Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, elevation of protein concentrations and 6-8 log10 cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae, Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin-resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes all responded to meropenem, which was as active as the comparator agents in all studies, and was more active in most. Of particular note were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than ceftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. Activity against L. monocytogenes was equivalent to that produced by treatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, meropenem penetrates into CSF in concentrations sufficient to produce significant reductions in the numbers of common and less common pathogens.
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PMID:Efficacy of meropenem in experimental meningitis. 854 1

Meropenem is a new DHP-I stable carbapenem with a very promising microbiological, pharmacokinetic and clinical profile. The antibacterial activity of this new agent has been assessed in vitro against 8741 aerobic and 854 anaerobic strains reflecting current incidence and epidemiology in Italy, France, Germany, Spain, Switzerland and United Kingdom. Comparator agents were imipenem, ceftriaxone, vancomycin, ciprofloxacin gentamicin and amikacin. The results of this study show that meropenem has a spectrum of antibacterial activity which embraces the vast majority of clinically significant Gram-positive and Gram-negative aerobes and anaerobes. This is due in part to excellent stability to chromosomal or plasmid mediated beta-lactamases including those which hydrolyse current cephalosporins. Data from the Italian study identified meropenem as the most potent agent against all Enterobacteriaceae, with the exception of Proteus species with were most susceptible to ciprofloxacin. Moreover, meropenem was 10 times more active than the other drugs against Haemophilus and Neisseria and was active against all the anaerobic strains. Conversely, staphylococci and enterococci were more susceptible to imipenem. Overall, these European data showed that meropenem was the most powerful drug against Enterobacteriaceae and it also was the most effective drug tested against the Italian and French Pseudomonas aeruginosa strains. Meropenem was less effective than imipenem or vancomycin against Enterococcus stains but had similar activity to imipen against anaerobes. Based on this microbiological profile, the use of meropenem is appropriate in the empirical treatment of serious infections, including those caused by multiple pathogens.
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PMID:[In vitro antibacterial activity of meropenem, a new carbapenem: European data]. 857 28

Meropenem is a new carbapenem antibiotic that is stable to human renal dehydropeptidase-I (DHP-I) and exhibits potent bactericidal activity against almost all clinically significant aerobic and anaerobic bacteria. Activity is achieved through rapid entry into bacteria, resisting hydrolysis by all serine-based beta-lactamases, both of chromosomal or plasmid origin, and high affinity for vital penicillin binding proteins. The antibacterial spectrum of meropenem has been investigated extensively in a world-wide programme of studies. The results from all of these studies are consistent and identify in vitro differences between meropenem and imipenem. Both agents demonstrate high activity against Gram-positive aerobes with meropenem slightly less active than imipenem but significantly more potent than imipenem against Haemophilus influenza, all Enterobacteriaceae and 2-4 fold more active against Pseudomonas aeruginosa and most other pseudomonas. The spectrum of carbapenems is superior to that of all other beta-lactams. This is achieved, in part, by stability to the chromosomal beta-lactamases which hydrolyse ceftazidime, cefotaxime and ceftriaxone and against which newer agents like cefpirome and cefepime are not fully stable. Meropenem is also stable to the new plasmid-mediated enzymes which are responsible for significant elevation of MIC's of all cephalosporins and penicillins. When tested against P. Aeruginosa which have become resistant to imipenem therapy, these strains remained susceptible to meropenem. The activity of meropenem against anaerobes is at least as potent as metronidazole and clindamycin. These impressive in vitro data have been the basis for an extensive clinical evaluation programme in many indications including infections caused by single or multiple pathogens.
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PMID:[Preclinical evaluation of meropenem, a new parenteral carbapenem]. 857 29

A collection of 300 Haemophilus influenzae clinical strains was used to assess in vitro susceptibility to carbapenems (meropenem, imipenem) by MIC and disk diffusion methods and to compare disk diffusion test results with two potencies of ampicillin disks (2 and 10 micrograms). The isolates included ampicillin-susceptible or- intermediate (167 strains), beta-lactamase-positive (117 strains), and beta-lactamase-negative ampicillin-resistant (BLNAR; 16 strains) organisms. Disk diffusion testing was performed with 10-micrograms meropenem disks from two manufacturers. Meropenem was highly active against H. influenzae strains (MIC50, 0.06 microgram/ml; MIC90, 0.25 microgram/ml; MIC50 and MIC90, MICs at which 50 and 90%, respectively, of strains are inhibited) and was 8- to 16-fold more potent than imipenem (MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml). Five non-imipenem-susceptible strains were identified (MIC, 8 micrograms/ml), but the disk diffusion test indicated susceptibility (zone diameters, 18 to 21 mm). MIC values of meropenem, doxycycline, ceftazidime, and ceftriaxone for BLNAR strains were two- to fourfold greater than those for other strains. The performance of both meropenem disks was comparable and considered acceptable. A single susceptible interpretive zone diameter of > or = 17 mm (MIC, < = or 4 micrograms/ml) was proposed for meropenem. Testing with the 2-micrograms ampicillin disk was preferred because of an excellent correlation between MIC values and zone diameters (r = 0.94) and superior interpretive accuracy with the susceptible criteria at > or = 17 mm (MIC, < or = 1 microgram/ml) and the resistant criteria at < or = 13 mm (MIC, > or = 4 micrograms/ml). Among the BLNAR strains tested, 81.3% were miscategorized as susceptible or intermediate when the 10-micrograms ampicillin disk was used, while the 2-micrograms disk produced only minor interpretive errors (12.5%). Use of these criteria for testing H. influenzae against meropenem and ampicillin should maximize reference test and standardized disk diffusion test performance with the Haemophilus Test Medium. The imipenem disk diffusion test appears compromised and should be used with caution for detecting strains for which imipenem MICs are elevated.
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PMID:Reevaluation of interpretive criteria for Haemophilus influenzae by using meropenem (10-microgram), imipenem (10-microgram), and ampicillin (2- and 10-microgram) disks. 881 92

This paper on bacterial meningitis looks at aspects inherent in the aetiology and mechanisms underlying neurological damage and pharmacological treatment. Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are the pathogens most commonly responsible and are able to colonise the host's respiratory mucosae, invade the vascular space, cross the haematoliquoral barrier and survive in the cerebrospinal fluid. The presence of germs in the subarachnoid spaces leads to the onset of inflammation and neurological damage. The most often used pharmacological treatments include, apart from antibiotics, anti-inflammatory drugs (although we have clinical data for corticosteroids only), pentoxyphillin and monoclonal antibodies. Initially empiric, antibiotic therapy is based on the use of drugs that act against the probable pathogenic agents, are capable of surmounting the haematoliquoral barrier and are well tolerated. Prior to the Eighties, the antibiotic of choice was ampicillin associated or otherwise with aminoglycosides. Subsequently, the availability of new drugs (cefotaxime and ceftriaxone) and the appearance of resistance led to changes in therapeutic protocols. Of the carbapenemics, wide spectrum antibiotics with high resistance to beta lactamase, imipenem /cilastatin proved effective although there was a high risk of inducing convulsions in patients with previous neurological damage or kidney failure. Meropenem was able to surmount the haematoliquoral barrier in sufficient concentrations and was well tolerated in patients with prior neurological changes. It has proved effective in clinical studies carried out up to the present.
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PMID:[Current problems in the treatment of bacterial meningitis]. 909 74

The in vitro antibacterial activity of meropenem and up to nine other antimicrobials was compared in studies at 26 North American centers from 1989 to 1992 with use of standardized and controlled procedures for determining minimal inhibitory concentrations (MICs) against 12,483 recent clinical isolates and additional drug-resistant strains. Overall, carbapenems were the most active drugs. The antibacterial activity of meropenem was consistent against random isolates in all centers; however, inclusion of large proportions of multidrug-resistant gram-negative aerobes by some centers did increase MICs of meropenem and the comparators. Meropenem was 4-64 times more active than imipenem against gram-negatives, including Enterobacteriaceae organisms, Pseudomonas aeruginosa, Burkholderia cepacia, Neisseria meningiditis, and Haemophilus influenzae. Imipenem was up to 2-4 times more active than meropenem against some gram-positive cocci, including Enterococcus faecalis. Carbapenems were similarly active against anaerobes, and resistant strains were rarely encountered. Meropenem, unlike imipenem or ceftazidime, was bactericidal for all strains of Enterobacteriaceae, P. aeruginosa, and gram-positive cocci tested at < or = 8 times the MIC. A lack of antibiotic cross-resistance was frequently observed between comparator-resistant strains and meropenem. These data suggest the potential utility of meropenem as a monotherapeutic agent against a broad range of pathogens.
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PMID:Comparative in vitro activity of meropenem versus other extended-spectrum antimicrobials against randomly chosen and selected resistant clinical isolates tested in 26 North American centers. 912 99

The in vitro activity of meropenem (formerly SM-7738), a new carbapenem, was compared with that of imipenem and five other broad-spectrum antimicrobials (ceftazidime, cefotaxime, piperacillin, piperacillin/tazobactam, and ciprofloxacin) against 30,254 clinically significant pathogens isolated in nine countries worldwide. Overall, the carbapenems, meropenem and imipenem, were the most active drugs. Meropenem was four- to 64-fold more active than imipenem against Gram-negative bacteria, including the Enterobacteriaceae, Pseudomonas aeruginosa, Burkholderia cepacia, Haemophilus influenzae, and Neisseria meningitidis. Meropenem was also quite active against ceftazidime-resistant strains of Enterobacteriaceae, inhibiting 87.5 to 100% at < or = 4 micrograms/ml. In contrast, imipenem was four- to eight-fold more active than meropenem against Gram-positive species, including methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis. Among the anaerobes, strains resistant to meropenem or imipenem were encountered very rarely. These extensive data provide additional in vitro support for the clinical use of meropenem as a broad spectrum antimicrobial agent active against key pathogenic species of bacteria.
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PMID:A review of the in vitro activity of meropenem and comparative antimicrobial agents tested against 30,254 aerobic and anaerobic pathogens isolated world wide. 932 42

Meropenem is a beta-lactamic carbapenem derived from thienamycin and is structurally characterized by the presence of a beta-methyl group in position C1 which confers stability to the molecule versus renal dehydropeptidase 1 (DHP-1), thereby making the coadministration of an enzyme inhibitor unnecessary. Its esterochemical configuration of the lateral chain in C2 (dimethyl carbomoilpyrrolidenethium) increases the activity versus gram negative bacteria (enterobacteria and pseudomonas) and moreover, may explain the reduction in the proconvulsive effect observed in imipenem/cilastatin. Meropenem has great bactericide power and has a very wide spectrum of activity depending on it low molecular weight and zwiterionic structure, stability versus almost all the clinically important beta-lactamases and high affinity for the PBPs. It covers gram positive aerobes (Staphylococcus aureus, coagulase negative staphylococci, streptococci including Streptococcus pneumoniae resistant to penicillin, Enterococcus faecalis, Rhodococcus equi, Listeria monocytogenes) and gram negative bacteria (enterobacteria, P. aeruginosa, Acinetobacter, Aeromonas, Plesiomonas, Vibrio, Haemophilus influenzae, Neisseria, Moraxella) and anaerobes (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Clostridium, Peptostreptococcus, and Propionibacterium acnes), being more active than imipenem versus gram negatives: P. aeruginosa (2-4-fold), enterobacteria (2-32-fold) and H. influenzae (4-8-fold) and less active versus the gram positives (enterococci, streptococci and staphylococci). Meropenem has no activity on Enterococcus faecium, S. aureus resistant to methycillin, Stenotrophomonas maltophilia and other genera producers of chromosomic methalo-beta-lactamases (carbapenemases). Resistance may be due to impermeability given the loss of the OprD porin (OprD2 in enterobacteria and P. aeruginosa) loss of different membrane proteins (Proteus mirabilis, Proteus rettgeri, Enterobacter cloacae, Enterobacter aerogenes), modifications of the PBPs (gram positive) and the production of carbapenemases (chromosomic methalo-beta-lactamases).
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PMID:[Meropenem: microbiologic perspective]. 941 64

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic. Combinations of beta-lactams plus aminoglycosides have been the standard empiric therapy for febrile granulocytopenic patients, especially those with profound long-lasting granulocytopenia. The advent of new broad-spectrum cephalosporins and carbapenems has favoured the possibility of empiric monotherapy. Meropenem is a parenteral carbapenem antibiotic stable to renal dehydropeptidase-I which has excellent bactericidal activity against almost all clinically significant aerobic and anaerobic organisms. Meropenem hasta an antibacterial spectrum similar to that of imipenem but it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae, Haemophilus influenzae, Proteus spp, Morganella spp and Providencia spp. Recently, the efficacy, safety, and tolerance of meropenem monotherapy for the empirical treatment of fever in granulocytopenic cancer patients have been compared in two large prospective randomized multicenter trials. The Meropenem Study Group compared monotherapy with meropenem versus ceftazidime and the EORTC conducted a comparative study of meropenem monotherapy versus the combination of ceftazidime plus amikacin. In both groups, success rates were similar by type of infection and infection-related mortality was low. Related adverse events were also similar in both groups. These studies confirm that monotherapy with meropenem is as effective as ceftazidime-containing regimens for the empiric treatment of fever in granulocytopenic patients.
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PMID:[Monotherapy with meropenem in febrile granulocytopenic patients]. 941 73

GV129606 is a new parenteral trinem antibiotic belonging to the beta-lactam class. It combines broad-spectrum activity (against gram-negative and -positive bacteria, aerobes and anaerobes), with high potency and resistance to beta-lactamases. Comparative in vitro and in vivo antibacterial activities were determined for GV129606 against more than 400 recent clinical isolates (aerobes, including beta-lactamase producers, and anaerobes), using representative antibacterial agents (meropenem, piperacillin, ceftazidime, cefpirome, ciprofloxacin, and gentamicin for aerobes and metronidazole, cefoxitin, piperacillin, and clindamycin for anaerobes). Against methicillin-susceptible staphylococci and streptococci, GV129606 and meropenem were the most active of the drugs tested. GV129606 showed an MIC for 90% of strains tested (MIC90) ranging from < or =0.015 to 0.06 microg/ml against methicillin-susceptible staphylococci and Streptococcus sanguis, Streptococcus pyogenes, and Streptococcus agalactiae. Against penicillin-susceptible and -resistant Streptococcus pneumoniae isolates, GV129606, meropenem, and cefpirome showed MIC90s of < or =0.015 and 1 microg/ml, respectively. Meropenem was the most active compound against members of the family Enterobacteriaceae with MIC90s of < or =0.5 microg/ml. Against these species, GV129606 possessed activity superior to those of piperacillin, ceftazidime, cefpirome, and gentamicin, with MIC90s of < or =8 microg/ml, but its activity was two- to sixfold less than that of ciprofloxacin (with the exception of Proteus rettgeri and Providencia stuartii). Haemophilus spp., Moraxella catarrhalis, Neisseria gonorrhoeae, and Pseudomonas aeruginosa were also included in the spectrum of GV129606. GV129606 showed good antianaerobe activity, similar to metronidazole. It was stable against all clinically relevant beta-lactamases (similar to meropenem). The in vitro activity was confirmed in vivo against septicemia infections induced in mice by selected gram-positive and -negative bacteria with 50% effective doses (ED50s) of < or =0.05 and < or =0.5 mg/kg of body weight/dose, respectively. GV129606 was as effective as meropenem against septicemia in mice caused by ceftazidime-resistant Pseudomonas aeruginosa, exhibiting an ED50 of 0.33 mg/kg/dose.
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PMID:In vitro and in vivo antibacterial activities of GV129606, a new broad-spectrum trinem. 942 50


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