Servicio de Microbiología, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, 28007 Madrid, Spain
Keywords: tigecycline, GAR-936, glycopeptide-resistant enterococci, glycopeptide-resistant staphylococci, Gram-positives
Sir,
Increasing antimicrobial resistance among clinical isolates of staphylococci and enterococci has complicated the treatment of infections caused by these microorganisms, and there is a need for therapeutic alternatives against them. The glycylcyclines are novel tetracycline analogues with activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, including tetracycline-resistant isolates. The glycylcycline tigecycline (GAR-936) is active against a variety of microorganisms;13 however, information concerning its activity against glycopeptide-resistant enterococci is very scarce, and there is none about its activity against staphylococci with diminished susceptibility to glycopeptides.2,4,5 In this study, we compared the in vitro activity of tigecycline with that of tetracycline, vancomycin and teicoplanin against 157 unrelated, non-duplicate clinical isolates obtained in our microbiology laboratory during 19982001. The isolates included 97 vancomycin-resistant enterococci (25 Enterococcus faecalis, 41 Enterococcus faecium, 21 Enterococcus casseliflavus, and 10 Enterococcus gallinarum), 54 coagulase-negative staphylococci and six Staphylococcus aureus with diminished susceptibility to glycopeptides. Among the enterococci, 28 isolates presented the VanA phenotype, 38 the VanB and 31 the VanC. Tigecycline (GAR-936) was provided by Wyeth-Ayerst Research Laboratories (Saint Davids, PA, USA), and vancomycin, teicoplanin and tetracycline by their respective manufacturers. Antimicrobials were tested at two-fold concentrations (tigecycline: 0.0332 mg/L, vancomycin and teicoplanin: 0.5512 mg/L and tetracycline: 0.58 mg/L). Susceptibility studies were performed by the broth microdilution method with cation-adjusted MuellerHinton broth (Oxoid, Unipath Ltd, Basingstoke, UK). The recommendations of the NCCLS were followed.6 S. aureus ATCC 29213 and E. faecalis ATCC 29212 were used as control strains. Isolates were stored at 70°C, with three subcultures being made before the organisms were tested. Following inoculation (final inoculum concentration, c. 5 x 105 cfu/mL), MIC trays were incubated at 35°C in ambient air for 24 h before examination. MBCs of tigecycline were defined as a 99.9% reduction of the initial inoculum, and were determined by subculturing 0.1 mL (all volume) of every MIC test onto blood agar plates. Colonies were enumerated after 24 h of incubation at 35°C in ambient air.
Tigecycline inhibited all isolates tested (157) at concentrations between ≤0.03 and 1 mg/L (Table 1). The MIC90 of tigecycline against all isolates was 0.5 mg/L, and all were inhibited at ≤1 mg/L, including tetracycline-resistant isolates. The MIC90 of tigecycline against all species of enterococci was 0.12 mg/L; it was 0.5 mg/L against coagulase-negative staphylococci, and all S. aureus tested were inhibited with 1 mg/L. Fifty-five enterococci were tetracycline-resistant (MIC > 8 mg/L), and all were inhibited with tigecycline 0.5 mg/L. Eight coagulase-negative staphylococci and four isolates of S. aureus were resistant to tetracycline, and all were inhibited with tigecycline 1 mg/L. Tigecycline was equally active against the VanA, VanB and VanC phenotypes of glycopeptide resistance of enterococci. The MICs (mg/L) of tigecycline for control organisms were as follows: for S. aureus ATCC 29213 (n = 10), 0.12 (n = 8) and 0.25 (n = 2); for E. faecalis ATCC 29212 (n = 10), 0.06 (n = 7) and ≤0.03 mg/L (n = 3). Tigecycline exhibited no bactericidal activity against any of the isolates tested. In all cases, the MBC90 was higher than 32 mg/L. Only three isolates of enterococci were killed with tigecycline 4, 8 and 16 mg/L, respectively, and one isolate of coagulase-negative staphylococci was killed with 16 mg/L.
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In summary, our results indicate that tigecycline is very active against glycopeptide-resistant enterococci, and staphylococci with diminished susceptibility to glycopeptides; it has potential for therapeutic application.
Acknowledgements
This study was presented in part at the Forty-first Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, USA, 1619 December, 2001. This is a fully independent study that has not received financial support.
Footnotes
* Corresponding author. Tel: +34-91-586-8459; Fax: +34-91-504-4906; E-mail: ecercenado@teleline.es
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