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)

Most Gram-positive organisms are highly susceptible to the streptogramin, quinupristin/dalfopristin (RP 59500; Synercid). Minimum inhibitory concentrations for 90% of isolates (MIC90) were < or = 1 mg/L for Staphylococcus aureus, S. epidermidis, S. haemolyticus, Streptococcus pneumoniae, S. pyogenes and Listeria monocytogenes. Importantly, quinupristin/dalfopristin shows similar activity against methicillin-susceptible and -resistant strains of S. aureus, and streptococci with benzylpenicillin (penicillin G)- or erythromycin-acquired resistance. Enterococci have varying susceptibility to quinupristin /dalfopristin, although most isolates tested are susceptible to the drug, including vancomycin-resistant and multiresistant Enterococcus faecium. E. faecalis are generally the least susceptible. Among the Gram-negative respiratory pathogens Moraxella catarrhalis is susceptible and Haemophilus influenzae is moderately susceptible to quinupristin/ dalfopristin; however, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. are resistant. The drug is active against anaerobic organisms tested, including Clostridium perfringens, Lactobacillus spp., Bacteroides fragilis and Peptostreptococcus. Synergy has been demonstrated in vancomycin-resistant and multiresistant E. faecium, and methicillin-sensitive and -resistant S. aureus with the combination of vancomycin and quinupristin/ dalfopristin. Quinupristin/dalfopristin shows antibacterial activity in vivo in animal models of infection, including methicillin-sensitive and -resistant S. aureus infection in rabbits, S. aureus and S. pneumoniae in mice, and erythromycin-sensitive and -resistant viridans group streptococci infections in rats. The drug is rapidly bactericidal against Gram-positive organisms (with the exception of enterococci) at concentrations similar to or within 4-fold of the MIC, and it has a long postantibiotic effect both in vitro and in vivo.
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PMID:Antibacterial activity of quinupristin/dalfopristin. Rationale for clinical use. 872 14

Quinupristin/dalfopristin (RP 59500, Synercid) is a parenteral streptogramin combination antimicrobial that possesses a synergistic and often bactericidal action against many Grampositive species. In this study, a collection of 1270 uncommonly isolated or tested strains were evaluated for susceptibility to quinupristin/dalfopristin using agar dilution minimum inhibitory concentration (MIC) methods described in the National Committe for Clinical Laboratory Standards. The greatest antimicrobial activity observed for quinupristin/dalfopristin was against staphylococci, streptococci, the pathogenic neisseria, Legionella spp., Lactobacillus spp., and Peptostreptococcus spp. (MIC90 range, 0.5-2 micrograms/ml). Marginal activity (MIC90s, 4 to 8 micrograms/ml) was identified for the rarer enterococci, Leuconostoc spp., Pediococcus spp., and Streptococcus bovis. Against Haemophilus parainfluenzae, Bacteroides thetaiotaomicron, Fusobacterium spp., and Prevotella spp., the streptogramin was inactive. Although no susceptible breakpoint has been approved for quinupristin/dalfopristin, three possible breakpoints (< or = 1, < or = 2, or < or = 4 micrograms/mL) were evaluated. Acceptance of the lower breakpoints (< or = 1 or < or = 2 micrograms/mL) would limit quinupristin/dalfopristin use to staphylococci, streptococci, gonococci, meningococci, and Legionella spp. These results markedly expand the understanding of the usable spectrum of quinupristin/dalfopristin.
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PMID:In vitro activity of quinupristin/dalfopristin (RP 59500) against a large collection of infrequently isolated or tested species. 890 12

Quinupristin/dalfopristin is a new streptogramin combination that occurs at a natural ratio and formulation of 30:70. Rapid metabolism of the dalfopristin component to RP 12536 in vivo puts in question the validity of in vitro test of spectrum with the parent combination. In studies of quinupristin with both dalfopristin and RP 12536, a wide range of ratios (30:70, 50:50, 70:30) were tested by reference MIC and MBC tests. No significant potency differences were observed between combination ratios or metabolic components when testing 256 bacterial strains. Quinupristin/dalfopristin or quinupristin/RP 12536 remained active, by bactericidal action against many staphylococci and Streptococcus ssp. Enterococcus faecium strains were susceptible (MIC90, 2 micrograms/ml; static effect only) to the streptogramin, but E. faecalis, Pasteurella multocida, Pediococcus ssp., Haemophilus influenzae, and Bacteroides fragilis were generally less susceptible (MIC90, > or = 8 micrograms/ml). The log phase inoculum was preferred for MBC and kill-curve tests with this combination. The 30:70 ratio in vitro susceptibility test of quinupristin/dalfopristin as used to date, seems to predict the potency and spectrum of this streptogramin accurately and all clinically important in vivo ratios of the injectable form or its major metabolites. Quinupristin/dalfopristin should be further investigated for clinical use against emerging resistant Gram-positive infections, especially penicillin-resistant streptococci and glycopeptide-resistant E. faecium that exhibit susceptibility in this investigation.
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PMID:Antimicrobial characteristics of quinupristin/dalfopristin (Synercid at 30:70 ratio) compared to alternative ratios for in vitro testing. 915 9

Quinupristin/dalfopristin is an injectable streptogramin antibiotic that is constituted in a 30:70 (w/w) ratio of the two components. Quinupristin and dalfopristin are thought to act synergically by binding to two separate sites on the bacterial 50S ribosomal subunit. The in-vitro activities of the two components separately and together in different ratios were determined for a collection of 100 Haemophilus influenzae strains representing various antimicrobial resistance phenotypes. The NCCLS microdilution susceptibility testing procedure incorporating Haemophilus test medium (HTM) broth was used to determine MICs of quinupristin, dalfopristin and seven other antimicrobial agents. The MIC50 and MIC90 values were 4 and 8, 4 and 16, and 64 and 128 mg/L for quinupristin/dalfopristin (30:70), dalfopristin and quinupristin, respectively. MICs of quinupristin and dalfopristin were also determined in Mueller-Hinton lysed horse blood broth and by HTM agar dilution testing. Compared with HTM broth-derived results, the MICs of quinupristin/dalfopristin and its components were the same or one dilution higher in lysed horse blood and HTM agar incubated in air, and were equivalent or one dilution lower in HTM agar incubated in a CO2 atmosphere. The MICs of quinupristin and dalfopristin separately or together were directly proportional to erythromycin MICs, but were otherwise unaffected by any of the resistance mechanisms represented in these strains. MICs of quinupristin and dalfopristin combined in ratios of 10:90, 70:30 and 90:10 did not differ significantly from those of the 30:70 ratio. Thus, unlike the synergic activity noted against Gram-positive bacteria, the activity of quinupristin/dalfopristin against H. influenzae appears to be due almost entirely to the dalfopristin component of the combination.
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PMID:Activity of quinupristin/dalfopristin and its components against Haemophilus influenzae. 951 Oct 67

Quinupristin/dalfopristin and RPR 106972 were active in vitro against a wide range of aerobic Gram-positive organisms including Enterococcus faecium. However, most isolates of Enterococcus faecalis were resistant or of intermediate sensitivity. Against Staphylococcus aureus quinupristin/dalfopristin was more active but for all other species the range of activity of the two drugs was the same or RPR 106972 was more active. RPR 106972 was also more active against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis. Quinupristin/dalfopristin MICs for isolates of H. influenzae (1-8 mg/L) clustered around the breakpoint. There were differences in the quality of growth, but little difference in MICs or zone diameters was obtained on three different media: Mueller-Hinton (MHA), Iso-Sensitest (ISA), and Diagnostic Sensitivity Test (DST) agars. The addition of blood to the medium increased MICs 2- to 4-fold, with MHA showing the greatest increase, and reduced zone diameters around quinupristin/dalfopristin discs by 3-4 mm, with the greatest effect on ISA.
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PMID:Comparative activity of quinupristin/dalfopristin and RPR 106972 and the effect of medium on in-vitro test results. 1005 93

The streptogramins are a class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally, but the therapeutic use of the natural compounds is limited because they do not dissolve in water. New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria. The streptogramins consist of two structurally unrelated compounds, group A and group B. The group A compounds are polyunsaturated macrolactones: the group B compounds are cyclic hexadepsipeptides. Modifications of the group B components have been mainly performed on the 3-hydroxypicolinoyl, the 4-dimethylaminophenylalanine and the 4-oxo pipecolinic residues. Semi-synthesis on this third residue led to the water-soluble derivative quinupristin. Water-soluble group A derivatives were obtained by Michael addition of aminothiols to the dehydroproline ring of pristinamycin IIA. Followed by oxidation of the intermediate sulfide into the sulfone derivatives (i.e., dalfopristin). Water-soluble derivatives (both group A and group B) can now be obtained at the industrial scale. Modified group B compounds are now also being produced by mutasynthesis, via disruption of the papA gene. Mutasynthesis has proved particularly useful for producing PIB, the group B component of the oral streptogramin RPR 106972. The streptogramins inhibit bacterial growth by disrupting the translation of mRNA into protein. Both the group A and group B compounds bind to the peptidyltransferase domain of the bacterial ribosome. The group A compounds interfere with the elongation of the polypeptide chain by preventing the binding of aa-tRNA to the ribosome and the formation of peptide bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and may also interfere with the release of the completed polypeptide by blocking its access to the channel through which it normally leaves the ribosome. The synergy between the group A and group B compounds appears to result from an enhanced affinity of the group B compounds for the ribosome. Apparently, the group A compound induces a conformational change such that B compound binds with greater affinity. The natural streptogramins are produced as mixtures of the group A and B compounds, the combination of which is a more potent antibacterial agent than either type of compound alone. Whereas the type A or type B compound alone has, in vitro and in animal models of infection, a moderate bacteriostatic activity, the combination of the two has strong bacteriostatic activity and often bactericidal activity. Minimal inhibitory concentrations of quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae, from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus faecium, the principal target organisms of this drug. Quinupristin/dalfopristin also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus influenz, Legionella spp. and Moraxella catarrhalis. Bacteria develop resistance to the streptogramms by ribosomal modification, by producing inactivating enzymes, or by causing an efflux of the antibiotic. Dimethylation of an adenine residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm gene class, affects the binding of group B compounds (as well as the macrolides and lincosamides; hence, MLSB resistance), but group A and B compounds usually maintain their synergy and their bactericidal effect against MLSB-resistant strains. erm genes are widespread both geographically and throughout numerous bacterial genera. Several types of enzymes (acetyltransferases, hydrolases) have been identified that inactivate the group A or the group B compounds. Genes involved in streptogramin efflux have so far been found only in staphylococci, particularly in coagulase-negative species
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PMID:Recent developments in streptogramin research. 1019 38

OBJECTIVE: To evaluate the activity of quinupristin/dalfopristin, a new injectable streptogramin, against 732 clinical strains recently isolated in Italy. METHODS: Susceptibility tests were performed according to NCCLS-guided MIC methodology. Pathogens included in the evaluation included 108 Staphylococcus aureus isolates, 124 coagulase-negative staphylococcal isolates, 158 Streptococcus pyogenes isolates, 30 Streptococcus agalactiae isolates, 30 b-hemolytic streptococcal isolates, 18 Streptococcus sanguis isolates, 80 Streptococcus pneumoniae isolates, 69 Enterococcal isolates, 40 Haemophilus influenzae isolates, 30 Moraxella catarrhalis isolates and, finally, 30 Gram-positive and 25 Gram-negative anaerobes. RESULTS: Quinupristin/dalfopristin inhibited Staphylococcus aureus and other Staphylococcus spp., irrespective of their oxacillin or erythromycin resistance phenotypes. Similarly, streptococci were fully inhibited by quinupristin/dalfopristin. Enterococcus faecalis was not included in the spectrum of this streptogramin, while isolates of Enterococcus faecium were inhibited by the new compound. Respiratory pathogens such as H. influenzae and M. catarrhalis were inhibited by quinupristin/dalfopristin as well as all Gram-negative anaerobes tested. CONCLUSIONS: These findings suggest a putative role for quinupristin/dalfopristin in the empirical treatment of severe nosocomial and community-acquired infections caused by pathogens often displaying resistance to multiple antibiotics. This drug may provide an alternative to glycopeptide compounds.
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PMID:In vitro activity of quinupristin/dalfopristin against selected bacterial pathogens isolated in Italy. 1185 92