- Email: [email protected]
Clinical and economic outcomes from a community hospital's antimicrobial stewardship program
American Journal of Infection Control 41 (2013) 145-8
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Clinical and economic outcomes from a community hospital’s antimicrobial stewardship program Anurag N. Malani MD a, b, *, Patrick G. Richards PharmD c, Shikha Kapila PharmD c, Michael H. Otto MD a, b, Jennifer Czerwinski BS d, Bonita Singal MD, PhD e a
Department of Internal Medicine, Saint Joseph Mercy Health System, Ann Arbor, MI Section of Infectious Diseases, Saint Joseph Mercy Health System, Ann Arbor, MI Department of Pharmacy, Saint Joseph Mercy Health System, Ann Arbor, MI d Quality Institute, Saint Joseph Mercy Health System, Ann Arbor, MI e Department of Clinical Research, Saint Joseph Mercy Health System, Ann Arbor, MI b c
Key Words: ASP Antimicrobial management Outcomes Non-university teaching hospital Clostridium difficile infection
Background: Data from community antimicrobial stewardship programs (ASPs) are limited. We describe clinical and economic outcomes from the first year of our hospital’s ASP. Methods: The ASP team comprised 2 infectious disease physicians and 3 intensive care unit pharmacists. The team prospectively audited the new starts and weekly use of 8 target antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. Using administrative data, outcomes from the first year of the program, including death within 30 days of hospitalization, readmission within 30 days of discharge, and development of Clostridium difficile infection (CDI), were compared with outcomes from a similar period before institution of the program. Results: A total of 510 antimicrobial orders were reviewed, of which 323 (63%) were appropriate, 94 (18%) prompted deescalation, 61 (12%) were denied, and 27 (5%) led to formal consultation with an infectious disease physician. On multivariate analysis, implementation of the ASP was associated with an approximate 50% reduction in the odds of developing CDI (odds ratio, 0.46; 95% confidence interval, 0.25-0.82). The ASP was not associated with decreased mortality at 30 days after discharge or readmission rate. The antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81. The antimicrobial budget decreased by 15.2%, resulting in a total savings of $228,911. There was a 25.4% decrease in defined daily doses of the target antimicrobials. Conclusions: Implementation of the ASP was associated with significant reductions in CDI rate, antimicrobial use, and pharmacy costs. Copyright Ó 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Antimicrobial resistance continues to burgeon, paralleling changes in antimicrobial use.1,2 Estimates suggest that up to 50% of antimicrobial use is inappropriate or unnecessary.3 Antimicrobial resistance is associated with increased morbidity, mortality, length of stay, and hospital expenditures.4 An effective antimicrobial stewardship program (ASP) combined with a comprehensive infection prevention and control (IPC) program can limit the emergence and transmission of antimicrobial-resistant bacteria.3 Given the impact of multidrug-resistant organisms, appropriate
* Address correspondence to Anurag N. Malani, MD, Saint Joseph Mercy Health System, 5333 McAuley Drive, Suite 3106, Ypsilanti, MI 48197. E-mail address: [email protected] (A.N. Malani). Conflict of interest: None to report.
use of antimicrobial agents has become an increasing focus of patient safety and quality assurance. At our institution, we developed an ASP to limit the inappropriate use of antimicrobials; optimize the selection, dosing, and duration of therapy; and limit unintended consequences of administration. Data on the development and outcomes from ASPs in the community setting are limited.5-8 A recent Infectious Disease Society of America Emerging Infections Network survey noted that ASPs were in place in 79% of university teaching hospitals, in 65% of nonuniversity teaching hospitals, but in only 40% of community hospitals.9 The objective of this study was to describe clinical and economic outcomes from the first year of our ASP and compare them with outcomes from a similar period before implementation of the ASP.
0196-6553/$36.00 - Copyright Ó 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.ajic.2012.02.021
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A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
METHODS
daily doses (DDD)/1,000 patient-days of the 8 target antimicrobials during the 2 study periods.
Setting Statistical methods St. Joseph Mercy Hospital (SJMH), located in Ann Arbor, MI, is a 535 bed noneuniversity-affiliated community teaching hospital that is a member of a 7-hospital network, the Saint Joseph Mercy Health System. The ASP team at SJMH includes 2 infectious disease (ID) physicians (0.3 full-time equivalent total) and 3 critical care clinical pharmacists (no dedicated stewardship time). On Monday through Friday, the team prospectively audits the initial orders, use within 24 hours, and weekly use (if duration of therapy is 7 days) of 8 antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. These agents were targeted based on susceptibility patterns of clinical isolates, spectrum of activity, risk of misuse, and cost. Together, these 8 antimicrobials accounted for almost one-third of SJMH’s 2008 antimicrobial budget. An informational real-time database developed by our internal decision support/health outcomes team, called the Quality Institute, is populated by daily use data (Monday through Friday) from the pharmacy utilization information system. The ASP pharmacist evaluates each order by reviewing the patient’s electronic medical record. The pharmacist then makes a recommendation and, if necessary, provides feedback to the provider, using the following categories: approve, stop, deescalate to an agent with a narrower spectrum, or obtain an ID consult. The ID physician provides clinical support and decision making on complex cases, aiding with feedback and communication to providers. Study design This was a retrospective observational study approved by the SJMH Institutional Review Board. We identified all unique patients who received a targeted antimicrobial during 2 time periods. Period 1 was defined as the 12 months before institution of the ASP (June 1, 2008, to May 31, 2009); period 2, as the first 12 months that the ASP was in place (July 1, 2009, to June 30, 2010). June 2009 was excluded because this is when the ASP was just getting started. Data collection All baseline and outcome variables were compiled from hospital administrative databases and the Social Security Death Index. The following covariates available from the administrative data sources were considered markers for severity of illness based on clinical grounds: whether the patient received more than 1 target antimicrobial, Charlson Comorbidity Index score, age, sex, race, and whether the patient was admitted to the intensive care unit (ICU) or placed on a ventilator within 2 days of admission. We defined ventilator support and ICU stay as events occurring within 2 days of admission, assuming that these were indicators of severity of illness and not a consequence of the ASP intervention at this time point. The outcomes of interest were death within 30 days of hospitalization, readmission to SJMH within 30 days of discharge, development of Clostridium difficile infection (CDI) during hospitalization, and hospital length of stay. Outcomes were evaluated using a coding algorithm that was the same for each patient regardless of study period. The development of CDI during hospitalization was identified using the International Classification of Diseases, 9th Revision (ICD-9) code for CDI (008.45).10,11 Antimicrobial utilization data was used to compare total antimicrobial costs, antimicrobial costs per patient-day, and defined
All analyses were done using SAS 9.2 (SAS Institute, Cary, NC). Statistical significance was set at P < .05. Demographic, clinical, and outcome variables were compared between periods using the t test for age, the Wilcoxon 2-sample test for Charlson Comorbidity Index and length of stay, and the c2 test for categorical variables. To determine whether the ASP was associated with each outcome, we performed multivariate logistic regression analyses controlling for age, race, sex, ICU stay within 2 days of admission, ventilator support within 2 days of admission, receipt of more than 1 target antimicrobial, and Charlson Comorbidity Index.12 Length of stay between the periods was compared using a linear model with the natural log of the length of stay as the dependent variable and the covariate patterns described above. The natural log was used to better comply with the distributional assumptions of the linear model. RESULTS We obtained administrative data on 895 patient encounters in which at least one of the target antimicrobials was prescribed. Of these, 716 were initial visits involving analyses of death within 30 days after discharge, length of stay, and development of CDI during hospitalization. For the outcome of readmission within 30 days, those who died within 30 days after discharge were not included in the analysis, leaving a total of 584 visits. A flow diagram of the study population is shown in Figure 1. There were 372 initial visits during period 1 and 344 initial visits during period 2. The study cohort had a mean age of 63.7 years and was 47% male and 84% white. A total of 132 patients died within 30 days of hospitalization, 77 (20.7%) during period 1 and 55 (16.0%) during period 2. Of those who did not die, 133 patients were readmitted within 30 days of discharge, 68 (23.1%) during period 1 and 65 (22.5%) during period 2. Sixty-six patients developed CDI during hospitalization, 46 (12.4%) during period 1 and 20 (5.8%) during period 2. Table 1 compares demographic and clinical characteristics and outcomes between the 2 periods. The associations between institution of the ASP and death within 30 days of hospitalization, readmission within 30 days of discharge, and the development of CDI during hospitalization are shown in Table 2. The ASP was not associated with a decreased likelihood of death at 30 days after discharge (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.50-1.18) or of readmission (OR, 0.95; 95% CI, 0.63-1.42). The likelihood of developing CDI decreased by approximately 50% in period 2 (OR, 0.46; 95% CI, 0.25-0.82; P < .01). These results were robust to the choice of covariates in the models. The ASP was not associated with a decreased length of stay in 3 different covariate models. During the first year of our ASP, a total of 510 orders were reviewed (Fig 1). Of these, 323 (63%) were considered appropriate, 94 (18%) prompted deescalation to a more narrow-spectrum antibiotic, 61 (12%) were denied, and 27 (5%) led to a formal ID consultation in 23 patients. Of the 23 consults (addressing 27 orders), 8 were considered appropriate, 11 led to deescalation, and 8 led to discontinuation. Five orders (1%) were continued against the advice of the ASP. Table 3 presents changes in antimicrobial-related costs associated with institution of the ASP at SJMH. In the year after implementation, the antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81, and the antimicrobial budget decreased by 15.2%, from $1,503,748 to $1,274,837, resulting in a savings of
A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
455 patient encounters on target antibiotic June 1, 2008 – May 31, 2009
440 patient encounters on target antibiotic July 1, 2009 – June 30, 2010
323 appropriate
372 initial patient encounters
295 alive
68 readmittedb 29 CDI
147
510 separate antibiotic orders
94 de-escalated
61 denied
27 ID consult
5 against ASP advice
344 initial patient encounters
77 dieda
17 CDI
289 alive
55 dieda
65 readmittedb 16 CDI
4 CDI
a
Died within 30 days of discharge. Readmitted within 30 days of discharge. ASP, Antimicrobial stewardship program; CDI, Clostridium difficile infection; ID, Infectious diseases.
b
Fig 1. Flow diagram of study population. aDied within 30 days of discharge. bReadmitted within 30 days of discharge.
Table 1 Demographic and clinical characteristics and outcomes of patients in periods 1 and 2
Age, years, mean SD Charlson Comorbidity Index score, median (IQR)* Length of stay, days, median (IQR)* Male sex, n (%) White race, n (%) ICU stay, n (%)y Ventilator use, n (%)y Receipt of more than 1 target antimicrobial, n (%) Death within 30 days, n (%) Readmitted within 30 days, n (%) CDI, n (%)
Period 1 (n ¼ 372)
Period 2 (n ¼ 344)
64.8 15.7 1 (0-2)
62.5 18.4 1 (1-2)
8.0 168 313 115 103 47
7.0 171 299 94 46 51
(4-8) (45.2) (84.1) (30.9) (27.7) (12.6)
77 (20.7) 76 (20.4) 46 (12.4)
P value .08 .08
(4-7) (49.7) (86.9) (27.3) (13.4) (14.8)
.44 .22 .29 .29 <.01 .39
55 (16.0) 69 (20.1) 20 (5.8)
.11 .87 <.01
*IQR is defined as the mathematical difference between the 75th and 25th percentiles. y Within 2 days of admission.
$228,911. The budget for the target antimicrobials decreased by 35.6%, from $462,404 to $297,851, for a savings of $164,553. There was a 25.4% decrease in utilization of the target antimicrobials, from 215.7 to 160.8 DDD/1,000 patient-days. DISCUSSION Similar to the experience of others, the odds of developing CDI decreased significantly (w50%) with the implementation of our ASP.13 Although this study is not designed to demonstrate causality,
an association seems highly plausible given the well-established link between antimicrobial exposure and CDI. In addition, the reduced incidence of CDI among the patients in our study was not temporally associated with other changes in our IPC program. The use of dilute bleach for disinfection of rooms occupied by patients with CDI was implemented well before the launch of our ASP in October 2007. No additional IPC measures or interventions were implemented for CDI during the study years. The costs of managing CDI pose a major financial drain on the US health care system, with annual costs of well over 1 billion dollars ($2,454 to $3,240 per case).14 As we and others have shown, antimicrobial stewardship is a critical element in reducing the burden of CDI.5,13 Recently published guidelines highlight the importance of antimicrobial stewardship for CDI prevention.15 Cost savings from ASPs are well documented in larger academic and smaller community hospitals.5-8 With limited resources (no dedicated pharmacist time) and targeting only 8 agents, our ASP has produced significant reductions in antimicrobial utilization and costs. Implementation of our ASP was associated with a 13.3% decrease in antimicrobial cost per patient-day and a 15.2% decrease in the total antimicrobial budget, resulting in a savings of $228,911 despite increases in purchase price for many of the target antimicrobials. We were unable to demonstrate an association between implementation of our ASP and decreases in mortality, readmission rate, or length of stay. All of these outcomes were either the same in both periods or favored period 2. Thus, we have no evidence of any substantial adverse effects associated with our ASP; however, the study was not designed to show equivalence or noninferiority for these outcomes.
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A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
Table 2 Multivariate analysis for association of ASP and patient outcomes Model covariates Age, race, sex, ICU stay,* ventilator use,* more than 1 antimicrobial, CCI
Death within 30 days
P
Readmission within 30 days
P
C difficile infection
P
0.77 (0.50-1.18)
.23
0.95 (0.63-1.42)
.80
0.46 (0.25-0.82)
<.01
CCI, Charlson Comorbidity Index. *Within 2 days of admission. Table 3 Antimicrobial costs by fiscal year
Antimicrobial agents, total costs Total patient-days Antimicrobial costs per patient-day (average) Targeted antimicrobial agents, total costs
Fiscal year 2009
Fiscal year 2010
Percent change ($ change)
$1,503,748 147,955 $10.16 $462,404
$1,274,837 144,783 $8.81 $297,851
15.2 (-$228,911)
In general, the medical staff has responded favorably to the ASP. Compliance with ASP recommendations was 99%, higher than compliance rates reported from other community teaching hospitals.5,8 Criteria for appropriate use of the target antimicrobials were agreed upon by all members of the ID division and approved by the Antimicrobial Subcommittee and the Pharmacy and Therapeutics Committee. A unique challenge facing community ASPs is occasional disagreement with ASP team recommendations by other private ID physicians. This is being addressed as a quality indicator through the Department of Internal Medicine’s ongoing professional practice evaluation process. Our study has several limitations. First, the intervention was not randomized, and the data were collected retrospectively from administrative databases. The choice of a pre-ASP control group is not optimal, because any secular trends that might have occurred coincident with the ASP are not separable from the intervention. Patient-level variables that could influence the measured outcomes may differ by chance between periods. We attempted to statistically control for some of these factors using multivariate modeling that included the Charlson Comorbidity Index and other measures of severity of illness, such as ICU stay and ventilator support, as covariates. The use of ICD-9 codes for surveillance of hospital-onset CDI has limitations related to the fact that discharge diagnosis codes reflect conditions diagnosed or treated during the entire hospitalization but do not give information regarding the date of CDI onset.16 Coding errors may occur with the use of administrative data. However, we know of no systematic change in coding practice during the study, and assumed that any coding errors were random over both time periods. Actually, the use of administrative data likely enhanced the methodology of the study by eliminating measurement bias, because the outcome variables were abstracted using the same coding algorithm for each patient regardless of study period. Implementation of our ASP was associated with a significant reduction in CDI rate. Despite lacking a clinical pharmacist with special training in ID, the ASP significantly reduced antimicrobial use and costs. Our experience demonstrates that a community ASP can be successful with limited resources, but that dedicated resources, such as pharmacy and ID physician full-time equivalents, are critical to long-term success.
13.3 35.6 (-$164,553)
References 1. McGowan JE Jr. Minimizing antimicrobial resistance: the key role of the infectious diseases physician. Clin Infect Dis 2004;38:939-42. 2. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32:470-85. 3. Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, et al. 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;44:159-77. 4. Maragakis LL, Perencevich EN, Cosgrove SE. Clinical and economic burden of antimicrobial resistance. Expert Rev Anti Infect Ther 2008;6:751-63. 5. Carling P, Fung T, Killion A, Terrin N, Barza M. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003;24:699-706. 6. LaRocco A Jr. Concurrent antibiotic review programs: a role for infectious diseases specialists at small community hospitals. Clin Infect Dis 2003;37:742-3. 7. Ruttimann S, Keck B, Hartmeier C, Maetzel A, Bucher HC. Long-term antibiotic cost savings from a comprehensive intervention program in a medical department of a university-affiliated teaching hospital. Clin Infect Dis 2004;38: 348-56. 8. Philmon C, Smith T, Williamson S, Goodman E. Controlling use of antimicrobials in a community teaching hospital. Infect Control Hosp Epidemiol 2006;27: 239-44. 9. Johannsson B, Beekmann SE, Srinivasan A, Hersh AL, Laxminarayan R, Polgreen PM. Improving antimicrobial stewardship: the evolution of programmatic strategies and barriers. Infect Control Hosp Epidemiol 2011;32:367-74. 10. Dubberke ER, Reske KA, McDonald LC, Fraser VJ. ICD-9 codes and surveillance for Clostridium difficileeassociated disease. Emerg Infect Dis 2006;12:1576-9. 11. Scheurer DB, Hicks LS, Cook EF, Schnipper JL. Accuracy of ICD-9 coding for Clostridium difficile infections: a retrospective cohort. Epidemiol Infect 2007; 135:1010-3. 12. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83. 13. Valiquette L, Cossette B, Garant MP, Diab H, Pepin J. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficileeassociated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007;45:S112-21. 14. Dubberke ER, Wertheimer AI. Review of current literature on the economic burden of Clostridium difficile infection. Infect Control Hosp Epidemiol 2009;30: 57-66. 15. Cohen SH, Gerding DN, Johnson S, Kelly C, Loo V, McDonald C, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31: 431-55. 16. Dubberke ER, Butler AM, Yokoe DS, Mayer J, Hota B, Mangino JE, et al. Multicenter study of surveillance for hospital-onset Clostridium difficile infection by the use of ICD-9-CM diagnosis codes. Infect Control Hosp Epidemiol 2010;31: 262-8.
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Clinical and economic outcomes from a community hospital’s antimicrobial stewardship program Anurag N. Malani MD a, b, *, Patrick G. Richards PharmD c, Shikha Kapila PharmD c, Michael H. Otto MD a, b, Jennifer Czerwinski BS d, Bonita Singal MD, PhD e a
Department of Internal Medicine, Saint Joseph Mercy Health System, Ann Arbor, MI Section of Infectious Diseases, Saint Joseph Mercy Health System, Ann Arbor, MI Department of Pharmacy, Saint Joseph Mercy Health System, Ann Arbor, MI d Quality Institute, Saint Joseph Mercy Health System, Ann Arbor, MI e Department of Clinical Research, Saint Joseph Mercy Health System, Ann Arbor, MI b c
Key Words: ASP Antimicrobial management Outcomes Non-university teaching hospital Clostridium difficile infection
Background: Data from community antimicrobial stewardship programs (ASPs) are limited. We describe clinical and economic outcomes from the first year of our hospital’s ASP. Methods: The ASP team comprised 2 infectious disease physicians and 3 intensive care unit pharmacists. The team prospectively audited the new starts and weekly use of 8 target antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. Using administrative data, outcomes from the first year of the program, including death within 30 days of hospitalization, readmission within 30 days of discharge, and development of Clostridium difficile infection (CDI), were compared with outcomes from a similar period before institution of the program. Results: A total of 510 antimicrobial orders were reviewed, of which 323 (63%) were appropriate, 94 (18%) prompted deescalation, 61 (12%) were denied, and 27 (5%) led to formal consultation with an infectious disease physician. On multivariate analysis, implementation of the ASP was associated with an approximate 50% reduction in the odds of developing CDI (odds ratio, 0.46; 95% confidence interval, 0.25-0.82). The ASP was not associated with decreased mortality at 30 days after discharge or readmission rate. The antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81. The antimicrobial budget decreased by 15.2%, resulting in a total savings of $228,911. There was a 25.4% decrease in defined daily doses of the target antimicrobials. Conclusions: Implementation of the ASP was associated with significant reductions in CDI rate, antimicrobial use, and pharmacy costs. Copyright Ó 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Antimicrobial resistance continues to burgeon, paralleling changes in antimicrobial use.1,2 Estimates suggest that up to 50% of antimicrobial use is inappropriate or unnecessary.3 Antimicrobial resistance is associated with increased morbidity, mortality, length of stay, and hospital expenditures.4 An effective antimicrobial stewardship program (ASP) combined with a comprehensive infection prevention and control (IPC) program can limit the emergence and transmission of antimicrobial-resistant bacteria.3 Given the impact of multidrug-resistant organisms, appropriate
* Address correspondence to Anurag N. Malani, MD, Saint Joseph Mercy Health System, 5333 McAuley Drive, Suite 3106, Ypsilanti, MI 48197. E-mail address: [email protected] (A.N. Malani). Conflict of interest: None to report.
use of antimicrobial agents has become an increasing focus of patient safety and quality assurance. At our institution, we developed an ASP to limit the inappropriate use of antimicrobials; optimize the selection, dosing, and duration of therapy; and limit unintended consequences of administration. Data on the development and outcomes from ASPs in the community setting are limited.5-8 A recent Infectious Disease Society of America Emerging Infections Network survey noted that ASPs were in place in 79% of university teaching hospitals, in 65% of nonuniversity teaching hospitals, but in only 40% of community hospitals.9 The objective of this study was to describe clinical and economic outcomes from the first year of our ASP and compare them with outcomes from a similar period before implementation of the ASP.
0196-6553/$36.00 - Copyright Ó 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.ajic.2012.02.021
146
A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
METHODS
daily doses (DDD)/1,000 patient-days of the 8 target antimicrobials during the 2 study periods.
Setting Statistical methods St. Joseph Mercy Hospital (SJMH), located in Ann Arbor, MI, is a 535 bed noneuniversity-affiliated community teaching hospital that is a member of a 7-hospital network, the Saint Joseph Mercy Health System. The ASP team at SJMH includes 2 infectious disease (ID) physicians (0.3 full-time equivalent total) and 3 critical care clinical pharmacists (no dedicated stewardship time). On Monday through Friday, the team prospectively audits the initial orders, use within 24 hours, and weekly use (if duration of therapy is 7 days) of 8 antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. These agents were targeted based on susceptibility patterns of clinical isolates, spectrum of activity, risk of misuse, and cost. Together, these 8 antimicrobials accounted for almost one-third of SJMH’s 2008 antimicrobial budget. An informational real-time database developed by our internal decision support/health outcomes team, called the Quality Institute, is populated by daily use data (Monday through Friday) from the pharmacy utilization information system. The ASP pharmacist evaluates each order by reviewing the patient’s electronic medical record. The pharmacist then makes a recommendation and, if necessary, provides feedback to the provider, using the following categories: approve, stop, deescalate to an agent with a narrower spectrum, or obtain an ID consult. The ID physician provides clinical support and decision making on complex cases, aiding with feedback and communication to providers. Study design This was a retrospective observational study approved by the SJMH Institutional Review Board. We identified all unique patients who received a targeted antimicrobial during 2 time periods. Period 1 was defined as the 12 months before institution of the ASP (June 1, 2008, to May 31, 2009); period 2, as the first 12 months that the ASP was in place (July 1, 2009, to June 30, 2010). June 2009 was excluded because this is when the ASP was just getting started. Data collection All baseline and outcome variables were compiled from hospital administrative databases and the Social Security Death Index. The following covariates available from the administrative data sources were considered markers for severity of illness based on clinical grounds: whether the patient received more than 1 target antimicrobial, Charlson Comorbidity Index score, age, sex, race, and whether the patient was admitted to the intensive care unit (ICU) or placed on a ventilator within 2 days of admission. We defined ventilator support and ICU stay as events occurring within 2 days of admission, assuming that these were indicators of severity of illness and not a consequence of the ASP intervention at this time point. The outcomes of interest were death within 30 days of hospitalization, readmission to SJMH within 30 days of discharge, development of Clostridium difficile infection (CDI) during hospitalization, and hospital length of stay. Outcomes were evaluated using a coding algorithm that was the same for each patient regardless of study period. The development of CDI during hospitalization was identified using the International Classification of Diseases, 9th Revision (ICD-9) code for CDI (008.45).10,11 Antimicrobial utilization data was used to compare total antimicrobial costs, antimicrobial costs per patient-day, and defined
All analyses were done using SAS 9.2 (SAS Institute, Cary, NC). Statistical significance was set at P < .05. Demographic, clinical, and outcome variables were compared between periods using the t test for age, the Wilcoxon 2-sample test for Charlson Comorbidity Index and length of stay, and the c2 test for categorical variables. To determine whether the ASP was associated with each outcome, we performed multivariate logistic regression analyses controlling for age, race, sex, ICU stay within 2 days of admission, ventilator support within 2 days of admission, receipt of more than 1 target antimicrobial, and Charlson Comorbidity Index.12 Length of stay between the periods was compared using a linear model with the natural log of the length of stay as the dependent variable and the covariate patterns described above. The natural log was used to better comply with the distributional assumptions of the linear model. RESULTS We obtained administrative data on 895 patient encounters in which at least one of the target antimicrobials was prescribed. Of these, 716 were initial visits involving analyses of death within 30 days after discharge, length of stay, and development of CDI during hospitalization. For the outcome of readmission within 30 days, those who died within 30 days after discharge were not included in the analysis, leaving a total of 584 visits. A flow diagram of the study population is shown in Figure 1. There were 372 initial visits during period 1 and 344 initial visits during period 2. The study cohort had a mean age of 63.7 years and was 47% male and 84% white. A total of 132 patients died within 30 days of hospitalization, 77 (20.7%) during period 1 and 55 (16.0%) during period 2. Of those who did not die, 133 patients were readmitted within 30 days of discharge, 68 (23.1%) during period 1 and 65 (22.5%) during period 2. Sixty-six patients developed CDI during hospitalization, 46 (12.4%) during period 1 and 20 (5.8%) during period 2. Table 1 compares demographic and clinical characteristics and outcomes between the 2 periods. The associations between institution of the ASP and death within 30 days of hospitalization, readmission within 30 days of discharge, and the development of CDI during hospitalization are shown in Table 2. The ASP was not associated with a decreased likelihood of death at 30 days after discharge (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.50-1.18) or of readmission (OR, 0.95; 95% CI, 0.63-1.42). The likelihood of developing CDI decreased by approximately 50% in period 2 (OR, 0.46; 95% CI, 0.25-0.82; P < .01). These results were robust to the choice of covariates in the models. The ASP was not associated with a decreased length of stay in 3 different covariate models. During the first year of our ASP, a total of 510 orders were reviewed (Fig 1). Of these, 323 (63%) were considered appropriate, 94 (18%) prompted deescalation to a more narrow-spectrum antibiotic, 61 (12%) were denied, and 27 (5%) led to a formal ID consultation in 23 patients. Of the 23 consults (addressing 27 orders), 8 were considered appropriate, 11 led to deescalation, and 8 led to discontinuation. Five orders (1%) were continued against the advice of the ASP. Table 3 presents changes in antimicrobial-related costs associated with institution of the ASP at SJMH. In the year after implementation, the antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81, and the antimicrobial budget decreased by 15.2%, from $1,503,748 to $1,274,837, resulting in a savings of
A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
455 patient encounters on target antibiotic June 1, 2008 – May 31, 2009
440 patient encounters on target antibiotic July 1, 2009 – June 30, 2010
323 appropriate
372 initial patient encounters
295 alive
68 readmittedb 29 CDI
147
510 separate antibiotic orders
94 de-escalated
61 denied
27 ID consult
5 against ASP advice
344 initial patient encounters
77 dieda
17 CDI
289 alive
55 dieda
65 readmittedb 16 CDI
4 CDI
a
Died within 30 days of discharge. Readmitted within 30 days of discharge. ASP, Antimicrobial stewardship program; CDI, Clostridium difficile infection; ID, Infectious diseases.
b
Fig 1. Flow diagram of study population. aDied within 30 days of discharge. bReadmitted within 30 days of discharge.
Table 1 Demographic and clinical characteristics and outcomes of patients in periods 1 and 2
Age, years, mean SD Charlson Comorbidity Index score, median (IQR)* Length of stay, days, median (IQR)* Male sex, n (%) White race, n (%) ICU stay, n (%)y Ventilator use, n (%)y Receipt of more than 1 target antimicrobial, n (%) Death within 30 days, n (%) Readmitted within 30 days, n (%) CDI, n (%)
Period 1 (n ¼ 372)
Period 2 (n ¼ 344)
64.8 15.7 1 (0-2)
62.5 18.4 1 (1-2)
8.0 168 313 115 103 47
7.0 171 299 94 46 51
(4-8) (45.2) (84.1) (30.9) (27.7) (12.6)
77 (20.7) 76 (20.4) 46 (12.4)
P value .08 .08
(4-7) (49.7) (86.9) (27.3) (13.4) (14.8)
.44 .22 .29 .29 <.01 .39
55 (16.0) 69 (20.1) 20 (5.8)
.11 .87 <.01
*IQR is defined as the mathematical difference between the 75th and 25th percentiles. y Within 2 days of admission.
$228,911. The budget for the target antimicrobials decreased by 35.6%, from $462,404 to $297,851, for a savings of $164,553. There was a 25.4% decrease in utilization of the target antimicrobials, from 215.7 to 160.8 DDD/1,000 patient-days. DISCUSSION Similar to the experience of others, the odds of developing CDI decreased significantly (w50%) with the implementation of our ASP.13 Although this study is not designed to demonstrate causality,
an association seems highly plausible given the well-established link between antimicrobial exposure and CDI. In addition, the reduced incidence of CDI among the patients in our study was not temporally associated with other changes in our IPC program. The use of dilute bleach for disinfection of rooms occupied by patients with CDI was implemented well before the launch of our ASP in October 2007. No additional IPC measures or interventions were implemented for CDI during the study years. The costs of managing CDI pose a major financial drain on the US health care system, with annual costs of well over 1 billion dollars ($2,454 to $3,240 per case).14 As we and others have shown, antimicrobial stewardship is a critical element in reducing the burden of CDI.5,13 Recently published guidelines highlight the importance of antimicrobial stewardship for CDI prevention.15 Cost savings from ASPs are well documented in larger academic and smaller community hospitals.5-8 With limited resources (no dedicated pharmacist time) and targeting only 8 agents, our ASP has produced significant reductions in antimicrobial utilization and costs. Implementation of our ASP was associated with a 13.3% decrease in antimicrobial cost per patient-day and a 15.2% decrease in the total antimicrobial budget, resulting in a savings of $228,911 despite increases in purchase price for many of the target antimicrobials. We were unable to demonstrate an association between implementation of our ASP and decreases in mortality, readmission rate, or length of stay. All of these outcomes were either the same in both periods or favored period 2. Thus, we have no evidence of any substantial adverse effects associated with our ASP; however, the study was not designed to show equivalence or noninferiority for these outcomes.
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A.N. Malani et al. / American Journal of Infection Control 41 (2013) 145-8
Table 2 Multivariate analysis for association of ASP and patient outcomes Model covariates Age, race, sex, ICU stay,* ventilator use,* more than 1 antimicrobial, CCI
Death within 30 days
P
Readmission within 30 days
P
C difficile infection
P
0.77 (0.50-1.18)
.23
0.95 (0.63-1.42)
.80
0.46 (0.25-0.82)
<.01
CCI, Charlson Comorbidity Index. *Within 2 days of admission. Table 3 Antimicrobial costs by fiscal year
Antimicrobial agents, total costs Total patient-days Antimicrobial costs per patient-day (average) Targeted antimicrobial agents, total costs
Fiscal year 2009
Fiscal year 2010
Percent change ($ change)
$1,503,748 147,955 $10.16 $462,404
$1,274,837 144,783 $8.81 $297,851
15.2 (-$228,911)
In general, the medical staff has responded favorably to the ASP. Compliance with ASP recommendations was 99%, higher than compliance rates reported from other community teaching hospitals.5,8 Criteria for appropriate use of the target antimicrobials were agreed upon by all members of the ID division and approved by the Antimicrobial Subcommittee and the Pharmacy and Therapeutics Committee. A unique challenge facing community ASPs is occasional disagreement with ASP team recommendations by other private ID physicians. This is being addressed as a quality indicator through the Department of Internal Medicine’s ongoing professional practice evaluation process. Our study has several limitations. First, the intervention was not randomized, and the data were collected retrospectively from administrative databases. The choice of a pre-ASP control group is not optimal, because any secular trends that might have occurred coincident with the ASP are not separable from the intervention. Patient-level variables that could influence the measured outcomes may differ by chance between periods. We attempted to statistically control for some of these factors using multivariate modeling that included the Charlson Comorbidity Index and other measures of severity of illness, such as ICU stay and ventilator support, as covariates. The use of ICD-9 codes for surveillance of hospital-onset CDI has limitations related to the fact that discharge diagnosis codes reflect conditions diagnosed or treated during the entire hospitalization but do not give information regarding the date of CDI onset.16 Coding errors may occur with the use of administrative data. However, we know of no systematic change in coding practice during the study, and assumed that any coding errors were random over both time periods. Actually, the use of administrative data likely enhanced the methodology of the study by eliminating measurement bias, because the outcome variables were abstracted using the same coding algorithm for each patient regardless of study period. Implementation of our ASP was associated with a significant reduction in CDI rate. Despite lacking a clinical pharmacist with special training in ID, the ASP significantly reduced antimicrobial use and costs. Our experience demonstrates that a community ASP can be successful with limited resources, but that dedicated resources, such as pharmacy and ID physician full-time equivalents, are critical to long-term success.
13.3 35.6 (-$164,553)
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