Determination of the Elution Capacity of Dalbavancin in Bone Cements: New Alternative for the Treatment of Biofilm-Related Peri-Prosthetic Joint Infections Based on an In Vitro Study

Abstract

Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.

In Vitro Efficacy of Dalbavancin as a Long-Acting Anti-Biofilm Agent Loaded in Bone Cement

“…In contrast, dalbavancin reached its highest concentration at 2 weeks before beginning to degrade, as there was no further elution; however, its concentration remained constant over time. These data differ from those of our previous study because the concentration analyzed was cumulative [ 13 ]. Either way, although the concentration of dalbavancin recovered during elution is lower than that of vancomycin, it is higher than the MIC against staphylococci.…”

“…In contrast, dalbavancin reached its highest concentration at 2 weeks before gradually decreasing at both concentrations used (Figure 1). in bone cement, we recently reported, for the first time, that dalbavancin was a suitable alternative in bone cement based on its good elution capacity over a 14-day in vitro study period [13]. However, it is necessary to assess whether elution is maintained over longer periods and whether eluted dalbavancin can reduce staphylococcal biofilm.…”

“…The most commonly used antibiotic bone cement in two-stage procedures is polymethylmethacrylate (PMMA), owing to the wide experience in its use and its favorable safety profile [11,12]. Given the low number of antibiotics recommended for loading in bone cement, we recently reported, for the first time, that dalbavancin was a suitable Antibiotics 2023, 12, 1445 2 of 10 alternative in bone cement based on its good elution capacity over a 14-day in vitro study period [13]. However, it is necessary to assess whether elution is maintained over longer periods and whether eluted dalbavancin can reduce staphylococcal biofilm.…”

Retrospective analysis of drug resistance characteristics and infection related risk factors of multidrug-resistant organisms (MDROs) isolated from the orthopedics department of a tertiary hospital

“…Infection is a commonly encountered complication in orthopedic patients 16 , 17 . With the continuous development of science and technology, the frequency of traffic and construction site accidents as well as the proportion of open and multiple injuries has increased significantly, leading to an escalation of nosocomial infections encountered in the inpatient departments of hospitals 18 , 19 .…”

A Narrative Review on the Role of Dalbavancin in the Treatment of Bone and Joint Infections

“…In addition, a retrospective multicenter study, which included only two patients with PJI, showed that dalbavancin may be used as suppressive antibiotic therapy in these infections, as clinical efficacy was observed in one of two patients and no adverse events were reported [74]. Finally, several in vitro and experimental in vivo studies demonstrate that dalbavancin successfully eliminates biofilms due to Gram-positive bacteria, indicating that it is an active therapy against biofilms [75][76][77][78][79][80][81].…”