Lipoglycopeptide Antibiotic Research Articles

Effect of Telavancin (Vibativ) on Routine Coagulation Test Results

Telavancin (Vibativ, Astellas Pharma US, Deerfield, IL) is a lipoglycopeptide antibiotic that has activity against gram-positive microorganisms, but also has the ability to bind to artificial phospholipids found in coagulation reagents. Normal pooled plasma was spiked with telavancin to obtain concentrations of 0, 12.5, 25, 50, 75, 100, 125, and 150 μg/mL of drug. Samples were tested using 3 different prothrombin time/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) reagent systems, as well as for fibrinogen level, thrombin time, D-dimer level, dilute Russell viper venom time (DRVVT), protein C activity, and protein S activity. There was no effect of telavancin seen with non-phospholipid-dependent assays: fibrinogen level, thrombin time, and D-dimer testing. All INR and aPTT systems demonstrated concentration-dependent increases in clotting times, with Innovin (Siemens Healthcare Diagnostics, Deerfield, IL) INRs the most dramatic. False-positive DRVVT ratios started at 12.5 μg/mL of telavancin, with no effect on protein C or protein S levels until the telavancin level reached more than 100 μg/mL.

Telavancin for the treatment of serious gram-positive infections, including hospital acquired pneumonia

Introduction: Hospital-acquired pneumonia is a common infection, associated with substantial mortality. Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited.Areas covered: This article reviews the pharmacokinetics, dosing, preclinical studies and clinical efficacy, and safety of telavancin, with a particular focus on results from trials in nosocomial pneumonia. PubMed and Congress websites were searched for relevant articles published between 2003 and 2010.Expert opinion: Telavancin is a lipoglycopeptide antibiotic with rapid, bactericidal activity against MRSA, and may provide another option for the treatment of nosocomial pneumonia, owing to Gram-positive pathogens.

In vitro Characterization of Oritavancin Clearance from Human Blood by Low-Flux, High-Flux, and Continuous Renal Replacement Therapy Dialyzers

Oritavancin is an investigational lipoglycopeptide antibiotic under clinical development for the treatment of gram-positive bacterial infections. The impact of hemodialysis on plasma concentrations of oritavancin is unknown and may be important in making dosage adjustments in such patients. The present study sought to determine the clearance of oritavancin from human blood by various commercially available dialyzers in an in vitro hemodialysis model. Three types each of low-flux (Dicea 130, F6, and Polyflux 14L) and high-flux (Revaclear, Exeltra 150, and Optiflux F160NR) dialyzers and one type of continuous renal replacement therapy (CRRT) dialyzer (Prismaflex M100) were studied. Heparinized human blood containing oritavancin (200 mg/L) was circulated from a reservoir to the dialyzers and back to the reservoir. Fresh dialysate was pumped through the dialyzers in a countercurrent manner. Blood samples from each side of the dialyzers and contaminated dialysate samples were collected at periodic intervals. Oritavancin levels were analyzed by a liquid chromatography/mass spectrometry method with a limit of quantification of 12.5 ng/mL and plasma clearances of oritavancin were calculated. The mean dialytic clearance of oritavancin was insignificant for each of the low-flux, high-flux and CRRT dialyzers. Clinically significant amounts of oritavancin were not detected in dialysate during any of the experimental dialysis sessions. The clearance of oritavancin from human blood by the dialyzers used in this study is insignificant. Further clinical studies would be required before making changes in dosage of oritavancin in hemodialysis patients.

Detection of vancomycin levels in patients receiving telavancin but not vancomycin

Sir, Telavancin is a lipoglycopeptide antibiotic with a chemical structure closely related to the glycopeptide antibiotic vancomycin. Telavancin has excellent in vitro activity against methicillinresistant staphylococci and, in the trials which led to its approval for the treatment of skin and soft tissue infections, it was shown to be non-inferior to vancomycin. 1 Renal toxicity is the principal significant adverse effect of telavancin. 2 A standard dose of 10 mg/kg daily is recommended in patients with normal renal function and monitoring of serum or plasma levels is neither recommended nor available commercially. 2 It is not known if telavancin serum levels correlate with the efficacy or renal toxicity of this antibiotic. Perhaps due to a lack of therapeutic superiority data and concerns about renal toxicity, telavancin has yet to be widely used in clinical practice. Recently, a patient receiving the standard dose of telavancin for a staphylococcal infection was demonstrated to have an apparent detectable serum vancomycin level (after the level was inadvertently ordered by a house officer). This serendipitous finding led us to check vancomycin levels in several other patients with normal renal function who were receiving standard doses of telavancin. No patients had received vancomycin. Trough levels were obtained immediately prior to a dose of telavancin and peak levels were obtained 1 h after the infusion was completed. The vancomycin serum levels were determined by a particle-enhanced turbidometric inhibition immunoassay method (Synchron LX System, Beckman Coulter, Inc., Brea, CA, USA). The results are shown in Table 1. Wespeculatethatif aconsistent correlationcanbeestablished between serum vancomycin and telavancin levels in patients treated with telavancin, a commercially available vancomycin serum level assay can then be used to monitor telavancin therapy, in place of an unavailable telavancin assay, in order to establish possible correlation between telavancin levels and its clinical efficacy and/or renal toxicity. Although telavancin plasma assays were apparently done as part of approval studies, we had no access to a telavancin assay to attempt to establish the correlation. 3 If the manufacturer of telavancin or an independent investigator is able to perform telavancin assays, they may choose to perform such a study.

Synthesis and Characterization of the Arylomycin Lipoglycopeptide Antibiotics and the Crystallographic Analysis of Their Complex with Signal Peptidase

Glycosylation of natural products, including antibiotics, often plays an important role in determining their physical properties and their biological activity, and thus their potential as drug candidates. The arylomycin class of antibiotics inhibits bacterial type I signal peptidase and is comprised of three related series of natural products with a lipopeptide tail attached to a core macrocycle. Previously, we reported the total synthesis of several A series derivatives, which have unmodified core macrocycles, as well as B series derivatives, which have a nitrated macrocycle. We now report the synthesis and biological evaluation of lipoglycopeptide arylomycin variants whose macrocycles are glycosylated with a deoxy-α-mannose substituent, and also in some cases hydroxylated. The synthesis of the derivatives bearing each possible deoxy-α-mannose enantiomer allowed us to assign the absolute stereochemistry of the sugar in the natural product and also to show that while glycosylation does not alter antibacterial activity, it does appear to improve solubility. Crystallographic structural studies of a lipoglycopeptide arylomycin bound to its signal peptidase target reveal the molecular interactions that underlie inhibition and also that the mannose is directed away from the binding site into solvent which suggests that other modifications may be made at the same position to further increase solubility and thus reduce protein binding and possibly optimize the pharmacokinetics of the scaffold.

Effect of telavancin on human intestinal microflora

Telavancin is a new lipoglycopeptide antibiotic for the treatment of Gram-positive infections. It has a dual mechanism of action by inhibiting bacterial cell wall synthesis and disrupting the bacterial plasma membrane. The purpose of the present study was to investigate the effect of administration of telavancin on the human intestinal microflora. Thirteen healthy subjects (six males and seven females; age range 18–40 years) received 10 mg/kg body weight telavancin by intravenous infusion over a 60-min period once every 24 h for 7 days. Plasma and urine were collected on Days 5, 6 and 7 for pharmacokinetic analysis of telavancin. Faecal samples were collected on Days −1 (pre-dose), 2, 5, 7, 9, 14 and 21. Faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated in pure culture and identified to genus level. No measurable concentrations of telavancin were found in faeces. No significant effects on the number of Enterobacteriaceae, enterococci, Candida albicans, bifidobacteria, lactobacilli, clostridia and Bacteroides spp. were observed during the study period. No Clostridium difficile strains or toxins were found. No new colonising aerobic and anaerobic Gram-positive bacteria with telavancin minimum inhibitory concentrations of ≥2 mg/L were found. Based on the microbiological data, telavancin has no significant ecological impact on the human intestinal microflora.

Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography–tandem mass spectrometry method

Dalbavancin is a novel second-generation lipoglycopeptide antibiotic with activity against broad range of Gram-positive pathogens. In order to determine the pharmacokinetics (PK) of dalbavancin in pediatric patients, a new High Performance Liquid Chromatography–Tandem Mass Spectrometry (HPLC–MS/MS) bioanalytical method has been developed for quantification of dalbavancin in plasma and in urine. The plasma method was validated for dalbavancin in the linear range from 0.5 μg/mL to 500 μg/mL using 50 μL of K 2 EDTA plasma. For dalbavancin spiked in urine, non-specific binding (NSB) of the drug to polypropylene (PP) urine collection containers was observed. The loss amounted to about 10% per transfer. After successfully establishing the collection/sampling procedure for urine by addition of Triton X-100 to the collection vessels (with a purpose of preventing NSB), the method was validated for dalbavancin in the range from 0.05 μg/mL to 50 μg/mL, using 100 μL of urine. These methods were used to quantify dalbavancin in plasma and urine of hospitalized children in a pediatric dalbavancin PK study. Eighteen percent of the total number of plasma study samples was reassayed for incurred samples reproducibility (ISR) and all the reassayed dalbavancin concentrations were within the ±20% limits. For urine, all the collected samples were reassayed for ISR and the original dalbavancin concentration was confirmed within the ±20% limits for 17 (94%) samples; the one remaining urine sample had its reassayed concentration confirmed within ±25% of the original result.

Telavancin: A novel lipoglycopeptide antibiotic

Telavancin: A novel lipoglycopeptide antibiotic

Effects of telavancin on coagulation test results

The lipoglycopeptide antibiotic, telavancin, may interfere with some laboratory coagulation tests including prothrombin time (PT) and activated partial thromboplastin time (aPTT). To evaluate the effects of telavancin on PT and aPTT assays in common use. Pooled normal human plasma was spiked with telavancin 10, 20, 100 or 200 μg/ml (equivalent to trough, 2 × trough, peak and 2 × peak clinical plasma concentrations, respectively) or diluent control (0.9% sodium chloride). Samples were analysed using 16 PT reagents and seven aPTT reagents. Telavancin 200 μg/ml (corresponding to 2 × peak clinical plasma concentration), produced significant PT prolongation (> 9% difference vs. diluent control) with all the 16 PT reagents (range 12% to > 600%). At lower telavancin concentrations, PT prolongation was dose-dependent and varied among reagents, but appeared greatest with preparations containing recombinant tissue factor. With telavancin 10 μg/ml (equivalent to trough), PT prolongation was 10% with HemosIL(®) PT-Fibrinogen Recombinant, while ranging from 5% to -1% with all other reagents. Significant (> 34% difference vs. baseline) and dose-dependent aPTT prolongation was observed with all the seven reagents in samples spiked with telavancin 100 or 200 μg/ml (range 65-142% at 200 μg/ml). aPTT reagents containing a silica activator appeared to be more sensitive to telavancin interference. Telavancin 10 μg/ml was not associated with increased aPTT with any of the reagents tested. Telavancin has the potential to prolong both PT and aPTT in vitro. It is recommended that samples for PT or aPTT be obtained just prior to a telavancin dose (trough).

Regioselective deacetylation based on teicoplanin-complexed Orf2* crystal structures

Lipoglycopeptide antibiotics are more effective than vancomycin against MRSA as they carry an extra aliphatic acyl side chain on glucosamine (Glm) at residue 4 (r4). The biosynthesis of the r4 N-acyl Glc moiety at teicoplanin (Tei) or A40926 has been elucidated, in which the primary amine nucleophile of Glm is freed from the r4 GlcNac pseudo-Tei precursor by Orf2* for the subsequent acylation reaction to occur. In this report, two Orf2* structures in complex with β-D-octyl glucoside or Tei were solved. Of the complexed structures, the substrate binding site and a previously unknown hydrophobic cavity were revealed, wherein r4 GlcNac acts as the key signature for molecular recognition and the cavity allows substrates carrying longer acyl side chains in addition to the acetyl group. On the basis of the complexed structures, a triple-mutation mutant S98A/V121A/F193Y is able to regioselectively deacetylate r6 GlcNac pseudo-Tei instead of that at r4. Thereby, novel analogs can be made at the r6 sugar moiety.

Telavancin: A lipoglycopeptide antimicrobial for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria in adults

Background: Telavancin, a lipoglycopeptide antibiotic, is a semisynthetic derivative of vancomycin. It was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by grampositive bacteria, including methicillin-resistant Staphylococcus aureus. Objective: This article summarizes the pharmacology, in vitro and in vivo activity, pharmacokinetic properties, and clinical efficacy and tolerability of telavancin. Methods: Relevant information was identified through a search of MEDLINE (1966–August 2010), Iowa Drug Information Service (1966–August 2010), International Pharmaceutical Abstracts (1970–August 2010), and Google Scholar using the terms telavancin, lipoglycopeptide, and TD-6424. Abstracts and posters from scientific meetings, as well as documents submitted by the manufacturer of telavancin to the FDA as part of the approval process, were consulted. In vivo and in vitro experimental and clinical studies and review articles that provided information on the activity, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of telavancin were reviewed. Results: In vitro, telavancin has potent activity against S aureus, including methicillin-resistant strains; Streptococcus pneumoniae; and vancomycin-susceptible enterococci with MICs generally <1 μg/mL. Telavancin appears to have a dual mechanism of action, inhibiting cell wall formation and disrupting the cell membrane. In Phase III studies (ATLAS 1 and ATLAS 2), telavancin was found to be noninferior to vancomycin, with clinical cure rates of 88.3% and 87.1%, respectively, in clinically evaluable patients in the treatment of cSSSIs (difference, 1.2%; 95% CI, −2.1 to 4.6; P = NS). The effectiveness of telavancin in the treatment of hospitalacquired pneumonia was assessed in 2 Phase III studies (ATTAIN 1 and ATTAIN 2). Preliminary findings were that the effectiveness of telavancin was not significantly different from that of vancomycin, with cure rates of 82.7% and 80.9% in the clinically evaluable population, respectively (difference, 1.8%; 95% CI, −4.1 to 7.7; P = NS). The most commonly (>10%) reported adverse events included taste disturbances, nausea, headache, vomiting, foamy urine, constipation, and insomnia. Conclusion: In clinical trials, the effectiveness of telavancin was not significantly different from that of vancomycin in the treatment of cSSSIs, and telavancin was generally well tolerated.

In vitro Activity of Dalbavancin against Staphylococci Isolated in Istanbul, Turkey

Background: Staphylococci are a major cause of both community- and hospital-acquired infections. Dalbavancin is a new bactericidal second-generation lipoglycopeptide antibiotic to use in the treatment of multidrug-resistant staphylococcal infections. It is important to determine its activity against staphylococci isolated in Turkey. Dalbavancin has not yet been used in antimicrobial therapy in our country. Method: Dalbavancin was tested against a total of 453 staphylococcal strains by using the reference broth microdilution method. Organisms tested included: methicillin-resistant Staphylococcus aureus (MRSA; 237 strains), methicillin-susceptible S. aureus (MSSA; 144 strains) and methicillin- resistant coagulase-negative staphylococci (MR-CoNS; 72 strains). Results: MIC₅₀ and MIC₉₀ values of dalbavancin against MRSA, MSSA and MR-CoNS were found as ≤0.008 and 0.25 mg/l; 0.016 and 0.125 mg/l; and 0.016 and 0.5 mg/l, respectively. The overall distribution of dalbavancin MIC values ranged from ≤0.008 to 2 mg/l. If the interpretive breakpoint MIC value is ≤1 mg/l, the susceptibility rates of MRSA, MSSA and MR-CoNS strains were determined as 99.6, 100 and 98.6%, respectively. Conclusion: The MIC results for dalbavancin have demonstrated a good activity against both methicillin-sensitive and -resistant staphylococci isolated from hospitalized patients.

Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains

Oritavancin is a lipoglycopeptide antibiotic under investigation for the treatment of serious infections caused by Gram-positive bacteria. Oritavancin has demonstrated rapid dose-dependent bactericidal activity towards vancomycin-susceptible and -resistant enterococci, meticillin-susceptible and -resistant Staphylococcus aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), vancomycin-resistant S. aureus (VRSA) and small-colony variants of S. aureus. It is also active against Clostridium difficile. Upon intravenous administration, oritavancin displays a three-compartment pharmacokinetic model, dose proportionality, a distribution volume of ca. 110 L, a terminal elimination half-life in excess of 2 weeks and it is not metabolised. Its pharmacodynamic properties make it an ideal antibiotic for a once-daily or even single-dose regimen. Oritavancin is currently under review by the US Food and Drug Administration. So far, oritavancin has demonstrated efficacy in two pivotal Phase III trials conducted in patients with complicated skin and skin-structure infections in which oritavancin was compared with vancomycin plus cefalexin. In both trials, the primary endpoint (clinical cure in clinically evaluable patients at first follow-up with a 10% non-inferiority margin) was met, with the advantages of shorter duration of therapy and fewer adverse events. Further results indicating its activity against bacteria growing in biofilms as well as stationary-phase bacteria open the way for its use to treat prosthetic device infections, which is to be investigated in upcoming trials.

Oritavancin, a New Lipoglycopeptide Antibiotic: Results From a Thorough QT Study

Oritavancin is a lipoglycopeptide with broad activity against gram-positive bacteria. To exclude an effect on cardiac repolarization, oritavancin was studied in a thorough QT study. In vitro assays have demonstrated a 10-fold safety margin between the concentration that resulted in 50% block of the cardiac potassium current and therapeutic plasma levels in patients and no safety margin for block of the sodium currents. In a parallel-group study, 240 male and female subjects received treatment with either the clinical dose (200 mg intravenously) or a supratherapeutic dose (800 mg intravenously) of oritavancin, placebo, or a positive control (400 mg of oral moxifloxacin). Electrocardiograms were recorded in triplicate at several time points after dosing. The primary end point was the largest baseline-adjusted, placebo-corrected QTcI observed at any point after oritavancin dosing. The study's sensitivity to demonstrate a sufficiently small QTc change was confirmed by the moxifloxacin effect. The baseline-adjusted, placebo-corrected QTcI was between -3 milliseconds and 3 milliseconds after 800 mg of oritavancin, and an effect exceeding 6 milliseconds was confidently excluded. Other electrocardiographic parameters were unaffected by the treatment. It was concluded that oritavancin did not cause QTc prolongation in this thorough QT study.

Characterization of the In Vitro Activity of Novel Lipoglycopeptide Antibiotics

The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely-used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin-resistant organisms. The newer agents currently being developed contain lipophilic side-chains, which distinguish them from vancomycin; as such, they are categorized as lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are lipoglycopeptides in late-stage development to combat Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of lipoglycopeptides. The methods include susceptibility assays, time-kill and time-kill-synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms.

Effect of Telavancin on the Pharmacokinetics of the Cytochrome P450 3A Probe Substrate Midazolam: A Randomized, Double‐Blind, Crossover Study in Healthy Subjects

To examine the effect of telavancin, a lipoglycopeptide antibiotic with potent gram-positive activity, on the pharmacokinetics of midazolam, a cytochrome P450 (CYP) 3A probe substrate. Design. Phase I, randomized, double-blind, placebo-controlled, crossover study. Setting. Clinical research center. Sixteen healthy adult volunteers. Intervention. Subjects were randomly assigned to receive an intravenous infusion of telavancin 10 mg/kg or placebo once/day for 7 days. On day 7, a single dose of intravenous midazolam 1 mg was given immediately after completion of the last infusion of telavancin or placebo. Patients crossed over to the alternate treatment regimen after a washout period of at least 7 days. Pharmacokinetic sampling was performed on study days 7 and 21. Blood was collected before telavancin or placebo dosing and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after midazolam administration. Formal equivalence analysis using the two one-sided t test method showed that the geometric mean ratios for maximum plasma concentration (C(max)) and areas under the plasma concentration-time curve (AUC) for midazolam coadministered with telavancin versus midazolam coadministered with placebo were close to unity. The 90% confidence intervals (CIs) around the ratios fell within the 0.8-1.25 bioequivalence bounds (geometric mean ratio for AUC from time zero to the last measured plasma concentration 0.95, 90% CI 0.910-0.984; C(max) geometric mean ratio 1.03, 90% CI 0.956-1.11). The multiple-dose pharmacokinetic profile of telavancin with concomitant administration of midazolam (C(max) 97 microg/ml, concentration 24 hrs after completion of telavancin infusion 9 microg/ml, terminal-phase elimination half-life 8.9 hrs, clearance 13.3 ml/hr/kg) was consistent with data from earlier studies. These pharmacokinetic data show that intravenous telavancin administered at the intended therapeutic dose does not affect the pharmacokinetics of intravenous midazolam. The results indicate that telavancin is unlikely to inhibit hepatic CYP3A activity to a clinically meaningful extent.

Bacteremic nosocomial pneumonia cases from the ATTAIN studies

Bacteremic pneumonia is associated with worse outcome including higher mortality. The ATTAIN program compared telavancin (TLV), a lipoglycopeptide antibiotic, with vancomycin (VAN) for treatment of nosocomial pneumonia (NP) due to Gram-positive pathogens including MRSA. This subgroup analysis examined the baseline characteristics and clinical outcomes in bacteremic HAP cases.

From Vancomycin to Oritavancin: The Discovery and Development of a Novel Lipoglycopeptide Antibiotic

From Vancomycin to Oritavancin: The Discovery and Development of a Novel Lipoglycopeptide Antibiotic

Lack of Effect of Moderate Hepatic Impairment on the Pharmacokinetics of Telavancin

To evaluate the pharmacokinetics of the lipoglycopeptide antibiotic, telavancin, in patients with moderate hepatic impairment compared with healthy controls. Phase I, open-label, single-dose, matched-control, pilot study. Clinical research unit. Eight adults with moderate hepatic impairment (Child-Pugh class B) and eight age-, sex-, and weight-matched healthy control subjects. All participants received a single 1-hour intravenous infusion of telavancin 10 mg/kg. Plasma samples were collected for pharmacokinetic analysis before the infusion and 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours after the start of the infusion. Concentrations of telavancin and the most prevalent of several minor hydroxylated metabolites, THRX-651540, were assayed with a validated liquid chromatography-tandem mass spectrometry technique. Telavancin binding to plasma proteins was determined in a preinfusion sample by using equilibrium dialysis. Pharmacokinetic parameters for telavancin and THRX-651540 were generally similar between the hepatic impairment and control groups. The mean maximum plasma concentration was 21% lower in patients with hepatic impairment than in controls, which was a statistically (analysis of variance, p<0.05), but not clinically, significant difference. There were no other statistically significant between-group differences. Adverse events were few and mild. No apparent differences were observed in the pharmacokinetic disposition of telavancin in patients with hepatic impairment compared with healthy controls in this pilot study. Thus, adjustment of the standard telavancin dosage regimen does not appear to be required in patients with mild-to-moderate hepatic impairment.

Telavancin: A Novel Lipoglycopeptide

Telavancin, a derivative of vancomycin, is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of complicated skin and skin-structure infections. It has also been effective in the treatment of gram-positive pneumonia. This antibiotic has a dual mechanism of action by inhibiting peptidoglycan synthesis and causing membrane depolarization. Telavancin is consistently active against Staphylococcus aureus, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus, linezolid-resistant S. aureus, and daptomycin-nonsusceptible strains. The drug is usually administrated intravenously at 10 mg/kg every 24 h. Telavancin is excreted by the kidneys, and thus, dosage adjustments are required in cases of renal failure. Clinical trials have demonstrated non-inferiority, compared with vancomycin, in the treatment of complicated skin and skin-structure infections and pneumonia. Telavancin is associated with higher rates of renal events, altered taste, nausea, and vomiting but lesser rates of pruritus and infusion-related events, compared with vancomycin.