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D H Bouanchaud - One of the best experts on this subject based on the ideXlab platform.
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A review of the in-vitro activity of quinupristin/Dalfopristin against intracellular pathogens and mycoplasmas.
Journal of Antimicrobial Chemotherapy, 1997Co-Authors: C Bébéar, D H BouanchaudAbstract: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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in vitro and in vivo antibacterial activity of quinupristin Dalfopristin
Journal of Antimicrobial Chemotherapy, 1997Co-Authors: D H BouanchaudAbstract: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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In-vitro and in-vivo antibacterial activity of quinupristin/Dalfopristin.
The Journal of antimicrobial chemotherapy, 1997Co-Authors: D H BouanchaudAbstract: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.
Oleg Krut - One of the best experts on this subject based on the ideXlab platform.
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subinhibitory quinupristin Dalfopristin attenuates virulence of staphylococcus aureus
Journal of Antimicrobial Chemotherapy, 2006Co-Authors: Carmen Koszczol, Katussevani Bernardo, Martin Krönke, Oleg KrutAbstract:Objectives: The semi-synthetic streptogramin quinupristin/Dalfopristin antibiotic exerts potent bactericidal activity against Staphylococcus aureus. We investigated whether, like other bactericidal antibiotics used at subinhibitory concentrations, quinupristin/Dalfopristin enhances release of toxins by Grampositive cocci. Methods: The activity of quinupristin/Dalfopristin on exotoxin release by S. aureus was investigated by 2D SDS–PAGE combined with MALDI-TOF/MS analysis and by western blotting. Results: We show that quinupristin/Dalfopristin at subinhibitory concentrations reduces the release of S. aureus factors that induce tumour necrosis factor secretion in macrophages. Furthermore, quinupristin/Dalfopristin but not linezolid attenuated S. aureus-mediated killing of infected host cells. When added to S. aureus cultures at different stages of bacterial growth, quinupristin/Dalfopristin reduced in a dose-dependent manner the release of specific virulence factors (e.g. autolysin, protein A, aand b-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins remained unchanged. Conclusions: The results of the present study suggest that subinhibitory quinupristin/Dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S. aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.
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Subinhibitory quinupristin/Dalfopristin attenuates virulence of Staphylococcus aureus
The Journal of antimicrobial chemotherapy, 2006Co-Authors: Carmen Koszczol, Katussevani Bernardo, Martin Krönke, Oleg KrutAbstract:Objectives: The semi-synthetic streptogramin quinupristin/Dalfopristin antibiotic exerts potent bactericidal activity against Staphylococcus aureus. We investigated whether, like other bactericidal antibiotics used at subinhibitory concentrations, quinupristin/Dalfopristin enhances release of toxins by Grampositive cocci. Methods: The activity of quinupristin/Dalfopristin on exotoxin release by S. aureus was investigated by 2D SDS–PAGE combined with MALDI-TOF/MS analysis and by western blotting. Results: We show that quinupristin/Dalfopristin at subinhibitory concentrations reduces the release of S. aureus factors that induce tumour necrosis factor secretion in macrophages. Furthermore, quinupristin/Dalfopristin but not linezolid attenuated S. aureus-mediated killing of infected host cells. When added to S. aureus cultures at different stages of bacterial growth, quinupristin/Dalfopristin reduced in a dose-dependent manner the release of specific virulence factors (e.g. autolysin, protein A, aand b-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins remained unchanged. Conclusions: The results of the present study suggest that subinhibitory quinupristin/Dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S. aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.
M J Rybak - One of the best experts on this subject based on the ideXlab platform.
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in vitro bactericidal activity of quinupristin Dalfopristin alone and in combination against resistant strains of enterococcus species and staphylococcus aureus
Journal of Antimicrobial Chemotherapy, 1997Co-Authors: S L Kang, M J RybakAbstract:In-vitro activities of quinupristin/ Dalfopristin, a semisynthetic injectable streptogramin, and vancomycin were compared against multidrug-resistant Enterococcus faecium and Enterococcus faecalis, methicillin-su sceptible Staphylococcus aureus ATCC 25923 and a methicillin-resistant S. aureus (MRSA). Combinations of quinupristin/Dalfopristin and/or vancomycin with ofloxacin or gentamicin were evaluated using the chequerboard technique. The only synergy observed was that between quinupristin/Dalfopristin plus vancomycin and quinupristin/Dalfopristin plus gentamicin against E. faecium (FIC index <0.5). Time‐kill curves were performed over 24 h with an inoculum of 1 x 10 7 cfu/mL and clinically achievable concentrations of quinupristin/Dalfopristin, vancomycin, ofloxacin and gentamicin (6, 30, 5 and 5 mg/L, respectively). In time‐kill studies, combinations of quinupristin/Dalfopristin plus vancomycin and quinupristin/Dalfopristin plus gentamicin were additive, not synergic, against E. faecium and achieved 99.9% killing in 21.2 h and 19.6 h, respectively. None of the combination regimens suppressed the regrowth of E. faecalis . Quinupristin/d alfopristin combined with vancomycin demonstrated consistent synergy against ATCC 25923 and the MRSA, achieving 99.9% killing in 12.1 h and 11.9 h, respectively. Overall, quinupristin/Dalfopristin alone demonstrated inhibitory activity against E. faecium, but not against E. faecalis, and bactericidal activity was achieved only with quinupristin/Dalfopristin in combination with vancomycin or gentamicin against E. faecium . Quinupristin/d alfopristin plus vancomycin was the most potent and reliable combination against both strains of S. aureus in time‐kill studies.
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In-vitro bactericidal activity of quinupristin/Dalfopristin alone and in combination against resistant strains of Enterococcus species and Staphylococcus aureus
Journal of Antimicrobial Chemotherapy, 1997Co-Authors: S L Kang, M J RybakAbstract:In-vitro activities of quinupristin/ Dalfopristin, a semisynthetic injectable streptogramin, and vancomycin were compared against multidrug-resistant Enterococcus faecium and Enterococcus faecalis, methicillin-su sceptible Staphylococcus aureus ATCC 25923 and a methicillin-resistant S. aureus (MRSA). Combinations of quinupristin/Dalfopristin and/or vancomycin with ofloxacin or gentamicin were evaluated using the chequerboard technique. The only synergy observed was that between quinupristin/Dalfopristin plus vancomycin and quinupristin/Dalfopristin plus gentamicin against E. faecium (FIC index
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In-vitro bactericidal activity of quinupristin/Dalfopristin alone and in combination against resistant strains of Enterococcus species and Staphylococcus aureus.
The Journal of antimicrobial chemotherapy, 1997Co-Authors: S L Kang, M J RybakAbstract:In-vitro activities of quinupristin/Dalfopristin, a semisynthetic injectable streptogramin, and vancomycin were compared against multidrug-resistant Enterococcus faecium and Enterococcus faecalis, methicillin-susceptible Staphylococcus aureus ATCC 25923 and a methicillin-resistant S. aureus (MRSA). Combinations of quinupristin/Dalfopristin and/or vancomycin with ofloxacin or gentamicin were evaluated using the chequerboard technique. The only synergy observed was that between quinupristin/Dalfopristin plus vancomycin and quinupristin/Dalfopristin plus gentamicin against E. faecium (FIC index < 0.5). Time-kill curves were performed over 24 h with an inoculum of 1 x 10(7) cfu/mL and clinically achievable concentrations of quinupristin/Dalfopristin, vancomycin, ofloxacin and gentamicin (6, 30, 5 and 5 mg/L, respectively). In time-kill studies, combinations of quinupristin/Dalfopristin plus vancomycin and quinupristin/Dalfopristin plus gentamicin were additive, not synergic, against E. faecium and achieved 99.9% killing in 21.2 h and 19.6 h, respectively. None of the combination regimens suppressed the regrowth of E. faecalis. Quinupristin/Dalfopristin combined with vancomycin demonstrated consistent synergy against ATCC 25923 and the MRSA, achieving 99.9% killing in 12.1 h and 11.9 h, respectively. Overall, quinupristin/Dalfopristin alone demonstrated inhibitory activity against E. faecium, but not against E. faecalis, and bactericidal activity was achieved only with quinupristin/Dalfopristin in combination with vancomycin or gentamicin against E. faecium. Quinupristin/Dalfopristin plus vancomycin was the most potent and reliable combination against both strains of S. aureus in time-kill studies.
Marcus J Zervos - One of the best experts on this subject based on the ideXlab platform.
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treatment of hospitalized patients with complicated gram positive skin and skin structure infections two randomized multicentre studies of quinupristin Dalfopristin versus cefazolin oxacillin or vancomycin
Journal of Antimicrobial Chemotherapy, 1999Co-Authors: Ronald Lee Nichols, Marcus J Zervos, Donald R Graham, Steven L Barriere, Anthony Rodgers, Samuel E Wilson, David L Dunn, Bruce KreterAbstract:Quinupristin/Dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/Dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/Dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/Dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/Dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/Dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/Dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/Dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/Dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/Dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/Dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/Dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ Dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus.
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treatment of vancomycin resistant enterococcus faecium with rp 59500 quinupristin Dalfopristin administered by intermittent or continuous infusion alone or in combination with doxycycline in an in vitro pharmacodynamic infection model with simulated
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Jeffrey R Aeschlimann, Marcus J Zervos, Michael J RybakAbstract:Quinupristin-Dalfopristin is a streptogramin antibiotic combination with activity against vancomycin-resistant Enterococcus faecium (VREF), but emergence of resistance has been recently reported. We studied the activity of quinupristin-Dalfopristin against two clinical strains of VREF (12311 and 12366) in an in vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to determine the potential for resistance selection and possible strategies for prevention. Baseline MICs/minimal bactericidal concentrations (microg/ml) for quinupristin-Dalfopristin, quinupristin, Dalfopristin, and doxycycline were 0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128, and 0.25/16 for VREF 12366, respectively. Quinupristin-Dalfopristin regimens had significantly less activity against VREF 12366 than VREF 12311. An 8-microg/ml simulated continuous infusion was the only bactericidal regimen with time to 99.9% killing = 90 hours. The combination of quinupristin-Dalfopristin every 8 h with doxycycline resulted in more killing compared to either drug alone. Quinupristin-Dalfopristin-resistant mutants (MICs, 4 microg/ml; resistance proportion, approximately 4 x 10(-4)) emerged during the quinupristin-Dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF 12311 and stable in VREF 12366. The 8-microg/ml continuous infusion or addition of doxycycline to quinupristin-Dalfopristin prevented the emergence of resistance for both strains over the 96-h test period. These findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance. The combination of quinupristin-Dalfopristin with doxycycline and the administration of quinupristin-Dalfopristin as a high-dose continuous infusion warrant further study to determine their potential clinical utility.
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comparative in vitro activity of quinupristin Dalfopristin against multidrug resistant enterococcus faecium
Diagnostic Microbiology and Infectious Disease, 1996Co-Authors: Hector F. Bonilla, Marcus J Zervos, Mary Beth Perri, Carol A. KauffmanAbstract:The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/Dalfopristin with a MIC 90% of 0.5 μg/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/Dalfopristin alone and quinupristin/Dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/Dalfopristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/Dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.
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Comparative in vitro activity of quinupristin/Dalfopristin against multidrug resistant Enterococcus faecium
Diagnostic microbiology and infectious disease, 1996Co-Authors: Hector F. Bonilla, Mary Beth Perri, Carol A. Kauffman, Marcus J ZervosAbstract:The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/Dalfopristin with a MIC 90% of 0.5 μg/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/Dalfopristin alone and quinupristin/Dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/Dalfopristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/Dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.
David M. Livermore - One of the best experts on this subject based on the ideXlab platform.
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Susceptibility to quinupristin/Dalfopristin and other antibiotics of vancomycin-resistant enterococci from the UK, 1997 to mid-1999
Journal of Antimicrobial Chemotherapy, 2000Co-Authors: Alan P. Johnson, Gill Hallas, Marina Warner, David M. LivermoreAbstract:: Susceptibility to quinupristin/Dalfopristin and other antibiotics was studied for clinical isolates of vancomycin-resistant enterococci (VRE) referred by UK hospitals between January 1997 and June 1999. Single isolates of VRE from 858 patients in 136 hospitals were received, of which 76% were Enterococcus faecium and 21% were Enterococcus faecalis, the remainder comprising minor species. Most isolates were multi-resistant. After allowing for the effect of blood, which raised the MICs of quinupristin/Dalfopristin four-fold, 98.3% of E. faecalis isolates and all the Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum appeared resistant to quinupristin/Dalfopristin, whereas 98.8% of the E. faecium isolates and the single Enterococcus raffinosus isolate were susceptible.
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Susceptibility to quinupristin/Dalfopristin and other antibiotics of vancomycin-resistant enterococci from the UK, 1997 to mid-1999
Journal of Antimicrobial Chemotherapy, 2000Co-Authors: Alan P. Johnson, Gill Hallas, Marina Warner, David M. LivermoreAbstract:: Susceptibility to quinupristin/Dalfopristin and other antibiotics was studied for clinical isolates of vancomycin-resistant enterococci (VRE) referred by UK hospitals between January 1997 and June 1999. Single isolates of VRE from 858 patients in 136 hospitals were received, of which 76% were Enterococcus faecium and 21% were Enterococcus faecalis, the remainder comprising minor species. Most isolates were multi-resistant. After allowing for the effect of blood, which raised the MICs of quinupristin/Dalfopristin four-fold, 98.3% of E. faecalis isolates and all the Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum appeared resistant to quinupristin/Dalfopristin, whereas 98.8% of the E. faecium isolates and the single Enterococcus raffinosus isolate were susceptible.
