Dalbavancin-resistant selection following a prosthetic joint infection: phenotypic and genomic characterization.

BACKGROUND

Dalbavancin is a lipoglycopeptide antibiotic with a wide spectrum of activity against Gram-positive bacteria, including MDR isolates. Its pharmacokinetic properties and administration patterns could be useful for the treatment of bone and joint infections, especially prosthetic joint infections (PJIs).

INTRODUCTION

We report the case of an 80-year-old man who experienced an acute periprosthetic joint infection of his right total knee arthroplasty (TKA). A DAIR procedure was done with tissue sampling, which allowed identification of a linezolid-resistant MDR (LR-MDRSE) strain. The patient was then treated with dalbavancin (four injections).

METHODS

We studied the phenotypic and genomic evolution of the strains and plasma through concentrations of dalbavancin at different points in time.

RESULTS

After four injections (1500 mg IV) of dalbavancin over a 6 month period, the dalbavancin MIC increased 4-fold. Calculated AUC/MIC ratios were 945, 1239 and 766.5, respectively, at Days 49, 71 and 106, assuming an MIC of 0.032 mg/L. The PFGE dendrogram revealed 97% similarity among all the isolates. These results suggest acquisition by the strain of dalbavancin resistance when the patient underwent dalbavancin treatment. A 4-amino-acid deletion in the gene coinciding with the emergence of phenotypic resistance was revealed by WGS without any other relevant indels.

CONCLUSIONS

Despite dalbavancin treatment with pharmacokinetic management, emerging dalbavancin resistance in was observed, resulting in treatment failure. This outcome led to a prosthesis revision and long-term suppressive antibiotic therapy, with no recurrence of PJI after an 18 month follow-up.