Systemic Safety of High-Dose Antibiotic-Loaded Cement Spacers after Resection of an Infected Total Knee Arthroplasty

Mayo Clinic - Rochester, Рочестер, Minnesota, United States
Clinical Orthopaedics and Related Research (Impact Factor: 2.77). 11/2004; 427(427):47-51. DOI: 10.1097/01.blo.0000144476.43661.10
Source: PubMed


The purpose of this study was to assess the systemic safety and potential adverse effects of using a high-dose antibiotic-impregnated cement spacer after resection arthroplasty of an infected total knee replacement. Between October 2000 and December 2002, 36 knees (34 patients) had a resection arthroplasty of an infected total knee prosthesis with placement of a high-dose antibiotic impregnated cement spacer. There were 24 men and 10 women with a mean age of 66.5 years (range, 48-84 years). All spacers placed contained an average of 3.4 batches of cement with an average total dose of 10.5 g of vancomycin (range, 3-16 g) and 12.5 g of gentamicin (range, 3.6-19.2 g). All patients were followed up post-operatively until reimplantation for evidence of renal failure. The preoperative creatinine ranged from 0.7 to 1.8 mg/dL. All patients were concomitantly treated with 6 weeks of intravenous organism-specific antibiotics. One patient with normal preoperative renal function (Cr 0.7 mg/dL) had a perioperative 1-day transient rise in serum creatinine (1.7 mg/dL) postoperatively that subsequently normalized. No patients showed any clinical evidence of acute renal insufficiency, failure, or other systemic side effects of the antibiotics. Treatment of patients with an infected total knee arthroplasty with high-dose vancomycin and gentamicin antibiotic spacers seems to be clinically safe.

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    • "A high concentration of vancomycin in the blood might raise safety concerns regarding the use of high-dose antibiotic-eluting carriers. Springer et al reported that only one out of 36 patients undergoing a staged operation using vancomycin-gentamicin cement spacers had a transient rise in serum creatinine level.22 No other patients suffered systemic side effects associated with the use of the antibiotics. "
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    ABSTRACT: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.
    Full-text · Article · Sep 2014 · International Journal of Nanomedicine
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    • "Knowledge about the local and systemic release characteristics is an essential premise for assessing the length of sufficient antibiotic elution in vivo, efficiency of local infection eradication, but also for prevention of possible side effects in case of a systemic toxicity. Experiences with other antibiotic-loaded drug systems (acrylic bone cement) have shown that systemic side effects (e.g., acute renal or hepatic failure) might occur [7] [8] although these carriers are regarded to be safe with no risk of systemic adverse reactions [9] [10]. "
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    ABSTRACT: The aim of the present study was to investigate the local pharmacokinetic properties and the systemic safety of vancomycin-impregnated cancellous bone grafts in the treatment of spondylodiscitis. Between 2010 and 2012, 8 patients (5 females, 3 males, mean age 68.75 y.) were treated with this method. Local vancomycin concentrations reached median values of 179 µg/mL (maximum 365 µg/mL) on day 1, decreasing to 98 µg/mL on day 3. The urine vancomycin concentrations showed similar pharmacokinetic properties as those locally determined. On day 1, median values were at 28.05 µg/mL (maximum 287 µg/mL). All serum vancomycin concentrations were in all cases and on every day below <2 µg/mL. The median serum creatinine values were preoperatively 0.87 mg/dL, followed by 0.625 mg/dL, 0.705 mg/dL, and 0.835 mg/dL on day 7, 14, and 28, respectively. No cases of ototoxicity could be observed. At a mean follow-up of 16.5 [4-36] months no cases of reinfections or persistent infections could be seen. In conclusion, the implantation of vancomycin-loaded cancellous bone grafts is an effective option in the treatment of spondylodiscitis with a high infection eradication rate and no risk of any systemic toxicity. The pharmacokinetic properties can be easily monitored locally, in the urine and the serum.
    Full-text · Article · Jul 2013
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    • "N A Springer et al. 2004 [19] "
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    ABSTRACT: Periprosthetic infections of hip and knee joints are now treated by two-stage revision arthroplasty with an infection control rate of 91%. The present systematic review studied the reported incidence of acute kidney injury (AKI) and infection recurrence from January 1989 to June 2012 to assess the risk-benefit ratio of antibiotic spacer use. Ten observational studies (n=544 patients) with clinical outcomes showed an average incidence of AKI of 4.8%. The average reported persistence or recurrence rate of infection was 11% during a follow-up period that ranged from 13 to 108months. The risk-benefit ratio presently favors treatment although there appears to be higher complication rates and incidence of AKI than previously reported. Marked heterogeneity in practice and lack of detail in reporting precluded more robust quantitative synthesis. Clinicians need to be aware of the potential risk of AKI, particularly in high-risk patients; practice patterns for the use of antibiotic spacers need to be standardized.
    Full-text · Article · Apr 2013 · The Journal of arthroplasty
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