Abstract
Dalbavancin is a new semisynthetic lipoglycopeptide with improved antimicrobial activity against various gram-positive pathogens. It demonstrates an extensive plasma half-life which permits outpatient parenteral antimicrobial therapy with weekly intervals and might therefore be an excellent treatment alternative for patients requiring prolonged antimicrobial therapy. The present study investigated dalbavancin monotherapy in an experimental implant-related methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. A clinical MRSA isolate and a Kirschner-wire were inserted into the proximal tibia of anaesthetized Sprague-Dawley rats. Four weeks after infection 34 animals were treated over 4 weeks with either dalbavancin (20 mg/kg loading-dose; 10 mg/kg daily), vancomycin (50 mg/kg twice daily) or left untreated. Twenty-four hours after the last treatment dose tibial bones and Kirschner-wires were harvested for microbiological examination. Based on quantitative bacterial cultures of osseous tissue, dalbavancin was as effective as vancomycin and both were superior to no treatment. No emergence of an induced glycopeptide-/lipoglycopeptide- resistance was observed after a treatment period of four weeks with either dalbavancin or vancomycin. In conclusion, monotherapy with dalbavancin was shown to be as effective as vancomycin for treatment of experimental implant-related MRSA osteomyelitis in rats, but both antimicrobials demonstrated only limited efficacy. Further studies are warranted to evaluate the clinical efficacy of dalbavancin for the treatment of periprosthetic S. aureus infections.
Highlights
The increasing prevalence of drug-resistant gram-positive cocci, such as methicillin-resistant Staphylococcus aureus (MRSA) has complicated the management of difficult to treat infections[1,2,3]
During induction of the experimental implant-related MRSA osteomyelitis, two out of 36 rats died during anesthesia and were not further analyzed
Significant differences were shown for dalbavancin (p < 0.01) and vancomycin (p = 0.03) when compared to no treatment but not between the two antimicrobial therapies
Summary
The increasing prevalence of drug-resistant gram-positive cocci, such as methicillin-resistant Staphylococcus aureus (MRSA) has complicated the management of difficult to treat infections[1,2,3]. The in vitro activity of dalbavancin against various gram positive pathogens including MRSA and vancomycin-intermediate S. aureus (VISA) isolates was shown to be even improved when compared to established antibiotics such as linezolid, teicoplanin or vancomycin[7]. For implant-related MRSA-infections, in particular in osseous tissue, current treatment strategies recommend a combination of a biofilm active substance like rifampicin or fosfomycin together with vancomycin[8,9]. In a recent study it was shown that dalbavancin was active in an MRSA-osteomyelitis model compared to vancomycin[10]. Hitherto no data on the efficacy of dalbavancin in the treatment of implant-related osteomyelitis is available. The present study set out to investigate the efficacy of dalbavancin compared to vancomycin in an experimental implant-related MRSA osteomyelitis rat-model. The three groups, dalbavancin, vancomycin and untreated, comprised twelve, eleven and eleven rats, respectively
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