BACKGROUND: The effect of systemic treatment of ventilator-associated pneumonia (VAP) with telavancin, a semisynthetic lipoglycopeptide with good penetration in vitro biofilms, has not been tested in vivo during mechanical ventilation. This study examined the efficacy of telavancin compared with linezolid against endotracheal tube (ETT) biofilms in a porcine model of methicillin-resistant Staphylococcus aureus (MRSA) VAP.
METHODS: VAP was induced in 18 pigs by instilling 107 colony-forming units (CFU/mL) of an MRSA strain susceptible to telavancin and linezolid into each pulmonary lobe. Randomization into three groups was done at pneumonia diagnosis: control (IV glucose 0.5% solution q24); linezolid (10 mg/kg q12) and telavancin groups (22.5 mg/kg q24). After 72 h of MV, data regarding bronchoalveolar lavage (BAL), tracheal aspirate (TA), ETT MRSA biofilm load and thickness measured by scanning electron microscopy were obtained.
RESULTS: All 18 pigs completed the study. MRSA was isolated in 100% of ETTs from the control and linezolid groups and in 67% from the telavancin group. Telavancin treatment presented a lower MRSA load compared to the control and linezolid treatments (telavancin median [interquartile range (IQR)] = 1.94 [0.00-5.45], linezolid 3.99 [3.22-4.68] and control 4.93 [4.41-5.15], P = 0.236). Telavancin treatment also resulted in the lowest biofilm thickness according to the SEM (4.04 [2.09-6.00], P < 0.001). We found a positive correlation between ETT and BAL load (rho = 0.511, P = 0.045).
CONCLUSIONS: In our VAP model, systemic telavancin treatment reduced ETT MRSA occurrence, load, and biofilm thickness. Our findings may have a bearing on ICU patients\' clinical outcomes.

Methicillin-resistant Staphylococcus aureus (MRSA) causes invasive infections and is associated with community-acquired infections (CAIs) and hospital-associated infections (HAIs). In 2020, 315 S. aureus isolates, including 145 methicillin-susceptible S. aureus (MSSA) and 170 MRSA, mainly associated with bacteremia and mostly CAIs, were collected from 16 hospitals in different regions of Taiwan. Minimum inhibitory concentrations (MICs) were determined using the Sensititre™ complete automated AST system. Staphylococcal cassette chromosome mec (SCCmec) types were analysed using multiplex polymerase chain reaction. The median age of patients infected with MRSA was significantly higher than that of patients infected with MSSA (72.5 years vs. 67.0 years, P=0.027). MIC50/MIC90 values of eravacycline and omadacycline were 0.06/0.12, and 0.25/0.5, respectively. Of the MRSA isolates, 4.1% presented susceptible dose-dependence to ceftaroline, most of which (85.7%) were HAI- and Panton-Valentine leukocidin (PVL)-negative. Among the MRSA isolates, 7.1% were not susceptible to telavancin and tedizolid (mainly type IV, PVL-negative, and CAI), 0.6% were not susceptible to daptomycin (type III, PVL-negative, and HAI), and 1.8% were not susceptible to quinupristin/dalfopristin (three isolates were type III, IV, and VT, respectively, and all were PVL-negative), but all were susceptible to dalbavancin. In conclusion, patients with bacteremia caused by MRSA were older than those with bacteremia caused by MSSA, SCCmec type IV was more predominant in CAI than in HAI, and MRSA isolates not susceptible to novel anti-MRSA antimicrobials belonged to types II, III, or IV. Further studies that include comprehensive demographics and more detailed descriptions of other antimicrobial-resistant genes are urgently needed.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates.
METHODS: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0).
RESULTS: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC50 and MIC90, (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC50 and MIC90, respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100).
CONCLUSIONS: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future.

Telavancin, a lipoglycopeptide antibiotic, is traditionally dosed at 10 mg/kg based on total body weight but is associated with toxicities that limit its use. This study supports the use of a capped dosing regimen of 750 mg in obese patients, which is associated with equal efficacy and fewer adverse effects compared to traditional dosing.

Members of the genus Corynebacterium are increasingly recognized as pathobionts and can be very resistant to antimicrobial agents. Previous studies have demonstrated that Corynebacterium striatum can rapidly develop high-level daptomycin resistance (HLDR) (MIC, ≥256 μg/ml). Here, we conducted a multicenter study to assay for this in vitro phenotype in diverse Corynebacterium species. Corynebacterium clinical isolates (n = 157) from four medical centers were evaluated. MIC values to daptomycin, vancomycin, and telavancin were determined before and after overnight exposure to daptomycin to identify isolates able to rapidly develop daptomycin nonsusceptibility. To investigate assay reproducibility, 18 isolates were evaluated at three study sites. In addition, the stability of daptomycin nonsusceptibility was tested using repeated subculture without selective pressure. The impact of different medium brands was also investigated. Daptomycin nonsusceptibility emerged in 12 of 23 species evaluated in this study (C. afermentans, C. amycolatum, C. aurimucosum, C. bovis, C. jeikeium, C. macginleyi, C. pseudodiphtheriticum, C. resistens, C. simulans, C. striatum, C. tuberculostearicum, and C. ulcerans) and was detected in 50 of 157 (31.8%) isolates tested. All isolates displayed low (susceptible) MIC values to vancomycin and telavancin before and after daptomycin exposure. Repeated subculture demonstrated that 2 of 9 isolates (22.2%) exhibiting HLDR reverted to a susceptible phenotype. Of 30 isolates tested on three medium brands, 13 (43.3%) had differences in daptomycin MIC values between brands. Multiple Corynebacterium species can rapidly develop daptomycin nonsusceptibility, including HLDR, after a short daptomycin exposure period.

OBJECTIVE: U.S. Food and Drug Administration (FDA) recommended telavancin dosing is based on total body weight (TBW) but lacks adjusted regimens for obese subjects with varying renal function. Our aim was to develop a physiologically based pharmacokinetic (PBPK) model of telavancin to design optimized dosing regimens for obese patients with hospital-acquired pneumonia (HAP) and varying renal function.
METHODS: The PBPK model was verified using clinical pharmacokinetic (PK) data of telavancin in healthy populations with varying renal function and obese populations with normal renal function. Then, the PBPK model was applied to predict the PK in obese HAP patients with renal impairment (RI).
RESULTS: The fold error values of PK parameters (AUC, Cmax, Tmax) were all within 1.5. The telavancin AUC0-inf was predicted to increase 1.07-fold in mild RI, 1.23-fold in moderate RI, 1.41-fold in severe RI, and 1.57-fold in end-stage renal disease (ESRD), compared with that in obese HAP with normal renal function. The PBPK model combined with Monte Carlo simulations (MCS) suggested that dose adjustment based on a 750-mg-fixed dose could achieve effectiveness with reduced risk of toxicity, compared with current TBW-based dosing recommendations.
CONCLUSIONS: The PBPK simulation proposed that using TBW-based regimen in obesity with RI should be avoided. Dose recommendations in obesity from the PBPK model are 750 mg daily for normal renal function and mild RI, 610 mg daily for moderate RI, 530 mg daily for severe RI, and 480 mg daily for ESRD.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Glycopeptides have an established role in the management of infective endocarditis, and feature in current treatment guidelines. Newer lipoglycopeptide agents (dalbavancin, telavancin and oritavancin), which are analogues of glycopeptides with structural modifications giving rise to added novel mechanisms of antimicrobial activity, are approved for the treatment of Gram-positive skin and skin structure infections, and also for nosocomial pneumonia (only telavancin has approval for the latter indication). Recent evidence has also emerged to support their use in the treatment of bone and joint infections. This article reviews the current literature on dalbavancin and telavancin in the treatment of infective endocarditis, a condition for which the role of these agents is yet to be established.

Glycopeptides, such as vancomycin and teicoplanin, are primarily used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, such as cellulitis, endocarditis, meningitis, pneumonia, and septicemia, and are some of the most commonly prescribed parenteral antimicrobials. Parenteral glycopeptides are first-line therapy for severe MRSA infections; however, oral vancomycin is used as a first-line treatment of Clostridioides difficile infections. Also, we currently have the longer-acting lipoglycopeptides, such as dalbavancin, oritavancin, and telavancin to our armamentarium for the treatment of MRSA infections. Lastly, vancomycin is often used as an alternative treatment for patients with β-lactam hypersensitivity. Common adverse effects associated with glycopeptide use include nephrotoxicity, ototoxicity, and Redman Syndrome (RMS). The RMS is often mistaken for a true allergy; however, it is a histamine-related infusion reaction rather than a true immunoglobulin E (IgE)-mediated allergic reaction. Although hypersensitivity to glycopeptides is rare, both immune-mediated and delayed reactions have been reported in the literature. We describe the various types of glycopeptide hypersensitivity reactions associated with glycopeptides and lipoglycopeptides, including IgE-mediated reactions, RMS, and linear immunoglobulin A bullous dermatosis, as well as describe cross-reactivity with other glycopeptides.

This study evaluated the in vitro antimicrobial activity of telavancin against a large collection of Gram-positive pathogens of clinical importance, which were collected worldwide from 2015 through 2017, including methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, Enterococcus spp., β-hemolytic streptococci (BHS), Streptococcus pneumoniae, and viridans group streptococci (VGS). This report completes 7 years of continuous surveillance data for telavancin using the approved reference method for in vitro testing methodology that includes the addition of polysorbate 80. For isolates collected from 2015 through 2017, telavancin exhibited potent activity against the following species and groups that have Clinical and Laboratory Standards Institute (CLSI)-approved interpretive criteria: MRSA (MIC90 value, 0.06 μg/mL; 100% susceptible), vancomycin-susceptible Enterococcus faecalis (MIC90 value, 0.25 μg/mL; 99.9% susceptible), BHS (MIC90 value, 0.03 μg/mL; 100% susceptible), and VGS (MIC90 value, 0.03 μg/mL; 99.0% susceptible). Importantly, telavancin maintained excellent antimicrobial activity against multidrug-resistant subsets of these pathogen groups and against ceftaroline-nonsusceptible (telavancin MIC90 value, 0.06 μg/mL; 100% susceptible) and ceftaroline-resistant (telavancin MIC90 value, 0.12 μg/mL; 100% susceptible) S. aureus isolates.