Drug Elution From High-Dose Antibiotic-Loaded Acrylic Cement: A Comparative, In Vitro Study

Abstract

High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing peri-prosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians toward alternative antimicrobial formulations loaded into acrylic bone cement. The aim of this in vitro study was to determine the elution kinetics of 14 different high-dose ALACs. All ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing over time, and elution curves strictly adhered to a nonlinear regression analysis formula. Among aminoglycosides, commonly seen as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, a class of antibiotics that should be considered to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution than teicoplanin. Clindamycin, which can be associated with aminoglycosides to prepare ALACs and represents a useful option against the most common pathogens responsible for PJIs, showed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multidrug-resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics not routinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent a useful option for physicians to eradicate PJIs. In vivo testing should be considered in the future to confirm the results of this study.

Simple method for increasing drug elution from polymethylmethacrylate bone cement

“…Otherwise, desired concentrations cannot be achieved with poorly soluble antibiotics like cefepime or ampicillin. [8][9][10] Nonetheless, this method may work in the same way even if the molecule had high or low solubility. The effect might be more prominent in low solubility drugs.…”

Current Options and Emerging Biomaterials for Periprosthetic Joint Infection

“…Furthermore, when higher quantities of antibiotics (2–4 g per 40 g of PMMA [42]) are placed within the articular space in the form of a bone cement spacer to treat PJI, retrieval studies have demonstrated that offending bacteria remain alive within the surrounding tissues [43]. More recent investigations have revealed the limitations of using PMMA as a method of antibiotic-delivery: antibiotics rapidly elute within the first 24 h, but logarithmically decline over a matter of days [44]; antibiotic release is limited to the outer 100 μm layer of the PMMA [45]; and that prolonged sub-therapeutic intra-articular concentrations of antibiotic can undesirably lead to the development of drug-resistant bacteria [24]. …”

“…In response to the above limitations, investigators have responded by changing the mixing process of PMMA to increase porosity and improve elution profiles [44], using binding agents to increase elution [46] and using newer antibiotics with longer half-lives in an effort to prolong their intraarticular effects [47]. More recently, good PJI treatment success rates have been reported by introducing a percutaneous catheter at the time of revision surgery and regularly infusing antibiotics into the joint space for several weeks [48].…”

Trowels and Tribulations: Review of Antimicrobial‐Impregnated Bone Cements in Prosthetic Joint Surgery

“…Linezolid is generally a bacteriostatic agent with a spectrum of activity comparable with that of daptomycin. From a practical standpoint, 22,49 0.5 g 1 g Y 1.25% w/w maximum studied in vitro Fluconazole 16,52 NR 2 g N 8% w/w maximum studied in vitro Gentamicin 21,22,24,37,44 0.5-1 g 0.25-4.8 g N Imipenem-cilastatin 41,44 NR NR Y 10% w/w maximum studied in vitro Linezolid 53,54 NR NR N 15% w/w maximum studied in vitro Meropenem 17, 55 5 g NR Y 20% w/w maximum studied in vitro Micafungin 16 NR NR Y 4% w/w maximum studied in vitro Moxifloxacin 17 NR NR N 20% w/w maximum studied in vitro Piperacillin 38,44 NR 8 g Y 2.5% w/w maximum studied in vitro Piperacillin-tazobactam 22 NR 4.5 g Y Rifampin 17 NR NR Y 20% w/w maximum studied in vitro Teicoplanin 35,41,44,56 NR 3.6-10 g e Y f 10% w/w maximum studied in vitro Tigecycline 35,57 NR NR Y 10% w/w maximum studied in vitro Tobramycin 22,42,44 0.5-1. linezolid incorporates into PMMA and appears to withstand the temperatures generated during polymerization. 53,54 Linezolid is commercially available as a solution for injection, a filmcoated tablet, and flavored granules for oral suspension.…”