In Vitro Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure

Abstract

Telavancin is a lipoglycopeptide with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). The activity of telavancin against MRSA and MSSA after prior vancomycin exposure was studied in an in vitro pharmacodynamic model. Two clinical MRSA and two MSSA isolates, all with vancomycin MICs of 2 g/ml, were subjected to humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) for 96 h, telavancin at 750 mg q24h for 96 h, and vancomycin at 1 g q12h for 72 h followed by telavancin at 750 mg q24h for 48 h (120 h total). The microbiological responses were measured by changes from 0 h in log 10 CFU/ml at the end of experiments and area under the bacterial killing and regrowth curves over 96 h (AUBC 0؊96 ). The control isolates grew to 8.8 ؎ 0.3 log 10 CFU/ml. Initially, all regimens caused ؊4.5 ؎ 0.9 reductions in log 10 CFU/ml by 48 h followed by slight regrowth over the following 48 to 72 h. After 96 h, vancomycin and telavancin achieved ؊3.7 ؎ 0.9 and ؊3.8 ؎ 0.8 log 10 CFU/ml changes from baseline, respectively (P ‫؍‬ 0.74). Sequential exposure to telavancin after vancomycin did not result in additional CFU reductions or increases, with ultimate log 10 CFU/ml reductions of ؊4.3 ؎ 1.1 at 96 h and ؊4.2 ؎ 1.3 at 120 h (P > 0.05 for all comparisons at 96 h). The AUBC 0 -96 was significantly smaller for the regimen of telavancin for 96 h than for the regimens of vancomycin for 96 h and vancomycin followed by telavancin (P < 0.04). No resistance was observed throughout the experiment. Against these MRSA and MSSA isolates with vancomycin MICs of 2 g/ml, telavancin was comparable with vancomycin and its activity was unaffected by prior vancomycin exposure. Staphylococcus aureus is one of the most globally prevalent infectious organisms in both hospital and community settings (1). Methicillin-resistant S. aureus (MRSA), in particular, represents a health care threat with Ͼ80,000 cases of invasive infections estimated to occur annually in the United States and 11,000 deaths according to a recent report by the Centers for Disease Control and Prevention (2). MRSA is a common cause of bloodstream infections, skin infections, and pneumonia (3). In addition to the risk of mortality, infections due to MRSA are also linked to an increased length of hospital stay and increased hospitalization costs (4).For decades, intravenous vancomycin has been considered the standard of care for treatment of MRSA infections in hospitalized patients and is often empirically initiated in patients when S. aureus is suspected. However, vancomycin therapy may fail in some patients due to increases in the MIC up to 2 g/ml (i.e., MIC creep) or secondary to the development of nephrotoxicity, which is reported to occur at a rate of 4 to 42% (5, 6). Therefore, alternative anti-MRSA agents are needed for patients who do not respond to vancomycin.Only in the recent decade has the pharmaceutical industry caught up with treatment options for resistant S. aureus infections. Several intr...

Real-World Clinical Use and Outcomes of Telavancin for the Treatment of Bone and Joint Infections: Results from the Telavancin Observational Use Registry (TOUR™)

“…Telavancin is a once-daily, parenterally administered, lipoglycopeptide antibacterial agent for the treatment of Gram-positive pathogens, including methicillin-susceptible S. aureus (MSSA) and MRSA [10]. Telavancin has demonstrated noninferiority to vancomycin in pneumonia treatment of both MSSA and MRSA [11,12]. The Telavancin Observational Use Registry (TOUR™) was conducted to record real-world telavancin usage patterns, including population characteristics and clinical outcomes of patients treated with telavancin for infections with Gram-positive pathogens [13,14].…”

A Molecular Switch‐Integrated Nanoplatform Enables Photo‐Unlocked Antibacterial Drug Delivery for Synergistic Abscess Therapy

“…[ 54 ] Conventional antibiotics have led to persistent drug resistance along with severe side effects, thereby creating substantial risks to public health. [ 55 ] Our strategy, presented in this work, offered several advantageous features to enhance the efficacy of antibiotic drugs. First, the drug releasing behavior of HAVH was highly controllable with the photothermally responsive molecular switch, thereby improving the bioavailability of Van to kill MRSA with a reduced concentration.…”

Antibacterial activity of recently approved antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) strains: A systematic review and meta-analysis

“…For two reasons, A) methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized public health problem worldwide [ 3 ], and B) Antibiotic-resistance pattern of MRSA. Currently, World Health Organization (WHO) considers S. aureus, especially MRSA, as one of the fundamental clinical challenges throughout the world.…”