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      Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin

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          Abstract

          <div class="section"> <a class="named-anchor" id="d9019319e128"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e129">Background</h5> <p id="d9019319e131">In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered. </p> </div><div class="section"> <a class="named-anchor" id="d9019319e136"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e137">Questions/purposes</h5> <p id="d9019319e139">(1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury? </p> </div><div class="section"> <a class="named-anchor" id="d9019319e141"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e142">Methods</h5> <p id="d9019319e144">A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During the same period, 5810 patients underwent primary TJA and received cefazolin monotherapy. A chart review was performed to obtain patient characteristics, antibiotic dose and timing of administration, and microbiology data. Adequate vancomycin dosing was defined as 15 mg/kg and within the 125-mg range. Vancomycin levels were calculated at the beginning and end of surgery using pharmacokinetic equations. Levels of 15 mg/L were considered adequate. Logistic regression, chi square tests, and analysis of variance were performed. </p> </div><div class="section"> <a class="named-anchor" id="d9019319e146"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e147">Results</h5> <p id="d9019319e149">Among primary TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 [2%]) compared with patients receiving cefazolin prophylaxis (62 of 5810 [1%]; adjusted odds ratio, 1.587 [1.004–2.508]; p = 0.048). Ten percent of PJIs in the vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was adequately dosed according to weight-based dosage recommendations. Furthermore, 94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom 64% (1105 of 1726) were underdosed. All patients had vancomycin infusion initiated within 2 hours before incision. A weight-based protocol would have resulted in fewer patients having unacceptably low vancomycin levels (&lt; 15 mg/L) compared with those with actual fixed dosing, both for the beginning of surgery at the time of incision (zero of 1828 [0%] versus 471 of 1828 [26%]; odds ratio, 0.001 [0.000–0.013]; p &lt; 0.001) and at the end of surgery (33 of 1828 [2%] versus 746 of 1828 [41%]; odds ratio, 0.027 [0.019–0.038]; p &lt; 0.001). Between the vancomycin dosage groups, there were no differences in the rate of nephrotoxicity (underdosed: 12 of 1130 [1%], adequately dosed: five of 518 [1%], overdosed: four of 180 [2%], p = 0.363) and acute kidney injury (underdosed: 28 of 1130 [2%], adequately dosed: 10 of 518 [2%], overdosed: six of 180 [3%], p = 0.561). </p> </div><div class="section"> <a class="named-anchor" id="d9019319e151"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e152">Conclusions</h5> <p id="d9019319e154">The majority of patients given vancomycin prophylaxis are underdosed according to the weight-based dosage recommendations, and MRSA did not occur in patients who were adequately dosed with vancomycin. Surgeons should thus ensure that their patients are adequately dosed with vancomycin using the recommendation of 15 mg/kg and that the dose of vancomycin is administered in a timely fashion. Furthermore, and based on the findings of this study, we have moved toward limiting the utilization of vancomycin prophylaxis for patients undergoing elective arthroplasty at our institution. </p> </div><div class="section"> <a class="named-anchor" id="d9019319e156"> <!-- named anchor --> </a> <h5 class="section-title" id="d9019319e157">Level of Evidence</h5> <p id="d9019319e159">Level III, therapeutic study.</p> </div>

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          Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists.

          Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.
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            Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter.

            In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter. The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (≥ 15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of <15 mg/liter. The relationship between a trough of ≥ 15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37). The relationship between troughs of ≥ 15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy.
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              Epidemiologic aspects of overweight and obesity in the United States.

              National survey data from the U.S. show that the prevalence of overweight and obesity among adults remained relatively constant over the 20-year period from 1960 to 1980, began to increase around the mid-1980s and has continued to increase. Data for children and adolescents, based on different definitions, show the same pattern. It can sometimes be more useful to look at the whole distribution of body mass index, rather than on prevalence estimates based on pre-defined cutoffs. Data from several countries suggest that for both adults and children, the distribution of BMI has become more skewed over time. Although many hypotheses have been put forward about the causes of the increases, data to address these issues are sparse. Obesity is a well-known risk factor for numerous health conditions. Nonetheless, the health consequences of the increases in obesity have not been fully delineated. Increases in diabetes have been noted in conjunction with the rise in obesity. On the other hand, declines in some other cardiovascular risk factors have been seen at all BMI levels. Rising life expectancy and decreasing heart disease mortality rates seem to confound some of the expectations about the effects of increasing obesity on mortality. The effects of obesity on morbidity may be greater than its effects on mortality. The increasing prevalence of obesity poses challenges for researchers and for policy makers.
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                Author and article information

                Journal
                Clinical Orthopaedics and Related Research®
                Clin Orthop Relat Res
                Springer Science and Business Media LLC
                0009-921X
                1528-1132
                July 2017
                April 11 2017
                July 2017
                : 475
                : 7
                : 1767-1774
                Article
                10.1007/s11999-017-5302-0
                5449331
                28401341
                d370c76b-e4e6-44b2-9f31-eb2a1a44aee4
                © 2017

                http://www.springer.com/tdm

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