Comparative Efficacies of Quinupristin-Dalfopristin, Linezolid, Vancomycin, and Ciprofloxacin in Treatment, Using the Antibiotic-Lock Technique, of Experimental Catheter-Related Infection Due to Staphylococcus aureus

Abstract

We performed in vitro studies to elucidate the bactericidal activity of the antibiotics in an adherent-cell biofilm model. Efficacy studies were performed in a staphylococcal central venous catheter (CVC) infection rat model. Silastic catheters were implanted into the superior cava. Via the CVC the rats were challenged with 1.0 ؋ 10 6 CFU of a live Staphylococcus aureus strain. Twenty-four hours later, the antibiotic-lock technique was started. All animals were randomized to receive daily isotonic sodium chloride solution, quinupristin-dalfopristin (Q/D), linezolid, vancomycin, or ciprofloxacin at the minimal bactericidal concentration (MBC) and at 1,024 g/ml in a volume of 0.1 ml that filled the CVC. The main outcome measures were MICs and MBCs for both planktonic and adherent cells, quantitative culture of the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. The killing activities of all antibiotics against the adherent bacteria were at least fourfold lower than those against freely growing cells, with the exception of Q/D, which showed comparable activities against both adherent and planktonic organisms. Overall, Q/D at 1,024 g/ml produced the greatest reduction in the number of cells recovered from the catheters, while at the same concentration, Q/D and vancomycin demonstrated higher activities than ciprofloxacin or linezolid in reducing the number of organisms recovered from the blood cultures. This study points out that treatment outcome of device-related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Our findings suggest that the clinically used antibiotics cannot eradicate the CVC infection through the antibiotic-lock technique, even at a concentration of 1,024 g/ml.

Searching for new strategies against polymicrobial biofilm infections: guanylated polymethacrylates kill mixed fungal/bacterial biofilms

“…aureus polymicrobial biofilms. Interestingly, while we observed that a high concentration of ciprofloxacin (1024 mg/L) failed to eliminate a mature S. aureus ATCC 25923 biofilm, in accordance with previously published studies, 35,44,45 a much lower concentration of ciprofloxacin (4 mg/L) used in combination with antifungal agents was effective against the same bacterium grown in a polymicrobial biofilm with C. albicans, causing a 99.6% reduction in viable cell counts. The difference in ciprofloxacin effectiveness against monomicrobial and polymicrobial biofilms might be due to differences in the biofilm structure, cell physiology or extracellular matrix composition between single bacterial and mixed fungal/bacterial biofilms.…”

In Vitro Approach for Identification of the Most Effective Agents for Antimicrobial Lock Therapy in the Treatment of Intravascular Catheter-Related Infections Caused by Staphylococcus aureus

“…While some previous in vitro studies have shown the effectiveness of antibiotics, such as vancomycin, daptomycin, and rifampin, as ALTs (7,8,19,23), others have demonstrated the opposite effect, as well as the ineffectiveness of other antibiotics, such as linezolid, gentamicin, and oxacillin (12,24,25). In our study, the antibiotics daptomycin, vancomycin, tigecycline, and rifampin resulted in a significant reduction in the viability of S. aureus biofilms formed over a 24-h incubation period.…”

Biofilms on Central Venous Catheters: Is Eradication Possible?

“…Heparin alone was completely ineffective, and heparin in combination with either ciprofloxacin or vancomycin did not improve efficacy. A study by Giacometti et al (2005) found that neither vancomycin nor ciprofloxacin were highly effective against catheterassociated biofilms of S. aureus in a rat model, though quinupristin-dalfopristin provided a 4-log biofilm plate count reduction compared to the untreated control under the same conditions. These results are not encouraging since none of the agents evaluated in these studies were capable of eradicating biofilms on implanted devices.…”

“…Linezolid is an oxazolidinone that inhibits protein synthesis of most Gram-positive bacteria, including strains that are resistant to the b-lactams and glycopeptides (Shinabarger et al 1997). Others have demonstrated the efficacy of linezolid (El-Azizi et al 2005;Giacometti et al 2005), rifampin (a RNA polymerase inhibitor) (Monzon et al 2002;Peck et al 2003), and ciprofloxacin (an inhibitor of DNA synthesis) (Giacometti et al 2005). The basis for the efficacy of these agents against biofilms of Gram-positive bacteria may be their rapid mode of action, ability to penetrate the biofilm extracellular polymeric substance (EPS) matrix (Souli and Giamarellou, 1998), or the fact that their activity is not growth rate-dependent.…”