Antimicrobial Reports

Implications and Impact of Prior Authorization Policy on Vancomycin Use at a Tertiary Pediatric Teaching Hospital Shannon Chan, Pharm D,* Jobayer Hossain, PhD,†‡ and M. Cecilia Di Pentima, MD, MPH§ Background: We evaluated the performance of two consecutive antimicrobial stewardship interventions on vancomycin use. Methods: Prospective audit with intervention and real time feedback to providers were implemented in April 2004. In February 2009, the institutional vancomycin policy was modified requiring preauthorization by the pediatric infectious diseases clinician on-call. Monthly vancomycin use was calculated as doses administered per 1000 patient-days. Results: After 5 years of prospective-audit vancomycin use declined from 378 doses administered/1000 patient-days to 208 doses administered/1000 patientdays (45%). Following the implementation of preauthorization, vancomycin use decreased by an additional 16% in the subsequent 4 years. When compared with the trend of vancomycin use with prospective-audit, the trend of vancomycin use after the implementation of the restriction policy increased by 3.9 doses per month (SE: 1.51, P=0.012) during the subsequent 51 months. Conclusions: Implementation of preauthorization didn’t significantly reduce the use of vancomycin beyond the accomplishments by prospective-audit and feedback by a team of an infectious disease pharmacist and physician. Key Words: vancomycin, stewardship, preauthorization, policy, pediatrics (Pediatr Infect Dis J 2015;34:506–508)

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n 2004, Alfred I. duPont Hospital for Children implemented an antimicrobial stewardship program (ASP) incorporating antibiotic ­indications for vancomycin, among other agents, as a mandatory field in the institutional computerized physician or prescriber order entry.1, 2 The implementation of prospective audit with direct interaction and real-time feedback to the prescriber reduced the unnecessary use of vancomycin by 34% during the first 3 years of the program.1 Nevertheless, during this initial study, 28% of vancomycin prescription orders did not meet the Institution’s approved indications for vancomycin use.1 To further reduce the unnecessary use of vancomycin, the hospital vancomycin policy was modified to require infectious disease preauthorization beyond two doses. We sought to evaluate the impact of preauthorization on intravenous vancomycin use.

METHODS The study was conducted at Alfred I. duPont Hospital for Children, Wilmington, DE, a 180-bed tertiary-care academic pediatric Accepted for publication October 13, 2014. From the *Department of Pediatrics, Alfred I. duPont Hospital for Children, Wilmington, Delaware; †Nemours Biomedical Research, Wilmington, Delaware; ‡Department of Food and Resource Economics, University of Delaware, Newark, Delaware; and §Infectious Diseases Division, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee. The authors have no conflicts of interest or funding to disclose. Presented in part at the 48th Annual Meeting of the Infectious Diseases S ­ ociety of America, Vancouver, British Columbia, CA, October 2010 (Poster N ­ umber: 281). Address for correspondence: M. Cecilia Di Pentima, MD, MPH, Infectious Diseases Division, Department of Pediatrics, Monroe Carell, Jr. Children’s Hospital at Vanderbilt, Vanderbilt University School of Medicine, 1161 21st Avenue South, D-7235 MCN, Nashville, TN 37232-2581. E-mail: cecilia. [email protected]. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/15/3405-0506 DOI: 10.1097/INF.0000000000000615

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hospital affiliated with Thomas Jefferson University, Philadelphia, PA. Detailed characterization of the ASP was published elsewhere.2 Prospective audit with intervention and real-time feedback to providers and mandatory vancomycin indications were implemented in April 2004. In February 2009, the institutional vancomycin policy was modified requiring that intravenous and oral vancomycin prescriptions, beyond the two initial doses, should require prior authorization by the pediatric infectious diseases faculty on-call. At the time of telephone interaction, vancomycin use was approved or an alternative antibiotic therapy was recommended. The name of the infectious disease clinician approving vancomycin use was recorded on the computerized physician or prescriber order entry and audited for compliance with the approval process by the infectious disease pharmacist within 24–48 hours. In November 2011, a restriction policy was implemented limiting the approval of restricted antibiotics to 7 days. Prospective-audit of vancomycin was continued throughout the study period. At Alfred I. duPont Hospital for Children, medication administration record data are stored in the Nemours Data Warehouse as described elsewhere.1, 2 The data were captured by dosages administered in unique patients. Monthly vancomycin use was calculated as doses administered per 1000 patient-days. Segmented regression analysis was performed to compare the monthly rate of change in pre-intervention and post-intervention vancomycin use. Durbin–Watson test was to check for the autocorrelation of the monthly data. All tests were two-tailed with a 0.05 level of significance. Analyses were performed using IBM® SPSS® software (Version 22; IBM Corp., Chicago, IL) and R 2.10.1 Nemours Institutional Review Board reviewed the antimicrobial stewardship protocol, and approval was granted as a quality improvement project in compliance with 45 CFR 46.110/117.

RESULTS Before the implementation of the ASP, vancomycin use steadily increased from 152 doses administered per 1000 patient-days in 2001–2002 to 378 doses administered per 1000 patient-days in 2003–2004.1 After the implementation of the ASP, the overall use of vancomycin at Alfred I. duPont Hospital for Children decreased by 61%, from 378 doses administered per 1000 patient-days to 146 doses administered per 1000 patient-days by 2013 (P < 0.001). Prospective-audit with feedback to providers was used as the single intervention during the initial 5 years of the program, decreasing vancomycin use by 45% in 2008–2009 [378 doses administered per 1000 patient-days to 208 doses administered per 1000 patient-days (P < 0.001)]. After implementation of the preauthorization policy, vancomycin use decreased by 16% during the subsequent 4 years. Figure 1 depicts the trend of monthly vancomycin use 21 months before and 51 months after the implementation of the vancomycin preauthorization policy. The mean number of vancomycin doses administered per 1000 patient-days before and after the implementation of the preauthorization policy were 239 and 176, respectively (P < 0.001). On regression analysis, a Durbin–Watson statistic of 1.47 indicated no severe autocorrelation of monthly use of vancomycin. The preintervention trend of vancomycin use continued to decline overtime as shown in Figure 1, with a monthly decreasing rate of −4.76 (SE: 1.45; P = 0.002). Although not significant, there was an immediate increase

The Pediatric Infectious Disease Journal  •  Volume 34, Number 5, May 2015

The Pediatric Infectious Disease Journal  •  Volume 34, Number 5, May 2015

Vancomycin Restriction Policy

FIGURE 1.  Trend of vancomycin use at the Alfred I. duPont Hospital for Children before and after the implementation of a preauthorization policy. in the mean number of vancomycin doses administered after the implementation of the preauthorization policy [mean (SE): 8.77 (21.61); P = 0.69]. When compared with the trend of vancomycin use throughout the first 21 months of prospective-audit interventions, the trend of vancomycin use after the implementation of the restriction policy increased by 3.9 doses per month (SE: 1.51; P = 0.012) during the subsequent 51 months.

DISCUSSION To the best of our knowledge, this is the first manuscript comparing the impact of formulary restriction and preauthorization as an intervention to further reduce the unnecessary use of vancomycin after the implementation of prospective-audit with intervention and feedback to the prescriber. As we previously reported, the implementation of a comprehensive ASP integrating active surveillance and real-time feedback to clinicians and incorporating mandatory vancomycin indications led to a 45% reduction of vancomycin use.1 In an effort to improve vancomycin use in accordance to approved criteria for vancomycin use, the Pediatric Infectious Disease Division and ASP, in conjunction with the pharmacy and hospital leadership, updated the vancomycin use policy restricting the use of the drug to two doses before requiring authorization by an infectious disease physician on-call. The modification of the institution’s vancomycin policy requiring preauthorization by an infectious diseases physician led to a decrease in the mean number of vancomycin doses administered, but on regression analysis, the trend of vancomycin use was not statistically improved beyond the achievements of prospective audit with direct interaction and feedback to prescriber. When prior-authorization was implemented, the ASP was a well-established program, and the recommendations made by the team were trusted by the medical staff. Restriction on vancomycin use was required after the initial two doses, meaning that many of these patients would have been evaluated by the ASP team during the first phase of the program. Prior-authorization implemented at the time of vancomycin ordering might have had a stronger impact, particularly because we measured doses administered rather than days of therapy. It is worth noting that our institution modified the vancomycin order-set in March 2011 to advocate © 2014 Wolters Kluwer Health, Inc. All rights reserved.

for higher dosage and target trough (15–20 μg/mL) for serious infections or critically ill patient as supported by the 2009 Consensus Statement of the American Society of Health-System Pharmacists and the Infectious Diseases Society of America.3 Achievement of higher trough levels may have required a higher number of doses per patient.4 Evaluation of days of therapy would help to resolve this discrepancy, but this was not evaluated in the current study due to limitations with the Nemours Data Warehouse. Antimicrobial restrictions are considered the most effective method of reducing antibiotic use.5 Some of the drawbacks to this intervention are the perceived loss of physician’s autonomy, trained personnel available for approvals and the potential challenge to physician’s professional relationships. A recent survey of our ASP among prescribers indicated that more than 60% of the respondents reported prior Infectious Diseases authorization to be more than somewhat helpful (4 or 5 on the Likert scale). Restrictions on antibiotic use were first described by Barber et al6 in 1960 as a successful mean to revert penicillin resistance among nosocomial strains of Staphylococcus aureus. Concomitant infection control initiatives at St. Thomas Hospital likely contributed to the lower mortality rates associated with nosocomial resistant strains.6 The authors argued about the value of restriction policies as means of preventing emergence of resistance provided that new antibiotics continue to be developed.6 Fifty decades of antibiotic misuse placed healthcare institutions in a different scenario. We previously reported lower rates of methicillin-resistant S. aureus and vancomycin-resistant Enterococcus spp. (VRE) blood-stream infections and their correlation with vancomycin use following the implementation of prospective-audit as the single ASP intervention.7 During the most recent years, 2010 through 2013, only three patients developed VRE blood-stream infections. Two events were associated with Enterococcus faecium, and one additional bacteremia was due to Enterococcus gallinarum. Nonetheless, the impact of vancomycin restriction policies on the prevalence of VRE has shown varying results.8, 9 Lautenbach et al8 suggested that restriction of >1 antibiotic agent may be necessary to control emergence of VRE among hospitalized adult patients. Contrary to our experience, the use of vancomycin at the Hospital of the University of www.pidj.com | 507

The Pediatric Infectious Disease Journal  •  Volume 34, Number 5, May 2015

Chan et al

Pennsylvania increased by 15% during the last years of the study when compared with the period without restriction.8 At Alfred I. duPont Hospital for Children, prospective-audit had a more significant impact on vancomycin utilization than the subsequent implementation of a restriction policy. This intervention in alliance with infection control initiatives halted rates of VRE blood-stream infections among hospitalized children.7 Prevalence of ASPs in pediatrics is limited, mainly due to lack of resources.10 A limitation of our study is that interventions were performed at a single pediatric institution. These findings might not be extrapolated to other academic and nonacademic children’s hospital or adult hospitals. Cosgrove et al11 determined that prospective-audit was superior to prior approval. In a recent study by Mehta et al,12 lifting the restriction of selected antibiotics was associated with increased utilization despite the implementation of prospective-audit. One of the main differences between this study and our experience is that prospective-audit was not used during the prior-authorization phase of the ASP.12 In tertiary care institutions, assigning additional subspecialty trained physician time to authorize the use of commonly prescribed antimicrobials requires investment of valuable resources. This can be challenging in these times of escalating healthcare cost and antibiotic resistance. Institutions should carefully assess the impact of different ASP interventions and use strategies that would result in the best yield based on careful assessment of their needs and resources. REFERENCES 1. Di Pentima MC, Chan S. Impact of antimicrobial stewardship program on vancomycin use in a pediatric teaching hospital. Pediatr Infect Dis J. 2010;29:707–711. 2. Di Pentima MC, Chan S, Hossain J. Benefits of a pediatric antimicrobial stewardship program at a children’s hospital. Pediatrics. 2011;128: 1062–1070.

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3. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. 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. Clin Infect Dis. 2009;49:325–327. 4. Frymoyer A, Hersh AL, Benet LZ, et al. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009;28:398–402. 5. Dellit TH, Owens RC, McGowan JE Jr, et al.; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44:159–177. 6. Barber M, Dutton AA, Beard MA, et al. Reversal of antibiotic resistance in hospital staphylococcal infection. Br Med J. 1960;1:11–17. 7. Di Pentima MC, Chan S, Briody C, et al. Driving forces of vancomycinresistant E. faecium and E. faecalis blood-stream infections in children. Antimicrob Resist Infect Control. 2014;3:29. 8. Lautenbach E, LaRosa LA, Marr AM, et al. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Clin Infect Dis. 2003;36:440–446. 9. Anglim AM, Klym B, Byers KE, et al. Effect of a vancomycin restriction policy on ordering practices during an outbreak of vancomycin-resistant Enterococcus faecium. Arch Intern Med. 1997;157:1132–1136. 10. Hersh AL, Beekmann SE, Polgreen PM, et al. Antimicrobial stewardship programs in pediatrics. Infect Control Hosp Epidemiol. 2009;30:1211–1217. 11. Cosgrove SE, Patel A, Song X, et al. Impact of different methods of feedback to clinicians after postprescription antimicrobial review based on the Centers For Disease Control and Prevention’s 12 Steps to Prevent Antimicrobial Resistance Among Hospitalized Adults. Infect Control Hosp Epidemiol. 2007;28:641–646. 12. Mehta JM, Haynes K, Wileyto EP, et al.; Centers for Disease Control and Prevention Epicenter Program. Comparison of prior authorization and prospective audit with feedback for antimicrobial stewardship. Infect Control Hosp Epidemiol. 2014;35:1092–1099.

© 2014 Wolters Kluwer Health, Inc. All rights reserved.

Implications and impact of prior authorization policy on vancomycin use at a tertiary pediatric teaching hospital.

We evaluated the performance of two consecutive antimicrobial stewardship interventions on vancomycin use...
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