To the Editor—The placement of an antibiotic-impregnated cement spacer (ACS) during a staged replacement of an infected prosthetic joint is frequently used to increase antibiotic concentration in the joint capsule, and the 2012 Infectious Diseases Society of America Clinical Practice Guidelines for management of prosthetic joint infections state that systemic toxicity from antibiotic-impregnated cement rarely occurs [1]. However, a recent retrospective study found that higher doses of tobramycin in the spacer cement were associated with increased risk of acute kidney injury (AKI) [2–4]. An estimated 1%–2% of the >725 000 total knee and hip arthroplasties performed yearly in United States hospitals become infected over the duration of use [5, 6]; therefore, complications from ACSs could be an important source of postoperative morbidity. A patient developed renal insufficiency after receiving a tobramycin-containing ACS and was found to have a serum tobramycin level of 19.8 µg/mL shortly after surgery and a level of 3.0 µg/mL 4 weeks later with no systemic aminoglycoside administration. To investigate this further, we identified patients with postoperative AKI and detectable serum tobramycin levels after receiving an ACS during 2-stage arthroplasty revision.
Between February 2011 and April 2012, physicians on the inpatient infectious diseases consultation service were asked to measure serum tobramycin concentrations in patients with a >50% rise in serum creatinine from the preoperative baseline following placement of a tobramycin-containing ACS. Approval for this study was obtained from the Vanderbilt Institutional Review Board. Ten patients were identified with an acute rise in serum creatinine and a detectable serum tobramycin level following placement of a tobramycin-containing ACS out of total of 46 revision arthroplasties with ACS placement performed at our institution during this period (Table 1). Patients ranged in age from 50 to 83 years and 6 were male. All patients had comorbid conditions that could predispose to postoperative renal dysfunction as well as perioperative interventions that may have increased the risk of renal dysfunction (Table 1). All patients also received concomitant oral or parenteral antibiotics, but none received systemic aminoglycosides.
Table 1.
Patient Characteristics, Serum Tobramycin Level, and Postoperative Creatinine Change
| Case | Sex | Age, y | Risk Factors for Kidney Injury | Joint | Infecting Organism | Oral or IV Antibioticsb | Preoperative Creatinine, mg/dL | Peak Postoperative Creatinine (% Increase) | Tobramycin Spacer Dose, g | Serum Tobramycin Level, µg/mL/POD | Vancomycin Spacer Dose, g |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1a | F | 66 | HTN, SLE | Knee | Unknown | LF, DN | 1.6 | 3.8 (138%) | 9.6 | 19.8/1 | 8 |
| 2 | M | 50 | RA, NSAIDs | Knee | S. aureus | VM, RN, DN | 0.9 | 2.3 (156%) | 12 | 1.3/11 | 10 |
| 3 | M | 63 | DM, HTN, CKD | Knee | Unknown | CF, DN, LZ | 2.2 | 4.8 (118%) | 9.6 | 3.6/3 | 0 |
| 4 | M | 76 | DM, TF, VP | Knee | S. aureus | NC, RN, MF, CF | 1.8 | 9.3 (417%) | 4.8 | 1.1/3 | 4 |
| 5 | M | 82 | HTN | Knee | Unknown | VM, DN | 0.8 | 2.4 (200%) | 9.6 | 1.9/8 | 8 |
| 6 | F | 74 | DM, HTN, IV contrast | Hip | Group B Streptococcus | LF, DN | 0.8 | 1.7 (113%) | 4.8 | 0.3/2 | 5 |
| 7 | M | 62 | DM, HTN | Hip | Unknown | NC, VM, RN | 1.4 | 2.3 (64%) | 2.4 | 0.1/3 | 9 |
| 8 | M | 65 | DM, HTN, TF, VP, NSAIDs | Knee | Unknown | CZ, CX, VM, CF, DN | 0.7 | 4.1 (486%) | 9.6 | 2.4/9 | 8 |
| 9 | F | 83 | CAD, HTN, TF, VP | Knee | PA, KO, CoNS, CP | VM, CF, DN | 1.1 | 1.8 (64%) | 9.6 | 0.7/9 | 8 |
| 10 | F | 51 | CAD, HTN, TF, VP | Knee | Unknown | CF, VM, DN | 0.9 | 8.5 (844%) | 9.6 | 2.0/7 | 8 |
Abbreviations: CAD, coronary artery disease; CF, ciprofloxacin; CKD, chronic kidney disease; CoNS, coagulase-negative Staphylococcus; CP, Clostridium perfringens; CX, ceftriaxone; CZ, cefazolin; DM, diabetes mellitus; DN, daptomycin; HTN, hypertension; IV, intravenous; KO, Klebsiella oxytoca; LF, levofloxacin; LZ, linezolid; MF, micafungin; NC, nafcillin; NSAID, nonsteroidal anti-inflammatory drug; PA, Pseudomonas aeruginosa; POD, postoperative day; RA, rheumatoid arthritis; RN, rifampin; SLE, systemic lupus erythematosus; TF, blood transfusion; VM, vancomycin; VP, vasopressors.
a Index patient.
b List may represent sequential selection of antibiotics in response to culture data or toxicity concerns.
All ACSs contained tobramycin (mean dose, 8.2 g), and 9 of 10 also contained vancomycin (mean dose, 7.6 g). The average postoperative increase was 260% of the baseline creatinine and occurred early in the postoperative course (range, postoperative day 1–11). All patients tested had detectable serum tobramycin (mean level, 3.3 µg/mL [range, 0.1–19.8 µg/mL]). Of the 9 patients with subsequent laboratory values, serum creatinine levels normalized after an average of 15.9 days postoperatively (range, 10–26 days).
The data provide evidence of systemic tobramycin absorption from ACSs placed during revision joint arthroplasty. This finding suggests that patients receiving an ACS may have prolonged exposure to elevated serum aminoglycoside levels, which could increase the risk of toxicity, including nephrotoxicity. Prospective studies are warranted to determine the true incidence of systemic aminoglycoside absorption from ACSs and the operative and patient risk factors that lead to nephrotoxicity.
Note
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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