Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 water-soluble streptogramin antimicrobial agent comprising quinupristin and dalfopristin in a ratio of 30:70. The in-vitro spectrum of activity includes most multi-resistant Gram-positive aerobes, important Gram-negative aerobes, Gram-positive anaerobes and intracellular bacteria that are causal agents of respiratory, blood and cutaneous infections. Of particular note, quinupristin/dalfopristin is active against multidrug-resistant isolates of Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium, and against penicillin-resistant and/or erythromycin-resistant Streptococcus pneumoniae. The combination is also active against staphylococci showing both constitutive and inducible erythromycin resistance. Bactericidal activity and a prolonged post-antibiotic effect have also been noted for quinupristin/dalfopristin against Gram-positive cocci. Gram-negative bacteria susceptible to quinupristin/dalfopristin include Moraxella catarrhalis, Legionella spp. and Mycoplasma spp. Overall, the spectrum of antibacterial activity indicates a potential role for this combination in the treatment of difficult-to-treat Gram-positive infections, including those caused by multidrug-resistant organisms. Since this activity extends to Gram-negative respiratory bacteria, quinupristin/dalfopristin may also find a role in the treatment of atypical, as well as typical, pneumonia.
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PMID:In-vitro and in-vivo antibacterial activity of quinupristin/dalfopristin. 951 Oct 57

Quinupristin/dalfopristin displays in-vitro bacteriostatic activity against all Legionella spp. (MICs = 0.06-2 mg/L), with Legionella pneumophila usually being at least two-fold more sensitive to quinupristin/dalfopristin than Legionella bozemanii, Legionella dumoffii, Legionella gormanii and Legionella micdadei (MIC = 0.06-2 vs 1-2 mg/L, respectively). Against Legionella spp., quinupristin/dalfopristin was at least as active as erythromycin. Quinupristin/dalfopristin was active in vitro against all Mycoplasma spp. tested (MIC = 0.05-2 mg/L), with Mycoplasma hominis being less susceptible than other species. Quinupristin/dalfopristin was active against erythromycin-resistant strains of Mycoplasma fermentans and M. hominis (MIC90 = 0.5 and 2 mg/L, respectively), and doxycycline-resistant strains of Ureaplasma urealyticum (MIC90 = 1 mg/L). The in-vitro bacteriostatic activity against Mycoplasma pneumoniae and Mycoplasma genitalium (MIC90 = 0.1 and 0.05 mg/L, respectively) was similar to that of erythromycin and doxycycline. Quinupristin/dalfopristin was actively taken up by murine macrophages, and incubation of the drug (2.5 mg/L) with macrophages containing ingested Staphylococcus aureus resulted in the death of 70% of intracellular bacteria within 120 min. Intracellular concentrations of quinupristin/dalfopristin reached 50 and 30 times the extracellular concentration, respectively, showing that these compounds readily penetrate into cells. The intracellular activity of quinupristin/dalfopristin may make it suitable for use in some, presently difficult-to-treat, infections caused by intracellular organisms.
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PMID:A review of the in-vitro activity of quinupristin/dalfopristin against intracellular pathogens and mycoplasmas. 951 Oct 64

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

The activities of quinupristin/dalfopristin (Synercid), erythromycin and azithromycin against 22 Legionella spp. isolates were measured by a microbroth dilution method. The MICs that inhibited 90% of strains tested were 0.5, 0.35, and 0.5 microg/mL for quinupristin/dalfopristin, erythromycin, and azithromycin, respectively. Quinupristin/dalfopristin was only partially active against intracellular L. pneumophila at high (2 microg/mL), but not low (1 microg/mL) concentration. Activity of the drug in a guinea pig model of Legionnaires' disease could not be accurately determined because of drug toxicity for the guinea pig, although there was evidence that the drug has in vivo activity.
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PMID:In vitro activity of quinupristin/dalfopristin (Synercid, RP 59500) against Legionella spp. 1074 67