Activities of the Glycylcycline Tigecycline(GAR-936) against 1,924 Recent European Clinical Bacterial Isolates
Eijkman-Winkler Institute for Medical Microbiology, Utrecht, The Netherlands&5.(]c;, 百拇医药
Received 13 June 2002/ Returned for modification 11 September 2002/ Accepted 15 October 2002&5.(]c;, 百拇医药
ABSTRACT&5.(]c;, 百拇医药
The in vitro activities of tigecycline against 1,924 clinical isolates were examined. The new glycylcycline exhibited excellent activity against all gram-positive cocci (MICs at which 90% of the isolates tested were inhibited [MIC90s], 1 µg/ml). In addition, it was also very potent against most members of the Enterobacteriaceae, with most MIC90s being 2 µg/ml. Among the nonfermenters, Acinetobacter spp. and Stenotrophomonas maltophilia are included in the in vitro spectrum of tigecycline activity.&5.(]c;, 百拇医药
TEXT&5.(]c;, 百拇医药
Although tetracyclines remain valuable therapeutic agents for a variety of infections, resistance to this class limits their use. A new generation of tetracyclines, the glycylcyclines, is being developed specifically to overcome the problem of resistance to other tetracyclines (4, 16). Tigecycline (GAR-936), the 9-t-butylglycylamido derivative of minocycline, appears to be both better tolerated and more active against tetracycline-resistant strains than are other glycylcyclines (14). The present study examined the in vitro activities of tigecycline and comparators against recent clinical isolates from various European countries.
In all, 1,924 clinical isolates were tested. The strains were sampled between 1998 and 2001 in 28 hospitals from 16 European countries and sent to the Eijkman-Winkler Institute at the University Hospital Utrecht. Only one isolate per patient was permitted. The isolates derived from bloodstream, respiratory tract, skin and soft tissue, and urinary tract infections. Identification of the strains was performed by a VITEK or API system (Biomerieux, s'Hertogenbosch, The Netherlands) and/or by standard laboratory procedures.;jx, 百拇医药
MICs were determined by the microdilution method according to NCCLS guidelines (12) by using cation-adjusted Mueller-Hinton broth. For the testing of Streptococcus spp., the broth was supplemented with 5% lysed horse blood; for the testing of Haemophilus influenzae, Haemophilus Test Medium was used. The inoculum was adjusted to 5 x 105 CFU/ml, and plates were read after incubation for 20 to 24 h at 35°C in ambient air.;jx, 百拇医药
Microtiter plates containing freeze-dried serial dilutions of the antibiotics were prepared by Trek Diagnostic Systems (Westlake, Ohio).
The results of the susceptibility testing of tigecycline and the comparator agents are shown in Table 1 and presented in terms of MIC50 (MIC at which 50% of the isolates tested were inhibited), MIC90, and the range of MICs.w!6;/&, http://www.100md.com
fig.ommitteedw!6;/&, http://www.100md.com
TABLE 1. In vitro activities of tigecycline and comparatorsw!6;/&, http://www.100md.com
Tigecycline was very active against staphylococci (range of MIC50s, 0.12 to 0.5 µg/ml; range of MIC90s, 0.25 to 1 µg/ml), with no difference being observed between the MIC90s for methicillin-susceptible and methicillin-resistant strains. Tigecycline was the most active agent against methicillin-resistant Staphylococcus aureus strains (MIC50 and MIC90, 0.25 µg/ml). Other authors have described an in vitro activity of minocycline against staphylococci that is higher than that of tigecycline (3, 6); however, in our study the new glycylcycline had a higher activity, with a concentration of 1 µg/ml inhibiting all S. aureus strains, including minocycline-resistant isolates, and a concentration of 2 µg/ml inhibiting all coagulase-negative staphylococci. A possible explanation for the lower minocycline activity in our study could be that in our bacterial population, the proportion of tetracycline-resistant isolates harboring the tet M gene was greater. As has been shown previously, 50% of the tetracycline-resistant Staphylococcus aureus strains in Europe carry the tet M gene, which confers resistance to both tetracycline and minocycline (15). In contrast, isolates harboring only the tet K gene are resistant to tetracycline but remain susceptible to minocycline.
Against Enterococcus faecalis and Enterococcus faecium, tigecycline showed high activity, with MIC50s of 0.12 and 0.06 µg/ml, respectively, and MIC90s of 0.25 and 0.12 µg/ml, respectively. It was the most active agent among all antibiotics tested. Approximately half of the enterococcal isolates were resistant to minocycline. However, all strains, including 27 vancomycin-resistant strains, were inhibited by tigecycline at a concentration of 1 µg/ml. Based on the MIC90s, tigecycline was at least eightfold more active than linezolid against Enterococcus spp. and 32-fold more active than quinupristin-dalfopristin against Enterococcus faecium.;krn, 百拇医药
Tigecycline was also highly active against beta-hemolytic streptococci belonging to Lancefield groups A and B (MIC50 and MIC90, 0.06 µg/ml), with all strains, including minocycline-resistant isolates, being inhibited by the antibiotic at a concentration of 0.5 µg/ml. The difference in activities between tigecycline and minocycline was most pronounced with group B streptococci: 78% of the strains were resistant to minocycline, with all of them being inhibited by 0.06 µg of tigecycline/ml.
Against pneumococci and viridans group streptococci, the MIC50s of tigecycline were 0.06 and 0.12 µg/ml, respectively, and the MIC90s were 0.5 µg/ml for both. For penicillin-susceptible and nonsusceptible pneumococcal strains, the MIC90s differed by only 1 dilution step (0.25 and 0.5 µg/ml, respectively). All pneumococcal isolates, including those resistant to minocycline (12.7%), were inhibited by tigecycline at a concentration of 1 µg/ml. Based on the MIC90s, the potency of tigecycline was found to be equivalent to that of gatifloxacin and slightly superior to that of linezolid and quinupristin-dalfopristin.mny)$ev, 百拇医药
Overall, the new glycylcycline exhibited very high activity against gram-positive bacteria, including multiresistant pathogens and minocycline-resistant isolates, all of which were inhibited by tigecycline at a concentration of 1 µg/ml. These results confirm and extend those of previous analyses using gram-positive clinical isolates mainly from the United States (1-3, 6, 7, 13, 14, 17).
Tigecycline exhibited very high activity against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, and Citrobacter freundii, with MIC50s ranging from 0.25 to 1 µg/ml and MIC90s ranging from 0.5 to 2 µg/ml. Against these species, tigecycline was four- to eightfold more active than minocycline based on a comparison of the MIC50s. Against Proteus mirabilis, Proteus vulgaris, Morganella morganii, and Serratia marcescens, tigecycline was less active, with MIC50s of 4, 4, 2, and 2 µg/ml, respectively, and MIC90s of 8, 4, 4, and 4 µg/ml, respectively. Compared with minocycline, it was 2- to 16-fold more active based on the MIC50s. Overall, 172 (27.4%) of the 627 enterobacterial strains tested were resistant to minocycline (MIC, ">="wk{67, http://www.100md.com
16 µg/ml). Interestingly, 65 (37.8%) of the 172 minocycline-resistant strains were inhibited by tigecycline at a concentration of 2 µg/ml. These results extend those of previous analyses using Enterobacteriaceae isolates mainly from the United States (1, 2, 6-8, 14, 17).
Remarkably, tigecycline showed high activity against defined gram-negative nonfermentative bacteria, i.e., Acinetobacter spp. (MIC50, 0.25 µg/ml; MIC90, 2 µg/ml) and Stenotrophomonas maltophilia (MIC50, 0.5 µg/ml; MIC90, 2 µg/ml), two multiresistant bacterial species often involved in nosocomial infections. Based on the MIC50s, tigecycline was 1 dilution less active than minocycline. However, isolates of Acinetobacter that were not susceptible to minocycline were all inhibited by tigecycline at a concentration of 2 µg/ml. Minocycline and tigecycline both exhibited lower potency against Burkholderia cepacia, with minocycline being slightly more active than tigecycline (MIC50s of 2 and 4 µg/ml, respectively, and MIC90s of 16 and 32 µg/ml, respectively). Against Pseudomonas aeruginosa, neither minocycline nor tigecycline had any clinically relevant activity. These results are in accordance with those of previous limited analyses using nonfermentative bacteria (1, 2, 6-8, 14, 17).
Against Haemophilus influenzae, the activity of tigecycline was comparable to that of minocycline and imipenem (MIC50, 0.5 µg/ml; MIC90, 1 µg/ml). However, gatifloxacin, piperacillin-tazobactam, and ceftriaxone were at least eightfold more active against this species (MIC50s and MIC90s, 0.06 µg/ml).-@j[, http://www.100md.com
Against Moraxella catarrhalis, tigecycline and minocycline were equally active, with both agents showing an MIC50 of 0.06 µg/ml and an MIC90 of 0.12 µg/ml (1, 6, 9, 14, 17). In addition, it has been demonstrated that the glycylcyclines are not only active against the classical respiratory pathogens, i.e., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, but also are active against Mycoplasma pneumoniae and Chlamydia pneumoniae (5, 10).-@j[, http://www.100md.com
The results of our in vitro investigation of tigecycline are in line with those of previous analyses that demonstrated its broad spectrum of antibacterial activity (1, 2, 3, 6, 11, 14, 17). Tigecycline exhibited excellent activity against gram-positive cocci (MIC90s, 1 µg/ml), including methicillin-resistant staphylococci, penicillin-resistant pneumococci, and vancomycin-resistant enterococci. Tigecycline also showed very high potency against members of the Enterobacteriaceae, with MIC90s of 2 µg/ml, with the exception of Proteus spp., Serratia marcescens, and Morganella morganii (MIC90s of 4 to 8 µg/ml). In general, it was two- to eightfold more active than minocycline against the enteric bacilli. Among the nonfermenters, Acinetobacter spp. and Stenotrophomonas maltophilia are included in the in vitro spectrum of tigecycline activity. In addition, a shift to lower MICs compared with the MIC distributions of minocycline was observed with several gram-negative species, e.g., Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter spp. Tigecycline exhibited high activity not only against pneumococci but also against the other two major respiratory tract pathogens, Haemophilus influenzae and Moraxella catarrhalis.
These results indicate that tigecycline holds promise as an important therapeutic option for infections caused by gram-positive and gram-negative bacteria, especially in view of the increasing problem of the resistance of various species to other classes of antibiotics.2jv'a'%, http://www.100md.com
ACKNOWLEDGMENTS2jv'a'%, http://www.100md.com
This study was supported by Wyeth-Ayerst.2jv'a'%, http://www.100md.com
Isolates were kindly provided by H. Mittermayer (Austria), M. Struelens (Belgium), K. Fuursted (Denmark), M. Vaara (Finland), F. Goldstein (France), V. Jarlier (France), J. Etienne (France), R. Courcol (France), F. Daschner (Germany), U. Hadding (Germany), N. Legakis (Greece), G. C. Schito (Italy), G. Raponi (Italy), E. Eijzerman (The Netherlands), A. van Belkum (The Netherlands), A. Jansz (The Netherlands), R. Jureen (Norway), W. Hryniewicz (Poland), P. Heczko (Poland), D. Costa (Portugal), E. Perea (Spain), F. Baquero (Spain), R. Martin Alvarez (Spain), H. Miorner (Sweden), J. Bille (Switzerland), G. French (United Kingdom), and J. Andrews (United Kingdom). We thank A. Florijn, M. Klootwijk, K. Kusters, and S. de Vaal for expert technical assistance.
REFERENCES8+6\', 百拇医药
Betriu, C., I. Rodriguez-Avial, B. A. Sanchez, M. Gomez, J. Alvarez, and J. J. Picazo. 2002. In vitro activities of tigecycline (GAR-936) against recently isolated clinical bacteria in Spain. Antimicrob. Agents Chemother. 46:892-895.8+6\', 百拇医药
Biedenbach, D. J., M. L. Beach, and R. N. Jones. 2001. In vitro antimicrobial activity of GAR-936 tested against antibiotic resistant gram-positive blood stream infection isolates and strains producing extended-spectrum beta-lactamases. Diagn. Microbiol. Infect. Dis. 40:173-177.8+6\', 百拇医药
Boucher, H. W., C. B. Wennersten, and G. M. Eliopoulos. 2000. In vitro activities of the glycylcycline GAR-936 against gram-positive bacteria. Antimicrob. Agents Chemother. 44:2225-2229.8+6\', 百拇医药
Chopra, I. 2001. Glycylcyclines: third generation tetracycline antibiotics. Curr. Opin. Pharmacol. 1:464-469.8+6\', 百拇医药
Deshpande, L. M., A. C. Gales, and R. N. Jones. 2001. GAR-936 (9-t-butylglycylamido-minocycline) susceptibility test development for streptococci, Haemophilus influenzae, and Neisseria gonorrhoeae: preliminary guidelines and interpretative criteria. Int. J. Antimicrob. Agents 18:29-35.
Gales, A. C., and R. N. Jones. 2000. Antimicrobial activity and spectrum of the new glycylcycline, GAR-936, tested against 1,203 recent clinical bacterial isolates. Diagn. Microbiol. Infect. Dis. 36:19-36.1n, http://www.100md.com
Goldstein, E. J., D. M. Citron, C. V. Merriam, Y. Warren, and K. Tyrrell. 2000. Comparative in vitro activities of GAR-936 against aerobic and anaerobic animal and human bite wound pathogens. Antimicrob. Agents Chemother. 44:2747-2751.1n, http://www.100md.com
Henwood, C. J., T. Gatward, M. Warner, D. James, M. W. Stockdale, R. P. Spence, K. J. Towner, D. M. Livermore, and N. Woodford. 2002. Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936). J. Antimicrob. Chemother. 49:479-487.1n, http://www.100md.com
Hoellman, D. B., G. A. Pankuch, M. R. Jacobs, and P. C. Appelbaum. 2000. Antipneumococcal activities of GAR-936 (a new glycylcycline) compared to those of nine other agents against penicillin-susceptible and -resistant pneumococci. Antimicrob. Agents Chemother. 44:1085-1088.
Kenny, G. E., and F. D. Cartwright. 2001. Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to GAR-936, dalfopristin, dirithromycin, evernimicin, gatifloxacin, linezolid, moxifloxacin, quinupristin-dalfopristin, and telithromycin compared to their susceptibilities to reference macrolides, tetracyclines, and quinolones. Antimicrob. Agents Chemother. 45:2604-2608.$u, 百拇医药
Murphy, T. M., J. M. Deitz, P. J. Petersen, S. M. Mickels, and W. J. Weiss. 2000. Therapeutic efficacy of GAR-936, a novel glycylcycline, in a rat model of experimental endocarditis. Antimicrob. Agents Chemother. 44:3022-3027.$u, 百拇医药
National Committee for Clinical Laboratory Standards. 1998. Performance standards for antimicrobial susceptibility testing: eighth informational supplement. NCCLS document M100-S8. National Committee for Clinical Laboratory Standards, Villanova, Pa.$u, 百拇医药
Patel, R., M. S. Rouse, K. E. Piper, and J. M. Steckelberg. 2000. In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Diagn. Microbiol. Infect. Dis. 38:177-179.
Petersen, P. J., N. V. Jacobus, W. J. Weiss, P. E. Sum, and R. T. Testa. 1999. In vitro and in vivo antibacterial activities of a new glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob. Agents Chemother. 43:738-744.g%q@4[w, 百拇医药
Schmitz, F. J., A. Krey, R. Sadursky, J. Verhoef, D. Milatovic, and A. C. Fluit. 2001. Resistance to tetracyclines and distribution of tetracycline resistance genes in European Staphylococcus aureus isolates. J. Antimicrob. Chemother. 47:239-240.g%q@4[w, 百拇医药
Sum, P. E., and P. Petersen. 1999. Synthesis and structure-activity relationship of novel glycylcycline derivatives leading to the discovery of GAR-936. Bioorg. Med. Chem. Lett. 17:1459-1462.g%q@4[w, 百拇医药
Van Ogtrop, M. L., D. Andes, T. J. Stamstad, B. Conklin, W. J. Weiss, W. A. Craig, and O. Vesga. 2000. In vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) against various gram-positive and gram-negative bacteria. Antimicrob. Agents Chemother. 44:943-949.(D. Milatovic F.-J. Schmitz J. Verhoef and A. C. Fluit)
Received 13 June 2002/ Returned for modification 11 September 2002/ Accepted 15 October 2002&5.(]c;, 百拇医药
ABSTRACT&5.(]c;, 百拇医药
The in vitro activities of tigecycline against 1,924 clinical isolates were examined. The new glycylcycline exhibited excellent activity against all gram-positive cocci (MICs at which 90% of the isolates tested were inhibited [MIC90s], 1 µg/ml). In addition, it was also very potent against most members of the Enterobacteriaceae, with most MIC90s being 2 µg/ml. Among the nonfermenters, Acinetobacter spp. and Stenotrophomonas maltophilia are included in the in vitro spectrum of tigecycline activity.&5.(]c;, 百拇医药
TEXT&5.(]c;, 百拇医药
Although tetracyclines remain valuable therapeutic agents for a variety of infections, resistance to this class limits their use. A new generation of tetracyclines, the glycylcyclines, is being developed specifically to overcome the problem of resistance to other tetracyclines (4, 16). Tigecycline (GAR-936), the 9-t-butylglycylamido derivative of minocycline, appears to be both better tolerated and more active against tetracycline-resistant strains than are other glycylcyclines (14). The present study examined the in vitro activities of tigecycline and comparators against recent clinical isolates from various European countries.
In all, 1,924 clinical isolates were tested. The strains were sampled between 1998 and 2001 in 28 hospitals from 16 European countries and sent to the Eijkman-Winkler Institute at the University Hospital Utrecht. Only one isolate per patient was permitted. The isolates derived from bloodstream, respiratory tract, skin and soft tissue, and urinary tract infections. Identification of the strains was performed by a VITEK or API system (Biomerieux, s'Hertogenbosch, The Netherlands) and/or by standard laboratory procedures.;jx, 百拇医药
MICs were determined by the microdilution method according to NCCLS guidelines (12) by using cation-adjusted Mueller-Hinton broth. For the testing of Streptococcus spp., the broth was supplemented with 5% lysed horse blood; for the testing of Haemophilus influenzae, Haemophilus Test Medium was used. The inoculum was adjusted to 5 x 105 CFU/ml, and plates were read after incubation for 20 to 24 h at 35°C in ambient air.;jx, 百拇医药
Microtiter plates containing freeze-dried serial dilutions of the antibiotics were prepared by Trek Diagnostic Systems (Westlake, Ohio).
The results of the susceptibility testing of tigecycline and the comparator agents are shown in Table 1 and presented in terms of MIC50 (MIC at which 50% of the isolates tested were inhibited), MIC90, and the range of MICs.w!6;/&, http://www.100md.com
fig.ommitteedw!6;/&, http://www.100md.com
TABLE 1. In vitro activities of tigecycline and comparatorsw!6;/&, http://www.100md.com
Tigecycline was very active against staphylococci (range of MIC50s, 0.12 to 0.5 µg/ml; range of MIC90s, 0.25 to 1 µg/ml), with no difference being observed between the MIC90s for methicillin-susceptible and methicillin-resistant strains. Tigecycline was the most active agent against methicillin-resistant Staphylococcus aureus strains (MIC50 and MIC90, 0.25 µg/ml). Other authors have described an in vitro activity of minocycline against staphylococci that is higher than that of tigecycline (3, 6); however, in our study the new glycylcycline had a higher activity, with a concentration of 1 µg/ml inhibiting all S. aureus strains, including minocycline-resistant isolates, and a concentration of 2 µg/ml inhibiting all coagulase-negative staphylococci. A possible explanation for the lower minocycline activity in our study could be that in our bacterial population, the proportion of tetracycline-resistant isolates harboring the tet M gene was greater. As has been shown previously, 50% of the tetracycline-resistant Staphylococcus aureus strains in Europe carry the tet M gene, which confers resistance to both tetracycline and minocycline (15). In contrast, isolates harboring only the tet K gene are resistant to tetracycline but remain susceptible to minocycline.
Against Enterococcus faecalis and Enterococcus faecium, tigecycline showed high activity, with MIC50s of 0.12 and 0.06 µg/ml, respectively, and MIC90s of 0.25 and 0.12 µg/ml, respectively. It was the most active agent among all antibiotics tested. Approximately half of the enterococcal isolates were resistant to minocycline. However, all strains, including 27 vancomycin-resistant strains, were inhibited by tigecycline at a concentration of 1 µg/ml. Based on the MIC90s, tigecycline was at least eightfold more active than linezolid against Enterococcus spp. and 32-fold more active than quinupristin-dalfopristin against Enterococcus faecium.;krn, 百拇医药
Tigecycline was also highly active against beta-hemolytic streptococci belonging to Lancefield groups A and B (MIC50 and MIC90, 0.06 µg/ml), with all strains, including minocycline-resistant isolates, being inhibited by the antibiotic at a concentration of 0.5 µg/ml. The difference in activities between tigecycline and minocycline was most pronounced with group B streptococci: 78% of the strains were resistant to minocycline, with all of them being inhibited by 0.06 µg of tigecycline/ml.
Against pneumococci and viridans group streptococci, the MIC50s of tigecycline were 0.06 and 0.12 µg/ml, respectively, and the MIC90s were 0.5 µg/ml for both. For penicillin-susceptible and nonsusceptible pneumococcal strains, the MIC90s differed by only 1 dilution step (0.25 and 0.5 µg/ml, respectively). All pneumococcal isolates, including those resistant to minocycline (12.7%), were inhibited by tigecycline at a concentration of 1 µg/ml. Based on the MIC90s, the potency of tigecycline was found to be equivalent to that of gatifloxacin and slightly superior to that of linezolid and quinupristin-dalfopristin.mny)$ev, 百拇医药
Overall, the new glycylcycline exhibited very high activity against gram-positive bacteria, including multiresistant pathogens and minocycline-resistant isolates, all of which were inhibited by tigecycline at a concentration of 1 µg/ml. These results confirm and extend those of previous analyses using gram-positive clinical isolates mainly from the United States (1-3, 6, 7, 13, 14, 17).
Tigecycline exhibited very high activity against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, and Citrobacter freundii, with MIC50s ranging from 0.25 to 1 µg/ml and MIC90s ranging from 0.5 to 2 µg/ml. Against these species, tigecycline was four- to eightfold more active than minocycline based on a comparison of the MIC50s. Against Proteus mirabilis, Proteus vulgaris, Morganella morganii, and Serratia marcescens, tigecycline was less active, with MIC50s of 4, 4, 2, and 2 µg/ml, respectively, and MIC90s of 8, 4, 4, and 4 µg/ml, respectively. Compared with minocycline, it was 2- to 16-fold more active based on the MIC50s. Overall, 172 (27.4%) of the 627 enterobacterial strains tested were resistant to minocycline (MIC, ">="wk{67, http://www.100md.com
16 µg/ml). Interestingly, 65 (37.8%) of the 172 minocycline-resistant strains were inhibited by tigecycline at a concentration of 2 µg/ml. These results extend those of previous analyses using Enterobacteriaceae isolates mainly from the United States (1, 2, 6-8, 14, 17).
Remarkably, tigecycline showed high activity against defined gram-negative nonfermentative bacteria, i.e., Acinetobacter spp. (MIC50, 0.25 µg/ml; MIC90, 2 µg/ml) and Stenotrophomonas maltophilia (MIC50, 0.5 µg/ml; MIC90, 2 µg/ml), two multiresistant bacterial species often involved in nosocomial infections. Based on the MIC50s, tigecycline was 1 dilution less active than minocycline. However, isolates of Acinetobacter that were not susceptible to minocycline were all inhibited by tigecycline at a concentration of 2 µg/ml. Minocycline and tigecycline both exhibited lower potency against Burkholderia cepacia, with minocycline being slightly more active than tigecycline (MIC50s of 2 and 4 µg/ml, respectively, and MIC90s of 16 and 32 µg/ml, respectively). Against Pseudomonas aeruginosa, neither minocycline nor tigecycline had any clinically relevant activity. These results are in accordance with those of previous limited analyses using nonfermentative bacteria (1, 2, 6-8, 14, 17).
Against Haemophilus influenzae, the activity of tigecycline was comparable to that of minocycline and imipenem (MIC50, 0.5 µg/ml; MIC90, 1 µg/ml). However, gatifloxacin, piperacillin-tazobactam, and ceftriaxone were at least eightfold more active against this species (MIC50s and MIC90s, 0.06 µg/ml).-@j[, http://www.100md.com
Against Moraxella catarrhalis, tigecycline and minocycline were equally active, with both agents showing an MIC50 of 0.06 µg/ml and an MIC90 of 0.12 µg/ml (1, 6, 9, 14, 17). In addition, it has been demonstrated that the glycylcyclines are not only active against the classical respiratory pathogens, i.e., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, but also are active against Mycoplasma pneumoniae and Chlamydia pneumoniae (5, 10).-@j[, http://www.100md.com
The results of our in vitro investigation of tigecycline are in line with those of previous analyses that demonstrated its broad spectrum of antibacterial activity (1, 2, 3, 6, 11, 14, 17). Tigecycline exhibited excellent activity against gram-positive cocci (MIC90s, 1 µg/ml), including methicillin-resistant staphylococci, penicillin-resistant pneumococci, and vancomycin-resistant enterococci. Tigecycline also showed very high potency against members of the Enterobacteriaceae, with MIC90s of 2 µg/ml, with the exception of Proteus spp., Serratia marcescens, and Morganella morganii (MIC90s of 4 to 8 µg/ml). In general, it was two- to eightfold more active than minocycline against the enteric bacilli. Among the nonfermenters, Acinetobacter spp. and Stenotrophomonas maltophilia are included in the in vitro spectrum of tigecycline activity. In addition, a shift to lower MICs compared with the MIC distributions of minocycline was observed with several gram-negative species, e.g., Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter spp. Tigecycline exhibited high activity not only against pneumococci but also against the other two major respiratory tract pathogens, Haemophilus influenzae and Moraxella catarrhalis.
These results indicate that tigecycline holds promise as an important therapeutic option for infections caused by gram-positive and gram-negative bacteria, especially in view of the increasing problem of the resistance of various species to other classes of antibiotics.2jv'a'%, http://www.100md.com
ACKNOWLEDGMENTS2jv'a'%, http://www.100md.com
This study was supported by Wyeth-Ayerst.2jv'a'%, http://www.100md.com
Isolates were kindly provided by H. Mittermayer (Austria), M. Struelens (Belgium), K. Fuursted (Denmark), M. Vaara (Finland), F. Goldstein (France), V. Jarlier (France), J. Etienne (France), R. Courcol (France), F. Daschner (Germany), U. Hadding (Germany), N. Legakis (Greece), G. C. Schito (Italy), G. Raponi (Italy), E. Eijzerman (The Netherlands), A. van Belkum (The Netherlands), A. Jansz (The Netherlands), R. Jureen (Norway), W. Hryniewicz (Poland), P. Heczko (Poland), D. Costa (Portugal), E. Perea (Spain), F. Baquero (Spain), R. Martin Alvarez (Spain), H. Miorner (Sweden), J. Bille (Switzerland), G. French (United Kingdom), and J. Andrews (United Kingdom). We thank A. Florijn, M. Klootwijk, K. Kusters, and S. de Vaal for expert technical assistance.
REFERENCES8+6\', 百拇医药
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