In Vitro Activity of Tigecycline against Burkholderia pseudomallei and Burkholderia thailandensis
http://www.100md.com
《抗菌试剂及化学方法》
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
ABSTRACT
Investigation of the in vitro activity of tigecycline against Burkholderia pseudomallei and Burkholderia thailandensis revealed that the inhibition zone diameters of tigecycline against all isolates were 20 mm and that the MIC50 values were 0.5 and 1 μg/ml and the MIC90 values were 2 and 1.5 μg/ml for B. pseudomallei and B. thailandensis, respectively.
Burkholderia pseudomallei, a gram-negative bacterium, causes in humans and animals a disease called melioidosis (22). The bacterium is a soil organism found mainly in Southeast Asia and northern Australia. Recently, two distinct biotypes of B. pseudomallei strains have been defined based on their ability to assimilate L-arabinose and their difference in pathogenicity (2, 7, 17, 23). Both biotypes have been found in soil of areas where melioidosis is endemic in Thailand (20, 21). The Ara+ B. pseudomallei is much less virulent than Ara– B. pseudomallei (2, 17). However, Ara+ B. pseudomallei has been reported to cause disease in humans (11). Subsequently, a distinct new species, Burkholderia thailandensis, was proposed for the Ara+ B. pseudomallei strain (3). B. pseudomallei is usually resistant to many antibiotics. Antibiotics currently recommended for therapy of melioidosis are ceftazidime, imipenem, meropenem, amoxicillin/clavulanate, cefoperazone/sulbactam, trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol (22). The development of resistance of B. pseudomallei to these antibiotics was recognized (6, 8, 19, 24), and hence a search for new agents effective against B. pseudomallei is needed.
Tigecycline is a glycylcycline antibiotic that shows promising activity against a wide range of organisms (25). Tigecycline is active against gram-positive cocci, including methicillin-resistant staphylococci, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. Tigecycline is also active against many gram-negative bacilli, including those resistant to multiple antibiotics as well as anaerobes. However, the activity of tigecycline against B. pseudomallei has not been reported. The present study was undertaken to explore the activity of tigecycline against B. pseudomallei and B. thailandensis.
One hundred twenty-six strains of B. pseudomallei and B. thailandensis were selected from our collection. One hundred two strains of B. pseudomallei were isolated from different infected patients, and 24 strains of B. thailandensis were isolated from 23 soil samples collected from different sites and from one infected patient. All Burkholderia species were identified with the API 20NE (bioMerieux, France). B. pseudomallei and B. thailandensis were differentiated by the arabinose assimilation test (20). In vitro susceptibilities were determined by Kirby-Bauer disk diffusion, Etest, and MicroScan. Paper disks containing tigecycline at 15 μg per disk (Becton Dickinson), Etest strips (AB Biodisk), and gram-negative MicroScan MIC panels (Dade Behring Inc.) were provided by Wyeth Research. Susceptibility testing was done by direct colony suspension according to guidelines suggested by CLSI (4). Quality control was performed by testing the susceptibility of Escherichia coli ATCC 25922 as recommended by Wyeth Research.
The distribution of inhibition zone diameters of tigecycline against B. pseudomallei and B. thailandensis is shown in Table 1. All strains had an inhibition zone diameter of 20 mm. The MIC50 and MIC90 values of tigecycline as determined by Etest are shown in Table 2. The MIC50 values were 0.5 and 1 μg/ml for B. pseudomallei and B. thailandensis, respectively. The MIC90 values were 2 and 1.5 μg/ml for B. pseudomallei and B. thailandensis, respectively. There was a significant correlation between inhibition zone diameters and MICs from Etest (P < 0.001; r = –0.68). The mean inhibition zone diameters of the strains with MIC of 3, 2, 1.5, 1. 0.75, and 0.5 μg/ml were 20, 21.8, 22.6, 23.5. 24.4, and 26.7 mm, respectively. The correlation of MICs determined by Etest and MicroScan was satisfactory, as shown in Table 3. Thirty-two strains (50%) had identical MICs determined by Etest and MicroScan, whereas another 50% had a difference in MICs of 0.25 to 0.5 μg/ml.
The MICs of tigecycline for B. pseudomallei and B. thailandensis observed in our study were higher than those for S. pneumoniae, Staphylococcus aureus, Enterococcus spp., and non-ESBL-producing Enterobacteriaceae (1). However, they were comparable to the MICs of tigecycline for Acinetobacter spp., Enterobacter aerogenes, and ESBL-producing Klebsiella pneumoniae (1). The breakpoints for inhibition zone diameter and MIC of tigecycline against B. pseudomallei and B. thailandensis are not available. The breakpoint of doxycycline against B. pseudomallei, adapted from data compiled by the National Committee for Clinical Laboratory Standards for similar organisms to be used for susceptibility testing, was 4 μg/ml (15). The U.S. FDA-approved breakpoints of tigecycline against Enterobacteriaceae to be used by local laboratories were an inhibition zone diameter of 19 mm and a MIC of 2 μg/ml (4). With the aforementioned breakpoints used to determine susceptibility of Burkholderia spp. to tigecycline, all isolates of B. pseudomallei and B. thailandensis were susceptible to tigecycline according to the inhibition zone diameter criteria and 98% of B. pseudomallei isolates and all B. thailandensis isolates were susceptible to tigecycline according to the MIC criteria. The MICs determined by Etest were significantly correlated with the inhibition zone diameters and the MICs determined by MicroScan. Therefore, disk diffusion and Etest methods are reliable for determination of susceptibility of tigecycline against B. pseudomallei and B. thailandensis.
Pharmacokinetic and pharmacodynamic studies of tigecycline in healthy subjects after a 100-mg loading dose given intravenously followed by 50 mg every 12 h have been reported (5, 12-14, 18). The mean maximum concentration (Cmax), the mean time to maximum concentration, the mean minimum concentration (Cmin), the mean area under the curve, and the mean half-life of tigecycline in serum were 0.72 μg/ml, 0.52 h, 0.1 μg/ml, 1.73 μg · h/ml, and 15 h, respectively. These profiles were favorable for many organisms, such as S. pneumoniae, Chlamydia pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae, and Haemophilus influenzae, since the MIC90 values of tigecycline for such organisms were very low. The mean Cmax of tigecycline in serum (0.72 μg/ml) after the conventional dose of tigecycline (100-mg loading dose followed by 50 mg every 12 h) was above the MICs of tigecycline for only 6% of B. pseudomallei and B. thailandensis isolates. However, it was found that tigecycline had a large volume of distribution (7 to 10 liters/kg), indicating extensive distribution into the tissues (13). In addition, the mean Cmax, the mean time to maximum concentration, the mean Cmin, the mean area under the curve, and the mean half-life of tigecycline in the alveolar cells were 15.2 μg/ml, 2 h, 6.4 μg/ml, 134 μg · h/ml, and 23.7 h, respectively (5). These observations imply that tigecycline accumulates in the cells and could be effective for infections caused by intracellular organisms. The mean Cmax and the mean Cmin of tigecycline in the alveolar cells were much higher than the MICs for all isolates of B. pseudomallei and B. thailandensis. Therefore, tigecycline should be a suitable antibiotic for therapy of melioidosis, since B. pseudomallei is an intracellular bacterium (9, 10, 16). This hypothesis needs further investigation by conducting clinical trials on therapy of melioidosis with tigecycline.
ACKNOWLEDGMENTS
We thank Wyeth Research for providing tigecycline susceptibility disks, Etest strips, and gram-negative MicroScan tests.
We thank the Thailand Research Fund for supporting the study.
REFERENCES
Bouchillona, S. K., D. J. Hobana, B. M. Johnsona, T. M. Stevensa, M. J. Dowzickyb, D. H. Wub, and P. A. Bradford. 2005. In vitro evaluation of tigecycline and comparative agents in 3049 clinical isolates: 2001 to 2002. Diagn. Microbiol. Infect. Dis. 51:291-295.
Brett, P. J., D. DeShazer, and D. E. Woods. 1997. Characterization of Burkholderia pseudomallei and Burkholderia pseudomallei-like strains. Epidemiol. Infect. 118:137-148.
Brett, P. J., D. DeShazer, and D. E. Woods. 1998. Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species. Int. J. Syst. Bacteriol. 48:317-320.
Clinical and Laboratory Standards Institute. 2005. Performance standards for antimicrobial susceptibility testing—15th informational supplement. Approved standard, CLSI document M100-S15. Clinical and Laboratory Standards Institute, Wayne, Pa.
Conte, J. E., Jr., J. A. Golden, M. G. Kelly, and E. Zurlinden. 2005. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int. J. Antimicrob. Agents 25:523-529.
Dance, D. A., V. Wuthiekanun, W. Chaowagul, Y. Suputtamongkol, and N. J. White. 1991. Development of resistance to ceftazidime and co-amoxiclav in Pseudomonas pseudomallei. J. Antimicrob. Chemother. 28:321-324.
Dharakul, T., B. Tassaneetrithep, S. Trakulsomboon, and S. Songsivilai. 1999. Phylogenetic analysis of Ara+ and Ara– Burkholderia pseudomallei isolates and development of a multiplex PCR procedure for rapid discrimination between the two biotypes. J. Clin. Microbiol. 37:1906-1912.
Godfrey, A. J., S. Wong, D. A. Dance, W. Chaowagul, and L. E. Bryan. 1991. Pseudomonas pseudomallei resistance to beta-lactam antibiotics due to alterations in the chromosomally encoded beta-lactamase. Antimicrob. Agents Chemother. 35:1635-1640.
Harley, V. S., D. A. B. Dance, B. S. Drasar, and G. Tovey. 1998. Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture. Microbios 96:71-93.
Inglis, T. J., F. Rodrigues, P. Rigby, R. Norton, and B. J. Currie. 2004. Comparison of the susceptibilities of Burkholderia pseudomallei to meropenem and ceftazidime by conventional and intracellular methods. Antimicrob. Agents Chemother. 48:2999-3005.
Lertpatanasuwan, N., Y. Suputtamongkol, S. Trakulsomboon, and V. Thamlikitkul. 1999. Arabinose-positive Burkholderia pseudomallei infection in humans: case report. Clin. Infect. Dis. 28:927-928.
Meagher, A. K., P. G. Ambrose, T. H. Grasela, and E. J. Ellis-Grosse. 2005. The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin. Infect. Dis. 41(Suppl. 5):S333-S340.
Muralidharan, G., R. J. Fruncillo, M. Micalizzi, D. G. Raible, and S. M. Troy. 2005. Effects of age and sex on single-dose pharmacokinetics of tigecycline in healthy subjects. Antimicrob. Agents Chemother. 49:1656-1659.
Muralidharan, G., M. Micalizzi, J. Speth, D. Raible, and S. Troy. 2005. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob. Agents Chemother. 49:220-229.
National Committee for Clinical Laboratory Standards. 1997. Performance standards for antimicrobial susceptibility testing. Methods for dilution antimicrobial susceptibility testing for bacteria that grow aerobically. NCCLS document M100-S8. National Committee for Clinical Laboratory Standards, Wayne, Pa.
Pruksachartvuthi, S., N. Aswapokee, and K. Thankerngpol, K. 1990. Survival of Pseudomonas pseudomallei in human phagocytes. J. Med. Microbiol. 31:109-114.
Smith, M. D., B. J. Angus, V. Wuthiekanum, and N. J. White. 1997. Arabinose assimilation defines a nonvirulent biotype of Burkholderia pseudomallei. Infect. Immun. 65:4319-4321.
Sun, H. K., T. C. T. Ong, A. Umer, D. Harper, S. Troy, C. H. Nightingale, and D. P. Nicolau. 2005. Pharmacokinetic profile of tigecycline in serum and skin blister fluid of healthy subjects after multiple intravenous administrations. Antimicrob. Agents Chemother. 49:1629-1632.
Thibault, F. M., E. Hernandez, D. R. Vidal, M. Girardet, and J. D. Cavallo. 2004. Antibiotic susceptibility of 65 isolates of Burkholderia pseudomallei and Burkholderia mallei to 35 antimicrobial agents. J. Antimicrob. Chemother. 54:1134-1138.
Trakulsomboon, S., V. Vuddhakul, P. Tharavichitkul, N. Na-gnam, Y. Suputtamongkol, and V. Thamlikitkul. 1999. Epidemiology of arabinose assimilation in Burkholderia pseudomallei isolated from patients and soil in Thailand. Southeast Asian J. Trop. Med. Public Health 30:756-759.
Vuddhakul, V., P. Tharavichitkul, N. Na-gnam, S. Jitsurong, B. Kunthawa, P. Noimay, P. Noimay, A. Binla, and V. Thamlikitkul. 1999. Epidemiology of B. pseudomallei in Thailand. Am. J. Trop. Med. Hyg. 60:458-461.
White, N. J. 2003. Melioidosis. Lancet 361:1715-1722.
Wuthiekanum, V., M. D. Smith, D. A. B. Dance, A. L. Walsh, T. L. Pitt, and N. J. White. 1996. Biochemical characteristics of clinical and environmental isolates of Burkholderia pseudomallei. J. Med. Microbiol. 45:408-412.
Wuthiekanun, V., A. C. Cheng, W. Chierakul, P. Amornchai, D. Limmathurotsakul, and W. Chaowagul. 2005. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei. J. Antimicrob. Chemother. 55:1029-1031.
Zhanel, G. G., K. Homenuik, K. Nichol, A. Noreddin, L. Vercaigne, J. Embil, A. Gin, J. A. Karlowsky, and D. J. Hoban. 2004. The glycylcyclines: a comparative review with the tetracyclines. Drugs 64:63-88.(Visanu Thamlikitkul and S)
ABSTRACT
Investigation of the in vitro activity of tigecycline against Burkholderia pseudomallei and Burkholderia thailandensis revealed that the inhibition zone diameters of tigecycline against all isolates were 20 mm and that the MIC50 values were 0.5 and 1 μg/ml and the MIC90 values were 2 and 1.5 μg/ml for B. pseudomallei and B. thailandensis, respectively.
Burkholderia pseudomallei, a gram-negative bacterium, causes in humans and animals a disease called melioidosis (22). The bacterium is a soil organism found mainly in Southeast Asia and northern Australia. Recently, two distinct biotypes of B. pseudomallei strains have been defined based on their ability to assimilate L-arabinose and their difference in pathogenicity (2, 7, 17, 23). Both biotypes have been found in soil of areas where melioidosis is endemic in Thailand (20, 21). The Ara+ B. pseudomallei is much less virulent than Ara– B. pseudomallei (2, 17). However, Ara+ B. pseudomallei has been reported to cause disease in humans (11). Subsequently, a distinct new species, Burkholderia thailandensis, was proposed for the Ara+ B. pseudomallei strain (3). B. pseudomallei is usually resistant to many antibiotics. Antibiotics currently recommended for therapy of melioidosis are ceftazidime, imipenem, meropenem, amoxicillin/clavulanate, cefoperazone/sulbactam, trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol (22). The development of resistance of B. pseudomallei to these antibiotics was recognized (6, 8, 19, 24), and hence a search for new agents effective against B. pseudomallei is needed.
Tigecycline is a glycylcycline antibiotic that shows promising activity against a wide range of organisms (25). Tigecycline is active against gram-positive cocci, including methicillin-resistant staphylococci, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. Tigecycline is also active against many gram-negative bacilli, including those resistant to multiple antibiotics as well as anaerobes. However, the activity of tigecycline against B. pseudomallei has not been reported. The present study was undertaken to explore the activity of tigecycline against B. pseudomallei and B. thailandensis.
One hundred twenty-six strains of B. pseudomallei and B. thailandensis were selected from our collection. One hundred two strains of B. pseudomallei were isolated from different infected patients, and 24 strains of B. thailandensis were isolated from 23 soil samples collected from different sites and from one infected patient. All Burkholderia species were identified with the API 20NE (bioMerieux, France). B. pseudomallei and B. thailandensis were differentiated by the arabinose assimilation test (20). In vitro susceptibilities were determined by Kirby-Bauer disk diffusion, Etest, and MicroScan. Paper disks containing tigecycline at 15 μg per disk (Becton Dickinson), Etest strips (AB Biodisk), and gram-negative MicroScan MIC panels (Dade Behring Inc.) were provided by Wyeth Research. Susceptibility testing was done by direct colony suspension according to guidelines suggested by CLSI (4). Quality control was performed by testing the susceptibility of Escherichia coli ATCC 25922 as recommended by Wyeth Research.
The distribution of inhibition zone diameters of tigecycline against B. pseudomallei and B. thailandensis is shown in Table 1. All strains had an inhibition zone diameter of 20 mm. The MIC50 and MIC90 values of tigecycline as determined by Etest are shown in Table 2. The MIC50 values were 0.5 and 1 μg/ml for B. pseudomallei and B. thailandensis, respectively. The MIC90 values were 2 and 1.5 μg/ml for B. pseudomallei and B. thailandensis, respectively. There was a significant correlation between inhibition zone diameters and MICs from Etest (P < 0.001; r = –0.68). The mean inhibition zone diameters of the strains with MIC of 3, 2, 1.5, 1. 0.75, and 0.5 μg/ml were 20, 21.8, 22.6, 23.5. 24.4, and 26.7 mm, respectively. The correlation of MICs determined by Etest and MicroScan was satisfactory, as shown in Table 3. Thirty-two strains (50%) had identical MICs determined by Etest and MicroScan, whereas another 50% had a difference in MICs of 0.25 to 0.5 μg/ml.
The MICs of tigecycline for B. pseudomallei and B. thailandensis observed in our study were higher than those for S. pneumoniae, Staphylococcus aureus, Enterococcus spp., and non-ESBL-producing Enterobacteriaceae (1). However, they were comparable to the MICs of tigecycline for Acinetobacter spp., Enterobacter aerogenes, and ESBL-producing Klebsiella pneumoniae (1). The breakpoints for inhibition zone diameter and MIC of tigecycline against B. pseudomallei and B. thailandensis are not available. The breakpoint of doxycycline against B. pseudomallei, adapted from data compiled by the National Committee for Clinical Laboratory Standards for similar organisms to be used for susceptibility testing, was 4 μg/ml (15). The U.S. FDA-approved breakpoints of tigecycline against Enterobacteriaceae to be used by local laboratories were an inhibition zone diameter of 19 mm and a MIC of 2 μg/ml (4). With the aforementioned breakpoints used to determine susceptibility of Burkholderia spp. to tigecycline, all isolates of B. pseudomallei and B. thailandensis were susceptible to tigecycline according to the inhibition zone diameter criteria and 98% of B. pseudomallei isolates and all B. thailandensis isolates were susceptible to tigecycline according to the MIC criteria. The MICs determined by Etest were significantly correlated with the inhibition zone diameters and the MICs determined by MicroScan. Therefore, disk diffusion and Etest methods are reliable for determination of susceptibility of tigecycline against B. pseudomallei and B. thailandensis.
Pharmacokinetic and pharmacodynamic studies of tigecycline in healthy subjects after a 100-mg loading dose given intravenously followed by 50 mg every 12 h have been reported (5, 12-14, 18). The mean maximum concentration (Cmax), the mean time to maximum concentration, the mean minimum concentration (Cmin), the mean area under the curve, and the mean half-life of tigecycline in serum were 0.72 μg/ml, 0.52 h, 0.1 μg/ml, 1.73 μg · h/ml, and 15 h, respectively. These profiles were favorable for many organisms, such as S. pneumoniae, Chlamydia pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae, and Haemophilus influenzae, since the MIC90 values of tigecycline for such organisms were very low. The mean Cmax of tigecycline in serum (0.72 μg/ml) after the conventional dose of tigecycline (100-mg loading dose followed by 50 mg every 12 h) was above the MICs of tigecycline for only 6% of B. pseudomallei and B. thailandensis isolates. However, it was found that tigecycline had a large volume of distribution (7 to 10 liters/kg), indicating extensive distribution into the tissues (13). In addition, the mean Cmax, the mean time to maximum concentration, the mean Cmin, the mean area under the curve, and the mean half-life of tigecycline in the alveolar cells were 15.2 μg/ml, 2 h, 6.4 μg/ml, 134 μg · h/ml, and 23.7 h, respectively (5). These observations imply that tigecycline accumulates in the cells and could be effective for infections caused by intracellular organisms. The mean Cmax and the mean Cmin of tigecycline in the alveolar cells were much higher than the MICs for all isolates of B. pseudomallei and B. thailandensis. Therefore, tigecycline should be a suitable antibiotic for therapy of melioidosis, since B. pseudomallei is an intracellular bacterium (9, 10, 16). This hypothesis needs further investigation by conducting clinical trials on therapy of melioidosis with tigecycline.
ACKNOWLEDGMENTS
We thank Wyeth Research for providing tigecycline susceptibility disks, Etest strips, and gram-negative MicroScan tests.
We thank the Thailand Research Fund for supporting the study.
REFERENCES
Bouchillona, S. K., D. J. Hobana, B. M. Johnsona, T. M. Stevensa, M. J. Dowzickyb, D. H. Wub, and P. A. Bradford. 2005. In vitro evaluation of tigecycline and comparative agents in 3049 clinical isolates: 2001 to 2002. Diagn. Microbiol. Infect. Dis. 51:291-295.
Brett, P. J., D. DeShazer, and D. E. Woods. 1997. Characterization of Burkholderia pseudomallei and Burkholderia pseudomallei-like strains. Epidemiol. Infect. 118:137-148.
Brett, P. J., D. DeShazer, and D. E. Woods. 1998. Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species. Int. J. Syst. Bacteriol. 48:317-320.
Clinical and Laboratory Standards Institute. 2005. Performance standards for antimicrobial susceptibility testing—15th informational supplement. Approved standard, CLSI document M100-S15. Clinical and Laboratory Standards Institute, Wayne, Pa.
Conte, J. E., Jr., J. A. Golden, M. G. Kelly, and E. Zurlinden. 2005. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int. J. Antimicrob. Agents 25:523-529.
Dance, D. A., V. Wuthiekanun, W. Chaowagul, Y. Suputtamongkol, and N. J. White. 1991. Development of resistance to ceftazidime and co-amoxiclav in Pseudomonas pseudomallei. J. Antimicrob. Chemother. 28:321-324.
Dharakul, T., B. Tassaneetrithep, S. Trakulsomboon, and S. Songsivilai. 1999. Phylogenetic analysis of Ara+ and Ara– Burkholderia pseudomallei isolates and development of a multiplex PCR procedure for rapid discrimination between the two biotypes. J. Clin. Microbiol. 37:1906-1912.
Godfrey, A. J., S. Wong, D. A. Dance, W. Chaowagul, and L. E. Bryan. 1991. Pseudomonas pseudomallei resistance to beta-lactam antibiotics due to alterations in the chromosomally encoded beta-lactamase. Antimicrob. Agents Chemother. 35:1635-1640.
Harley, V. S., D. A. B. Dance, B. S. Drasar, and G. Tovey. 1998. Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture. Microbios 96:71-93.
Inglis, T. J., F. Rodrigues, P. Rigby, R. Norton, and B. J. Currie. 2004. Comparison of the susceptibilities of Burkholderia pseudomallei to meropenem and ceftazidime by conventional and intracellular methods. Antimicrob. Agents Chemother. 48:2999-3005.
Lertpatanasuwan, N., Y. Suputtamongkol, S. Trakulsomboon, and V. Thamlikitkul. 1999. Arabinose-positive Burkholderia pseudomallei infection in humans: case report. Clin. Infect. Dis. 28:927-928.
Meagher, A. K., P. G. Ambrose, T. H. Grasela, and E. J. Ellis-Grosse. 2005. The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin. Infect. Dis. 41(Suppl. 5):S333-S340.
Muralidharan, G., R. J. Fruncillo, M. Micalizzi, D. G. Raible, and S. M. Troy. 2005. Effects of age and sex on single-dose pharmacokinetics of tigecycline in healthy subjects. Antimicrob. Agents Chemother. 49:1656-1659.
Muralidharan, G., M. Micalizzi, J. Speth, D. Raible, and S. Troy. 2005. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob. Agents Chemother. 49:220-229.
National Committee for Clinical Laboratory Standards. 1997. Performance standards for antimicrobial susceptibility testing. Methods for dilution antimicrobial susceptibility testing for bacteria that grow aerobically. NCCLS document M100-S8. National Committee for Clinical Laboratory Standards, Wayne, Pa.
Pruksachartvuthi, S., N. Aswapokee, and K. Thankerngpol, K. 1990. Survival of Pseudomonas pseudomallei in human phagocytes. J. Med. Microbiol. 31:109-114.
Smith, M. D., B. J. Angus, V. Wuthiekanum, and N. J. White. 1997. Arabinose assimilation defines a nonvirulent biotype of Burkholderia pseudomallei. Infect. Immun. 65:4319-4321.
Sun, H. K., T. C. T. Ong, A. Umer, D. Harper, S. Troy, C. H. Nightingale, and D. P. Nicolau. 2005. Pharmacokinetic profile of tigecycline in serum and skin blister fluid of healthy subjects after multiple intravenous administrations. Antimicrob. Agents Chemother. 49:1629-1632.
Thibault, F. M., E. Hernandez, D. R. Vidal, M. Girardet, and J. D. Cavallo. 2004. Antibiotic susceptibility of 65 isolates of Burkholderia pseudomallei and Burkholderia mallei to 35 antimicrobial agents. J. Antimicrob. Chemother. 54:1134-1138.
Trakulsomboon, S., V. Vuddhakul, P. Tharavichitkul, N. Na-gnam, Y. Suputtamongkol, and V. Thamlikitkul. 1999. Epidemiology of arabinose assimilation in Burkholderia pseudomallei isolated from patients and soil in Thailand. Southeast Asian J. Trop. Med. Public Health 30:756-759.
Vuddhakul, V., P. Tharavichitkul, N. Na-gnam, S. Jitsurong, B. Kunthawa, P. Noimay, P. Noimay, A. Binla, and V. Thamlikitkul. 1999. Epidemiology of B. pseudomallei in Thailand. Am. J. Trop. Med. Hyg. 60:458-461.
White, N. J. 2003. Melioidosis. Lancet 361:1715-1722.
Wuthiekanum, V., M. D. Smith, D. A. B. Dance, A. L. Walsh, T. L. Pitt, and N. J. White. 1996. Biochemical characteristics of clinical and environmental isolates of Burkholderia pseudomallei. J. Med. Microbiol. 45:408-412.
Wuthiekanun, V., A. C. Cheng, W. Chierakul, P. Amornchai, D. Limmathurotsakul, and W. Chaowagul. 2005. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei. J. Antimicrob. Chemother. 55:1029-1031.
Zhanel, G. G., K. Homenuik, K. Nichol, A. Noreddin, L. Vercaigne, J. Embil, A. Gin, J. A. Karlowsky, and D. J. Hoban. 2004. The glycylcyclines: a comparative review with the tetracyclines. Drugs 64:63-88.(Visanu Thamlikitkul and S)