Cost Efficacy of Methicillin-Resistant Staphylococcus aureus Decolonization With Intranasal Povidone-Iodine

The Journal of Arthroplasty xxx (2018) 1e4

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Cost Efficacy of Methicillin-Resistant Staphylococcus aureus Decolonization With Intranasal Povidone-Iodine G. Ryan Rieser, MD, Joseph T. Moskal, MD * Virginia Tech e Carilion Clinic, Institute for Orthopaedics and Neurosciences, Roanoke, VA

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Article history: Received 9 June 2017 Received in revised form 16 January 2018 Accepted 19 January 2018 Available online xxx

Background: With increasing rates of virulent drug resistant organisms, MRSA (methicillin-resistant Staphylococcus aureus) decolonization has been demonstrated to decrease infection rates. Recent research has shown the antiseptic povidone-iodine to be equally effective and potentially cost saving compared to intranasal mupirocin. This study's purpose is to evaluate the incidence of MRSA colonization in a more rural community-based population, rates of infection on a mupirocin decolonization protocol, and develop a cost analysis model to compare costs of utilizing povidone-iodine. Methods: Utilizing over 4 years of data, the incidence of MRSA decolonization of consecutive total knee and hip arthroplasties, as well as the rates of infection of patients uncolonized, colonized with successful decolonization, and unsuccessful decolonization were evaluated. Utilizing these data, cost data, and known infection rate utilizing povidone-iodine decolonization, a cost analysis model was developed. Results: Of the 5584 cases with MRSA data at a single institution, only 3.5% tested positive for intranasal MRSA. Of those patients, 69% were successfully decolonized. Of the 3864 cases with infection data, 21 sustained a surgical site infection within 90 days (0.54%). Of these patients, all tested negative for intranasal MRSA initially and therefore did not undergo the decolonization protocol. The cost analysis predicts a potential savings of $74.72 per patient at our institution to use a global intranasal povidoneiodine protocol prior to total joint arthroplasty. Conclusion: Even with a lower incidence of MRSA than typically reported, utilization of intranasal povidone-iodine would potentially save $74.42 per patient. © 2018 Elsevier Inc. All rights reserved.

Keywords: MRSA infection complication primary hip and knee arthroplasty cost

Total joint arthroplasty (TJA) is a pain relieving operation that allows patients to return to many functions of their daily life with improved quality. We continue to strive to improve the functional results as well as the longevity of the joint replacement. One of the most common early reasons for failure is infection. Periprosthetic joint infections account for about 15% of total knee arthroplasty (TKA) revisions and 6% of total hip arthroplasty (THA) revision [1,2]. On average, 1 in every 50 primary TJA patients will develop a surgical site infection (SSI) [3]. We continue to strive to reduce the infection for the immediate postoperative period, as well as the life of the implant. Drug resistant organisms continue to increase in

One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2018.01.033. * Reprint requests: Joseph T. Moskal, MD, Virginia Tech e Carilion Clinic, Institute for Orthopaedics and Neurosciences, 2331 Franklin Rd SW, Roanoke, VA 24014. https://doi.org/10.1016/j.arth.2018.01.033 0883-5403/© 2018 Elsevier Inc. All rights reserved.

prevalence and virility. Staphylococcus aureus is a commensal organism found on the skin and mucous membranes of 20%-30% of patients pursuing TJA and other elective orthopedic procedures [4e7]. Decolonization of patients colonized with methicillinresistant Staphylococcus aureus (MRSA) was initiated in many institutions and shown to decrease the infection rate. The best method of decolonization has yet to be determined. Previous authors have shown that many of the current orthopedic SSIs are secondary to strains of S aureus, which originated from the patient and that nasal colonization of S aureus is one of the most important risk factors for the development of an SSI [8]. A common decolonization method is to use nasal mupirocin twice daily for 5 days along with chlorhexidine wipes or bathing. This has reduced the infection rate in an entire population cohort from 1.11% to 0.34% [9]. There are some issues related to the use of mupirocin. Institutions that use mupirocin as MRSA prophylaxis broadly to all patients have demonstrated resistance strains of bacteria to mupirocin. Also, the strains that are resistance to mupirocin are frequently multidrug resistant, including chlorhexidine, gentamicin, rifampin,

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and trimethoprim/sulfamethoxazole [10]. Chlorhexidine is a common surgical prepping agent. Using mupirocin as a broad decolonization protocol may potentially increase the resistance to surgical prep and perioperative antibiotic prophylaxis. A common method utilized to increase antibiotic stewardship is to use a polymerase chain reaction (PCR) screening test for MRSA, and treat only the patients detected to be nasally colonized with MRSA. This has reduced the incidence of mupirocin resistant organisms, but also increases cost [11]. Nasal mupirocin treatment also does not successfully decolonize approximately 15% or more of the patients treated [4]. Another downside to mupirocin as illustrated by Phillips et al [12] is that patients feel that the mupirocin treatment is more unpleasant than povidone-iodine (PI) treatment. In the intent to treat analysis, those in the mupirocin group were more likely to report headache, rhinorrhea, congestion, sore throat, or any treatment-related symptom [12]. A significantly higher proportion of mupirocin subjects (213 of 555, 38%) reported application of the nasal treatment to be unpleasant compared to PI subjects (19 of 536, 3.6%) (P < .0001). Alternatives to mupirocin for decolonization would be beneficial. A nasal PI solution has been introduced to the market for decolonization purposes. Bebko et al [13] performed a prospective cohort study with a retrospective control demonstrating a SSI reduction from 3.8% in the nontreated group to 1.1% in the group treated with intranasal PI (P ¼ .02). Houang et al and Klossner et al [14,15] demonstrated the nondevelopment of resistance to PI. There is a paucity of literature reports of S aureus resistance to PI. Phillips et al [12] have demonstrated equivalent efficacy of PI to mupirocin in arthroplasty and spinal fusion cases, but decreased cost with PI utilization. Compliance can also be monitored as the PI is given in preop on the day of surgery. Torres et al [16] also investigated the cost-effectiveness of an MRSA screening and mupirocin treatment protocol vs universal PI treatment, and found the PI treatment to be more cost effective. Universal application would also help to reduce methicillin sensitive Staphylococcus aureus colonization, which is also a risk factor for increased SSI [17]. We wished to investigate the cost-effectiveness of universal intranasal PI treatment vs screening and treatment of MRSA positive patients with mupirocin within our institution. Methods After obtaining Institutional Review Board exemption, we performed a retrospective review of prospectively collected quality control data for consecutive THA and TKA patients at our institution from February 1, 2012 to November 16, 2016. During this time our institutional policy was to screen patients preoperatively by PCR analysis for nasal MRSA colonization. If the patients were found to be positive they would undergo a 5-day course of twice daily nasal mupirocin treatment. These patients would then be tested again for MRSA nasal colonization. Of those that remained positive, they would receive perioperative vancomycin in addition to the standard cefazolin antibiotic prophylaxis to include MRSA coverage. All patients underwent chlorhexidine gluconate bathing for 5 days before surgery. The data we reviewed were the initial MRSA screening result, subsequent screening result, and if the patient had a documented perioperative infection. These data allowed us to calculate the incidence of MRSA colonization in the preoperative THA and TKA population of our community, and the success of our decolonization protocol. Our institution also kept records of postoperative infection starting November 1, 2013, which were reviewed, and allowed us to calculate our rates of infection associated with patients who were never colonized, decolonized, and/ or failed decolonization. To calculate costs, we obtained the costs to our hospital for the following items: PCR MRSA screen, mupirocin cost for 5 day

treatment, 2 g intravenous vancomycin, and the 3M intranasal PI swab treatment. According to Torres et al [16], the infection rate between the globally treated PI treatment cohort and the screened cohort treated with mupirocin treatment, identical to our treatment protocol, was the same at 0.8%. As the infection rates were similar between cohorts, the cost of infection was neutral between groups. We however included the cost of infection in our equations, to make it easier to adopt the equations to be used in scenarios of differing infection rates between cohorts. The following equations were used to calculate the associated costs:

CostCohortPI ¼ ðCostpi  nÞ þ ð%infectionPI  n  CostinfectionÞ CostPPPI ¼ CostCohortPI=n CostCohortMR ¼ ðCostPCR  nÞ þ ð%infectionmp  n  CostinfectionÞ þ ðn  %MRSApos  CostmpÞ þ ðCostpcr  %MRSApos  nÞ þ ðCostVanc  %Failed  %MRSApos  nÞ CostPPMR ¼ CostCohortMR=n where CostCohortPI is the cost to treat the cohort of patients globally treated with intranasal PI; n the number of patients in the cohort; Costpi the cost of the PI intranasal swab treatment; % infectionPI the rate of infection of patients globally treated with PI; Costinfection the cost to treat a patient with a periprosthetic joint infection; CostPPPI the cost per patient in the PI cohort; CostCohortMR the cost to treat the cohort of patients treated with PCR rescreening and mupirocin treatment; CostPCR the cost for PCR MRSA screen; %infectionmp the rate of infection for the cohort screened and treated for MRSA with intranasal mupirocin decolonization; %MRSApos the incidence of nasal MRSA colonization in the cohort; Costmp the cost of the mupirocin; CostVanc the cost of perioperative vancomycin treatment with 2 doses of 2 g intravenous; %Failed the rate of failed conversions with mupirocin treatment; and CostPPMR the cost per patient in the cohort of patients treated with PCR rescreening and mupirocin treatment. Results During the time period of February 1, 2012 to November 16, 2016, our institution performed 3400 TKAs and 2184 THAs, for a total of 5584 cases available to evaluate the incidence of MRSA colonization, and success of the decolonization protocol. Only 12 patients had missing data secondary to lack of testing. During the fiscal year of 2016, our institution performed 809 primary TKAs and 551 primary THAs, for a total of 1360 total hip and knee joint replacements. From August 1, 2013 to November 16, 2016, we were able to evaluate infection data on the same patients, for a total of 3864 cases. The itemized costs from our institution are provided in Table 1. The cost utilized for treating infection was obtained from data provided by Stambough et al [11]. The rate of infection utilized for both cohorts was obtained from data provided by Torres et al [16]. The incidence of MRSA positive patients in our community over the study period was 3.5%. Of these patients, 69% were successfully converted using the mupirocin decolonization protocol. Of the 3864 patients with infection data, 21 patients had an SSI (0.54%). All 21 of these patients tested negative for MRSA initially,

G.R. Rieser, J.T. Moskal / The Journal of Arthroplasty xxx (2018) 1e4 Table 1 Itemized Costs. PCR MRSA Screening Test Mupirocin tube for 5 d BID treatment 2 g IV vancomycin dose  2 Povidone-iodine swabs

$83.86 $5.13 $19.98 $12.50

BID, twice daily; IV, intravenous.

and thus received no mupirocin treatment. Calculating the cost utilizing the above equations, results in a cost of $492,729.08 for the fiscal year 2016 with 1360 patients, or $362.30 per patient (Table 2). The cost includes the cost of global decolonization with intranasal PI, and treating periprosthetic joint infection. The calculation for MRSA rescreening and mupirocin decolonization cohort results in a cost of $594,351.16 for the year 2016 cohort, or $437.02 per patient. The difference between MRSA rescreening and mupirocin decolonization protocol compared to global PI decolonization could save our institution $101,622.08 annually with 1360 patients, or $74.72 per patient.

Discussion Controlling infections after arthroplasty remain a challenge to the orthopedic community both in morbidity to the patient and financial costs. Decolonization of the nares has proven to provide benefit in reducing immediate postoperative SSIs [18]. Our institution adopted a commonly accepted protocol of testing the patients' nares for MRSA preoperatively, adding 5 days of twice daily intranasal mupirocin treatment to the chlorhexidine bathing for the MRSA colonized patients, rescreening colonized patients, and adding vancomycin prophylaxis for those patients who failed decolonization. It has been suggested that universal treatment with mupirocin rather than screening is a cost saving measure [11]. This may not be wise, as universal mupirocin use is associated with increased risk of development of mupirocin resistance, which is also associated with resistance to chlorhexidine via multidrug efflux pumps, in addition to gentamicin, rifampin, and trimethoprim/sulfamethoxazole [10]. The orthopedic community needs to follow the guidelines of good antibiotic stewardship in addition to cost savings. A decolonizing agent that is inexpensive, effective, and in which bacteria do not develop resistance would be ideal. Both Houang et al [14] and Klossner et al [15] demonstrated the lack of development of resistance to PI, in addition to a 3M study[19], suggesting PI may be a better alternative to use in a universal treatment program. The 21 patients who developed an SSI at our institution all tested negative for MRSA, and therefore received no mupirocin. Kim et al [6] demonstrated that patients with methicillin sensitive Staphylococcus aureus also benefit from decolonization. A universal screening program may have benefitted some of the 21 infected patients who received no decolonization. There are other potential benefits of intranasal PI use. Patients may not follow the mupirocin decolonization protocol up to a rate of 11% [12]. The intranasal PI can be applied by nursing staff in the preoperative area the day of surgery, which would likely insure a higher compliance rate. Also, patients rated higher satisfaction with intranasal PI than intranasal mupirocin [12]. Intranasal PI reduces bacterial load in the nares Table 2 Results.

Cost per 1360 patients Cost per patient

PI Decolonization

Mupirocin Protocol

Difference

$492,729.08 $362.30

$594,351.16 $437.02

$101,622.08 $74.72

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within 1 hour, including S aureus, by 99.5%, and this is retained for at least 12 hours [19]. Overall, the PI would likely have a higher compliance rate, patient satisfaction, and at least equivalent effectiveness at controlling perioperative infections, as compared to screening and treating patients with mupirocin. Our calculations based on the patients and supply costs at our institution, assuming equivalent infection rates in both treatment groups as illustrated by Torres et al [16], reveal a $74.72 savings per patient, or $101,622 annual savings at our institution. The supply costs, equations, and excel sheet in the appendix is provided to assist other institutions in calculating potential cost savings. Our institution has a lower incidence of MRSA than is reported by several institutions [13,16,17,20]. Institutions with higher incidences of MRSA colonization will likely have increased cost savings compared to our institution. The equations allow other systems to input their own incidence, and data that are available, to estimate their cost to convert. Decreasing health costs while maintaining or improving quality of patient care is paramount with the ever increasing regulations placed on cost containment. This study does have several limitations. First, this is a retrospective study at a single institution. We included all consecutive primary TKA and THA without a history of prior joint infection. Second, we have no comparison of our own to the efficacy of the PI. We based the calculations on an equivalent infection rate as illustrated by Torres et al [16]. This is a descriptive analysis only. Differences in infection rates between mupirocin and PI would result in varying cost savings, when including the cost to treat a perioperative periprosthetic joint infection. Utilizing intranasal PI for a global decolonization protocol has the potential to reduce costs, increase patient compliance, and increase patient satisfaction, while eliminating the risk of mupirocin resistance and maintaining otherwise equivalent infection rates as compared to the current standard of screening and treating with intranasal mupirocin ointment. We conclude that intranasal PI antiseptic use is cost effective. Appendix A. Supplementary Data Supplementary data related to this article can be found at https://doi.org/10.1016/j.arth.2018.01.033. References [1] Khan M, Osman K, Green G, Haddad FS. The epidemiology of failure in total knee arthroplasty: avoiding your next revision. Bone Joint J 2016;98-B(1 Suppl A):105e12. https://doi.org/10.1302/0301-620X.98B1.36293. [2] Ulrich SD, Seyler TM, Bennett D, Delanois RE, Saleh KJ, Thongtrangan I, et al. Total hip arthroplasties: what are the reasons for revision? Int Orthop 2008;32:597e604. https://doi.org/10.1007/s00264-007-0364-3. [3] Bozic KJ, Lau E, Kurtz S, Ong K, Rubash H, Vail TP, et al. Patient-related risk factors for periprosthetic joint infection and postoperative mortality following total hip arthroplasty in Medicare patients. J Bone Joint Surg Am 2012;94: 794e800. [4] Chen AF, Heyl AE, Xu PZ, Rao N, Klatt BA. Preoperative decolonization effective at reducing staphylococcal colonization in total joint arthroplasty patients. J Arthroplasty 2013;28:18e20. [5] Coates T, Bax R, Coates A. Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects. J Antimicrob Chemother 2009;64:9e15. [6] Kim DH, Spencer M, Davidson SM, Li L, Shaw JD, Gulczynski D, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Joint Surg 2010;92:1820e6. [7] Price CS, Williams A, Philips G, Dayton M, Smith W, Morgan S, et al. Staphylococcus aureus nasal colonization in preoperative orthopaedic outpatients. Clin Orthop 2008;466:2842e7. [8] Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997;10:505e20. [9] Sporer SM, Rogers T, Abella L. Methicillin-resistant and methicillin-sensitive Staphylococcus aureus screening and decolonization to reduce surgical site

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[10]

[11]

[12]

[13]

[14]

G.R. Rieser, J.T. Moskal / The Journal of Arthroplasty xxx (2018) 1e4 infection in elective total joint arthroplasty. J Arthroplasty 2016;31(9 Suppl): 144e7. https://doi.org/10.1016/j.arth.2016.05.019. Poovelikunnel T, Gethin G, Humphreys H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother 2015;70:2681e92. https://doi.org/10.1093/jac/dkv169. Stambough JB, Nam D, Warren DK, Keeney JA, Clohisy JC, Barrack RL, et al. Decreased hospital costs and surgical site infection incidence with a universal decolonization protocol in primary total joint arthroplasty. J Arthroplasty 2017;32:728e734.e1. https://doi.org/10.1016/j.arth.2016.09.041. Phillips M, Rosenberg A, Shopsin B, Cuff G, Skeete F, Foti A, et al. Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution. Infect Control Hosp Epidemiol 2014;35:826e32. Bebko SP, Green DM, Awad SS. Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation. JAMA Surg 2015;150:390e5. https:// doi.org/10.1001/jamasurg.2014.3480. Houang ET, Gilmore OJ, Reid C, Shaw EJ. Absence of bacterial resistance to povidone iodine. J Clin Pathol 1976;29:752e5.

[15] Klossner BL, Widmer HR, Frey F. Nondevelopment of resistance by bacteria during hospital use of povidone-iodine. Dermatology 1997;195(Suppl 2):10e3. [16] Torres EG, Lindmair-Snell JM, Langan JW, Burnikel BG. Is preoperative nasal povidone-iodine as efficient and cost-effective as standard methicillin-resistant Staphylococcus aureus screening protocol in total joint arthroplasty? J Arthroplasty 2016;31:215e8. https://doi.org/10.1016/j.arth.2015.09.030. [17] Ramos N, Stachel A, Phillips M, Vigdorchik J, Slover J, Bosco JA. Prior Staphylococcus aureus nasal colonization: a risk factor for surgical site infections following decolonization. J Am Acad Orthop Surg 2016;24:880e5. [18] Schweizer ML, Chiang HY, Septimus E, Moody J, Braun B, Hafner J, et al. Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery. JAMA 2015;313:2162e71. https://doi.org/10.1001/jama.2015.5387. [19] 3M Study-05-011322. [20] Baratz MD, Hallmark R, Odum SM, Springer BD. Twenty percent of patients may remain colonized with methicillin-resistant Staphylococcus aureus despite a decolonization protocol in patients undergoing elective total joint arthroplasty. Clin Orthop Relat Res 2015;473:2283e90. https://doi.org/ 10.1007/s11999-015-4191-3.