In vitro activity of telavancin and occurrence of vancomycin heteroresistance in isolates from patients enrolled in phase 3 clinical trials of hospital-acquired pneumonia

Krause, Kevin M.; Blais, Johanne; Lewis, Stacey R.; Lunde, Christopher S.; Barriere, Steven L.; Friedland, H. David; Kitt, Michael M.; Benton, Bret M.

doi:10.1016/j.diagmicrobio.2012.08.010

Cited by 14 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Telavancin possesses bactericidal activity against clinically relevant pathogens, such as S. aureus, including MRSA, heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA isolates, and vancomycin-susceptible enterococci (5)(6)(7)(8)(9)(10)(11). This bactericidal activity derives from a dual mechanism of action consisting of inhibition of peptidoglycan biosynthesis, similar to the glycopeptides, and interaction with the bacterial membrane to effect changes in membrane permeability and depolarization (12).…”

mentioning

confidence: 99%

Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

Mendes

Farrell

Sader

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Telavancin had MIC 50 and MIC 90 values of 0.03 and 0.06 g/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible Staphylococcus aureus. Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC 50/90 , 0.12/0.12 g/ml; 100% susceptible) and Enterococcus faecium (MIC 50/90 , 0.03/0.06 g/ml), while higher MIC values were obtained against vancomycin-resistant E. faecium (MIC 50/90 , 1/2 g/ml) and E. faecalis (MIC 50/90 , >2/>2 g/ml). Streptococci showed telavancin modal MIC results of <0.015 g/ml, except against Streptococcus agalactiae (i.e., 0.03 g/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method. Telavancin is a once-daily parenteral semisynthetic lipoglycopeptide agent approved in the United States and Canada for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible Gram-positive pathogens. Telavancin was also approved in the United States and Europe for the treatment of adult patients with hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia (HABP/VABP) due to susceptible isolates of Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] strains only in Europe), when alternative medicines are unsuitable (1, 2). These indications were based on phase 3 clinical trials demonstrating noninferiority of telavancin over vancomycin (3,4).Telavancin possesses bactericidal activity against clinically relevant pathogens, such as S. aureus, including MRSA, heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA isolates, and vancomycin-susceptible enterococci (5-11). This bactericidal activity derives from a dual mechanism of action consisting of inhibition of peptidoglycan biosynthesis, similar to the glycopeptides, and interaction with the bacterial membrane to effect changes in membrane permeability and depolarization (12).Early in 2014, the Food and Drug Administration (FDA) approved a labeling supplement for Vibativ (telavancin) containing a revised broth microdilution method (1) that is similar to that utilized for other members of the lipoglycopeptide class (i.e., oritavancin and dalbavancin) (13,14). This revised method includes the use of dimethyl sulfoxide (DMSO) as the solvent for stock solution preparations and as the diluent for the dilution of stock solutions when manufacturing 96-well MIC plates. This procedure follows the current Clinical and Laboratory Standards Institute (CLSI) guidelines for water-insoluble agents (1, 15, 16). Moreover, this revised method includes the addition of polysorbate 80 (P-80; 0.002%) to the test medium (1,15,16).This revised broth microdilution method for telavancin provides more accurate and reproducible results by minimizing drug loss during panel preparation (increased solubility) and testing (decreasing binding on plastic trays) (16). However, this revised broth microdilution method als...

show abstract

mentioning

confidence: 99%

Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

Mendes

Farrell

Sader

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In vitro studies of intrinsic resistance development, including both single-step and multi-passage experiments, suggest that telavancin has a low potential to select for resistance [30]. During clinical trials, there was no evidence of resistance developing to telavancin [24,31].…”

Section: Resistance Development Studiesmentioning

confidence: 99%

“…Non-VanA-type vancomycin-resistant organisms are typically susceptible to telavancin [24]. No other cross-resistance between telavancin and other classes of antibiotics has been identified to date.…”

Section: Resistance Development Studiesmentioning

confidence: 99%

“…Representative telavancin potency against a collection of Gram-positive clinical isolates collected from US hospitals in 2011 and 2012 is provided in TABLE 1 [23]. In addition to the international surveillance program, a number of studies have focused specifically on the activity of telavancin against Grampositive organisms with reduced susceptibility to vancomycin, with particular emphasis given to vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) strains [24][25][26][27]. Collectively, these studies have demonstrated that telavancin possesses potent activity against VISA and hVISA, with all isolates tested remaining susceptible to telavancin according to the FDA MIC Data taken from [9,12,65].…”

Section: Microbiologymentioning

confidence: 99%

“…breakpoint for staphylococci (susceptibility £1 mg/ml) in place at the time that these studies were performed 1 [24,[26][27][28].…”

Section: Microbiologymentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of Gram-positive infection

Hegde

Janc

2014

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

Treatment of Infections Due to Resistant Staphylococcus aureus

Anstead

Cadena

Javeri

2013

Methods in Molecular Biology

View full text Add to dashboard Cite

This chapter reviews data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review covers findings reported in the English language medical literature up to January of 2013. Despite the emergence of resistant and multidrug-resistant S. aureus, we have seven effective drugs in clinical use for which little resistance has been observed: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, telavancin, ceftaroline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a higher MIC within the susceptible range. Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections (SSTIs); whether it is drug of choice in pneumonia remains debatable. Daptomycin has shown to be non-inferior to either vancomycin or β-lactams in the treatment of staphylococcal SSTIs, bacteremia, and right-sided endocarditis. Tigecycline was also non-inferior to comparator drugs in the treatment of SSTIs, but there is controversy about whether it is less effective than other therapeutic options in the treatment of more serious infections. Telavancin has been shown to be non-inferior to vancomycin in the treatment of SSTIs and pneumonia, but has greater nephrotoxicity. Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA; it is non-inferior to vancomycin in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, rifampin, moxifloxacin, and minocycline are oral anti-staphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are also several drugs with broad-spectrum activity against Gm-positive organisms that have reached the phase II and III stages of clinical testing that will hopefully be approved for clinical use in the upcoming years: oritavancin, dalbavancin, omadacycline, tedizolid, delafloxacin, and JNJ-Q2. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary, and despite our deep bullpen of potential therapies, there are still frequent treatment failures and unfortunate clinical outcomes. The following discussion summarizes the clinical challenges presented by MRSA, the clinical experience with our current anti-MRSA antibiotics, and the gaps in our knowledge on how to use these agents to most effectively combat MRSA infections.

show abstract

In vitro activity of telavancin and occurrence of vancomycin heteroresistance in isolates from patients enrolled in phase 3 clinical trials of hospital-acquired pneumonia

Cited by 14 publications

References 18 publications

Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of Gram-positive infection

Treatment of Infections Due to Resistant Staphylococcus aureus

Contact Info

Product

Resources

About