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Query: UNIPROT:Q96DG6 (Pseudomonas)
 76,258 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimicrobial activity of meropenem, a new parenteral carbapenem, was tested in vitro by an agar dilution method against 200 clinical isolates (gram-negative/positive aerobes and anaerobes). Meropenem was compared with imipenem, ceftazidime, cefotaxime, piperacillin, ciprofloxacin, gentamicin; and metronidazole, cefoxitin, chloramphenicol, clindamycin, vancomycin when appropriate. Meropenem and imipenem exhibited an extended spectrum of activity with low minimal inhibitory concentrations (MICs). Only one strain each of Enterococcus faecium and Pseudomonas (Xanthomonas) maltophilia were resistant. Of the carbapenems, imipenem was slightly more active against Enterococcus faecalis, Streptococcus agalactiae, and staphylococci, but meropenem was obviously more active against enterobacteriaceae and Clostridium perfringens. Both, meropenem and imipenem had similar activities towards Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Streptococcus pyogenes and Bacteroides sp. All other antibiotics tested were less potent than the carbapenems with the exception of ciprofloxacin which generally exhibited similar antibacterial activities, except for anaerob microorganisms.
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PMID:Antibacterial in vitro-activity of meropenem against 200 clinical isolates in comparison to 11 selected antibiotics. 130 91

Mutational loss of the D2 porin causes imipenem resistance in Pseudomonas aeruginosa. It was found that this mechanism could function only when the chromosomal beta-lactamase was expressed. Mutants lacking both the beta-lactamase and the D2 porin were almost as susceptible as those that lacked the beta-lactamase but retained the porin. Thus, imipenem resistance reflected an interplay of the enzyme and impermeability, not either factor alone. These findings suggest that the activity of a carbapenem more beta-lactamase stable than imipenem should be less affected by the porin loss. Meropenem approached this behavior.
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PMID:Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. 132 41

The outer membrane permeability to meropenem and imipenem in Escherichia coli K-12 was investigated, and its porin-deficient mutants were transformed with a constructed vector carrying the carbapenem-hydrolyzing CphA metallo-beta-lactamase gene. By using the method of Zimmermann and Rosselet, meropenem was shown to penetrate through the outer membrane of E. coli K-12 five times faster than cephaloridine but twice as slowly as imipenem. Lack of one or both porins significantly reduced the penetration of both carbapenems. No evidence of specific porin pathways of the type described in Pseudomonas aeruginosa was found. Despite its slower penetration, meropenem was two to eight times more active than imipenem against both parent and porin-defective mutants, whether harbouring CphA beta-lactamase or not. Meropenem was also more active than imipenem against E. coli DC2, a strain with a breakdown in the outer membrane permeability which made periplasmic concentrations of beta-lactams similar to the external concentrations. In this strain, meropenem caused a more than 50% reduction in cell number increase at a concentration very close to the 50% inhibitory concentration for penicillin-binding protein type 2 (PBP 2), whereas imipenem, at the same concentration, did not significantly inhibit cell growth. This result was explained by the higher affinity of meropenem for PBP 3 compared with imipenem and supports the conclusion that synergistic inhibition of both PBPs was the main mechanism in the better antibacterial activity of meropenem.
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PMID:Diffusion of meropenem and imipenem through the outer membrane of Escherichia coli K-12 and correlation with their antibacterial activities. 141 80

The affinity of meropenem for various known types of beta-lactamases and its stability to them were tested in comparison with other beta-lactams, including imipenem. Meropenem exhibited a marked stability to all beta-lactamases tested and was only hydrolyzed by Xanthomonas maltophilia beta-lactamase, as were other beta-lactams. This was responsible for the potent antibacterial activities of meropenem against beta-lactamase-producing strains. Meropenem and imipenem had almost the same, relatively high affinity for beta-lactamases; however, they had a lower affinity than clavulanic acid for penicillin beta-lactamases and cefoxitin for cephalosporin beta-lactamases. Meropenem also had higher beta-lactamase inhibitory activity than imipenem. Meropenem inhibited type III (TEM-1), Ia Citrobacter freundii and Ic Proteus vulgaris beta-lactamases in a progressive manner. Meropenem was thought to be a potent inhibitor of various beta-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes. Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C. freundii, Enterobacter cloacae and Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced beta-lactamases at concentrations above the MIC.
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PMID:Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity. 147 60

Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Basic and clinical study of meropenem in pediatric field]. 147 87

Meropenem, a new broad-spectrum carbapenem antibiotic, demonstrated excellent in vitro activity against major respiratory pathogens including Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae. Minimal inhibitory concentrations of meropenem for Moraxella catarrhalis and Haemophilus influenzae isolates were frequently less than those of imipenem. For nosocomial amikacin-resistant gram-negative bacilli, meropenem had eightfold lower MIC90 values compared to imipenem against strains of Serratia marcescens, Enterobacter cloacae and Escherichia coli; it was 32-fold more active than imipenem against Proteus mirabilis isolates. Activity was similar to that of imipenem against Pseudomonas aeruginosa isolates. Overall, meropenem showed excellent activity against common community-acquired pathogens as well as amikacin-resistant nosocomial pathogens.
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PMID:Comparative activity of meropenem (SM-7338) against major respiratory pathogens and amikacin-resistant nosocomial isolates. 156 88

The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.
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PMID:In vitro and in vivo antibacterial activities of meropenem, a new carbapenem antibiotic. 164 10

Twenty Pseudomonas maltophilia isolates were examined for susceptibility to beta-lactam antibiotics, including carbapenems, and for beta-lactamase production. All the isolates were resistant to imipenem (MICs 64-512 mg/l) and to a lesser extent, to meropenem (MICs 16-256 mg/l). None of the isolates produced significant amounts of beta-lactamase without induction. Among the beta-lactams studied imipenem proved to be the most potent inducer; meropenem was a weaker inducer. Interestingly, 6-amino-penicillanic acid, even in concentrations up to 100 mg/l, entirely lacked induction activity. In any case enzyme production was drug concentration dependent and transient. Isoelectric focusing revealed 6 different enzymes distinguished by their different isoelectric points (pH 6.2, 8.3, 8.5, 9.0, 9.2 and 9.4). This suggested the lack of a unique beta-lactamase profile in P. maltophilia. Addition of 5 mM cyclic AMP (cAMP) or 0.5 mM cAMP-N6, O2-dioctanoyl (a lipophilic derivative) resulted in a marked drop of beta-lactamase induction by imipenem as compared to the control assay. Monitoring of carbapenem hydrolysis by cell-free supernatants revealed inactivation of both carbapenems. Meropenem was inactivated about 5 times more rapidly than imipenem. Our studies revealed that beta-lactamase production in P. maltophilia as well as growth kinetics were influenced to a considerable extent by the nutrient medium employed.
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PMID:Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen. 231 40

Meropenem is a new carbapenem antibiotic with activity similar to that of imipenem. Development of resistance to imipenem by Pseudomonas aeruginosa has occurred in therapy and is associated with loss of a 45,000-48,000 molecular weight outer membrane protein (OMP) and decreased imipenem penetration. Seven pairs of isolates of P. aeruginosa obtained before treatment and after emergence of resistance were examined for changes in MIC of both imipenem and meropenem, and for changes in OMP profile. Resistant mutants were obtained also from the pre-therapy strains on Mueller-Hinton agar containing increasing amounts of either drug, and maintained under antibiotic pressure. OMP preparations of all pre- and post-therapy strains and laboratory mutants were separated by polyacrylamide gel electrophoresis. Loss of a 45,000-48,000 molecular weight protein occurred in variants selected under carbapenem pressure and in all post-therapy isolates. Meropenem remained four-fold more active than imipenem against the resistant strains and mutants.
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PMID:Emergence of resistance to carbapenem antibiotics in Pseudomonas aeruginosa. 250 13

The antibacterial activity in vitro of meropenem was compared with another carbapenem, imipenem, the penem HRE 664, and ceftazidime. MICs were not influenced by pH nor by inoculum size below 5 X 10(5) cfu/ml: higher inocula caused a modest increase in MIC. Cation supplementation of Mueller-Hinton broth was without effect. Meropenem was more active than imipenem and the other comparative agents against the majority of Gram-negative species (in particular proteus, providencia, morganella, haemophilus, neisseria and Pseudomonas aeruginosa, including isolates from patients with cystic fibrosis). Against Gram-positive organisms, the activity of meropenem was equal to or slightly less that of imipenem. Neither meropenem nor imipenem were influenced by the extended spectrum beta-lactamases that confer resistance to third generation cephalosporins produced by Escherichia coli, Klebsiella pneumoniae, K. oxytoca or Serratia marcescens.
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PMID:In-vitro activity of meropenem imipenem, the penem HRE 664 and ceftazidine against clinical isolates from West Germany. 250 18


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