Antibiotics and Cement

Introduction

The use of antibiotics in cement predates the widespread use of systemic intravenous antibiotics for perioperative prophylaxis. In the 1950s, published data recommended avoiding administration of systemic antibiotics with the fear that they may actually increase infection rates. ^, The debate over utilization of antibiotics perioperatively continued into the 1970s. Intriguingly, while controversy about systemic perioperative antibiotic prophylaxis continued, local antibiotic mixture into the cement for arthroplasty fixation, for the same reason of infection prevention, had been well documented. By 1974, a series of 1119 total hips in Hamburg had been followed using the routine mixture of antibiotic cement with a deep infection rate of 0.1%, which was significantly lower than contemporary rates.

The foundations on which are built the type of cement and antibiotic impregnation used to maximize infection-free success are far from standardized. The reason for this lack of clarity is the wide variety of presenting scenarios, patients, and bone and soft-tissue statuses. Today, as periprosthetic joint infections (PJIs) are treated with a combination of systemic and local antibiotic delivery and both have significant contributions to effectiveness and toxicity, it is still important to focus attention on how surgeons can maximize this therapeutic ratio through the orthopaedic construct.

The existing literature is composed of an enormous collection of varying quality articles, often supporting and corroborating the findings of one another but also at times seemingly providing directly conflicting data. While there is a significant wealth of experience with this technique, the optimal antibiotic dosing/structural (cement) carrier/surgical construct, if one exists, remains elusive.

Polymethylmethacrylate (PMMA)

PMMA is the most common formulation of bone cement used in total joint arthroplasty (TJA). Preparation of PMMA consists of a polymer powder and a liquid monomer mixed in a typical 2:1 polymer-to-monomer ratio. This mixture creates an exothermic reaction on the order of 130 kcal/g of liquid ( Fig. 29.1 ).

Duration of Local Antibiotic Treatment

The optimal duration of antibiotic spacer treatment is not well understood. In one basic science study, 6 weeks after antibiotic spacer treatment, periarticular membrane tissue was extracted and analyzed by mass spectrometry; concentrations of vancomycin, tobramycin, and clindamycin were all detected above their minimal inhibitory concentrations. However, clinical studies have cast doubt on whether antibiotics in cement are eluted beyond the first several days/week of implantation. In a PROSTALAC ( prost hesis with a ntibiotic- l oaded a crylic c ement) study, 3.6 g of tobramycin mixed per 40 g of cement was detectable at 118 days, whereas 2.4 g of tobramycin was not, suggesting that three vials of tobramycin per pack of cement is necessary if prolonged elution over the course of a 3-month period is desirable. Duration of vancomycin elution was inferior to tobramycin. While prolonged elution into the joint space is desirable, systemic absorption is a by-product and can cause remote toxicity (see Toxicity section that follows). Therefore, the elution profile is inherently linked with the starting concentration of antibiotics, which is also limited by biomechanical constraints of construction preparation.

As biomechanical and elution profiles are kept in mind for temporary spacers, spacer retention warrants consideration in some cases. Although conventional two-stage revision TJA for infection remains the standard of care for most PJIs, this treatment comes with significant morbidity, disruption of life, and decrease in overall functional outcome. As such, spacer retention is an attractive option, when appropriate, and evidence suggests it may be appropriate in certain scenarios. If spacer retention is to be a standard option at the surgeon’s disposal, prolonged antimicrobial activity and biomechanical durability are essential considerations.

Two common commercial forms of PMMA bone cement are Simplex and Palacos. Head-to-head in vitro comparisons of Simplex and Palacos with respect to the delivery of tobramycin and vancomycin showed that Palacos has a superior antibiotic elution profile. At high loads of antibiotic impregnation, eluates from Palacos cement also demonstrated two to three times longer duration of detectable bioactivity.