Comparative Time-Kill Study of Doxycycline, Tigecycline, Cefazolin and Vancomycin Against Several Clones of Staphylococcus aureus

Background: We present herein, a comparative study assessing the bactericidal kinetics of tigecycline, doxycycline, cefazolin and vancomycin against several methicllin-susceptible (MSSA) and –resistant (MRSA) Staphylococcus aureus isolates recovered from patients of 24 different cities in Argentina. Methods: After genotypic characterization, 20 strains (10 MRSA and 10 MSSA) were selected for time-kill studies. Results: Vancomycin showed bactericidal effect (i.e. ≥3-log10 CFU/mL decrease) against 50% and 10% of the MRSA strains at 4 x Minimal Inhibitory Concentration (MIC) and 2xMIC, respectively, after 24 h of incubation and displayed bactericidal activity against all MSSA isolates at 4xMIC. Cefazolin was bactericidal against 30% of MSSA strains at the higher concentration (4xMIC) and against 10% at 2 x MIC and MIC dose concentrations. The bactericidal magnitude of cefazolin observed after 24 h of incubation was lower than the vancomycin one. Albeit bacteriostactic, tigecycline at 2xMIC exerted a -1 to2-log decrease in the viable cell counts after 24-h incubation against 19 of the 20 S. aureus strains. Doxycycline was the least inhibitory of the antibiotics tested against both MRSA and MSSA, displaying no bactericidal activity in any of the cases and showing regrowth after 24 h of incubation at MIC level. Conclusion: Vancomycin at high concentrations showed the best activity. Cefazolin did not show the activity expected for a beta-lactam antibiotic against MSSA. Tigecycline may be a useful option in infections caused by MRSA, where bactericidal activity is not an exclusive requirement and doxycycline does not seem an attractive alternative in serious infections.