCFB and CF to treat pulmonary exacerbations. In CF, a subpopulation of PsA exists that is hypersusceptible to ticarcillin (Tichs) in vitro , (minimum inhibitory concerntration [MIC] The aim of this study was to investigate whether this Tichs strain exists in NCFB patients and compare this to the prevalence rates from CF and control cohorts. We also assessed whether this strain correlated with enhanced susceptibility to temocillin and other anti-pseudomonal antibiotics. Methods 18 isolates of PsA from NCFB patients, 23 PsA isolates from CF patients and 18 PsA isolates from controls with no chronic lung disease were analysed. MICs for each isolate were determined by agar dilution using ISO20776–1 for the antibiotics listed in Table 1 and interpreted using EUCAST breakpoints. Results The NCFB isolates had the highest prevalence of the Tichs strain of the three cohorts we tested, with a prevalence of 76%, compared to a prevalence of 48% in the CF cohort and 0% in the controls. Resistant strains of PsA were more prevalent in the CF cohort compared to the NCFB and control cohorts, except for temocillin and ticarcillin where the CF and NCFB cohorts had lower MICs compared to the control cohort (Table 1). The Tichs strain in NCFB and CF was associated with reduced MICs to all antibiotics apart from ciprofloxacin in comparison to the non- Tichs strain. In CF, the Tichs strain was also associated with increased MICs to gentamicin. Conclusion Our data supports the existence of a Tichs strain of PsA in NCFB patients, which existed in greater prevalence compared to our CF cohort. This appears to correlate with reduced MICs to temocillin, to which PsA would normally be resistant. Therefore, temocillin may provide a useful alternative to the current anti-pseudomonal antibiotics in treating NCFB and CF patients.
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120 The prevalence of ticarcillin hypersusceptible Pseudomonas aeruginosa isolates from cystic fibrosis patients compared to non-cystic fibrosis patients
Journal of Cystic Fibrosis, 2015Co-Authors: I. T. Hettiarachchi, R.p. Dhillon, M WoottonAbstract:Background Ticarcillin, a Carboxypenicillin, is rarely used to treat pulmonary infections in CF patients. A subpopulation of P. aeruginosa exists that is hypersusceptible to ticarcillin (Tic hs ) in vitro, (MIC ≥4 mg/ml). Aims To determine the prevalence of Tic hs in P. aeruginosa isolated from CF patients and to assess if this strain correlates with enhanced susceptibility to temocillin and other conventional antibiotics. We are correlating with clinical outcomes and associated VNTR type (work ongoing). Methods 23 isolates of P. aeruginosa from CF patients were compared to 18 non-CF P. aeruginosa isolates. MICs were determined by MicroBroth dilution and interpreted using EUCAST breakpoints. Results Resistant strains were more prevalent in the CF cohort compared to the non-CF cohort for all antibiotics except for ticarcillin and temocillin (Table 1). The prevalence of the Tic hs strain in our CF P. aeruginosa isolates was 48% compared to the non-CF Pseudomonas of 0%. The Tic hs strain was associated with reduced MICs to all antibiotics apart from gentamicin and ciprofloxacin (Table 2). Table 1MIC and percentage of resistant isolatesMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFMIC R0.008–160.008–80.25–1282–160.125–12816–1280.5–128128–1280.03–160.03–41–640.25–4MIC 500.50.12544432412810.0621MIC 90411281612812812812840.125642%Res20%6%26%17%35%78%NANA60%7%30%0%%Sens80%94%74%83%65%22%NANA40%93%70%100%MIC R, MIC range; %Res, % resistant; % Sens, % Sensitive. Table 2Geometric mean MICs, Tic hs vs. Non Tic hs strainsMIC, geometric meanMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinTic hs strain0.132.180.832.740.662.83Non Tic hs strain0.366.2339.4068.590.281.80 Conclusion Our data supports the existence of a Tic hs strain of P. aeruginosa in our CF patients. This appears to correlate with reduced MICs to temocillin to which P. aeruginosa would normally be resistant.
I. T. Hettiarachchi - One of the best experts on this subject based on the ideXlab platform.
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Ticarcillin Hypersusceptibility in Pseudomonas Aeruginosa in Cystic Fibrosis
2017Co-Authors: I. T. Hettiarachchi, T O’sullivan, M Wootton, A Smith, J Duckers, R. DhillonAbstract:Background: A subpopulation of Pseudomonas aeruginosa (PsA) exists in cystic fi brosis (CF) patients that is hypersusceptible to ticarcillin, a Carboxypenicillin, in vitro (Tichs strain) defi ned as a minimum inhibitory concentration (MIC) ≤4μg/ml.
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P276 The Prevalence of Ticarcillin Hyper-susceptible Pseudmonoas aeruginosa isolates from Non Cystic Fibrosis Bronchiectasis patients compared to patients with Cystic Fibrosis and controls
Thorax, 2015Co-Authors: I. T. Hettiarachchi, T O’sullivan, M Wootton, J Duckers, R.p. DhillonAbstract:Background and aims Pseudomonas aeruginosa (PsA) is associated with considerable morbidity and mortality in Non-Cystic Fibrosis bronchiectasis (NCFB) and Cystic Fibrosis (CF) patients. Ticarcillin, a Carboxypenicillin, is occasionally used in NCFB and CF to treat pulmonary exacerbations. In CF, a subpopulation of PsA exists that is hypersusceptible to ticarcillin (Tichs) in vitro , (minimum inhibitory concerntration [MIC] The aim of this study was to investigate whether this Tichs strain exists in NCFB patients and compare this to the prevalence rates from CF and control cohorts. We also assessed whether this strain correlated with enhanced susceptibility to temocillin and other anti-pseudomonal antibiotics. Methods 18 isolates of PsA from NCFB patients, 23 PsA isolates from CF patients and 18 PsA isolates from controls with no chronic lung disease were analysed. MICs for each isolate were determined by agar dilution using ISO20776–1 for the antibiotics listed in Table 1 and interpreted using EUCAST breakpoints. Results The NCFB isolates had the highest prevalence of the Tichs strain of the three cohorts we tested, with a prevalence of 76%, compared to a prevalence of 48% in the CF cohort and 0% in the controls. Resistant strains of PsA were more prevalent in the CF cohort compared to the NCFB and control cohorts, except for temocillin and ticarcillin where the CF and NCFB cohorts had lower MICs compared to the control cohort (Table 1). The Tichs strain in NCFB and CF was associated with reduced MICs to all antibiotics apart from ciprofloxacin in comparison to the non- Tichs strain. In CF, the Tichs strain was also associated with increased MICs to gentamicin. Conclusion Our data supports the existence of a Tichs strain of PsA in NCFB patients, which existed in greater prevalence compared to our CF cohort. This appears to correlate with reduced MICs to temocillin, to which PsA would normally be resistant. Therefore, temocillin may provide a useful alternative to the current anti-pseudomonal antibiotics in treating NCFB and CF patients.
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120 The prevalence of ticarcillin hypersusceptible Pseudomonas aeruginosa isolates from cystic fibrosis patients compared to non-cystic fibrosis patients
Journal of Cystic Fibrosis, 2015Co-Authors: I. T. Hettiarachchi, R.p. Dhillon, M WoottonAbstract:Background Ticarcillin, a Carboxypenicillin, is rarely used to treat pulmonary infections in CF patients. A subpopulation of P. aeruginosa exists that is hypersusceptible to ticarcillin (Tic hs ) in vitro, (MIC ≥4 mg/ml). Aims To determine the prevalence of Tic hs in P. aeruginosa isolated from CF patients and to assess if this strain correlates with enhanced susceptibility to temocillin and other conventional antibiotics. We are correlating with clinical outcomes and associated VNTR type (work ongoing). Methods 23 isolates of P. aeruginosa from CF patients were compared to 18 non-CF P. aeruginosa isolates. MICs were determined by MicroBroth dilution and interpreted using EUCAST breakpoints. Results Resistant strains were more prevalent in the CF cohort compared to the non-CF cohort for all antibiotics except for ticarcillin and temocillin (Table 1). The prevalence of the Tic hs strain in our CF P. aeruginosa isolates was 48% compared to the non-CF Pseudomonas of 0%. The Tic hs strain was associated with reduced MICs to all antibiotics apart from gentamicin and ciprofloxacin (Table 2). Table 1MIC and percentage of resistant isolatesMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFMIC R0.008–160.008–80.25–1282–160.125–12816–1280.5–128128–1280.03–160.03–41–640.25–4MIC 500.50.12544432412810.0621MIC 90411281612812812812840.125642%Res20%6%26%17%35%78%NANA60%7%30%0%%Sens80%94%74%83%65%22%NANA40%93%70%100%MIC R, MIC range; %Res, % resistant; % Sens, % Sensitive. Table 2Geometric mean MICs, Tic hs vs. Non Tic hs strainsMIC, geometric meanMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinTic hs strain0.132.180.832.740.662.83Non Tic hs strain0.366.2339.4068.590.281.80 Conclusion Our data supports the existence of a Tic hs strain of P. aeruginosa in our CF patients. This appears to correlate with reduced MICs to temocillin to which P. aeruginosa would normally be resistant.
R.p. Dhillon - One of the best experts on this subject based on the ideXlab platform.
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P276 The Prevalence of Ticarcillin Hyper-susceptible Pseudmonoas aeruginosa isolates from Non Cystic Fibrosis Bronchiectasis patients compared to patients with Cystic Fibrosis and controls
Thorax, 2015Co-Authors: I. T. Hettiarachchi, T O’sullivan, M Wootton, J Duckers, R.p. DhillonAbstract:Background and aims Pseudomonas aeruginosa (PsA) is associated with considerable morbidity and mortality in Non-Cystic Fibrosis bronchiectasis (NCFB) and Cystic Fibrosis (CF) patients. Ticarcillin, a Carboxypenicillin, is occasionally used in NCFB and CF to treat pulmonary exacerbations. In CF, a subpopulation of PsA exists that is hypersusceptible to ticarcillin (Tichs) in vitro , (minimum inhibitory concerntration [MIC] The aim of this study was to investigate whether this Tichs strain exists in NCFB patients and compare this to the prevalence rates from CF and control cohorts. We also assessed whether this strain correlated with enhanced susceptibility to temocillin and other anti-pseudomonal antibiotics. Methods 18 isolates of PsA from NCFB patients, 23 PsA isolates from CF patients and 18 PsA isolates from controls with no chronic lung disease were analysed. MICs for each isolate were determined by agar dilution using ISO20776–1 for the antibiotics listed in Table 1 and interpreted using EUCAST breakpoints. Results The NCFB isolates had the highest prevalence of the Tichs strain of the three cohorts we tested, with a prevalence of 76%, compared to a prevalence of 48% in the CF cohort and 0% in the controls. Resistant strains of PsA were more prevalent in the CF cohort compared to the NCFB and control cohorts, except for temocillin and ticarcillin where the CF and NCFB cohorts had lower MICs compared to the control cohort (Table 1). The Tichs strain in NCFB and CF was associated with reduced MICs to all antibiotics apart from ciprofloxacin in comparison to the non- Tichs strain. In CF, the Tichs strain was also associated with increased MICs to gentamicin. Conclusion Our data supports the existence of a Tichs strain of PsA in NCFB patients, which existed in greater prevalence compared to our CF cohort. This appears to correlate with reduced MICs to temocillin, to which PsA would normally be resistant. Therefore, temocillin may provide a useful alternative to the current anti-pseudomonal antibiotics in treating NCFB and CF patients.
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120 The prevalence of ticarcillin hypersusceptible Pseudomonas aeruginosa isolates from cystic fibrosis patients compared to non-cystic fibrosis patients
Journal of Cystic Fibrosis, 2015Co-Authors: I. T. Hettiarachchi, R.p. Dhillon, M WoottonAbstract:Background Ticarcillin, a Carboxypenicillin, is rarely used to treat pulmonary infections in CF patients. A subpopulation of P. aeruginosa exists that is hypersusceptible to ticarcillin (Tic hs ) in vitro, (MIC ≥4 mg/ml). Aims To determine the prevalence of Tic hs in P. aeruginosa isolated from CF patients and to assess if this strain correlates with enhanced susceptibility to temocillin and other conventional antibiotics. We are correlating with clinical outcomes and associated VNTR type (work ongoing). Methods 23 isolates of P. aeruginosa from CF patients were compared to 18 non-CF P. aeruginosa isolates. MICs were determined by MicroBroth dilution and interpreted using EUCAST breakpoints. Results Resistant strains were more prevalent in the CF cohort compared to the non-CF cohort for all antibiotics except for ticarcillin and temocillin (Table 1). The prevalence of the Tic hs strain in our CF P. aeruginosa isolates was 48% compared to the non-CF Pseudomonas of 0%. The Tic hs strain was associated with reduced MICs to all antibiotics apart from gentamicin and ciprofloxacin (Table 2). Table 1MIC and percentage of resistant isolatesMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFCFNo CFMIC R0.008–160.008–80.25–1282–160.125–12816–1280.5–128128–1280.03–160.03–41–640.25–4MIC 500.50.12544432412810.0621MIC 90411281612812812812840.125642%Res20%6%26%17%35%78%NANA60%7%30%0%%Sens80%94%74%83%65%22%NANA40%93%70%100%MIC R, MIC range; %Res, % resistant; % Sens, % Sensitive. Table 2Geometric mean MICs, Tic hs vs. Non Tic hs strainsMIC, geometric meanMeropenemCeftazidimeTicarcillinTemocillinCiprofloxacinGentamicinTic hs strain0.132.180.832.740.662.83Non Tic hs strain0.366.2339.4068.590.281.80 Conclusion Our data supports the existence of a Tic hs strain of P. aeruginosa in our CF patients. This appears to correlate with reduced MICs to temocillin to which P. aeruginosa would normally be resistant.
Roger Labia - One of the best experts on this subject based on the ideXlab platform.
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Inhibitor-Resistant OXY-2-Derived β-Lactamase Produced by Klebsiella oxytoca
Antimicrobial agents and chemotherapy, 1998Co-Authors: D. Sirot, Roger Labia, P. Pouedras, C. Chanal-claris, Claude Cerceau, Jacques SirotAbstract:Klebsiella oxytoca strains are generally moderately resistant to amoxicillin and ticarcillin due to the activities of the chromosomally encoded OXY-1 and OXY-2 class A b-lactamase families. These enzymes have the ability to hydrolyze not only penicillins but also cephalosporins, including cefuroxime, ceftriaxone, and aztreonam, and are inhibited by clavulanic acid. A Klebsiella oxytoca strain was isolated from a culture of blood from a patient who had been treated with amoxicillin-clavulanate (3 g/day) for 10 days 1 month earlier. This strain harbored an unusual phenotype characterized by resistance to amoxicillin-clavulanate. It produced an OXY2-type b-lactamase (pI 6.3), as confirmed by PCR amplification with primers specific for the OXY-2-encoding gene. Gene sequencing revealed a point mutation (A3G) corresponding to the amino acid substitution Ser3Gly at position 130. This mutant enzyme was poorly inhibited by inhibitors, and its kinetic constants compared to those of the parent enzyme were characterized by an increased Km value for ticarcillin, with a drastically reduced activity against cephalosporins, as is observed with inhibitor-resistant TEM enzymes. The substitution Ser3Gly-130 was previously described in the inhibitor-resistant b-lactamase SHV-10 derived from an SHV-5 variant, but this is the first report of such a mutant in OXY enzymes from K. oxytoca. Klebsiella oxytoca, like Klebsiella spp., carries a chromosomally encoded b-lactamase belonging to class A. Recently, the b-lactamase genes of K. oxytoca were divided into two main groups: blaoxy-1 and blaoxy-2 (9). These chromosomal enzymes preferentially inactivate penicillins, conferring resistance on amino- and Carboxypenicillins. The ability of the K. oxytoca b-lactamases to hydrolyze extended-spectrum b-lactams could confer resistance to these antibiotics when the b-lactamase is overproduced from a modified promoter (5, 6, 8). The synergistic effects of the three b-lactamase inhibitors clavulanate, sulbactam, and tazobactam were generally poor and varied according to the type of OXY enzymes, the combination of drugs examined, and the type of inhibitor (7). Clavulanate was effective against the overproducing strains, even though it had a relatively high 50% inhibitory concentration (IC50). We report here on a clinical strain of K. oxytoca harboring an unusual resistance phenotype characterized by high-level resistance to amoxicillin, amoxicillin-clavulanate, piperacillin, piperacillin-tazobactam, and, to a lesser extent, ticarcillin and ticarcillin-clavulanate; these resistances were associated with susceptibility to all cephalosporins including cephalothin and aztreonam. This resistance phenotype was very similar to that observed when an inhibitor-resistant TEM (IRT) enzyme was produced in Escherichia coli (19). MATERIALS AND METHODS Bacterial strains. K. oxytoca KER producing a mutant of OXY-2 b-lactamase was isolated from the blood of a patient hospitalized in a gastroenterology unit of the hospital of Vannes, France. Seventeen clinical K. oxytoca strains were used for comparison of MICs: 14 K. oxytoca strains that produced an OXY-1 or an OXY-2 b-lactamase and that harbored the usual resistance phenotype of wild strains of this species and 3 b-lactamase-overproducing K. oxytoca strains that had high levels of resistance to penicillins, cephalothin, cefuroxime, and aztreonam but that were susceptible to cefoxitin, cefotaxime, ceftazidime, and imipenem. K. oxytoca HB60 (OXY-2-2 producing) was used for comparison of kinetic constants. Susceptibility to b-lactams. The MICs of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, piperacillin, piperacillin-clavulanate, piperacillin-sulbactam, piperacillin-tazobactam, cephalothin, cefotaxime, ceftazidime, and aztreonam were determined by dilution in Mueller-Hinton agar (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) at an inoculum of 10 4 CFU
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Characterization and amino acid sequence analysis of a new oxyimino cephalosporin-hydrolyzing class A β-lactamase from Serratia fonticola CUV
Biochimica et biophysica acta, 1997Co-Authors: Jean Peduzzi, S. Farzaneh, Alain Reynaud, M. Barthelemy, Roger LabiaAbstract:Serratia fonticola CUV produces two isoenzymes (forms I and II) with beta-lactamase activity which were purified by a five-step procedure. The isoenzymes had identical kinetic parameters and isoelectric point (pI = 8.12). They were characterized by a specific activity towards benzylpenicillin of 1650 U/mg. The beta-lactamase hydrolyzed benzylpenicillin, amoxycillin, ureidopenicillins, first- and second-generation cephalosporins. Carboxypenicillins and isoxazolylpenicillins were hydrolyzed to a lesser extent. Towards cefotaxime and ceftriaxone (third-generation cephalosporins), the S. fonticola enzyme exhibited catalytic efficiencies much higher than those of MEN-1 and extended-spectrum TEM derivative beta-lactamases. The beta-lactamase from S. fonticola was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam. The purified isoenzymes were digested by trypsin, endoproteinase Asp-N and chymotrypsin. Amino acid sequence determinations of the resulting peptides allowed the alignment of 267 amino acid residues (Swiss-Prot, accession number P 80545) for form I beta-lactamase. Form II is five residues shorter than form I at its N-terminus. From amino acid sequence comparisons, S. fonticola CUV beta-lactamase was found to share more than 69.3% identity with the chromosomally encoded beta-lactamases of Klebsiella oxytoca, Proteus vulgaris, Citrobacter diversus and the plasmid-mediated enzymes MEN-1 and Toho-1. Therefore, the oxyimino cephalosporin-hydrolyzing beta-lactamase of S. fonticola belongs to Ambler's class A. Contribution of the serine at ABL 237 in the broad-spectrum activity of these beta-lactamases is discussed.
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Site‐directed mutagenesis of β‐lactamase TEM‐1
European journal of biochemistry, 1993Co-Authors: Françise Lenfant, Agnès Petit, Roger Labia, Laurent Maveyraud, Jean-pierre Samama, Jean-michel MassonAbstract:From sequence alignments, two groups can be defined for the carbenicillin-hydrolysing β-lactamases (CARB enzymes). One group includes the Pseudomonas-specific enzymes PSE-1, PSE-4, CARB-3, CARB-4 and also the Proteus mirabilis GN79, for which the well-conserved residue Lys 234 in all class-A β-lactamases is changed to an arginine residue. The second group includes the enzymes PSE-3 and AER-1 which have an arginine or a lysine residue at position 165. All these enzymes also have leucine at position 68, threonine at position 104 and glycine at position 240. We engineered these mutations into the TEM-1 β-lactamase to study their potential role in defining the substrate profile of the CARB enzymes. The mutations K234R and E240G in TEM-1 noticeably increased the hydrolysis of Carboxypenicillins relative to other penicillins by approximately sixfold and twofold, respectively. The variant E240G also demonstrated an improved rate of second-generation cephalosporin and cefotaxime hydrolysis. In contrast, the substitution of Trp165 by arginine does not extend the substrate profile to α-Carboxypenicillins nor does it noticeably modify the kinetic behavior of the enzyme. The mutations M68L and E104T do not have a large effect on the hydrolysis rate but the mutation E104T enhances the affinity of the enzyme for third-generation cephalosporins. As the mutation K234R resulted in a severe decrease in the affinity for Carboxypenicillins, the double mutant E240G/K234R was constructed in an attempt to enhance the CARB character of the enzyme. Contrary to what could be expected, the additional mutation E240G for the TEM-1 K234R enzyme increases neither the catalytic constant for the Carboxypenicillins nor the affinity towards these substrates. Consequently, this study strongly suggests that the three-dimensional structures of the active site of the TEM-1 enzyme and PSE-3, PSE-4 or other related enzymes are significantly different. This probably explains the discrepancy of the substrate profile between the CARB enzymes and the TEM-1 protein variants.
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Replacement of lysine 234 affects transition state stabilization in the active site of beta-lactamase TEM1.
The Journal of biological chemistry, 1991Co-Authors: Francoise Lenfant, Roger Labia, Jean-michel MassonAbstract:Lysine 234 is a residue highly conserved in all beta-lactamases, except in the carbenicillin-hydrolyzing enzymes, in which it is replaced by an arginine. Informational suppression has been used to create amino acid substitutions at this position in the broad spectrum Escherichia coli beta-lactamase TEM-1, in order to elucidate the role of this residue which lies on the wall at the closed end of the active site cavity. The mutants K234R and K234T were constructed and their kinetic constants measured. Replacement of lysine 234 by arginine yields an enzyme with similar activity toward cephalosporins and most penicillins, except toward the Carboxypenicillins for which the presence of the guanidine group enhances the transition state binding. The removal of the basic group in the mutant K234T yields a protein variant which retains a low activity toward penicillins, but losts drastically its ability to hydrolyze cephalosporins. Moreover, these two mutations largely decreased the affinity of the enzyme for penicillins (10-fold for K234R and 50-fold for K234T). This can be correlated with the disruption of the predicted electrostatic binding between the C3 carboxylic group of penicillins and the amine function of the lysine. Therefore, lysine 234 in the E. coli beta-lactamase TEM-1 is involved both in the initial recognition of the substrate and in transition state stabilization.
Christophe Adrie - One of the best experts on this subject based on the ideXlab platform.
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impact of ureido Carboxypenicillin resistance on the prognosis of ventilator associated pneumonia due to pseudomonas aeruginosa
Critical Care, 2011Co-Authors: Catherine Kaminski, Jean-françois Timsit, Yohann Dubois, Jean-ralph Zahar, Aurélien Vesin, Elie Azoulay, Céline Feger, Anne-sylvie Dumenil, Maite Garrousteorgeas, Christophe AdrieAbstract:Introduction Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated.
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Impact of ureido/Carboxypenicillin resistance on the prognosis of ventilator-associated pneumonia due to Pseudomonas aeruginosa
Critical care (London England), 2011Co-Authors: Catherine Kaminski, Maité Garrouste-orgeas, Jean-françois Timsit, Yohann Dubois, Jean-ralph Zahar, Aurélien Vesin, Elie Azoulay, Céline Feger, Anne-sylvie Dumenil, Christophe AdrieAbstract:Introduction Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated.
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Impact of ureido/Carboxypenicillin resistance on the prognosis of ventilator-associated pneumonia due to Pseudomonas aeruginosa.
Critical Care, 2011Co-Authors: Catherine Kaminski, Maité Garrouste-orgeas, Jean-françois Timsit, Yohann Dubois, Jean-ralph Zahar, Aurélien Vesin, Elie Azoulay, Céline Feger, Anne-sylvie Dumenil, Christophe AdrieAbstract:INTRODUCTION: Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated. METHODS: A total of 223 episodes of PA-VAP recorded into the Outcomerea database were evaluated. Patients with ureido/carboxy-resistant P. aeruginosa (PRPA) were compared with those with ureido/carboxy-sensitive P. aeruginosa (PSPA) after matching on duration of ICU stay at VAP onset and adjustment for confounders. RESULTS: Factors associated with onset of PRPA-VAP were as follows: admission to the ICU with septic shock, broad-spectrum antimicrobials at admission, prior use of ureido/Carboxypenicillin, and colonization with PRPA before infection. Adequate antimicrobial therapy was more often delayed in the PRPA group. The crude ICU mortality rate and the hospital mortality rate were not different between the PRPA and the PSPA groups. In multivariate analysis, after controlling for time in the ICU before VAP diagnosis, neither ICU death (odds ratio (OR) = 0.73; 95% confidence interval (CI): 0.32 to 1.69; P = 0.46) nor hospital death (OR = 0.87; 95% CI: 0.38 to 1.99; P = 0.74) were increased in the presence of PRPA infection. This result remained unchanged in the subgroup of 87 patients who received adequate antimicrobial treatment on the day of VAP diagnosis. CONCLUSIONS: After adjustment, and despite the more frequent delay in the initiation of an adequate antimicrobial therapy in these patients, resistance to ureido/Carboxypenicillin was not associated with ICU or hospital death in patients with PA-VAP.