SLR - September 2016 - Kristin Visco

Effects of Implant-Associated Osteomyelitis on Cefuroxime Bone Pharmacokinetics: Assessment in a Porcine Model

Reference: Tottrup M, Bue M, Koch J, Jensen LK, Hanberg P, Aalbaek B, Fuursted K, Jensen HE, Soballe K. (2016). Effects of Implant-Associated Osteomyelitis on Cefuroxime Bone Pharmacokinetics: Assessment in a Porcine Model. J Bone Joint Surg Am. 2016 Mar 2;98(5): 363–369.

Scientific Literature Review

Reviewed By: Kristin Visco, DPM
Residency Program: New York Presbyterian – Queens, NY

Podiatric Relevance: A common complication seen among all surgeons are postoperative infections. These infections can range in severity from soft tissue to bone involvement and can be associated with implants. Current thoughts regarding treatment of osteomyelitis lean toward surgical resection to achieve complete resolution. Although these infections are often treated with long-term IV antibiotics, there is debate as to whether or not there is enough bone penetration by the antibiotic to achieve effective treatment. This study aimed to assess the effects of implant-associated osteomyelitis on cefuroxime into bone.

Methods: This study used 10 female pigs as subjects. Beta-hemolytic S. aureus (S54F9 of spa type t1333) was isolated from porcine lung abscess and prepared for inoculation. On day 0, a K-wire was used to create a cavity in the proximal tibia under fluoroscopic guidance. Ten microliters of inoculum was then injected into the cavity, and subsequently, the implant (K-wire) was introduced into the cavity and the soft tissue was closed. On day 5, 1.5g of cefuroxime was infused over 15 minutes into the subjects. Microdialysis was the technique used for sampling antibiotic concentration in tissues. The sampling began with the cefuroxime infusion and was continued every 30 minutes over an eight-hour period. ESR, CRP and CT scan were also used to assess the infection. Samples were taken from free plasma, subcutaneous tissue, infected subcutaneous tissue, cancellous bone, infected cancellous bone and the implant cavity. The contralateral limb was used as a control sample in each pig.

Results: Nine out of 10 infected subjects were used to calculate the data. No bacterium was grown in any of the control samples. The average CRP levels increased from 27 (+/- 13.2 mg/L) to 117 (+/- 41.9) when comparing day 1 to 5. CT revealed significant bone destruction in the implant cavity in all but one sample, as demonstrated by the increase in diameter of the implant cavity. The area under the curve and the peak drug concentration was shown to be significantly lower in the implant cavity as compared to other locations that were sampled. Tissue penetration of the antibiotic was calculated and was found to be decreased in the implant cavity, cancellous bone and infected cancellous bone. The time to achieve various MIC was calculated, and the percentage of animals reaching the targets of 40 percent (low) and 65 percent (high) were shown. The implant cavity was only able to exceed the low target of 40 percent for an MIC of 2 mg/L.

Conclusions: This study concluded that the implant cavity had the lowest tissue penetration and thus concentration of antibiotic than that of the other tissues tested. This supports the general thought that antibiotic therapy must be initiated early before implants become infected if nonsurgical treatment is to be pursued. This study also showed that there was significant impairment of bone penetration after only 5 days of initiation of infection. However, there was still good penetration into infected soft tissue, concluding it would be unsafe and not definitive to treat an implant-associated acute osteomyelitis secondary to the impaired bone penetration associated with concurrent infection. This study helps reinforce the thought that osteomyelitis can only be eradicated with surgical debridement. Therefore, patients with postoperative infections associated with an implant should return to the operating room to have the implant removed as well as the infected bone debrided. Of note, the antibiotic used in this study, Cefuroxime, is not typically used to treat osteomyelitis. It is more typically used to treat bronchitis, gonorrhea, sinus infections and pneumonia. It would be interesting if this study were reproduced using antibiotics more typically used to treat osteomyelitis, such as vancomycin, ceftriaxone, ceftaroline, daptomycin and or rifampin.

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