Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm

Abstract

In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

FIG. 1.

Activities of antibiotics against MRSA bacteria embedded in biofilm after 24 h of exposure. Dapto, daptomycin; Lzd, linezolid; Vanco, vancomycin; Tige, tigecycline; Mino, minocycline; Rifam, rifampin. The standard deviations for linezolid, vancomycin, and the control are 0 because our upper limit of detection was 5,000 CFU/ml, and any value greater than that was considered 5,000 in analysis.

FIG. 2.

Time-kill activities of antibiotics against 10 strains of MRSA embedded in biofilm after 4-hour daily exposures over 5 days. (A) Activities of daptomycin (Dapto), minocycline (Mino), and tigecycline (Tige). (B) Activities of rifampin (Rifam), vancomycin (Vanco), and linezolid (Lzd). Our lower limit of detection was 50 CFU/ml, and our upper limit of detection was 5,000 CFU/ml.

FIG. 3.

Time-kill activities of rifampin (Rifam) in combination with either vancomycin (Vanco) (A) or linezolid (Lzd) (B) against 10 strains of MRSA embedded in biofilm after 4-hour daily exposures over 5 days.