Use Of Telavancin Research Articles

Clinical Outcomes for Telavancin for Salvage Therapy in Methicillin-resistant Staphylococcus Aureus Bacteremia

Background Little evidence exists for the use of telavancin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia as salvage therapy. This study aims to evaluate the efficacy and safety of telavancin as salvage therapy in the treatment of MRSA bacteremia. Methods Electronic medical charts of patients who received telavancin for the treatment of MRSA bacteremia at an academic, tertiary care medical center in the United States between January 1, 2015, and May 31, 2019, were reviewed for clinical cure, reinfection, prior antibiotic use, source of infection, microbiological culture clearance, patient mortality, and adverse effects. The primary outcome was clinical cure. Results Thirty-eight charts were identified, and 11 met inclusion criteria for this analysis. Vancomycin or daptomycin was given for an average of 5.4 and 2.6 days, respectively, before the initiation of telavancin. The average telavancin dose used was 7.5 mg/kg. All patients achieved clinical cure, and there were no instances of 60-day mortality. Two patients experienced reinfection: 1 patient after 268 days and another after 467 days. Four patients experienced either QTc prolongation or acute renal failure. Conclusions The use of telavancin in MRSA bacteremia demonstrated microbiological cure, clinical cure, and minimal reinfection in the reviewed patient population. Telavancin may be a potential treatment option for patients with MRSA bacteremia as salvage therapy.

Clinical Experience with Telavancin: Real-World Results from the Telavancin Observational Use Registry (TOUR™).

BackgroundTelavancin—a lipoglycopeptide antibacterial agent active against Gram-positive pathogens including methicillin-sensitive and -resistant Staphylococcus aureus (MRSA)—is approved in the USA for once-daily intravenous use. This registry study captured patient characteristics, prescribing patterns, and treatment outcomes associated with telavancin use in real-world clinical practice.ObjectiveThis prospective, multicenter, observational study will characterize current real-world practice patterns for the use of telavancin in the USA by describing demographic and clinical conditions, examining the process of care and rationale for use, and describing the clinical effectiveness and selected safety outcomes among patients treated with telavancin.MethodsThe Telavancin Observational Use Registry (TOUR™) is an observational multicenter registry study. Clinical data—including patient demographics, pathogens, telavancin dosing and treatment duration, and adverse events—along with investigators’ assessments of outcome, were collected through retrospective medical chart review.ResultsData from 1063 patients were collected from 45 US sites. Of these patients, 29.4% were ≥ 65 years of age [mean age ± standard deviation, 55.2 ± 15.4 years; median age (interquartile range), 57.0 (46.0–66.0)], 53.4% were male, and 83.4% were White. The primary infections in these patients included complicated skin and skin-structure infection (48.7%), bone and joint infections (27.4%), bacteremia and endocarditis (14.2%), and lower respiratory tract infections (8.5%). The predominant pathogen identified was MRSA (37.7%). The mean telavancin dose and duration of treatment were 741.7 ± 194.3 mg and 17 ± 17 days, respectively. Of the 964 (90.7%) patients for whom an end-of-treatment assessment was available, 77.7% had a positive clinical response, 10.1% failed treatment, and 12.2% had indeterminate outcomes.ConclusionsReal-world data collected from the TOUR study show once-daily telavancin is being used for the treatment of a variety of Gram-positive infections with generally positive clinical outcomes.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00165-8) contains supplementary material, which is available to authorized users.

Regional analysis of telavancin and comparator antimicrobial activity against multidrug-resistant Staphylococcus aureus collected in the USA 2014-2016.

The in vitro antimicrobial activities of telavancin and comparator antimicrobials were evaluated against recent Staphylococcus aureus (S. aureus) clinical isolates collected in the United States of America (USA). A total of 15882 S. aureus isolates were collected (2014-2016) as part of the SENTRY Antimicrobial Surveillance Program from sites located in all US Census Bureau divisions. Broth microdilution MIC values were measured using current reference methods. Data were stratified by year and census division, and resistance rates were analysed for significant trends. Previously published data on methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) MRSA isolates (collected 2011-2013) were merged with the current isolate set to examine longer term resistance trends. Telavancin antimicrobial activity against MRSA and MDR MRSA isolates (MIC50/90 values, 0.03/0.06μg/mL for both subsets) remained unchanged over the 3-year surveillance period, and all isolates were susceptible to telavancin. No difference in telavancin activity was noted when MIC data were stratified by year or US Census Bureau division. When merged data (2011-2016) were analysed, the MRSA rate decreased for the entire USA and six individual census divisions, although the overall rate remained considerable. The overall US MDR MRSA rate also remained considerable and was unchanged from 2011-2016. The sustained potent activity of telavancin against US S. aureus isolates (100% susceptible) and the high rates of MRSA and MDR MRSA in the USA support the continued use of telavancin to treat indicated serious infections caused by S. aureus.

Real-world use of telavancin in the treatment of osteomyelitis

This is a retrospective analysis of patients with osteomyelitis who received telavancin at some time during their treatment course. The primary outcome was the percent of patients cured or improved at the end of telavancin therapy (EOTT). The secondary outcome was the percent of patients cured or improved three months after discontinuation of telavancin therapy. There were 32 cases of osteomyelitis with methicillin-resistant Staphylococcus aureus identified in 17 (56.7%), methicillin-sensitive Staphylococcus aureus 2(6.6%), coagulase negative staphylococci 6 (20.0%) and other pathogens, 5 (16.7%). At EOTT, 87.5% of patients had their osteomyelitis cured and 94.6% had the infection cured at three months after telavancin was completed. The most common adverse events associated with telavancin were gastrointestinal in nature (nausea (25.8%), vomiting (9.7%) and diarrhea (3.2%)) followed by metallic taste (6.5%). A favorable outcome was achieved for many patients receiving the antimicrobial regimen that included telavancin for the treatment of osteomyelitis.

Use of telavancin in adolescent patients with cystic fibrosis and prior intolerance to vancomycin: A case series

Use of telavancin in adolescent patients with cystic fibrosis and prior intolerance to vancomycin: A case series

Telavancin for the treatment of methicillin-resistant Staphylococcus aureus bone and joint infections

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.

Outpatient treatment of osteomyelitis with telavancin

Telavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens including Staphylococcus aureus, the most frequent cause of osteomyelitis. Treatment is often challenging due to needs for surgical intervention along with prolonged administration of intravenous antimicrobials, frequently in an outpatient setting. This was a retrospective analysis of the efficacy and safety of telavancin for treatment of osteomyelitis provided as outpatient parenteral antimicrobial therapy (OPAT) in physician office infusion centres. Medical records of 60 patients receiving telavancin for osteomyelitis in 22 physician office infusion centres from 2010 to 2011 and 2013 to 2015 were reviewed. Of these, 60% were treated without hospitalisation, 37% had orthopaedic hardware and 56% had concurrent infections. Staphylococcus aureus was the most common pathogen (78%), primarily methicillin-resistant. The median duration of telavancin treatment in the outpatient setting was 21 days (range 3–105 days). Telavancin was used as first-line therapy in 32% of cases, following prior antibiotic failure in 47% and due to intolerance to previous agents in 22%, predominantly daptomycin or vancomycin. The telavancin dose was 10 mg/kg/day, adjusted for renal function in 25% of patients. The majority of patients self-administered telavancin at home via an elastomeric infusion pump. Overall clinical success was 73%. No significant differences in outcomes were observed with the presence of hardware, concurrent infection, concomitant therapies or type of osteomyelitis. Telavancin-associated adverse events occurred in 57%, with discontinuation in three patients (5%). These data demonstrate the effective and safe OPAT use of telavancin, providing an alternative for successful treatment of patients with osteomyelitis.

Real-World Use of Telavancin in the Treatment of Osteomyelitis

Real-World Use of Telavancin in the Treatment of Osteomyelitis

Analysis of Telavancin In Vitro Activity Tested Against a USA Collection of Staphylococcus aureus Clinical Isolates Causing Hospital-Acquired Pneumonia (2013–2014)

Background: Telavancin is approved in the USA and Europe (methicillin-resistant [MRSA] only) for the treatment of hospital-acquired (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by S. aureus when alternative treatments are not suitable. This study provides a current in vitro activity analysis for telavancin and comparators against S. aureus causing HABP in USA hospitals during 2013 – 2014. Methods: 1,353 S. aureus collected from 29 USA sites located in the nine USA Census regions were included. Susceptibility testing was performed based on CLSI guidelines (M07-A10 and M100-S25). MIC interpretation was guided by FDA (2014), CLSI (2015) and/or EUCAST (2015) criteria. MRSA resistant to three or more drug classes were defined as multidrugresistant (MDR). Results: Telavancin had MIC50, MIC90 and MIC100 of 0.03, 0.06 and 0.06 mg/mL, respectively, against methicillin-susceptible, MRSA, non-MDR and MDR subsets. All isolates were inhibited by telavancin at the susceptible breakpoint (i.e. ≤0.12 mg/mL). Telavancin MIC values were at least 16-fold lower than vancomycin (MIC50/90, 1/1 μg/mL) and linezolid (MIC50/90, 1/1 μg/mL) MIC results against MRSA isolates (all 100.0% susceptible to vancomycin and linezolid). Telavancin, vancomycin (MIC50/90, 1/1 μg/mL) and linezolid (MIC50/90, 1/1 μg/mL) showed activity against the MDR subset, while other agents had limited coverage. S. aureus with vancomycin MIC=2 μg/mL had telavancin MIC50 (0.06 μg/mL) twofold higher than those with vancomycin MIC at ≤1 μg/mL. However, telavancin had MIC100 results of 0.06 μg/mL, regardless of subset. Conclusions: Telavancin had potent in vitro activity against S. aureus causing HABP, including less susceptible and MDR subsets, inhibiting all S. aureus at ≤0.06 μg/mL. These results confirm the potent in vitro activity of telavancin against S. aureus causing HABP in USA hospitals. CONCLUSIONS • Telavancin had potent in vitro activity against S. aureus causing HABP among hospitalized patients in USA institutions, including isolates less susceptible to vancomycin and MDR subsets. • All S. aureus were inhibited by telavancin at ≤0.06 μg/mL and telavancin was consistently more potent than comparator agents. These in vitro results support the use of telavancin for the treatment of HABP caused by S. aureus in USA hospitals.

The role of telavancin in hospital-acquired pneumonia and ventilator-associated pneumonia.

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.

Update on the emerging role of telavancin in hospital-acquired infections.

Telavancin is a lipoglycopeptide that has activity against Gram-positive aerobic and anaerobic bacteria. It has activity against methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus and non-Van-A strains of vancomycin-resistant enterococci. It has been approved by the US Food and Drug Administration (FDA) for complicated skin and skin structure infections and hospital-acquired pneumonia. There is a need for more clinical studies to determine the role of telavancin in treating bacteremia and prosthetic device infections. In this review, we discuss the published data on the use of telavancin in treating hospital-acquired infections and provide an update on new research.

Telavancin for refractory methicillin-resistant Staphylococcus aureus bacteremia and infective endocarditis

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure

ObjectivesTelavancin is approved in Europe for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus when other alternatives are not suitable. The approved European prescribing information contraindicates the use of telavancin in patients with severe renal impairment (creatinine clearance <30 mL/min, including patients on haemodialysis) and pre-existing acute renal failure owing to the higher observed mortality in these patients. Data from the ATTAIN studies were reanalysed, excluding patients with these contraindicating conditions at baseline. (At the time of submission of this article, the European marketing authorization of telavancin for the treatment of nosocomial pneumonia was suspended pending evidence of a new European Medicines Agency-approved supplier. Clinigen Healthcare Ltd, Theravance's commercialization partner for telavancin in Europe, is in the process of seeking approval of a new manufacturing source.)MethodsA post hoc analysis of data from two Phase 3 ATTAIN trials of telavancin for the treatment of Gram-positive nosocomial pneumonia assessing clinical outcomes and safety.ResultsThe all-treated population for this analysis represented 84.2% (1266/1503) of the ATTAIN all-treated population. The cure rates in the clinically evaluable population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups [treatment difference (95% CI): 1.3% (−5.0% to 7.6%)], and were consistent with the overall ATTAIN study results. The cure rate was higher in the telavancin than the vancomycin treatment group in microbiologically evaluable patients with only Gram-positive pathogens isolated at baseline [85.0% (130/153) versus 75.2% (109/145), respectively; treatment difference (95% CI): 9.7% (0.6%–18.8%)]. The incidences of adverse events were similar between treatment groups and consistent with the overall findings of the ATTAIN study.ConclusionsThis analysis demonstrated that in the subset of patients without severe renal impairment or pre-existing acute renal failure, clinical and safety outcomes were similar in the telavancin and vancomycin treatment groups.

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults

To summarize available literature regarding the potential role of linezolid, daptomycin, telavancin, tigecycline and ceftaroline for the treatment of osteomyelitis caused by resistant gram-positive organisms. Literature was obtained through PubMed searches from January 1980 to October 2011 using the terms osteomyelitis, bone, linezolid, daptomycin, telavancin, tigecycline and ceftaroline. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. Any published data related to bone penetration (animal or human) or clinical outcomes in adult osteomyelitis of these agents were included in the review. Animal models report bone concentrations of 2·3mcg/dL (vertebral) for linezolid, 0·45mcg/mL (tibiae) for daptomycin, 0·78mcg/mL (tibiae) for tigecycline and 0·27mcg/mL (tibiae) for telavancin; no data are available for ceftaroline. Human studies demonstrate bone concentrations of 4·6, 17·0 and 3·9mcg/mL (sternal, metatarsal and cancellous bone respectively) for linezolid, 4·7mcg/mL (metatarsal) for daptomycin and 0·078mcg/mL (unspecified) for tigecycline; no data are available for telavancin and ceftaroline. Retrospective cohort data, and prospective/retrospective case series support the use of linezolid in this setting; however, side-effects may limit use. Retrospective and prospective cohort data support daptomycin use. A retrospective case series is available supporting the use of telavancin. No data are available supporting clinical effectiveness for ceftaroline or tigecycline in the setting of osteomyelitis. Limited data are available evaluating the safety and efficacy of these agents in osteomyelitis in adults. Daptomycin and telavancin may be potential alternatives or second-line agents to vancomycin in selected patients. Linezolid, because of an increase in clinically important ADRs with prolonged use, should be reserved as a second- or third-line agent. Due to a lack of clinical data and poor bone penetration, along with concerns regarding outcomes in severe infections, tigecycline's potential is limited. Little data exist regarding ceftaroline use in osteomyelitis.

Telavancin in the treatment of invasive Gram-positive infections

Telavancin in the treatment of invasive Gram-positive infections Yoav Keynan,1&ndash;4 Ethan Rubinstein2,31Department of Community Health Sciences, 2Department of Medical Microbiology, 3Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 4Department of Medical Microbiology, University of Nairobi, Nairobi, KenyaAbstract: Telavancin is a newer once-daily lipoglycopeptide with activity against Gram-positive bacteria, including those that are resistant to conventional antibiotics like beta-lactams. The results of recent clinical trials led to registration of telavancin for use in skin and skin structure infections in the US and Canada and for nosocomial pneumonia in Europe, based primarily on the favorable results of clinical trials. We review the evidence for use of telavancin in Gram-positive intravascular infections, focusing on bacteremic subpopulations in the large clinical trials as well as anecdotal evidence for use of the drug in the setting of infective endocarditis.Keywords: telavancin, Gram-positive bacteria, skin infections, infective endocarditis

Comment on: Successful treatment of methicillin-resistant Staphylococcus aureus mitral valve endocarditis with sequential linezolid and telavancin monotherapy following daptomycin failure

Sir, Joson et al. recently published a report using telavancin to complete treatment of endocarditis due to methicillin-resistant Staphylococcus aureus. While in agreement with their discussion and informative thoughts, some other points should also be considered. While the authors correctly point out the initial underdosing of daptomycin and its potential contribution to the subsequent emergence of daptomycin-non-susceptible isolates, they did not comment on the vancomycin dose (which was also underdosed initially). This may also contribute to future issues with reduced antimicrobial susceptibilities. Persistent bacteraemia should prompt consideration of a search for an undrained focus of infection. While paraspinal fluid collections were found and drained under CT guidance, the report does not mention any follow-up imaging performed to assess the adequacy of drainage. Transoesophageal echocardiography, if performed earlier in the hospital course, might have demonstrated the mitral valve vegetation and have led to more expeditious surgery. Blood cultures appear to have cleared with linezolid and surgery. Linezolid has been previously used as therapy for staphylococcal endocarditis. In the reported case, thrombocytopenia, which developed after an 3 week course of linezolid, led to the use of telavancin. While not disagreeing with the use of telavancin or discounting its role in the successful treatment of the patient, difficulty exists in quantifying the contribution of telavancin to the clinical success. The removal of the foci of infection and lengthy course of antimicrobials prior to the telavancin probably played a more significant role than telavancin in achieving cure. We are appreciative of the authors’ sharing of their case and of the Journal for publishing it. Clinical circumstances often lead to the need for unlabelled use of antimicrobials and communication about this serves the medical community well in the care of our patients.

Successful treatment of methicillin-resistant Staphylococcus aureus endocarditis with telavancin

Sir, Within our institution, we have recently seen an increase in bloodstream infections due to methicillin-resistant Staphylococcus aureus (MRSA) having decreased responsiveness to glycopeptides. Testing has revealed that these isolates are neither vancomycin intermediate nor heterogeneous vancomycin intermediate. Patients continue to be bacteraemic despite therapeutic levels of vancomycin. In September 2009, the FDA approved telavancin for the treatment of complicated skin and soft-tissue infections. To date, there have been no reports of the use of telavancin in bacteraemic patients. Here we report the successful use of telavancin for MRSA bacteraemia and right-sided endocarditis. A patient with a history of hepatitis C and intravenous drug use presented with fevers and chills. Blood cultures grew MRSA (vancomycin MIC≤0.5 mg/L, daptomycin MIC≤1 mg/L) and he was begun on 15 mg/kg vancomycin every 12 h. He was found to have septic pulmonary emboli and a pleural effusion. A transoesophageal echocardiogram showed severe tricuspid valve regurgitation with a large tricuspid valve vegetation. Blood cultures remained positive through 8 days of vancomycin treatment with documented trough levels of 15–20 mg/L. Treatment was changed to 10 mg/kg telavancin intravenously every 24 h. Blood cultures became negative within 1 day of the start of telavancin. The patient’s creatinine was monitored and remained stable from admission. The patient underwent a tricuspid valve repair for severe tricuspid regurgitation 1 month after his initial positive culture. He completed 4 weeks of telavancin and was discharged home in a stable condition 6 weeks after his admission. At follow-up 6 weeks after completing treatment, the patient was afebrile with documented negative blood cultures. To our knowledge, this is the first case of persistent MRSA bacteraemia treated successfully with telavancin. Telavancin is a lipoglycopeptide with a mechanism of action similar to that of the glycopeptides but with an added mechanism that interferes with cell membrane function. It is reportedly rapidly bactericidal against S. aureus, thus having potential for use in bacteraemic patients. The study of telavancin in MRSA bacteraemia has been completed in murine models with the comparator being vancomycin. In this model, telavancin demonstrated greater killing activity than vancomycin, and a statistically significant difference in survival was found between the two groups with 0% survival for vancomycin and 93% for telavancin. These results have been attributed to the dual mechanism of action of telavancin as well as a longer post-antibiotic effect. With the increasing frequency of persistent MRSA bacteraemia with decreased responsiveness to vancomycin and failures reported with daptomycin after vancomycin use, new therapeutic options are desirable. Clinical studies will be necessary to determine whether telavancin offers advantages over other currently available antibiotics.

Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus

To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA). Determination of cfu changes (3-24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000x MIC. Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration-effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3-1x MIC and 100-1000x MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [-3 log (MSSA) to -1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. -0.5 log decrease at 24 h and at Cmax). Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.