| InChI | InChI=1S/C80H106Cl2N11O27P.ClH/c1-7-8-9-10-11-12-13-14-21-85-22-23-87-80(5)32-57(115-37(4)71(80)103)119-70-68(102)67(101)55(34-94)118-79(70)120-69-53-28-41-29-54(69)117-52-20-17-40(27-46(52)82)65(99)63-77(109)91-61(78(110)111)43-30-50(96)44(33-86-35-121(112,113)114)66(100)58(43)42-25-38(15-18-49(42)95)59(74(106)93-63)90-75(107)60(41)89-73(105)48(31-56(83)97)88-76(108)62(92-72(104)47(84-6)24-36(2)3)64(98)39-16-19-51(116-53)45(81)26-39;/h15-20,25-30,36-37,47-48,55,57,59-65,67-68,70-71,79,84-87,94-96,98-103H,7-14,21-24,31-35H2,1-6H3,(H2,83,97)(H,88,108)(H,89,105)(H,90,107)(H,91,109)(H,92,104)(H,93,106)(H,110,111)(H2,112,113,114);1H/t37-,47+,48-,55+,57-,59+,60+,61-,62+,63-,64+,65+,67+,68-,70+,71+,79-,80-;/m0./s1 |
| Reference | 1. Pharmacotherapy. 2010 Jan;30(1):80-94. doi: 10.1592/phco.30.1.80. <br />
A comparative review of the lipoglycopeptides: oritavancin, dalbavancin, and
telavancin. <br />
Guskey MT(1), Tsuji BT. <br />
Author information: <br />
(1)New York State Center of Excellence in Bioinformatics and Life Sciences,
University at Buffalo, 14260, USA. <br />
Resistance to antibiotics among gram-positive bacteria, especially enterococci
and staphylococci, has led to the need to develop new antibiotics. Vancomycin, a
glycopeptide antibiotic, has been used for over 3 decades to treat serious
methicillin-resistant Staphylococcus aureus infections. The increased frequency
of multidrug-resistant bacteria, especially vancomycin-resistant strains, has
focused interest on three new lipoglycopeptides for the treatment of infections
caused by gram-positive bacteria: oritavancin, dalbavancin, and telavancin.
Although oritavancin and dalbavancin are still in development, telavancin
received approval from the United States Food and Drug Administration in
September 2009 for treatment of complicated skin and skin structure infections.
Structurally different from vancomycin and teicoplanin, all three
lipoglycopeptides have greater potency and less potential for development of
resistant organisms. Of particular importance is the activity of oritavancin,
dalbavancin, and telavancin against vancomycin-resistant organisms. In addition,
the pharmacokinetic properties of these new antimicrobials substantially differ
from those of vancomycin. Both oritavancin and dalbavancin have long terminal
half-lives, which may allow for infrequent dosing. In addition, oritavancin is
primarily cleared through hepatic pathways, which makes it potentially useful in
patients with renal compromise. In animal models, these new lipoglycopeptides
were effective in treating serious gram-positive infections, including
complicated skin and skin structure infections, endocarditis, bacteremia, and
pneumonia; in clinical studies, however, efficacy was shown only in complicated
skin and skin structure infections for all three agents. According to preliminary
data, the adverse-effect profile of these lipoglycopeptides is generally similar
to that of drugs currently used to treat severe gram-positive infections.
However, further evaluation and monitoring is necessary as more patients are
exposed to these agents. As antimicrobial resistance continues to increase
worldwide, the lipoglycopeptides may provide clinicians with a useful
antimicrobial in the continued fight against multidrug-resistant gram-positive
bacteria. <br />
2. Drugs Today (Barc). 2009 Mar;45(3):159-73. doi: 10.1358/dot.2009.45.3.1343792. <br />
Telavancin: a new lipoglycopeptide for gram-positive infections. <br />
Smith WJ(1), Drew RH. <br />
Author information: <br />
(1)University of Oklahoma Health Sciences Center College of Pharmacy, Oklahoma
City, Oklahoma 73126, USA. [email protected] <br />
Telavancin is a lipoglycopeptide derivative of vancomycin. Similar to vancomycin,
it demonstrates activity in vitro against a variety of Gram-positive pathogens,
including but not limited to methicillin-resistant Staphylococccus aureus (MRSA)
and penicillin-resistant Streptococcus pneumoniae (PRSP). Modifications to
vancomycin/’s structure expanded telavancin/’s spectrum of activity in vitro to
include organisms such as glycopeptide-intermediate S. aureus (GISA),
vancomycin-resistant S. aureus (VRSA) and vancomycin-resistant enterococci (VRE).
However, the clinical implications of this are currently unknown. Similar to
other glycopeptides, televancin binds to the D-alanyl-D-alanine (D-Ala-D-Ala)
terminus in Gram-positive organisms, resulting in inhibition of bacterial cell
wall synthesis. In addition, telavancin causes depolarization of the bacterial
cell membrane and increased membrane permeability. The resulting activity in
vitro is rapidly bactericidal and concentration dependent, with the ratio of area
under the time concentration curve to minimum inhibitory concentration (AUC/MIC)
as the best predictor of activity in animal models to date. In humans, telavancin
exhibits a pharmacokinetic profile that permits once-daily intravenous
administration. Doses of 7.5 and 10 mg/kg/day have been studied in clinical
trials. The need for dosage adjustments based on age, gender and obesity appear
unnecessary. In addition, moderate hepatic impairment does not appreciably alter
the pharmacokinetics of the drug. Because telavancin is extensively cleared by
the kidneys, dosage adjustments will be required in patients with moderate to
severe renal impairment. Published phase II and III clinical trials have shown
telavancin to be comparable to standard therapy for the treatment of complicated
skin and soft tissue infections. Clinical trials in the treatment of S. aureus
bacteremia and hospital-acquired pneumonia are under way. Adverse effects overall
appear to be mild and reversible, with taste disturbance, foamy urine, headache,
procedural site pain, nausea and vomiting being the most commonly reported.
However, renal toxicity was reported more frequently with telavancin than with
vancomycin in two phase III clinical trials (3% versus 1%). Prolongation of the
corrected QT (QTc) interval has been more common with telavancin than comparator
agents, but no clinically significant electrocardiogram (ECG) changes or cardiac
abnormalities have been observed to date. Although human pregnancy data is not
currently available, animal data revealed limb malformations that were possibly
related to telavancin therapy. Therefore, the potential teratogenicity of this
agent must be considered in women who are pregnant or may become pregnant. <br />
3. Expert Rev Anti Infect Ther. 2006 Oct;4(5):743-9. <br />
Telavancin: a new lipoglycopeptide with multiple mechanisms of action. <br />
Kanafani ZA(1). <br />
Author information: <br />
(1)Duke University Medical Center, Duke Clinical Research Institute, Division of
Infectious Diseases, 2400 Pratt Street, Rm 7543, Durham, NC 27710, USA.
[email protected] <br />
Antimicrobial resistance among Gram-positive organisms continues to increase and
has reached epidemic proportions in numerous countries. Telavancin is a
semisynthetic lipoglycopeptide with a dual mechanism of action that involves the
inhibition of cell-wall synthesis and disruption of bacterial cell-membrane
barrier functions. Telavancin exhibits a rapid bactericidal activity against
Staphylococcus aureus. It is also active against coagulase-negative
staphylococci, enterococci, streptococci and various anaerobic Gram-positive
organisms. Telavancin has a prolonged postantibiotic effect and distributes well
into cutaneous and pulmonary tissues. Furthermore, it has a low potential for
development of resistance and is well tolerated. The overall incidence of adverse
events in patients receiving telavancin was similar to that observed with
standard therapy and recent data from preliminary clinical trials have
demonstrated similar efficacy to standard therapy in the treatment of complicated
skin and skin-structure infections. Therefore, telavancin is a promising new
antimicrobial agent for the treatment of infections caused by resistant
Gram-positive pathogens. <br />
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