Kheir Michael M, Tan Timothy L, Azboy Ibrahim, Tan Dean D, Parvizi Javad
The Rothman Institute, Thomas Jefferson University, 125 S 9th Street, Suite 1000, Philadelphia, PA, 19107, USA.
Clin Orthop Relat Res. 2017 Jul;475(7):1767-1774. doi: 10.1007/s11999-017-5302-0.
In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant Staphylococcus aureus (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.
QUESTIONS/PURPOSES: (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?
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.
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 (< 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 < 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 < 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).
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.
Level III, therapeutic study.
在全关节置换术（TJA）中，对于青霉素过敏患者或耐甲氧西林金黄色葡萄球菌（MRSA）定植患者，万古霉素用作围手术期抗生素预防用药。尽管万古霉素给药应基于体重（15mg/kg），但并非所有外科医生都知晓这一点；相反，经常给予固定的1g剂量。
问题/目的：（1）初次全关节置换术后接受万古霉素或头孢唑林预防的患者，假体周围关节感染（PJI）风险是否存在差异？（2）万古霉素给药剂量合适的患者比例是多少？（3）与实际固定剂量相比，基于体重的给药方案是否会使更多患者在手术开始和结束时保持在推荐的15mg/L水平以上？（4）万古霉素用药过量的患者发生肾毒性和急性肾损伤的风险是否更高？
对2008年至2014年间接受万古霉素预防的1828例初次全关节置换术患者进行了单机构回顾性研究。同期，5810例患者接受了初次全关节置换术并接受头孢唑林单药治疗。通过查阅病历获取患者特征、抗生素剂量和给药时间以及微生物学数据。万古霉素给药剂量合适定义为15mg/kg且在125mg范围内。使用药代动力学方程计算手术开始和结束时的万古霉素水平。15mg/L的水平被认为是合适的。进行了逻辑回归、卡方检验和方差分析。
在初次全关节置换术中，接受万古霉素的患者发生PJI的比例（1828例中的32例[2%]）高于接受头孢唑林预防的患者（5810例中的62例[1%]；调整后的优势比，1.587[1.004 - 2.508]；p = 0.048）。万古霉素剂量不足组中10%的PJI（20例中的2例）由MRSA引起，万古霉素剂量合适或过量的患者均未发生由MRSA引起的PJI。在所有使用万古霉素单药治疗的手术中，根据基于体重的剂量建议，28%（1828例中的518例）给药剂量合适。此外，94%（1828例中的1726例）患者接受了1g固定剂量的万古霉素，其中64%（1726例中的1105例）剂量不足。所有患者均在切口前2小时内开始输注万古霉素。与实际固定剂量相比，基于体重的方案在手术开始时（切口时1828例中的0例[0%]对1828例中的471例[26%]；优势比，0.001[0.000 - 0.013]；p < 0.001）和手术结束时（1828例中的33例[2%]对1828例中的746例[41%]；优势比，0.027[0.019 - 0.038]；p < 0.001）会使万古霉素水平过低（< 15mg/L）的患者更少。在万古霉素剂量组之间，肾毒性发生率（剂量不足：1130例中的12例[1%]，剂量合适：518例中的5例[1%]，过量：180例中的4例[2%]，p = 0.363）和急性肾损伤发生率（剂量不足：1130例中的28例[2%]，剂量合适：518例中的10例[2%]，过量：180例中的6例[3%]，p = 0.561）无差异。
大多数接受万古霉素预防的患者根据基于体重的剂量建议剂量不足，万古霉素剂量合适的患者未发生MRSA感染。因此，外科医生应确保按照15mg/kg的建议为患者给予合适剂量的万古霉素，并及时给药。此外，基于本研究结果，我们已在本机构限制对接受择期关节置换术患者使用万古霉素预防。
III级，治疗性研究。
