Efficacy of Daptomycin in Implant-Associated Infection Due to Methicillin-Resistant Staphylococcus aureus : Importance of Combination with Rifampin

Abstract

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 g/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 g/ml, daptomycin reduced the counts by >3 log 10 CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 g/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log 10 CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log 10 CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms

“…These results are consistent with the values in the literature. 14,27 Regarding both strains, the MHIC obtained by isothermal microcalorimetry were consistent with the MIC and MBC obtained by the macro-broth dilution method ( Figure 5). In addition, it was possible to observe that MRSA and S. epidermidis growth was delayed at 0.125 µg/mL of daptomycin and at 1 µg/mL of vancomycin, when compared to the GC.…”

Evaluation of an interdisciplinary therapy algorithm in patients with prosthetic joint infections

“…The optimal procedure remains unclear if no agents are available matching these standards (e. g. rifampicin-resistant gram-positive species or ciprofloxacin-resistant gram-negative species). Other antibiotics like Fosfomycin, Daptomycin, Moxifloxacin, and Tigecyclin also show activity against biofilms [44,45], and they find their role in treatment of PJI in appropriate combinations.…”

Central venous catheter-related biofilm infections: An up-to-date focus on meticillin-resistant Staphylococcus aureus

“…In combination therapy, daptomycin treatment with rifampicin or gentamicin has shown conflicting results, but its clinical use has proven successful against several forms of biofilm infections [48,49]. Finally, in a rat model study by Van Praagh et al, combined daptomycin ALT and systemic dosing resulted in clearance of S. aureus CVC-related infection after two daily ALT treatments [50].…”