Daptomycin: local application in implant-associated infection and complicated osteomyelitis

Abstract

Background: The rise of highly resistant bacteria creates a persistent urge to develop new antimicrobial agents. This paper investigates the application of the lipopeptide antibiotic daptomycin in infections involving the human bone.

Methods: Compressive and tensile strength testing of daptomycin-laden PMMA was performed referring to the ISO 5833. The microstructure of the antibiotic-laden PMMA was evaluated by scanning electron microscopy. Intracellular activity of daptomycin was determined by a human osteoblast infection model. Elution kinetics of the antibiotic-laden bone cement was measured by using a continuous flow chamber setup.

Results: There was no significant negative effect of adding 1.225% and 7.5% per weight of daptomycin to the PMMA. There was no significant difference in intracellular activity comparing gentamicin to daptomycin. Elution of daptomycin from PMMA showed within the first-hour initial peak values of 15-20 μg/mL.

Conclusion: Daptomycin has a certain degree of activity in the intracellular environment of osteoblasts. Daptomycin admixed to PMMA remains bactericidal and does not significantly impair structural characteristics of the PMMA. The results of this paper suggest that daptomycin might be a potent alternative for treating osteomyelitis and implant-associated infection in trauma and orthopedic surgery caused by multiresistant strains.

Figure 1

Test setup for (a) compressive strength testing and (b) bending modulus and bending strength testing stated by the ISO 5833.

Figure 2

Scanning electron microscopy: daptomycin-laden PMMA at magnifications of (a) 3000 and (b) 1200.

Figure 3

Continuous flow chamber modified according to Perry et al. [51].

Figure 4

In vitro infection model—internalization rate for 20 h and 40 h of 3 different. Staphylococcus strains with application of different antibiotics. Invasiveness of Cowan with gentamicin set at 100%. TM 300 served as a negative control group.

Figure 5

Average bending modulus, bending strength and compression strength.

Figure 6

Elution kinetics for daptomycin measured by means of a bioassay with S. epidermidis and E. faecium.