Tevalancin
Ds Trịnh Nguyễn Đàm Giang
thông tin
10/24/2007
Approvable Letter Issued for Telavancin
The FDA has issued an approvable letter to Theravance and Astellas Pharma
US for telavancin for the treatment of complicated skin and skin structure
infections caused by gram-positive bacteria, including resistant pathogens
such as methicillin-resistant Staphylococcus aureus
Information from Theravance
WASHINGTON, DC -- December 19, 2005 -- A new drug in
a similar class as vancomycin -- a last resort antibiotic -- appears to
clear up dangerous methicillin-resistant Staphylococcus aureus (MRSA)
skin infections more effectively than standard treatment.
"Usually that standard of care is vancomycin," said Martin Stryjewski,
MD, attending physician, internal medicine and infectious diseases, Cemic
Hospital, Buenos Aires, Argentina.
"Telavancin achieved significantly [P = .04] higher eradication rates
in patients infected with MRSA. Although not statistically significant
[P = .07], in patients infected with S. aureus, the clinical response
rates at test of cure were higher in telavancin-treated patients,"
Dr. Stryjewski said in his poster presentation December 18th at the 45th
Annual Interscience Conference on Antimicrobial Agents and Chemotherapy
(ICAAC).
Telavancin is a bactericidal lipoglycopeptide now in phase 3 clinical
studies.
Dr. Stryjewski and colleagues assigned 100 patients with complicated Gram-positive
skin and skin-structure infections to telavancin 10 mg/kg once a day and
95 patients to a standard treatment with 1 of the following regimens:
comycin at 1 g every 12 hours, nafcillin or oxacillin 2 g every 6 hours,
or cloxacillin 0.5 to 1 g every 6 hours. All were by intravenous administration.
In the entire group, the drugs were similar in their ability to eradicate
the infections -- with cure rates of 82% in patients treated with telavancin
and 85% in patients treated with standard of care.
When Dr. Stryjewski analyzed the patient groups further, he found that
telavancin cured 48 of 59 patients (81.4%) with S. aureus compared with
32 of 41 patients (78.1%) who were treated with standard regimens.
Telavancin cured 92% of 26 patients with S. aureus patients that were
methicillin resistant compared with 68% of 19 treated with standard care.
"The overall incidence and severity of adverse events were similar
in the telavancin-treated and standard therapy groups," Dr. Stryjewski
said.
"The results of this study support further investigation of telavancin
for the treatment of serious infections due to resistant Gram-positive
pathogens, particularly those caused by MRSA," he said.
Theravance is developing telavancin and sponsored the study.
Telavancin, a Multifunctional Lipoglycopeptide, Disrupts
both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant
Staphylococcus aureus
Theravance, Inc., South San Francisco, California1
Received 8 July 2004/ Returned for modification 16 August 2004/ Accepted
31 October 2004
The emergence and spread of multidrug-resistant gram-positive bacteria
represent a serious clinical problem. Telavancin is a novel lipoglycopeptide
antibiotic that possesses rapid in vitro bactericidal activity against
a broad spectrum of clinically relevant gram-positive pathogens. Here
we demonstrate that telavancin's antibacterial activity derives from at
least two mechanisms. As observed with vancomycin, telavancin inhibited
late-stage peptidoglycan biosynthesis in a substrate-dependent fashion
and bound the cell wall, as it did the lipid II surrogate tripeptide N,N'-diacetyl-L-lysinyl-D-alanyl-D-alanine,
with high affinity. Telavancin also perturbed bacterial cell membrane
potential and permeability. In methicillin-resistant Staphylococcus aureus,
telavancin caused rapid, concentration-dependent depolarization of the
plasma membrane, increases in permeability, and leakage of cellular ATP
and K+. The timing of these changes correlated with rapid , concentration-dependent
loss of bacterial viability, suggesting that the early bactericidal activity
of telavancin results from dissipation of cell membrane potential and
an increase in membrane permeability. Binding and cell fractionation studies
provided direct evidence for an interaction of telavancin with the bacterial
cell membrane; stronger binding interactions were observed with the bacterial
cell wall and cell membrane relative to vancomycin. We suggest that this
multifunctional mechanism of action confers advantageous antibacterial
properties.
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