Elution Profiles of Synthetic CaSO4 Hemihydrate Beads Loaded with Vancomycin and Tobramycin

Eur J Drug Metab Pharmacokinet. 2020 Aug;45(4):547-555. doi: 10.1007/s13318-020-00622-8.

Abstract

Backgrounds and objectives: The use of local antibiotic delivery vehicles is common in the management of biofilm-related infections as they provide high concentrations of local antibiotics while simultaneously avoiding complications from systemic toxicity. We present a 100% pure synthetic calcium sulfate hemi-hydrate mixed with 240 mg tobramycin and 500 mg vancomycin per 10 cc mixture for use in revision surgeries of periprosthetic joint infections (PJIs). The purified carrier demonstrates bioabsorbablity, promotion of bone growth, a physiologically favorable pH, and hydrophilicity. These unique properties may alleviate persistent postoperative wound drainage seen in patients with PJI. Our questions consist of two parts: (1) does the novel calcium sulfate carrier provide therapeutic concentrations of antibiotic locally that can kill biofilm related infections? (2) Are serum concentrations of antibiotic significant to cause concern for systemic toxicity?

Methods: To address these questions, we assayed the elution of antibiotic concentrations obtained from surgical drains and serum among 50 patients in the first 5 postoperative days.

Results: The elution of vancomycin and tobramycin was greatest on day 1 compared with those concentrations obtained on days 2, 3, 4, and 5; serum concentrations were largely undetectable. Our findings demonstrate that this calcium sulfate preparation provides therapeutic delivery of vancomycin and tobramycin locally at log 2-3 above the minimum inhibitory concentration (MIC), while avoiding toxic serum concentrations.

Conclusions: When used in one-stage revision arthroplasties, the bioabsorbable, purified carrier delivers high concentrations of antibiotic while avoiding systemic toxicity.

Keywords: Antibiotics; Biofilm; Calcium sulfate carrier; Infected total joint prosthetics.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Calcium Sulfate / chemistry*
  • Drainage
  • Drug Carriers*
  • Drug Combinations
  • Drug Monitoring
  • Female
  • Humans
  • Joint Prosthesis / adverse effects*
  • Male
  • Middle Aged
  • Prosthesis-Related Infections / blood
  • Prosthesis-Related Infections / drug therapy*
  • Prosthesis-Related Infections / microbiology
  • Reoperation
  • Time Factors
  • Tobramycin / administration & dosage
  • Tobramycin / adverse effects
  • Tobramycin / blood*
  • Treatment Outcome
  • Vancomycin / administration & dosage
  • Vancomycin / adverse effects
  • Vancomycin / blood*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Drug Combinations
  • Stimulan
  • Vancomycin
  • Tobramycin
  • Calcium Sulfate