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A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Local delivery of tobramycin and vancomycin in primary total knee arthroplasty achieves minimum inhibitory
Charles M Lawrie1, Sally Jo1, Toby Barrack1
1Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Aims:
The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI).
Methods:
Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder.
Results:
A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms.
Conclusion:
One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163-169.
Insights
Local antibiotic delivery in total knee arthroplasty (TKA) is crucial for preventing infection. This study found that combining tobramycin in bone cement with vancomycin powder effectively targets bacteria causing acute prosthetic joint infection (PJI).
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Pharmacology
Background:
- Acute prosthetic joint infection (PJI) is a serious complication following total knee arthroplasty (TKA).
- Antibiotic resistance is a growing concern in managing PJI.
- Effective local antibiotic delivery strategies are needed to achieve therapeutic intra-articular concentrations.
Purpose of the Study:
- To evaluate if local vancomycin and tobramycin delivery in primary TKA achieves intra-articular concentrations above minimum inhibitory concentrations (MICs) for common PJI pathogens.
- To assess the susceptibility patterns of bacteria causing acute PJI after TKA to commonly used antibiotics.
Main Methods:
- Retrospective analysis of TKA patients with acute PJI within 90 days of surgery.
- Bacterial isolate susceptibility testing to gentamicin, tobramycin, and vancomycin.
- Prospective study measuring intra-articular antibiotic concentrations with various local delivery methods (PMMA-mixed or powder).
Main Results:
- Of 19 PJI patients, 31% of isolates were gentamicin-resistant, 34% tobramycin-resistant, and 24% vancomycin-resistant.
- Most isolates resistant to one aminoglycoside were susceptible to vancomycin, and vice versa.
- A combination of tobramycin in polymethylmethacrylate (PMMA) and vancomycin powder achieved concentrations exceeding MICs for susceptible organisms.
Conclusions:
- A significant proportion of bacteria causing PJI after TKA exhibit resistance to commonly used aminoglycosides and vancomycin.
- Combining tobramycin in antibiotic cement with vancomycin powder provides optimal coverage for most bacteria implicated in acute PJI.
- This dual-local antibiotic strategy is recommended for preventing and treating PJI in TKA.
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