Telavancin microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Microbiology
Telavancin is a semisynthetic, lipoglycopeptide antibiotic. Telavancin exerts concentration-dependent, bactericidal activity against Gram-positive organisms in vitro, as demonstrated by time-kill assays and MBC/MIC (minimum bactericidal concentration/minimum inhibitory concentration) ratios using broth dilution methodology. In vitro studies demonstrated a telavancin post-antibiotic effect ranging from 1 to 6 hours against S. aureus and other Gram-positive pathogens.
Although telavancin is approximately 90% protein bound, the presence of human serum or human serum albumin has minimal impact on the in vitro activity of telavancin against staphylococci, streptococci, and vancomycin-susceptible enterococci.
Mechanism of Action
Telavancin inhibits bacterial cell wall synthesis by interfering with the polymerization and cross-linking of peptidoglycan. Telavancin binds to the bacterial membrane and disrupts membrane barrier function.
Interactions with Other Antibacterials
In vitro investigations demonstrated no antagonism between telavancin and amikacin, aztreonam, cefepime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, meropenem, oxacillin, piperacillin/tazobactam, rifampin, and trimethoprim/sulfamethoxazole, when tested in various combinations against telavancin susceptible staphylococci, streptococci, and enterococci. This information is not available for other bacteria.
Cross-Resistance
Some vancomycin-resistant enterococci have a reduced susceptibility to telavancin. There is no known cross-resistance between telavancin and other classes of antibiotics.
Antibacterial Activity
Telavancin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections as described in the Indications and Usage section [see Indications and Usage ]:
Facultative Gram-Positive Microorganisms
- Staphylococcus aureus (including methicillin-resistant isolates)
- Enterococcus faecalis (vancomycin-susceptible isolates only)
- Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus)
Greater than 90% of the following microorganisms exhibit an in vitro MIC less than or equal to the telavancin-susceptible breakpoint for organisms of similar genus shown in Table 7. The safety and effectiveness of telavancin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Facultative Gram-Positive Microorganisms
- Enterococcus faecium (vancomycin-susceptible isolates only)
- Streptococcus dysgalactaie subsp. equisimilis
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution technique
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure [see References (15)]. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of telavancin powder. The MIC values should be interpreted according to the criteria provided in Table 7.
Diffusion technique
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations [see References (15)]. This procedure uses paper disks impregnated with 30 mcg of telavancin to test the susceptibility of microorganisms to telavancin. The disk diffusion interpretive criteria are provided in Table 7.
| [[File:|800px|thumb]] |
A report of “susceptible" indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentrations usually achievable.
Quality Control
Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor the performance of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard telavancin powder should provide the range of values noted in Table 8.
Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within bacteria; the specific strains used for microbiological quality control are not clinically significant.[1]
| [[File:|800px|thumb]] |
References
Adapted from the FDA Package Insert.