European in vitro antibacterial activity of tigecycline against methicillin-resistant and methicillin-sensitive Staphylococcus aureus isolates from the Tigecycline Evaluation Surveillance Trial (TEST)

Abstract number: 1134_02_15

Bouchillon S., Stevens T., Johnson B., Johnson J., Hoban D., Hackel M., Person M., Dowzicky M.

Objective:

Despite the introduction of new antimicrobials to treat resistant gram-positive bacteria, Staphylococcus aureus continues to be a therapeutic challenge for the clinician. Glycylcyclines are showing the promise of significant activity against many gram-positive pathogens including methicillin-resistant S. aureus. Tigecycline, the first glycylcycline to enter clinical trials, has shown excellent activity against Staphylococcus spp. This study was initiated to evaluate the in vitro activity of tigecycline as compared with those of 9 comparator agents (ampicillin, amoxicillin-clavulanic acid, imipenem, ceftriaxone, levofloxacin, minocycline, vancomycin, linezolid, piperacillin-tazobactam) against S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) from 5 European centres in the TEST program.

Methods:

A total of 216 clinical isolates were identified to the species level at each of participating sites and confirmed by the central laboratory. Isolates were collected throughout 2004. MICs were determined by each participating laboratory using broth microdilution panels from Dade Microscan. All testing was performed and interpreted according to NCCLS guidelines and manufacturer's instructions.

Results:

Among the 216 isolates, 76 (35.2%) were found to be resistant to methicillin (MRSA). Besides the cross resistance of MRSA isolates to imipenem, ceftriaxone, penicillin, ampicillin, and piperacillin/tazobactam, it was observed that all of MRSA isolates were also non-susceptible to levofloxacin. No resistance was observed against vancomycin and linezolid. The MICs of tigecycline ranged from 0.06 to 0.5 mcg/mL for all isolates of S. aureus, and tigecycline presented the lowest MIC50/MIC90 of 0.25/0.25 mcg/mL against MRSA isolates, being several folds lower than all the comparator agents. The MSSA isolates showed the expected profile of high resistance to ampicillin and penicillin. Opposite to MRSA isolates, MSSA presented very little resistance to levofloxacin (2.5%). Tigecycline's MIC50/MIC90 of 0.12/0.25 was also the lowest among all MSSA isolates.

Conclusion:

The in vitro activity of tigecycline was comparable in all S. aureus tested regardless of methicillin phenotype. Tigecycline activity against MRSA was more potent than all antimicrobial agents tested in this study including imipenem, minocycline, linezolid, and vancomycin.