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)

The in-vitro activity of HMR 3647 and seven comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, penicillin G, ciprofloxacin and levofloxacin) were tested against 207 Streptococcus pneumoniae and 200 beta-haemolytic streptococci. Ten comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, ampicillin, co-amoxiclav, cefuroxime, cefotaxime, ciprofloxacin and levofloxacin) were tested against 143 Haemophilus influenzae and 58 Moraxella catarrhalis. The MIC50 of HMR 3647 for S. pneumoniae was < or =0.008 mg/L, less than that for the macrolides or quinolones tested. Pneumococci with an erythromycin A MIC of 0.06 mg/L (n = 23) had an MIC50 of HMR 3647 < or =0.008 mg/L, whereas isolates with an erythromycin A MIC > or =1 mg/L (n = 34) had an MIC50 of HMR 3647 of 0.03 mg/L, a four-fold increase. In contrast, the difference in macrolide MIC50s for the two groups was > or =64-fold. The MIC50s foro beta-haemolytic streptococci, classified by Lancefield group, were in the range 0.015 to 0.06 mg/L for HMR 3647. H. influenzae were categorized into three groups according to cefuroxime MIC: <1 mg/L (n = 72); 2-4 mg/L (n = 29); and >4 mg/L (n = 42). The MIC50 of HMR 3647 increased two-fold with increasing cefuroxime MICs; beta-lactam MICs increased much more markedly. The MIC50 of HMR 3647 for M. catarrhalis was 0.03 mg/L. HMR 3647 has good activity against respiratory tract pathogens but in-vitro susceptibility is affected by erythromycin A susceptibility in S. pneumoniae and beta-haemolytic streptococci.
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PMID:In-vitro activity of HMR 3647 against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and beta-haemolytic streptococci. 1058 4

Telithromycin (HMR 3647) is a new ketolide that belongs to a new class of semisynthetic 14-membered-ring macrolides which have expanded activity against multidrug-resistant gram-positive bacteria. The aim of the present study was to investigate different basic pharmacodynamic properties of this new compound. The following studies of telithromycin were performed: (i) studies of the rate and extent of killing of respiratory tract pathogens with different susceptibilities to erythromycin and penicillin exposed to a fixed concentration that corresponds to a dose of 800 mg in humans, (ii) studies of the rate and extent of killing of telithromycin at five different concentrations, (iii) studies of the rate and extent of killing of the same pathogens at three different inocula, (iv) studies of the postantibiotic effect and the postantibiotic sub-MIC effect of telithromycin, and (v) determination of the rate and extent of killing of telithromycin in an in vitro kinetic model. In conclusion, telithromycin exerted an extremely fast killing of all strains of Streptococcus pneumoniae both with static concentrations and in the in vitro kinetic model. A slower killing of the strains of Streptococcus pyogenes was noted, with regrowth in the kinetic model of a macrolide-lincosamide-streptogramin B-inducible strain. The strains of Haemophilus influenzae were not killed at all at a concentration of 0.6 mg/liter due to high MICs. A time-dependent killing was seen for all strains. No inoculum effect was seen for the strains of S. pneumoniae, with a 99.9% reduction in the numbers of CFU for all inocula at both 8 h and 24 h. The killing of the strains of S. pyogenes was reduced by 1 log(10) CFU at 8 h and 2 to 3 log(10) CFU at 24 h when the two lower inocula were used but not at all at 8 and 24 h when the highest inoculum was used. For both of the H. influenzae strains there was an inoculum effect, with 1 to 2 log(10) CFU less killing for the inoculum of 10(8) CFU/ml in comparison to that for the inoculum of 10(6) CFU/ml. Overall, telithromycin exhibited long postantibiotic effects and postantibiotic sub-MIC effects for all strains investigated.
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PMID:Pharmacodynamics of telithromycin In vitro against respiratory tract pathogens. 1112 Sep 39

Telithromycin (HMR 3647) is a ketolide suitable for the treatment of respiratory infections. The aim of this study was to demonstrate its antibacterial efficacy against an erythromycin-susceptible Staphylococcus aureus, an erythromycin-resistant Streptococcus pneumoniae and Haemophilus influenzae. The free serum concentrations of telithromycin, produced by repeated oral administration of 800 mg to adults for 10 days, was simulated in an in vitro system. The ketolide displayed bacteriostatic activity against all three strains tested. This study supported the observation that an 800 mg po dose of telithromycin demonstrated antibacterial efficacy against respiratory tract pathogens.
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PMID:Antibacterial activity of telithromycin (HMR 3647) in relation to in vitro simulated human plasma kinetics. 1126 24

We compared the oral antibacterial activities of telithromycin (HMR 3647), a new ketolide drug, in different infections induced in mice by Staphylococcus aureus, Streptococcus pneumoniae, streptococci, enterococci, and Haemophilus influenzae with those of various macrolides and pristinamycin. Unlike all other comparators, telithromycin displayed a high therapeutic activity, particularly in septicemia induced by erythromycin A-resistant pathogens, where the ketolide was the only active compound, displaying effective doses between 3 and 26 mg/kg of body weight. Against H. influenzae, telithromycin was the most effective compound. Telithromycin displayed bacteriostatic behavior against S. pneumoniae and H. influenzae. The ketolide was also active against thigh muscle infection induced by S. aureus. The pharmacokinetic properties of telithromycin accounted for its outstanding well-balanced oral in vivo efficacy against both gram-positive cocci, whatever their phenotype of resistance, and H. influenzae.
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PMID:In vivo efficacy of the new ketolide telithromycin (HMR 3647) in murine infection models. 1135 12

Community-acquired respiratory tract infections (RTIs) are among the most prevalent infectious diseases in the developed world. They cause considerable morbidity, resulting in a major impact on public health both clinically and socioeconomically. The bacterial pathogens most commonly associated with community-acquired RTIs are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, with Streptococcus pyogenes predominating in pharyngitis. Over the past years, each of these pathogens has developed mechanisms to evade susceptibility to antibacterials, leading to an alarming global increase in antibacterial resistance among these pathogens. There is great concern that currently available antibacterials are insufficient to treat community-acquired RTIs and there is an urgent requirement for new agents with activity against all strains of common community-acquired RTI pathogens. Telithromycin (HMR 3647) belongs to a new family of antibacterials, the ketolides, and has been specifically designed for the treatment of community-acquired RTIs. This review covers the potent in vitro activity of telithromycin against the most common community-acquired RTI pathogens compared with other currently available antimicrobial agents.
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PMID:Activity of the ketolide antibacterial telithromycin against typical community-acquired respiratory pathogens. 1156 74

The age-related and T cell-independent immunological properties of most capsular polysaccharides limit their use as vaccines, especially in children under 2 years of age. To overcome these limitations, polysaccharide antigens have been successfully conjugated to a variety of carrier proteins, such as diphtheria toxoid or tetanus toxoid (TT) and the diphtheria mutant (CRM197) to produce very successful glycoconjugate vaccines. The increasing demand for new conjugate vaccines requires the availability of additional carriers providing high and long-lasting T helper cell immunity. Here we describe the design and construction of three recombinant carrier proteins (N6, N10, N19) constituted by strings of 6, 10 or 19 human CD4(+) T cell epitopes from various pathogen-derived antigens, including TT and proteins from Plasmodium falciparum, influenza virus and hepatitis B virus. Each of these epitopes is defined as universal in that it binds to many human MHC class II molecules. When conjugated to Haemophilus influenzae type b (Hib) oligosaccharide, these carriers elicit a potent anti-Hib antibody response in mice. In the case of the N19-Hib conjugate, this response is at least as good as that observed with CRM197-Hib, a conjugate vaccine currently used for mass immunization. We also show that some of the universal epitopes constituting the recombinant carriers are specifically recognized by two human in vitro systems, suggesting that T cell memory is provided by the selected epitopes. The data indicate that rationally designed recombinant polyepitope proteins represent excellent candidates for the development and clinical testing of new conjugate vaccines.
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PMID:Rationally designed strings of promiscuous CD4(+) T cell epitopes provide help to Haemophilus influenzae type b oligosaccharide: a model for new conjugate vaccines. 1174 3

Among adults, acute sinusitis, tonsillitis/pharyngitis, community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are the most commonly encountered respiratory tract infections (RTIs) in the community. Empiric antibacterial therapy is the most widely used approach for the treatment of such infections. The appropriate antibacterial requires consideration of a number of patient-, pathogen- and drug-related factors. One additional factor is the global spread of resistance among common respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, which limits the utility of existing antibacterials. Telithromycin (HMR 3647), the first of a new family of antibacterials, the ketolides, was designed specifically to provide optimal therapy for community-acquired RTIs. This agent, which has a broad spectrum of antibacterial activity against common respiratory pathogens (including resistant strains and atypical/intracellular organisms), has been clinically and bacteriologically evaluated against gold-standard comparators in a series of phase III clinical trials. The results of these studies demonstrate that telithromycin, at a dosage of 800 mg once daily, is an effective, well-tolerated agent for the treatment of the most commonly encountered community-acquired RTIs. Moreover, telithromycin meets the challenge of increasing antibacterial resistance. High rates of clinical cure and bacteriologic eradication were achieved, even in patients infected with problematic resistant pathogens such as penicillinG- and macrolide-resistant S. pneumoniae. In summary, telithromycin represents a promising new antibacterial for the treatment of community-acquired RTIs. With high efficacy and bacterial eradication rates, good tolerability and convenient once-daily administration, telithromycin therapy should result in increased patient compliance and improved outcomes, thereby minimizing the risk of developing antibacterial resistance.
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PMID:Clinical management of respiratory tract infections in the community: experience with telithromycin. 1178 52

OBJECTIVE: The pharmacodynamic properties of the novel ketolide (a new class of macrolide) antibiotic, HMR 3004, were investigated by studying time-kill kinetics and postantibiotic effect. METHODS: The time-kill kinetics were studied at two inocula against three strains each of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Bacteroides fragilis. The postantibiotic effects of HMR 3004 were also investigated on these organisms at concentrations equivalent to 1, 4 and 10 x MIC. RESULTS: The time kill-kinetic data demonstrated that HMR 3004 is inoculum dependent and predominantly bacteriostatic being only slowly bactericidal at higher concentrations. HMR 3004 exhibited a significant postantibiotic effect with all strains studied, ranging from 1.9--6.2 h at 10 x MIC. CONCLUSIONS: The bacteriostatic activity and significant postantibiotic effect demonstrated by HMR 3004 are similar to those previously obtained with other macrolides.
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PMID:Pharmacodynamic properties of HMR 3004, a novel ketolide, on respiratory pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time kill kinetics and postantibiotic effect. 1186 24

Aventis Pharma (formerly Hoechst Marion Roussel) is investigating the ketolides HMR-3562 and HMR-3787 as potential antibacterial agents. The compounds belong to a series of 2-fluoroketolides. They have exhibited potency against a range of gram-positive bacteria and other respiratory tract pathogens including Haemophilus influenzae in vitro and in vivo.
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PMID:HMR-3562. Aventis Pharma. 1189 31

The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhi, Yersinia pestis, Haemophilus influenzae, Pasteurella multocida, Actinobacillus actinomycetemcomitans, and Vibrio cholerae. The palindromic binding site of the purine repressor (consensus ACGCAAACGTTTGCGT) is fairly well retained of genes encoding enzymes that participate in the synthesis of inosinemonophosphate from phosphoribozylpyrophosphate and in transfer of unicarbon groups, and also upstream of some transport protein genes. These genes may be regarded as the main part of the purine regulon. In terms of physiology, the regulation of the purC and gcvTHP/folD genes seems to be especially important, because the PurR site was found upstream of nonorthologous but functionally replaceable genes. However, the PurR site is poorly retained in front of orthologs of some genes belonging to the E. coli purine regulon, such as genes involved in general nitrogen metabolism, biosynthesis of pyrimidines, and synthesis of AMP and GMP from IMP, and also upstream of the purine repressor gene. It is predicted that purine regulons of the examined bacteria include the following genes: upp participating in synthesis of pyrimidines; uraA encoding an uracil transporter gene; serA involved in serine biosynthesis; folD responsible for the conversion of N5,N10-methenyl tetrahydrofolate into N10-formyltetrahydrofolate; rpiA involved in ribose metabolism; and protein genes with an unknown function (yhhQ and ydiK). The PurR site was shown to have different structure in different genomes. Thus, the tendency for a decline of the conservatism of site positions 2 and 15 was observed in genomes of bacteria belonging to the Pasteurellaceae and Vibrionaceae groups.
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PMID:[Purine regulon of gamma-proteobacteria: a detailed description]. 1239 81


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