telavancin and Bacteremia

Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteremia; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Humans; Lipoglycopeptides; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Hospital-acquired pneumonia (HAP) due to gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of morbid conditions and death. Telavancin is a lipoglycopeptide antibiotic with potent in vitro activity against a range of gram-positive pathogens, including MRSA, methicillin-susceptible S. aureus, and Streptococcus species. In 2 phase 3 clinical trials, telavancin was noninferior to vancomycin in patients with HAP due to gram-positive pathogens. Clinically evaluable patients with S. aureus as the sole pathogen or S. aureus with a vancomycin minimum inhibitory concentration >1 µg/mL, however, had higher cure rates with telavancin than with vancomycin. In patients with bacteremic HAP, telavancin resulted in clearance of blood cultures. It was associated with increased serum creatinine levels and higher mortality rates in patients with moderate to severe renal impairment at baseline; however, on subsequent analysis, the outcomes seemed to have been at least partially affected by the adequacy of empiric gram-negative antimicrobial therapy. Thus, clinicians need to consider the risk-benefit balance when choosing telavancin in patients with severe renal impairment at baseline. Overall, these data support the use of telavancin in the treatment of HAP due to S. aureus, including MRSA and strains with elevated vancomycin minimum inhibitory concentrations, but clinicians should always weigh the risks and benefits of various treatment options.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Clinical Trials, Phase III as Topic; Cross Infection; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Staphylococcal Infections

Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.).

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Female; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Hematologic Neoplasms; Humans; Lipoglycopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Pilot Projects; Recurrence; Treatment Outcome; Vancomycin

Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia.. Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days.. In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%).. This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Double-Blind Method; Female; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Penicillins; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecium; Epidemiological Monitoring; Gram-Positive Bacterial Infections; Humans; Linezolid; Lipoglycopeptides; Microbial Sensitivity Tests; Oxazolidinones; Taiwan; Tetracyclines; Tetrazoles; Tigecycline; Vancomycin; Vancomycin-Resistant Enterococci; Virginiamycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Drug Resistance, Bacterial; Hospitalization; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Pneumonia, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; United States

Telavancin is a lipoglycopeptide semi-synthetic derivative of vancomycin used for select infections caused by Gram-positive bacteria including

Topics: Acute Kidney Injury; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Nephritis, Interstitial; Staphylococcal Infections

Patients with end-stage renal disease (ESRD) requiring intermittent haemodialysis (IHD) are at high risk of MRSA bacteraemia (MRSA-B) and often fail first-line therapy. The safety, effectiveness and optimal dosing of telavancin for MRSA-B in this patient population are unclear.. We aimed to describe clinical outcomes of telavancin in the treatment of refractory MRSA-B in patients with ESRD requiring IHD.. This was a retrospective study of hospitalized patients at two tertiary care academic medical centres with recurrent or persistent (≥3 days) MRSA-B treated with telavancin monotherapy. Outcomes included duration of MRSA-B (pre-telavancin versus post-telavancin) and microbiological failure (duration of MRSA-B ≥3 days after initiation of telavancin).. Telavancin dosed 10 mg/kg three times weekly post-IHD or 10 mg/kg every 48 h resulted in microbiological cure in 7/8 (87.5%) refractory MRSA-B cases. Telavancin monotherapy was associated with a significant reduction in median duration of bacteraemia [16 days pre-telavancin (IQR 8-19 days) versus 1 day post-telavancin (IQR 0-2 days); P = 0.018]. Telavancin was well tolerated by all patients and no adverse events were reported.. Telavancin was very safe and highly effective in the treatment of refractory MRSA-B in a cohort of patients with ESRD requiring IHD. These data support the utility of telavancin in the armamentarium against refractory MRSA-B, particularly in the high-risk IHD-dependent population.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Female; Hospitalization; Humans; Kidney Failure, Chronic; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Renal Dialysis; Retrospective Studies; Staphylococcal Infections; Tertiary Care Centers; Treatment Outcome

This retrospective, case series describes our experience with the use of telavancin in patients with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and prosthetic joint infection. The primary objectives were clinical outcomes and adverse events (AEs), and a secondary outcome described microbiological susceptibility. Fourteen patients were enrolled. Median duration of therapy was 58 days, and four patients had concurrent bacteremia. End-of-treatment outcomes were available in 78% of patients, with a clinical success rate of 91%. Thirty-day and 12-month outcomes were also obtained. Seven patients experienced AEs. Infusion-related reactions were most common, and three AEs required discontinuation of therapy. All MRSA isolates had a telavancin MIC ≤0.06μg/ml, which is susceptible. This study indicates that telavancin may have a role in treatment of MRSA osteomyelitis and prosthetic joint infection. Our study describes clinical success and adverse events for long duration of therapy, up to 8 weeks.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Body Mass Index; Female; Follow-Up Studies; Humans; Joint Diseases; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Retrospective Studies; Staphylococcal Infections

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and infective endocarditis (IE) have become increasingly difficult to treat over the past decade, with suboptimal response rates of less than 50%. Although vancomycin and daptomycin are standard therapeutic options, treatment failures with either or both agents are common. Telavancin is a lipoglycopeptide antibiotic with activity against MRSA. In vitro, telavancin displays bactericidal activity and has lower minimum inhibitory concentrations to MRSA than vancomycin.. We present a retrospective, case-series report of 14 patients treated with telavancin for refractory MRSA bacteremia with and without IE at our institution from 9 September 2010 to 2 April 2012.. Of the 14 patients who received telavancin for refractory MRSA bacteremia and IE, eight survived their inpatient admission and were able to be followed for 30 days. The overall survival rate was 57% (n = 8). Of the eight surviving patients, five were diagnosed with MRSA IE and the remaining three were diagnosed with complicated MRSA bacteremia. All six patients who did not survive the inpatient admission were diagnosed with left-sided IE involving the mitral valves.. This retrospective case series provides clinical evidence for the use of telavancin as a treatment option for refractory MRSA bacteremia and IE. With limited effective agents in the treatment of MRSA-complicated bacteremia and IE, telavancin represents a potential treatment option. Further randomized, controlled trials are necessary to define the optimal role of telavancin in the treatment of MRSA bacteremia and IE.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Endocarditis, Bacterial; Female; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Retrospective Studies; Salvage Therapy; Staphylococcal Infections; Survival Rate; Time Factors; Young Adult

The alarming growth of antibiotic resistant superbugs such as vancomycin-resistant Enterococci and Staphylococci has become a major global health hazard. To address this issue, we report the development of lipophilic cationic vancomycin analogues possessing excellent antibacterial activity against several drug-resistant strains. Compared to vancomycin, efficacy greater than 1000-fold was demonstrated against vancomycin-resistant Enterococci (VRE). Significantly, unlike vancomycin, these compounds were shown to be bactericidal at low concentrations and did not induce bacterial resistance. An optimized compound in the series, compared to vancomycin, showed higher activity in methicillin-resistant Staphylococcus aureus (MRSA) infected mouse model and exhibited superior antibacterial activity in whole blood with no observed toxicity. The remarkable activity of these compounds is attributed to the incorporation of a new membrane disruption mechanism into vancomycin and opens up a great opportunity for the development of novel antibiotics.

Topics: Animals; Bacteremia; Cell Membrane Permeability; Drug Resistance, Bacterial; Enterococcus; Female; HeLa Cells; Hemolysis; Humans; Mice; Microbial Sensitivity Tests; Neutropenia; Quaternary Ammonium Compounds; Staphylococcal Infections; Staphylococcus; Structure-Activity Relationship; Triazoles; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cross Infection; Humans; Lipoglycopeptides; Pneumonia, Bacterial; Treatment Outcome; Vancomycin

Vancomycin-intermediate Staphylococcus aureus (VISA) infections are an emerging problem and antibiotic options are limited. We report the first case, to our knowledge, of heteroresistant VISA mediastinitis and bacteremia in a patient with a ventricular assist device who underwent orthotopic heart transplantation with clinical cure.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Debridement; Defibrillators, Implantable; Female; Heart Transplantation; Heart-Assist Devices; Humans; Lipoglycopeptides; Mediastinitis; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin; Vancomycin Resistance

Infections caused by heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) are associated with high rates of vancomycin treatment failure. Telavancin is a bactericidal lipoglycopeptide active in vitro against Gram-positive pathogens including hVISA and vancomycin-intermediate S. aureus (VISA). This study characterizes the microbiological activity of telavancin against vancomycin-susceptible S. aureus (VSSA), hVISA and VISA strains.. Reference strains of VSSA, hVISA and VISA were assessed for potential telavancin heteroresistance by population analysis. In addition, the efficacies of telavancin (40 mg/kg subcutaneously every 12 h for 4 days) and vancomycin (110 mg/kg subcutaneously every 12 h for 8 days) were compared in a neutropenic murine model (immunocompromised female non-Swiss albino mice) of bacteraemia caused by hVISA strain Mu3. Blood and spleen bacterial titres were quantified from cohorts of mice euthanized pre-treatment and at 24 h intervals post-treatment for 8 days.. Telavancin was active against all strains of S. aureus tested, with MIC values < or =0.5 mg/L. Population analyses revealed no evidence of subpopulations with reduced susceptibility to telavancin. In the murine bacteraemia model of hVISA infection, all animals were bacteraemic pre-treatment and mortality was 100% within 16-24 h post-infection in untreated animals. Treatment with telavancin was associated with lower spleen bacterial titres, lower rates of bacteraemia and lower overall mortality than treatment with vancomycin.. These in vitro and pre-clinical in vivo studies demonstrate that telavancin has the potential to be efficacious in infections caused by hVISA.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteremia; Blood; Disease Models, Animal; Female; Lipoglycopeptides; Mice; Microbial Sensitivity Tests; Spleen; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin Resistance

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Endocarditis, Bacterial; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Treatment Outcome

The aim of the study was to compare the efficacies of telavancin and vancomycin against glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous vancomycin-intermediate S. aureus (hVISA) in a neutropenic murine bacteraemia model.. Immunocompromised mice (female non-Swiss albino, 18-30 g) were inoculated intraperitoneally with 10(7) cfu/mL of GISA (strain HIP-5836 or Mu50) or hVISA (strain Mu3). Infected mice received a subcutaneous dose of telavancin (40 mg/kg) or vancomycin (110 mg/kg) at 4 and 16 h post-inoculation. Control animals received a subcutaneous dose of vehicle at 4 h post-inoculation only. Blood and spleen bacterial titres were quantified in drug-treated mice at 16, 28 and 52 h post-inoculation.. Telavancin was 8-fold more potent than vancomycin against HIP-5836 (MIC 1 versus 8 mg/L), 16-fold more potent against Mu50 (MIC 0.5 versus 8 mg/L) and 8-fold more potent against Mu3 (MIC 0.25 versus 2 mg/L). Telavancin produced significant (P < 0.05) and sustained reductions in blood and spleen titres from pre-treatment levels in mice infected with HIP-5836, Mu50 or Mu3. Vancomycin lowered blood and spleen HIP-5836 counts transiently, but did not lower blood or spleen Mu50 or Mu3 counts significantly at any timepoint. Reductions in blood and spleen HIP-5836 and Mu3 titres and in spleen Mu50 titres at 52 h post-inoculation were significantly greater with telavancin than vancomycin (P < 0.05).. Telavancin was more efficacious than vancomycin in clearing infections caused by GISA strains HIP-5836 and Mu50 and hVISA strain Mu3 in a neutropenic mouse bacteraemia model. Further evaluation of telavancin for GISA and hVISA bacteraemia is warranted.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteremia; Blood; Colony Count, Microbial; Drug Resistance, Bacterial; Female; Glycopeptides; Lipoglycopeptides; Mice; Spleen; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

The efficacy of telavancin, a bactericidal lipoglycopeptide, was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in an immunocompromised murine model of bacteraemia.. Immunocompromised mice were inoculated intraperitoneally with S. aureus ATCC 33591 and treated with two subcutaneous doses (once every 12 h) of vehicle or test compound. Mouse pharmacokinetic data were generated and used to choose doses of telavancin (40 mg/kg) and vancomycin (110 mg/kg) in order to equate clinical exposures. Reduction in bacterial titre (in blood and spleen) and mortality were the two pharmacodynamic endpoints of the study.. Mortality was 100% in animals treated with vehicle or vancomycin but was significantly lower (7%) in telavancin-treated animals. Telavancin produced significantly greater reductions in blood and spleen bacterial titres compared with vancomycin.. The data described here demonstrate that telavancin's in vivo bactericidal activity is superior to that of vancomycin against a single strain of MRSA and results in successful infection resolution and, consequently, improved survival in the murine bacteraemia model.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteremia; Blood; Disease Models, Animal; Lipoglycopeptides; Methicillin Resistance; Mice; Spleen; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis; Vancomycin