Dalbavancin

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 747 Experts worldwide ranked by ideXlab platform

Helio S Sader - One of the best experts on this subject based on the ideXlab platform.

  • antimicrobial activity of Dalbavancin against clinical isolates of coagulase negative staphylococci from the usa and europe stratified by species
    Journal of global antimicrobial resistance, 2021
    Co-Authors: Helio S Sader, Jennifer M Streit, Cecilia G Carvalhaes, S Ryan J Arends, Rodrigo E Mendes
    Abstract:

    Abstract Objectives To evaluate the in vitro activity of Dalbavancin compared with vancomycin, daptomycin and other agents against a large collection of coagulase-negative staphylococci (CoNS) isolates. Methods A total of 5088 CoNS causing clinically significant infection were consecutively collected from 122 medical centres in the USA and Europe over 6 years (2014–2019). Isolates were tested for susceptibility by the reference broth microdilution method. Species identification was confirmed by MALDI-TOF. Most isolates were from bloodstream infections (BSIs) (53.5%) or skin/skin structure infections (28.5%). Results Staphylococcus epidermidis was the most common species overall (54.6%) and for BSI (61.3%). The second most common species were Staphylococcus lugdunensis overall (12.3%) and Staphylococcus hominis for BSI (14.7%). Dalbavancin (MIC50/90, 0.03/0.06 mg/L) inhibited >99.9% of CoNS isolates at ≤0.25 mg/L (susceptible breakpoint for Staphylococcus aureus per CLSI). All species were inhibited at ≤0.25 mg/L Dalbavancin, except some S. epidermidis (>99.9%) and Staphylococcus warneri (98.9%) isolates. Staphylococcus capitis and Staphylococcus simulans exhibited the lowest Dalbavancin MIC50/90 values (0.015/0.03 mg/L) and Staphylococcus haemolyticus and Staphylococcus saprophyticus the highest (MIC50/90, 0.06/0.12 mg/L); 47.8% of S. epidermidis and 34.7% of S. haemolyticus exhibited decreased susceptibility to vancomycin (MIC ≥ 2 mg/L) and 23.2% of S. capitis and 28.4% of S. warneri showed decreased susceptibility to daptomycin (MIC ≥ 1 mg/L). Conclusion Antimicrobial susceptibility varied widely among CoNS species. Dalbavancin inhibited >99.9% and 99.1% of isolates at the US-FDA and EUCAST breakpoints, respectively. Clinical studies of Dalbavancin for treatment of CoNS infections should be considered based on these in vitro data.

  • antimicrobial activity of Dalbavancin tested against gram positive organisms isolated from patients with infective endocarditis in us and european medical centres
    Journal of Antimicrobial Chemotherapy, 2019
    Co-Authors: Helio S Sader, Rodrigo E Mendes, Michael A Pfaller, Robert K Flamm
    Abstract:

    Background The management of endocarditis requires aggressive and prolonged antimicrobial treatment. We evaluated the in vitro activity of Dalbavancin against bacteria from patients with infective endocarditis. Methods A total of 626 Gram-positive organisms were collected from patients with a diagnosis of bacterial endocarditis in the USA (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility to Dalbavancin and comparators by broth microdilution. Results The most common organisms were Staphylococcus aureus (48.4%), Enterococcus faecalis (19.6%) and viridans group streptococci (VGS; 12.5%). Dalbavancin and daptomycin showed complete activity (100.0% susceptibility per CLSI criteria) against S. aureus, but Dalbavancin MIC values were 4- to 8-fold lower. Vancomycin, linezolid and teicoplanin were also active against all S. aureus when CLSI criteria were applied. Ceftaroline was active against all MSSA (MIC90 0.25 mg/L) and 78.4% of MRSA isolates at ≤1 mg/L. All E. faecalis isolates were susceptible to ampicillin, daptomycin and linezolid, whereas 97.6% of isolates were susceptible to Dalbavancin (MIC90 0.06 mg/L) and 96.7% were susceptible to vancomycin (MIC90 2 mg/L). All VGS and CoNS isolates were susceptible to Dalbavancin, daptomycin, vancomycin and linezolid. Against Enterococcus faecium, 65.7% of isolates were inhibited by ≤0.25 mg/L Dalbavancin and 62.9% were vancomycin susceptible. Conclusions Dalbavancin exhibited potent in vitro activity against a large collection of Gram-positive isolates recovered from patients with endocarditis in US and European medical centres. These results support further investigations to determine the role of Dalbavancin in the treatment of infective endocarditis.

  • activity of Dalbavancin and comparator agents against gram positive cocci from clinical infections in the usa and europe 2015 16
    Journal of Antimicrobial Chemotherapy, 2018
    Co-Authors: Michael A Pfaller, Rodrigo E Mendes, Robert K Flamm, Leonard R Duncan, Helio S Sader
    Abstract:

    Background Many infections due to Gram-positive cocci (GPC; staphylococci, streptococci and enterococci) regularly involve prolonged systemic antibiotic use. Dalbavancin has demonstrated activity against GPC isolates and has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Objectives To evaluate the activity of Dalbavancin against GPC isolated from a variety of infection types in the USA and Europe. Methods A total of 14 319 Staphylococcus aureus, 1992 CoNS, 3269 β-haemolytic streptococci (BHS), 2071 Enterococcus faecalis, 936 Enterococcus faecium, 71 Enterococcus gallinarum/casseliflavus and other Enterococcus spp., 3487 Streptococcus pneumoniae and 1063 viridans group streptococci (VGS) causing clinical infections were consecutively collected (2015-16) and tested for susceptibility by broth microdilution methods. Results All S. aureus (36.4% MRSA) isolates were susceptible to Dalbavancin, teicoplanin and vancomycin, while daptomycin and linezolid showed susceptibility rates of >99.9% (according to CLSI criteria). Dalbavancin MIC results were at least 16-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS [62.2%/59.6% methicillin-resistant (CLSI/EUCAST)], followed by daptomycin, linezolid and vancomycin. All vancomycin-susceptible E. faecalis isolates were inhibited by Dalbavancin at ≤0.25 mg/L (FDA susceptible breakpoint). Dalbavancin was very active against BHS (MIC90 0.03 mg/L) and the most active agent against S. pneumoniae and VGS (highest MIC 0.25 mg/L). Ceftriaxone, daptomycin, levofloxacin and vancomycin were also active (93.5%-100.0% susceptible) against VGS, whereas clindamycin, erythromycin, penicillin and tetracycline had lower activity. Conclusions Dalbavancin appears to be a viable candidate for treating serious infections caused by GPC.

  • activity of Dalbavancin tested against gram positive clinical isolates causing skin and skin structure infections in paediatric patients from us hospitals 2014 2015
    Journal of global antimicrobial resistance, 2017
    Co-Authors: Michael A Pfaller, Helio S Sader, Rodrigo E Mendes, Mariana Castanheira, Robert K Flamm
    Abstract:

    Abstract Objectives This study provides an in vitro analysis of Dalbavancin activity against isolates causing skin and skin-structure infections (SSSIs) in children. Methods A total of 770 Staphylococcus aureus, 167 β-haemolytic streptococci (BHS), 42 coagulase-negative staphylococci (CoNS), 25 Enterococcus faecalis and 13 viridans group streptococci (VGS) were collected from children ( Results Dalbavancin had MIC50/90 values of 0.03/0.06 μg/mL against S. aureus and CoNS, including methicillin-resistant (MRSA) and -susceptible (MSSA) isolates. Dalbavancin MICs were 8–32-fold lower than those of daptomycin (MIC50/90, 0.25/0.5 μg/mL), vancomycin (MIC50/90, 0.5/1 μg/mL) and linezolid (MIC50/90, 1/1 μg/mL) against MRSA. These agents showed 100.0% susceptibility against MRSA, and clindamycin also had a high (92.7%) susceptibility rate. Dalbavancin (MIC50/90, 0.03/0.06 μg/mL) and daptomycin (MIC50/90, 0.25/0.5 μg/mL) were the most active agents against CoNS. When tested against E. faecalis, Dalbavancin was up to 32-fold more active than ampicillin (MIC50/90, ≤0.5/1 μg/mL), daptomycin (MIC50/90, 1/1 μg/mL), linezolid (MIC50/90, 1/2 μg/mL) and vancomycin (MIC50/90, 1/2 μg/mL). Dalbavancin (MIC50/90, 0.008/0.03 μg/mL), ceftriaxone (MIC50/90, ≤0.06/ ≤ 0.06 μg/mL) and penicillin (MIC50/90, ≤0.06/ ≤ 0.06 μg/mL) were the most active against BHS. VGS isolates were susceptible to Dalbavancin (MIC100, 0.03 μg/mL), with MICs 32–64-fold lower than daptomycin (MIC50/90, 0.5/0.5 μg/mL), linezolid (MIC50/90, 0.5/1 μg/mL) and vancomycin (MIC50/90, 0.5/0.5 μg/mL). Conclusions Approved agents available for the treatment of SSSI in children are limited. Dalbavancin demonstrated potent in vitro activity against isolates causing SSSI in children. Developing Dalbavancin for SSSI treatment in children is warranted, provided safety and tolerability are satisfactory.

  • Dalbavancin in vitro activity obtained against gram positive clinical isolates causing bone and joint infections in us and european hospitals 2011 2016
    International Journal of Antimicrobial Agents, 2017
    Co-Authors: Michael A Pfaller, Helio S Sader, Robert K Flamm, Mariana Castanheira, Rodrigo E Mendes
    Abstract:

    Abstract Background Osteomyelitis is a difficult-to-treat infection that regularly involves prolonged use of systemic antibiotics. Dalbavancin has demonstrated activity against Gram-positive isolates, and has been considered as a candidate for the treatment of osteomyelitis in adults and children. This study evaluated the activity of Dalbavancin against pathogens isolated from bone and joint infections (BJI). Methods Eight hundred and one Staphylococcus aureus, 160 coagulase-negative staphylococci (CoNS), 164 β-haemolytic streptococci (BHS), 82 Enterococcus faecalis and 45 viridans group streptococci (VGS) causing BJI were collected consecutively (2011–2016) and tested for susceptibility by broth microdilution methods. Results S. aureus (64.0%) was the most common pathogen associated with BJI, followed by BHS (13.1%) and CoNS (12.8%). All S. aureus (33.3% meticillin-resistant) isolates were susceptible to Dalbavancin, linezolid and vancomycin, while daptomycin and clindamycin showed susceptibility rates of 99.5% and 89.0%, respectively. The minimum inhibitory concentration (MIC) results for Dalbavancin were at least eight-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS (63.1% meticillin-resistant), followed by daptomycin, linezolid and vancomycin. All E. faecalis isolates were inhibited by Dalbavancin at ≤0.25 mg/L (US Food and Drug Administration susceptibility breakpoint), except for three vancomycin-resistant isolates. High susceptibility rates for ampicillin (98.8%), daptomycin (100.0%), linezolid (100.0%) and vancomycin (95.1%) were obtained against E. faecalis. Dalbavancin was very active against BHS (MIC90 ≤0.03 µg/mL), and was the most active agent against VGS (highest MIC ≤0.06 mg/L). Ceftriaxone, daptomycin and vancomycin were also active (93.3–100.0% susceptible) against VGS, whereas clindamycin (84.4% susceptible) had marginal activity. Conclusion Dalbavancin appears to be a viable candidate for treating BJI/osteomyelitis caused by Gram-positive cocci.

James A. Dowell - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetics of Dalbavancin in plasma and skin blister fluid
    2015
    Co-Authors: David P. Nicolau, Elyse Seltzer, Mary Buckwalter, Heather K. Sun, James A. Dowell
    Abstract:

    Objectives: Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of com-plicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of Dalbavancin into skin blister fluid. Methods: Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of Dalbavancin at a dose of 1000 mg. Skin blisters were induced by application of cantharidin ointment. Plasma and blister fluid samples were collected over 7 days post-dose, and concentrations of Dalbavancin were assessed by a validated LC/MS/MS assay. Pharmacokinetics were determined by non-compartmental methods, and drug penetration was assessed based on the ratio of area under the curve (AUC) in the blister fluid versus plasma for each subject. Results: The mean (SD) peak concentration of Dalbavancin in plasma and blister fluid was 285 (31.1) and 67.3 (18.2) mg/L, respectively; the corresponding AUCDay 7 values were 10 806 (1926) and 6438 (1238) mg.h/L, respectively. The mean (SD) penetration of Dalbavancin into blister fluid was 59.6% (6.3%). By Day 7, the mean concentration of Dalbavancin in plasma and blister fluid was 46.5 and 30.3 mg/L, respectively. Conclusions: Dalbavancin concentrations in blister fluid remained well above the MIC90 values for pathogens commonly implicated in cSSSIs such as Staphylococcus aureus, including methicillin-resistant S. aureus (MIC905 0.06 mg/L) and b-haemolytic streptococci (MIC905 0.03 mg/L) through Day 7. These pharmacokinetic data support the use of Dalbavancin in the treatment of cSSSIs caused by susceptible Gram-positive pathogens

  • pharmacokinetics of Dalbavancin in patients with renal or hepatic impairment
    The Journal of Clinical Pharmacology, 2009
    Co-Authors: Thomas Marbury, Elyse Seltzer, James A. Dowell, Mary Buckwalter
    Abstract:

    Three open-label studies assessed the safety, tolerability, and pharmacokinetics of intravenous Dalbavancin in patients with hepatic or renal impairment, including patients with end-stage renal disease (ESRD) receiving dialysis. In each study, 4 to 10 patients with mild, moderate, or severe impairment and age-, sex-, and weight-matched controls were administered either a single dose (500 or 1000 mg) or 2 doses (1000 mg followed by 500 mg 1 week apart) of Dalbavancin. Dalbavancin exposures were not increased due to mild renal impairment. The mean area under the concentration-time curve from time 0 to infinity (AUC0-infinity) values were approximately 50% higher in patients with moderate renal impairment or ESRD and 100% higher in patients with severe renal impairment. Dose adjustment is not considered necessary in patients with mild or moderate renal impairment or for patients with ESRD receiving hemodialysis; however, a lower dose of Dalbavancin (750 mg followed 1 week later by 375 mg) may be considered for patients with severe renal impairment (creatinine clearance<30 mL/min). AUC0-infinity values were similar in patients with mild hepatic impairment and were about 27% to 36% lower in patients with moderate to severe hepatic impairment compared with controls. No dosage adjustment is recommended in patients with any degree of hepatic impairment. Dalbavancin was well tolerated in all impairment groups.

  • pharmacokinetic pharmacodynamic modeling of Dalbavancin a novel glycopeptide antibiotic
    The Journal of Clinical Pharmacology, 2008
    Co-Authors: James A. Dowell, Martin Stogniew, Beth P. Goldstein, Mary Buckwalter, Bharat Damle
    Abstract:

    Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for Dalbavancin using population pharmacokinetic data and minimum inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MICfor 14 days (t > MIC). The concentration-dependent target was an area under the concentration-time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for Dalbavancin. For S aureus, the estimated susceptibility breakpoint was ≤0.5 μg/mL using AUC 14 days /MIC and ≤1 μg/mL using t > MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 μg/mL. Because Dalbavancin MIC 90 s for these species are well below these values, the analysis supports the use of once-weekly dosing regimens of Dalbavancin in the treatment of complicated skin and skin structure infections.

  • pharmacokinetics of Dalbavancin in plasma and skin blister fluid
    Journal of Antimicrobial Chemotherapy, 2007
    Co-Authors: David P. Nicolau, Elyse Seltzer, Mary Buckwalter, Heather K. Sun, James A. Dowell
    Abstract:

    Objectives Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of Dalbavancin into skin blister fluid. Methods Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of Dalbavancin at a dose of 1000 mg. Skin blisters were induced by application of cantharidin ointment. Plasma and blister fluid samples were collected over 7 days post-dose, and concentrations of Dalbavancin were assessed by a validated LC/MS/MS assay. Pharmacokinetics were determined by non-compartmental methods, and drug penetration was assessed based on the ratio of area under the curve (AUC) in the blister fluid versus plasma for each subject. Results The mean (SD) peak concentration of Dalbavancin in plasma and blister fluid was 285 (31.1) and 67.3 (18.2) mg/L, respectively; the corresponding AUC(Day 7) values were 10 806 (1926) and 6438 (1238) mg . h/L, respectively. The mean (SD) penetration of Dalbavancin into blister fluid was 59.6% (6.3%). By Day 7, the mean concentration of Dalbavancin in plasma and blister fluid was 46.5 and 30.3 mg/L, respectively. Conclusions Dalbavancin concentrations in blister fluid remained well above the MIC90 values for pathogens commonly implicated in cSSSIs such as Staphylococcus aureus, including methicillin-resistant S. aureus (MIC90 = 0.06 mg/L) and beta-haemolytic streptococci (MIC90 = 0.03 mg/L) through Day 7. These pharmacokinetic data support the use of Dalbavancin in the treatment of cSSSIs caused by susceptible Gram-positive pathogens.

  • distribution of radioactivity in bone and related structures following administration of 14c Dalbavancin to new zealand white rabbits
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Eric Solon, James A. Dowell, Jonghui Lee, Peter S King, Bharat Damle
    Abstract:

    Penetration of Dalbavancin into noninfected bone and joint tissues was assessed after an intravenous dose of 20 mg/kg (of body weight) [14C]Dalbavancin given to rabbits. Drug-derived radioactivity, determined over 14 days by either liquid scintillation counting or autoradiography, remained above the MIC for common gram-positive pathogens that cause bone and joint infections.

Ronald N. Jones - One of the best experts on this subject based on the ideXlab platform.

  • Dalbavancin activity when tested against streptococcus pneumoniae isolated in medical centers on six continents 2011 to 2014
    Antimicrobial Agents and Chemotherapy, 2016
    Co-Authors: Ronald N. Jones, Jason E Schuchert, Rodrigo E Mendes
    Abstract:

    Dalbavancin, a novel lipoglycopeptide, was approved for use in 2014 by regulatory agencies in the United States and Europe for the treatment of skin and skin structure infections. The activity of Dalbavancin was also widely assessed by determination of its activity against Streptococcus pneumoniae clinical isolates collected from patients on six continents monitored during two time intervals (2011 to 2013 and 2014). A total of 18,186 pneumococcal isolates were obtained from 49 nations and submitted to a monitoring laboratory as part of the SENTRY Antimicrobial Surveillance Program for reference susceptibility testing. The potency of Dalbavancin against S. pneumoniae was consistent across the years that it was monitored, with the MIC50 and MIC90 being 0.015 and 0.03 μg/ml, respectively, and all isolates were inhibited by ≤0.12 μg/ml. The activity of Dalbavancin was not adversely influenced by nonsusceptibility to β-lactams (ceftriaxone or penicillin), macrolides, clindamycin, fluoroquinolones, or tetracyclines or multidrug resistance (MDR). Regional variations in Dalbavancin activity were not detected, but S. pneumoniae strains isolated in the Asia-Pacific region were more likely to be nonsusceptible to penicillin and ceftriaxone as well as to be MDR than strains isolated in North or South America and Europe. Direct comparisons of potency illustrated that Dalbavancin (MIC50 and MIC90, 0.015 and 0.03 μg/ml, respectively) was 16-fold or more active than vancomycin (MIC50, 0.25 μg/ml), linezolid (MIC50, 1 μg/ml), levofloxacin (MIC50, 1 μg/ml), ceftriaxone (MIC90, 1 μg/ml), and penicillin (MIC90, 2 μg/ml). In conclusion, Dalbavancin had potent and consistent activity against this contemporary (2011 to 2014) collection of S. pneumoniae isolates.

  • in vitro activity of Dalbavancin against multidrug resistant staphylococcus aureus and streptococci from patients with documented infections in europe and surrounding regions 2011 2013
    International Journal of Antimicrobial Agents, 2016
    Co-Authors: Michael D Huband, Helio S Sader, Ronald N. Jones, Robert K Flamm, Mariana Castanheira, David J Farrell, Rodrigo E Mendes
    Abstract:

    The in vitro activity of Dalbavancin was evaluated against 9303 Staphylococcus aureus and 2670 streptococci, including multidrug-resistant (MDR) isolates, collected from hospitalised patients in Europe and surrounding regions from 2011 to 2013. Dalbavancin recently received approval for the treatment of acute bacterial skin and skin-structure infections by the US Food and Drug Administration (FDA) and the European Medicines Agency. Bacterial identification was confirmed by standard microbiological methods (including MALDI-TOF), and susceptibility testing was performed by reference broth microdilution methods. Dalbavancin susceptibility interpretations followed FDA/EUCAST criteria. Meticillin-resistant S. aureus (MRSA) and streptococci exhibiting resistance to at least three other drug classes were considered as MDR. Dalbavancin was highly active (MIC50/90, 0.06/0.06 mg/L; ≥99.9% susceptible) against MDR and non-MDR MRSA isolates. Vancomycin, daptomycin and linezolid were also active (99.6-100.0% susceptible) against MDR MRSA, however MIC90 values for these drugs were 8- to 16-fold higher than Dalbavancin (MIC90 values of 1, 0.5 and 1 mg/L, respectively). All viridans group streptococci (VGS) and β-haemolytic streptococci were susceptible to Dalbavancin regardless of resistance phenotype (MIC50/90 values of ≤0.03 mg/L and 0.06 mg/L, respectively). Dalbavancin MIC50/90 results (MIC50/90, ≤0.03/0.06 mg/L) against MDR VGS were at least eight-fold lower than those of vancomycin (MIC50/90, 0.5/1 mg/L), daptomycin (MIC50/90, 0.5/1 mg/L) and linezolid (MIC50/90, 0.5/1 mg/L). Overall, Dalbavancin exhibited potent in vitro antibacterial activity against S. aureus and streptococci, including MDR phenotypes. Dalbavancin had the lowest MIC50/90 results against the isolates tested, relative to comparator agents, regardless of resistance phenotypes.

  • in vitro activity of Dalbavancin against drug resistant staphylococcus aureus isolates from a global surveillance program
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Sandra P Mccurdy, Ronald N. Jones, Sailaja Puttagunta, Rodrigo E Mendes, Michael W Dunne
    Abstract:

    In over a decade (2002 to 2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, Dalbavancin was demonstrated to be active against isolates that were either susceptible or nonsusceptible to daptomycin, linezolid, or tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistant S. aureus isolates were inhibited by Dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current U.S. Food and Drug Administration (U.S. FDA) breakpoint. Overall, only 0.35% of the monitored S. aureus isolates had a Dalbavancin MIC of either 0.25 or 0.5 μg/ml (i.e., were nonsusceptible).

  • comprehensive update of Dalbavancin activity when tested against uncommonly isolated streptococci corynebacterium spp listeria monocytogenes and micrococcus spp 1357 strains
    Diagnostic Microbiology and Infectious Disease, 2013
    Co-Authors: Ronald N. Jones, Matthew G Stilwell
    Abstract:

    Dalbavancin is an investigational lipoglycopeptide having an extended serum elimination half-life allowing once-weekly dosing. Data from testing 1357 strains of uncommonly isolated species expand the Dalbavancin spectrum details as follows (MIC50/90): β-haemolytic streptococcal serogroups C, F, and G (≤0.03/≤0.03 μg/mL), 7 viridans group of streptococci (≤0.03/≤0.03-0.06 μg/mL), 5 Corynebacterium spp. (0.06/0.12 μg/mL), Listeria monocytogenes (0.06/0.12 μg/mL), and Micrococcus spp. (≤0.03/≤0.03 μg/mL). Among all reported isolates, 99.8% of tested strains were inhibited at Dalbavancin MIC values at ≤0.12 μg/mL. Dalbavancin remains very potent against rarer Gram-positive pathogens, using in vitro test experience with organisms cultured through 2011.

  • multicenter evaluation of the in vitro activity of Dalbavancin tested against staphylococci and streptococci in 5 european countries results from the decide surveillance program 2007
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Douglas J. Biedenbach, Ronald N. Jones
    Abstract:

    Abstract Dalbavancin is an antimicrobial lipoglycopeptide agent that has proven activity against Gram-positive pathogens and a once weekly dosing advantage compared with other agents in the glycopeptide class. The most common pathogens isolated from skin and skin structure infections (SSSIs) include Staphylococcus aureus and β-hemolytic streptococci (βHS), and Dalbavancin has demonstrated excellent activity against these species. This study used 18 medical center laboratories in 5 European countries to assess the activity of Dalbavancin, vancomycin, and teicoplanin against S. aureus , coagulase-negative staphylococci (CoNS), and βHS. The rank order of potency was Dalbavancin (MIC 50 , 0.06 μg/mL) > teicoplanin (MIC 50 , 0.5 μg/mL) > vancomycin (MIC 50 , 2 μg/mL) and Dalbavancin (MIC 50 , 0.06 μg/mL) > teicoplanin and vancomycin (MIC 50 , 2 μg/mL) against S. aureus and CoNS, respectively. Dalbavancin was the most active glycopeptide tested against βHS with all strains inhibited by ≤0.12 μg/mL. Susceptibility to other antimicrobial classes was also evaluated with noticeable differences demonstrated between countries. Higher methicillin-resistant S. aureus (MRSA) rates were observed in Italy (44.2%) and the United Kingdom (36.8%) compared with other countries, but resistance to erythromycin (51.6–83.1%) and clindamycin (5.7–68.4%) among MRSA also varied significantly between countries. The excellent contemporary activity of Dalbavancin against common Gram-positive pathogens collected in European countries suggests that Dalbavancin could have a role in the treatment of various types of SSSIs.

Michael W Dunne - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of Dalbavancin in the treatment of mrsa rat sternal osteomyelitis with mediastinitis
    Journal of Antimicrobial Chemotherapy, 2016
    Co-Authors: Yoav Barnea, Sailaja Puttagunta, Michael W Dunne, Anat Or Lerner, Asaf Aizic, Shiri Navonvenezia, Eleanor Rachi, Yehuda Carmeli
    Abstract:

    OBJECTIVES: Dalbavancin, a semi-synthetic lipoglycopeptide, is characterized by a long plasma half-life, which allows weekly dosing. Dalbavancin may be a good treatment option for patients with deep sternal wound infections owing to its improved pharmacokinetic profile and antibacterial activity compared with currently used antibiotics. Here we evaluated the efficacy of 7 or 14 days of treatment with Dalbavancin, compared with vancomycin and with saline, in reducing sternal bone MRSA counts in a rat Staphylococcus aureus deep sternal wound infection model. METHODS: A mid-sternal wound was surgically induced in anaesthetized rats. A clinical strain of MRSA was injected into the sternum to establish infection. Rats were treated intraperitoneally for 7 or 14 days with Dalbavancin, vancomycin or saline. The number of cfu per gram of sternum or spleen tissue was determined using viable counts. The antibacterial efficacy was determined by the reduction in bacterial counts per gram of sternum or spleen tissue in each treatment group. RESULTS: Treatment with Dalbavancin was superior to treatment with saline for 7 days (0.75 log reduction in bone cfu) or 14 days (>3 log reduction in bone cfu) and similar to treatment with vancomycin. Additionally, Dalbavancin was also effective in reducing systemic dissemination of MRSA. CONCLUSIONS: Dalbavancin is effective in the treatment of MRSA rat sternal osteomyelitis.

  • safety of Dalbavancin in the treatment of skin and skin structure infections a pooled analysis of randomized comparative studies
    Drug Safety, 2016
    Co-Authors: Michael W Dunne, Helen W Boucher, Mark H Wilcox, George H Talbot, Sailaja Puttagunta
    Abstract:

    Dalbavancin is a new lipoglycopeptide that is active against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It has a half-life of 14.4 days, permitting intravenous treatment of acute bacterial skin and skin structure infections without the need for daily dosing. The objective of these analyses was to compare the adverse event profile of Dalbavancin with that of the comparator agents in the treatment of skin and skin structure infections. Data on adverse events and laboratory assessments collected from 3002 patients enrolled in seven late-stage, randomized clinical trials were analyzed for patients receiving Dalbavancin or a comparator antibiotic. Overall adverse event rates were similar or lower for patients receiving Dalbavancin (799/1778; 44.9 %) compared with those receiving comparator agents (573/1224; 46.8 %, p = 0.012). The most common treatment-emergent adverse events were nausea, headache, diarrhea, constipation, vomiting, rash, urinary tract infection, pruritus, and insomnia. The duration and timing of the onset of adverse events were similar for patients receiving Dalbavancin relative to the comparators. Dalbavancin exhibits a favorable overall safety profile for treatment of acute bacterial skin and skin structure infections due to Gram-positive bacteria.

  • in vitro activity of Dalbavancin against drug resistant staphylococcus aureus isolates from a global surveillance program
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Sandra P Mccurdy, Ronald N. Jones, Sailaja Puttagunta, Rodrigo E Mendes, Michael W Dunne
    Abstract:

    In over a decade (2002 to 2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, Dalbavancin was demonstrated to be active against isolates that were either susceptible or nonsusceptible to daptomycin, linezolid, or tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistant S. aureus isolates were inhibited by Dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current U.S. Food and Drug Administration (U.S. FDA) breakpoint. Overall, only 0.35% of the monitored S. aureus isolates had a Dalbavancin MIC of either 0.25 or 0.5 μg/ml (i.e., were nonsusceptible).

  • a thorough qt study with Dalbavancin a novel lipoglycopeptide antibiotic for the treatment of acute bacterial skin and skin structure infections
    International Journal of Antimicrobial Agents, 2015
    Co-Authors: Michael W Dunne, Meijian Zhou, Borje Darpo
    Abstract:

    Two hundred healthy subjects were enrolled in a randomised, partially double-blinded, single-centre, parallel design thorough QT study to demonstrate that Dalbavancin had no clinical effect on the 12-lead ECG QTc. Fifty patients in each group received either Dalbavancin 1000 mg intravenous (i.v.), Dalbavancin 1500 mg i.v. or placebo i.v., each infused over 30 min, or 400 mg oral moxifloxacin. Ten replicate 12-lead ECGs were extracted at pre-defined time points before and up to 24 h post dosing and at corresponding time points during baseline. Dalbavancin did not have an effect on the QTcF interval, and an effect exceeding 10 ms could be excluded at all time points after a single i.v. dose of 1000 mg and 1500 mg. The largest placebo-corrected change-from-baseline QTcF (ΔΔQTcF) was 1.5 ms in the 1000 mg Dalbavancin group at 6 h and 0.2 ms in the 1500 mg group at 24 h. A small concentration-dependent effect of Dalbavancin on ΔΔQTcF was identified with an estimated negative population slope of -0.0051 ms per μg/mL. Assay sensitivity was demonstrated by the effect of 400 mg moxifloxacin, which peaked at 2 h at ΔΔQTcF of 12.9 ms, with the lower bound of the 90% CI of the effect exceeding 5 ms at all three pre-defined time points. Dalbavancin did not exert a relevant effect on heart rate or PR or QRS intervals. Dalbavancin in i.v. doses up to 1500 mg did not prolong the QTc interval and had no effect on heart rate or PR and QRS intervals.

  • extended duration dosing and distribution of Dalbavancin into bone and articular tissue
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Michael W Dunne, Sailaja Puttagunta, Craig R Sprenger, Chris Rubino, Scott A Van Wart, James Baldassarre
    Abstract:

    Dalbavancin is an intravenous lipoglycopeptide with activity against Gram-positive pathogens and an MIC90 for Staphylococcus aureus of 0.06 μg/ml. With a terminal half-life of >14 days, dosing regimens with infrequent parenteral administration become available to treat infectious diseases such as osteomyelitis and endocarditis that otherwise require daily dosing for many weeks. In order to support a rationale for these novel regimens, the pharmacokinetics over an extended dosing interval and the distribution of Dalbavancin into bone and articular tissue were studied in two phase I trials and pharmacokinetic modeling was performed. Intravenous administration of 1,000 mg of Dalbavancin on day 1 followed by 500 mg weekly for seven additional weeks was well tolerated and did not demonstrate evidence of drug accumulation. In a separate study, Dalbavancin concentrations in cortical bone 12 h after infusion of a single 1,000-mg intravenous infusion were 6.3 μg/g and 2 weeks later were 4.1 μg/g. A two-dose, once-weekly regimen that would provide tissue exposure over the Dalbavancin MIC for Staphylococcus aureus for 8 weeks, maximizing the initial exposure to treatment while minimizing the frequency of intravenous therapy, is proposed.

Rodrigo E Mendes - One of the best experts on this subject based on the ideXlab platform.

  • antimicrobial activity of Dalbavancin against clinical isolates of coagulase negative staphylococci from the usa and europe stratified by species
    Journal of global antimicrobial resistance, 2021
    Co-Authors: Helio S Sader, Jennifer M Streit, Cecilia G Carvalhaes, S Ryan J Arends, Rodrigo E Mendes
    Abstract:

    Abstract Objectives To evaluate the in vitro activity of Dalbavancin compared with vancomycin, daptomycin and other agents against a large collection of coagulase-negative staphylococci (CoNS) isolates. Methods A total of 5088 CoNS causing clinically significant infection were consecutively collected from 122 medical centres in the USA and Europe over 6 years (2014–2019). Isolates were tested for susceptibility by the reference broth microdilution method. Species identification was confirmed by MALDI-TOF. Most isolates were from bloodstream infections (BSIs) (53.5%) or skin/skin structure infections (28.5%). Results Staphylococcus epidermidis was the most common species overall (54.6%) and for BSI (61.3%). The second most common species were Staphylococcus lugdunensis overall (12.3%) and Staphylococcus hominis for BSI (14.7%). Dalbavancin (MIC50/90, 0.03/0.06 mg/L) inhibited >99.9% of CoNS isolates at ≤0.25 mg/L (susceptible breakpoint for Staphylococcus aureus per CLSI). All species were inhibited at ≤0.25 mg/L Dalbavancin, except some S. epidermidis (>99.9%) and Staphylococcus warneri (98.9%) isolates. Staphylococcus capitis and Staphylococcus simulans exhibited the lowest Dalbavancin MIC50/90 values (0.015/0.03 mg/L) and Staphylococcus haemolyticus and Staphylococcus saprophyticus the highest (MIC50/90, 0.06/0.12 mg/L); 47.8% of S. epidermidis and 34.7% of S. haemolyticus exhibited decreased susceptibility to vancomycin (MIC ≥ 2 mg/L) and 23.2% of S. capitis and 28.4% of S. warneri showed decreased susceptibility to daptomycin (MIC ≥ 1 mg/L). Conclusion Antimicrobial susceptibility varied widely among CoNS species. Dalbavancin inhibited >99.9% and 99.1% of isolates at the US-FDA and EUCAST breakpoints, respectively. Clinical studies of Dalbavancin for treatment of CoNS infections should be considered based on these in vitro data.

  • antimicrobial activity of Dalbavancin tested against gram positive organisms isolated from patients with infective endocarditis in us and european medical centres
    Journal of Antimicrobial Chemotherapy, 2019
    Co-Authors: Helio S Sader, Rodrigo E Mendes, Michael A Pfaller, Robert K Flamm
    Abstract:

    Background The management of endocarditis requires aggressive and prolonged antimicrobial treatment. We evaluated the in vitro activity of Dalbavancin against bacteria from patients with infective endocarditis. Methods A total of 626 Gram-positive organisms were collected from patients with a diagnosis of bacterial endocarditis in the USA (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility to Dalbavancin and comparators by broth microdilution. Results The most common organisms were Staphylococcus aureus (48.4%), Enterococcus faecalis (19.6%) and viridans group streptococci (VGS; 12.5%). Dalbavancin and daptomycin showed complete activity (100.0% susceptibility per CLSI criteria) against S. aureus, but Dalbavancin MIC values were 4- to 8-fold lower. Vancomycin, linezolid and teicoplanin were also active against all S. aureus when CLSI criteria were applied. Ceftaroline was active against all MSSA (MIC90 0.25 mg/L) and 78.4% of MRSA isolates at ≤1 mg/L. All E. faecalis isolates were susceptible to ampicillin, daptomycin and linezolid, whereas 97.6% of isolates were susceptible to Dalbavancin (MIC90 0.06 mg/L) and 96.7% were susceptible to vancomycin (MIC90 2 mg/L). All VGS and CoNS isolates were susceptible to Dalbavancin, daptomycin, vancomycin and linezolid. Against Enterococcus faecium, 65.7% of isolates were inhibited by ≤0.25 mg/L Dalbavancin and 62.9% were vancomycin susceptible. Conclusions Dalbavancin exhibited potent in vitro activity against a large collection of Gram-positive isolates recovered from patients with endocarditis in US and European medical centres. These results support further investigations to determine the role of Dalbavancin in the treatment of infective endocarditis.

  • activity of Dalbavancin and comparator agents against gram positive cocci from clinical infections in the usa and europe 2015 16
    Journal of Antimicrobial Chemotherapy, 2018
    Co-Authors: Michael A Pfaller, Rodrigo E Mendes, Robert K Flamm, Leonard R Duncan, Helio S Sader
    Abstract:

    Background Many infections due to Gram-positive cocci (GPC; staphylococci, streptococci and enterococci) regularly involve prolonged systemic antibiotic use. Dalbavancin has demonstrated activity against GPC isolates and has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Objectives To evaluate the activity of Dalbavancin against GPC isolated from a variety of infection types in the USA and Europe. Methods A total of 14 319 Staphylococcus aureus, 1992 CoNS, 3269 β-haemolytic streptococci (BHS), 2071 Enterococcus faecalis, 936 Enterococcus faecium, 71 Enterococcus gallinarum/casseliflavus and other Enterococcus spp., 3487 Streptococcus pneumoniae and 1063 viridans group streptococci (VGS) causing clinical infections were consecutively collected (2015-16) and tested for susceptibility by broth microdilution methods. Results All S. aureus (36.4% MRSA) isolates were susceptible to Dalbavancin, teicoplanin and vancomycin, while daptomycin and linezolid showed susceptibility rates of >99.9% (according to CLSI criteria). Dalbavancin MIC results were at least 16-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS [62.2%/59.6% methicillin-resistant (CLSI/EUCAST)], followed by daptomycin, linezolid and vancomycin. All vancomycin-susceptible E. faecalis isolates were inhibited by Dalbavancin at ≤0.25 mg/L (FDA susceptible breakpoint). Dalbavancin was very active against BHS (MIC90 0.03 mg/L) and the most active agent against S. pneumoniae and VGS (highest MIC 0.25 mg/L). Ceftriaxone, daptomycin, levofloxacin and vancomycin were also active (93.5%-100.0% susceptible) against VGS, whereas clindamycin, erythromycin, penicillin and tetracycline had lower activity. Conclusions Dalbavancin appears to be a viable candidate for treating serious infections caused by GPC.

  • activity of Dalbavancin tested against gram positive clinical isolates causing skin and skin structure infections in paediatric patients from us hospitals 2014 2015
    Journal of global antimicrobial resistance, 2017
    Co-Authors: Michael A Pfaller, Helio S Sader, Rodrigo E Mendes, Mariana Castanheira, Robert K Flamm
    Abstract:

    Abstract Objectives This study provides an in vitro analysis of Dalbavancin activity against isolates causing skin and skin-structure infections (SSSIs) in children. Methods A total of 770 Staphylococcus aureus, 167 β-haemolytic streptococci (BHS), 42 coagulase-negative staphylococci (CoNS), 25 Enterococcus faecalis and 13 viridans group streptococci (VGS) were collected from children ( Results Dalbavancin had MIC50/90 values of 0.03/0.06 μg/mL against S. aureus and CoNS, including methicillin-resistant (MRSA) and -susceptible (MSSA) isolates. Dalbavancin MICs were 8–32-fold lower than those of daptomycin (MIC50/90, 0.25/0.5 μg/mL), vancomycin (MIC50/90, 0.5/1 μg/mL) and linezolid (MIC50/90, 1/1 μg/mL) against MRSA. These agents showed 100.0% susceptibility against MRSA, and clindamycin also had a high (92.7%) susceptibility rate. Dalbavancin (MIC50/90, 0.03/0.06 μg/mL) and daptomycin (MIC50/90, 0.25/0.5 μg/mL) were the most active agents against CoNS. When tested against E. faecalis, Dalbavancin was up to 32-fold more active than ampicillin (MIC50/90, ≤0.5/1 μg/mL), daptomycin (MIC50/90, 1/1 μg/mL), linezolid (MIC50/90, 1/2 μg/mL) and vancomycin (MIC50/90, 1/2 μg/mL). Dalbavancin (MIC50/90, 0.008/0.03 μg/mL), ceftriaxone (MIC50/90, ≤0.06/ ≤ 0.06 μg/mL) and penicillin (MIC50/90, ≤0.06/ ≤ 0.06 μg/mL) were the most active against BHS. VGS isolates were susceptible to Dalbavancin (MIC100, 0.03 μg/mL), with MICs 32–64-fold lower than daptomycin (MIC50/90, 0.5/0.5 μg/mL), linezolid (MIC50/90, 0.5/1 μg/mL) and vancomycin (MIC50/90, 0.5/0.5 μg/mL). Conclusions Approved agents available for the treatment of SSSI in children are limited. Dalbavancin demonstrated potent in vitro activity against isolates causing SSSI in children. Developing Dalbavancin for SSSI treatment in children is warranted, provided safety and tolerability are satisfactory.

  • Dalbavancin in vitro activity obtained against gram positive clinical isolates causing bone and joint infections in us and european hospitals 2011 2016
    International Journal of Antimicrobial Agents, 2017
    Co-Authors: Michael A Pfaller, Helio S Sader, Robert K Flamm, Mariana Castanheira, Rodrigo E Mendes
    Abstract:

    Abstract Background Osteomyelitis is a difficult-to-treat infection that regularly involves prolonged use of systemic antibiotics. Dalbavancin has demonstrated activity against Gram-positive isolates, and has been considered as a candidate for the treatment of osteomyelitis in adults and children. This study evaluated the activity of Dalbavancin against pathogens isolated from bone and joint infections (BJI). Methods Eight hundred and one Staphylococcus aureus, 160 coagulase-negative staphylococci (CoNS), 164 β-haemolytic streptococci (BHS), 82 Enterococcus faecalis and 45 viridans group streptococci (VGS) causing BJI were collected consecutively (2011–2016) and tested for susceptibility by broth microdilution methods. Results S. aureus (64.0%) was the most common pathogen associated with BJI, followed by BHS (13.1%) and CoNS (12.8%). All S. aureus (33.3% meticillin-resistant) isolates were susceptible to Dalbavancin, linezolid and vancomycin, while daptomycin and clindamycin showed susceptibility rates of 99.5% and 89.0%, respectively. The minimum inhibitory concentration (MIC) results for Dalbavancin were at least eight-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS (63.1% meticillin-resistant), followed by daptomycin, linezolid and vancomycin. All E. faecalis isolates were inhibited by Dalbavancin at ≤0.25 mg/L (US Food and Drug Administration susceptibility breakpoint), except for three vancomycin-resistant isolates. High susceptibility rates for ampicillin (98.8%), daptomycin (100.0%), linezolid (100.0%) and vancomycin (95.1%) were obtained against E. faecalis. Dalbavancin was very active against BHS (MIC90 ≤0.03 µg/mL), and was the most active agent against VGS (highest MIC ≤0.06 mg/L). Ceftriaxone, daptomycin and vancomycin were also active (93.3–100.0% susceptible) against VGS, whereas clindamycin (84.4% susceptible) had marginal activity. Conclusion Dalbavancin appears to be a viable candidate for treating BJI/osteomyelitis caused by Gram-positive cocci.

Related terms

Dalbavancin - 15 days free trial to Access Experts & Abstracts