In Vitro Antimicrobial Activity of Telavancin against Methicillin-resistant Staphylococcus aureus Clinical Isolates from Japan (2006)

Abstract

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 m g/ml to 0.5 m g/ml and a MIC 90 value of 0.5 mg/ml. The MIC 90 s of vancomycin and linezolid were 1.0m g/ml and 2 m g/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.Keywords telavancin, S. aureus, MRSA, surveillance, vancomycin, Japan, lipoglycopeptideThe global emergence of severe infections caused by Gram-positive pathogens with resistance or reduced susceptibility to antibiotics has become a major public health concern. Importantly, among Staphylococcus aureus isolates, the frequency with which methicillin-resistant strains (MRSA) are isolated is rising [1]. In addition, MRSA strains with reduced susceptibility to vancomycin, teicoplanin and linezolid are reported with increasing frequency [2ϳ4]. Failure of vancomycin to effectively treat serious staphylococcal infections has been reported and many experts believe that this may be due to its limited bactericidal activity [5,6].Telavancin (Fig. 1), a novel lipoglycopeptide antibiotic with a unique, multifunctional mechanism of action and rapid, concentration-dependent bactericidal activity, has completed two Phase III trials for complicated skin and skin structure infections, and is currently under evaluation for the treatment of hospital-acquired pneumonia [7]. Unlike vancomycin and teicoplanin, telavancin disrupts bacterial cell membrane integrity in addition to inhibiting peptidoglycan synthesis [8]. This dual mechanism of action may be the reason for the potent bactericidal activity observed with telavancin, which may also be a factor in limiting the emergence of resistance

Comparative Activity of Telavancin and Other Antimicrobial Agents against Methicillin-Resistant Staphylococcus aureus Isolates Collected from 1991 to 2006

“…This period encompassed three newer anti-MRSA agents before and after their introduction, which allowed us to determine whether there was evidence of preexisting reduced susceptibility and to test for declines in susceptibility since the clinical introduction of these agents. The in vitro MIC 50 , MIC 90 and MIC ranges reported in our study are identical or extremely similar to those involving recent isolates from Japan [26] , the US [8] and the UK [27] , and from isolates dating back to 1998 from the US [7] and back to 2001 from the UK [28] . The isolates tested from the VAMC track the MIC history back to 1991, and these data showed no significant differences in MICs between historical and more current isolates and no narrowing of the ranges with increasingly distant dates from the current time ( table 1 ).…”

Telavancin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA)

“…Similar in vitro activity against MRSA was also observed with an MIC 90 of 0.25–1 μg/mL compared to 1–2 μg/mL for vancomycin 9,10,16. Currently, the Clinical and Laboratory Standards Institute (CLSI) has not published susceptibility breakpoints for telavancin.…”

The efficacy and safety of sitafloxacin and garenoxacin for the treatment of pneumonia in elderly patients: A randomized, multicenter, open-label trial

“…gram-negative bacteria and anaerobic bacteria, are lower than those of other respiratory quinolones (garenoxacin, moxifloxacin, and levofloxacin) [4,22]. The median serum and sputum concentrations of sitafloxacin were 1.39 mg/mL and 0.313 mg/g, respectively, which are within the previously reported range [23] and higher than the MICs for major causative organisms of respiratory infections [22]. These results are consistent with evidence of its high efficacy against infections in dentistry, oral cavity surgery, and otorhinolaryngology [6].…”