telavancin and Skin-Diseases--Bacterial

Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and mortality among hospitalized patients and a major therapeutic challenge for clinicians. Although uncomplicated SSTIs are managed successfully on an outpatient basis, more serious infections extending to the subcutaneous tissue, fascia, or muscle require complex management. Early diagnosis, selection of appropriate antimicrobials, and timely surgical intervention are key to successful treatment. Surgical-site infections, an important category of SSTI, occur in approximately half a million patients in North America annually. SSTIs are also a potential source for life-threatening bacteremia and metastatic abscesses. Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pyogenes, are the dominant organisms isolated early in the infectious process, whereas gram-negative organisms are found in chronic wounds. Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that requires aggressive antimicrobial treatment and surgery. Recent concerns regarding vancomycin activity include heteroresistance in MRSA and increase in the minimum inhibitory concentrations (>1 or 2 µg/mL); however, alternative agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin, oritavancin, and tedizolid, are now available for the treatment of severe MRSA infections. Here, we present a review of the epidemiology, etiology, and available treatment options for the management of SSTIs.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clinical Trials as Topic; Daptomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; North America; Oxazolidinones; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections

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.. 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.. 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.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cross Infection; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Staphylococcal; Skin Diseases, Bacterial

There is a choice of anti-MRSA antibiotic available with proven efficacy in the treatment of complicated skin and skin structure infection (cSSSI). Additional anti-MRSA antibiotics are in development, which have the potential to influence how such infections are managed. The emergence of resistance to current anti-MRSA agents, toxicity, and general lack of oral agents with proven efficacy for deep seated infection justify the development of new agents. However, there is a relative dearth of information specific to patients with orthopaedic-related infection. Combination therapy is often used in these patients, although there is a paucity of controlled trial data to support particular antibiotic combinations. As the choice of anti-MRSA agents increases, so does the need to identify which are best for the large variety of infections included in the group of cSSSIs. This is particular true for infections occurring in orthopaedic patients where poorly vascularised tissue, trauma or implanted prosthetic material, pose specific challenges.

Topics: Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Teicoplanin

To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of telavancin, a new lipoglycopeptide antibiotic.. Literature was obtained from MEDLINE (1966-April 2009) and International Pharmaceutical Abstracts (1971-April 2009) using the search terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma US, Inc.. Available English-language articles were reviewed, as well as information obtained from Theravance, Inc., and Astellas Pharma US, Inc.. Telavancin has rapid bactericidal activity against gram-positive aerobic and anaerobic bacteria through multiple mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of telavancin against antibiotic-resistant gram-positive organisms. On March 4, 2008, the Food and Drug Administration (FDA) accepted as complete for review Theravance's response to the October 19, 2007, New Drug Application approvable letter for telavancin to be used as treatment for complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval prolongation has been reported, although the clinical impact of this has not been determined. Drug interactions have not been identified as of yet.. Telavancin is currently under review by the FDA for the treatment of cSSSIs caused by gram-positive bacteria. The completion of Phase 3 trials will determine whether telavancin will have a role in the treatment of other infections caused by resistant gram-positive bacteria.

Topics: Aminoglycosides; Anti-Infective Agents; Clinical Trials as Topic; Drug Interactions; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Models, Molecular; Skin Diseases, Bacterial; Soft Tissue Infections

During phase 3 clinical studies of telavancin for treatment of complicated skin and skin structure infections, a total of 1530 aerobic Gram-positive isolates were identified at baseline. The majority of these strains were Staphylococcus aureus (n = 1214; 62% methicillin-resistant). All isolates were inhibited by ≤ 1 μg/mL of telavancin.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Skin; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Vancomycin

Telavancin is an injectable lipoglycopeptide that is bactericidal in vitro against staphylococci, streptococci and vancomycin-susceptible enterococci. Telavancin inhibits bacterial cell wall synthesis by interfering with the synthesis of peptidoglycan, and binds to the bacterial membrane and disrupts membrane barrier function. The Assessment of Telavancin in cSSSI (ATLAS) program, comprising of two Phase III clinical trials, demonstrated noninferiority of telavancin to vancomycin for the treatment of complicated skin and skin-structure infections including infections due to methicillin-resistant Staphylococcus aureus (MRSA). Among clinically evaluable patients with MRSA isolated at baseline in the pooled study population, the clinical cure rate was 87.0% (208 out of 239) for patients treated with telavancin and 85.9% (225 out of 262) for patients treated with vancomycin. The most common telavancin treatment-emergent adverse events were taste disturbance, nausea, vomiting and foamy urine. Renal adverse events occurred in 3% of telavancin-treated patients and 1% of vancomycin-treated patients. Telavancin is now approved in the USA and Canada for the treatment of Gram-positive complicated skin and skin-structure infections.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Female; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Treatment Outcome; Vancomycin

Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients > or = 18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Double-Blind Method; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Male; Penicillins; Skin Diseases, Bacterial; Treatment Outcome; Vancomycin

Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains.. We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients > or = 18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily).. For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (< or = 0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (approximately 5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9).. Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Double-Blind Method; Female; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Male; Middle Aged; Penicillins; Skin Diseases, Bacterial; Soft Tissue Infections; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Interactions; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Skin Diseases, Bacterial; Treatment Outcome

Telavancin is approved in the United States and Canada for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by susceptible Gram-positive organisms. The antimicrobial activity of telavancin and comparators was evaluated against 5,027 (2007-2008) Gram-positive bacteria responsible for SSSI in medical centers in Asia-Pacific, European, Latin American, and North American regions. Telavancin was active against Staphylococcus aureus (MIC₅₀(/)₉₀, 0.12/0.25 mg/l; 100.0% susceptible) and coagulase-negative staphylococci (MIC₅₀(/)₉₀, 0.12/0.25 mg/l). telavancin inhibited all Enterococcus faecalis, including four strains displaying a VanB phenotype, at ≤ 1 mg/L (MIC₅₀(/)₉₀, 0.25/0.5 mg/l), except for two isolates with a VanA phenotype (MIC, >2 mg/l). Vancomycin-susceptible and VanB vancomycin-resistant E. faecium were inhibited by telavancin at ≤ 0.25 mg/L, while this drug exhibited elevated MIC values (≥ 0.5 mg/l) against E. faecium of VanA phenotype (MIC₅₀(/)₉₀, 2/>2 mg/l). Telavancin was potent against β-haemolytic streptococci (MIC₅₀(/)₉₀, 0.03/0.12 mg/l; 100.0% susceptible) and viridans group streptococci (MIC₅₀(/)₉₀, 0.03/0.06 mg/l; 100.0% susceptible). These in vitro data document the activity of telavancin against contemporary Gram-positive isolates and support its clinical use for the treatment of cSSSI caused by the indicated pathogens.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Toxins; Drug Resistance, Bacterial; Enterococcus; Exotoxins; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Leukocidins; Lipoglycopeptides; Microbial Sensitivity Tests; Population Surveillance; Skin; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus; Staphylococcus aureus; Streptococcus; Vancomycin

Antibiotics currently under study by the Food and Drugs Administration include: faropenem (for treatment of sinusitis, bronchitis, and community-acquired pneumonia), dalbavancin (for catheter infections), telavancin (for treatment of nosocomial pneumonia), oritavancin (for bacteremia), ceftobiprole and iclaprim (for pneumonias). Moreover, all of them would be useful for skin and soft tissue infections.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteria; beta-Lactams; Cephalosporins; Drug Approval; Drug Resistance, Bacterial; Glycopeptides; Humans; Lipoglycopeptides; Pyrimidines; Skin Diseases, Bacterial; Skin Diseases, Viral; Teicoplanin; United States; United States Food and Drug Administration

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Drug Approval; Drug Discovery; Drug Resistance, Bacterial; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Staphylococcal Infections; United States; United States Food and Drug Administration