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Antimicrobial stewardship: bridging the gap between quality care and cost

Goff, Debra A

Current Opinion in Infectious Diseases: February 2011 - Volume 24 - Issue - p S11–S20
doi: 10.1097/01.qco.0000393484.17894.05
Supplement Articles

Purpose of review: Antibiotic resistance continues to rise, whereas development of new agents to counter it has slowed. A heightened need exists to maintain the effectiveness of currently available agents. This review focuses on the need for better antimicrobial stewardship, expected benefits of well designed antimicrobial stewardship programs (ASPs), and provides suggestions for development of an effective ASP.

Recent findings: Healthcare-associated infections (HAIs) are a significant cause of poor treatment outcomes and elevated healthcare and societal costs worldwide. HAIs are often caused by antibiotic-resistant pathogens; overuse of antibiotics has been linked with antibiotic resistance. Benefits of improved antimicrobial stewardship include reduced emergence of antibiotic resistance, limitation of drug-related adverse events, minimization of other consequences of antibiotic use (e.g., superinfection), and reduction of societal and healthcare-related costs. In 2007, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) provided guidelines for the development of institutional programs to enhance antimicrobial stewardship. Experiences at The Ohio State University Medical Center (OSUMC) reinforce this message, while providing specific examples of ways to optimize ASP development and implementation. The focus of an ASP should be on improving quality of care, reducing drug resistance, and cost savings. When implementing an ASP, it is important to identify those most likely to resist the ASP, understand their concerns, and develop easy-to-understand messages that address these concerns and highlight the benefits of the proposed changes. Antibiograms play a key role in identifying local and interdepartmental trends in antibiotic susceptibility or resistance. These data are important not only in devising best-treatment practices for the institution, but also in evaluating the impact of a recently implemented ASP. Other measures of the impact of an ASP should include patient outcomes and overall costs or savings.

Summary: Better antimicrobial stewardship is needed to limit the emergence of antibiotic resistance, prolong the effectiveness of currently available agents, improve patient outcomes, and reduce healthcare and societal costs associated with HAIs. Guidelines from the IDSA/SHEA and experiences at OSUMC provide examples of how best to develop an institutional ASP to accomplish these goals.

The Ohio State University Medical Center, Columbus, Ohio, USA

Correspondence to Debra A. Goff, PharmD, FCCP, Clinical Associate Professor, Infectious Diseases Specialist, 410W 10th Ave, 368 Doan Hall, Columbus, OH 43082, USA E-mail: Debbie.goff@osumc.edu

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Introduction

Based on data from the 1990–2002 National Nosocomial Infections Surveillance system, National Hospital Discharge Survey, and American Hospital Association Survey for 2000, each year an estimated 1.7 million individuals acquire an infection while in a US hospital, resulting in approximately 100 000 deaths per year [1]; 4.5 of every 100 hospital patients develop a hospital-acquired infection (HAI), for an infection rate of 9.3 per 1000 patient-days. HAIs account for more than $6.5 billion in annual healthcare expenditures [2], and according to current projections, 18.4% of the US gross domestic product will be spent on healthcare in 2013, many of the costs related to HAIs [3]. To provide incentives to reduce the occurrence of HAIs and associated costs, beginning on 1 October 2008, the Centers for Medicare & Medicaid Services (CMS) limited reimbursement for hospital-acquired conditions deemed reasonably preventable through the application of evidence-based guidelines, including HAIs [4,5].

This article examines efforts to reduce HAIs through better antimicrobial stewardship. The antimicrobial stewardship program (ASP) at The Ohio State University Medical Center (OSUMC) is used to illustrate several important points regarding how best to develop an ASP.

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Campaign to improve health, safety, and well being

In response to growing concerns about the societal impact of HAIs, the Healthcare Infection Control Practices Advisory Committee (HICPAC), in conjunction with the Department of Health and Human Services (HHS), has developed a campaign to improve awareness of HAIs and ways to prevent their occurrence and spread [6,7], including preventing the development and subsequent transmission of antimicrobial-resistant pathogens [8]. Appropriate use of antimicrobial agents plays a key role in reducing the emergence of antimicrobial resistant bacteria and other pathogens.

A group of experts from the HICPAC/HHS was recently charged with identifying potential targets and metrics for six categories of HAIs, giving rise to the following 5-year targets: 75% reduction in central line-associated bloodstream infections/stratified infection ratio; 100% compliance with central line bundle (nonemergent insertions); 25% reduction in catheter-associated urinary tract infections; 30% reduction in Clostridium difficile infections; 50% reduction in the incidence of healthcare-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections; 95% adherence rates to each infection process measure for surgical site infections; and surgical site infections (median deep incision and organ space infection rate for each procedure/risk group) to be at or below the current 25th National Healthcare Safety Network percentile [9]. Healthcare institutions can use these targets to assess where they currently stand and to determine what changes are needed to reach them.

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Antibiotic resistance and its impact

Antibiotic resistance has ‘exploded’ at the same time large pharmaceutical companies have reduced their research and development programs for newer agents with different mechanisms of action that might be useful in combating the emergence of resistance [10–13]. Some investigators have described this situation as a ‘perfect storm’ for healthcare in the United States and other countries [14]. This highlights the importance of antimicrobial stewardship, given that antimicrobial use (and particularly misuse or overuse) has been associated with antibiotic resistance [15–17].

Antimicrobial resistance is associated with increased patient mortality, longer hospital stays, and increased healthcare costs [18,19]. This has been demonstrated for various bacteria and types of infections. Table 1 illustrates the relationship between MRSA bacteremia or surgical infection, vancomycin-resistant enterococci (VRE) infection, or infections caused by resistant species of Pseudomonas aeruginosa or Enterobacter and risk of mortality, length of hospital stay (LOS), and healthcare costs. Mortality risk and LOS are increased with resistant vs. nonresistant bacterial pathogens.

Healthcare costs are also dramatically higher for patients infected with antimicrobial-resistant bacteria. In the studies reviewed by Maragakis et al. [19], the attributable cost with a resistant vs. susceptible pathogen ranged from approximately $7000 to $29 000. Even greater relative costs were observed when comparing patients with antimicrobial-resistant organisms vs. patients without an HAI. In 2004, the Infectious Diseases Society of America (IDSA) estimated total costs to the United States for antibiotic-resistant infection as greater than $5 billion annually [10].

A recent study examined hospital and societal costs of antimicrobial-resistant infections (ARIs) in a Chicago public teaching hospital [20]. The study included 1253 patients randomly selected from the pool of 4944 patients hospitalized at the institution in 2000 who met eligibility requirements, and an additional 138 patients from the same eligibility pool with evidence of ARI, for a total of 188 patients with ARI and 1203 without ARI (Table 2) [20]. Patients with ARI (vs. without) were sicker, as measured by their Acute Physiology and Chronic Health Evaluation (APACHE) III score (54.8 vs. 40.1, P < 0.001), and a greater percentage had a concurrent HAI (71.8 vs. 10.4%, P < 0.001). Patients with ARI also spent more time in the hospital (24.2 vs. 8.0 days, P < 0.001), at a higher cost per day ($2098 vs. $1581, P < 0.001), and had a higher total cost of care ($58 029 vs. $13 210, P < 0.001). The mortality rate was also higher for patients with ARI compared with those without ARI (18.1 vs. 3.0%, P < 0.001), yielding a mortality odds ratio (OR) of 2.16 after adjustment for APACHE III, ICU care, and HAI. The attributable mortality rate was 6.5%, or 12 excess deaths caused by ARI alone.

Antimicrobial-resistant organisms for the ARI group included MRSA (43% of ARIs at a mean total cost per patient of $46 236), VRE (31% at $66 416 per patient), Escherichia coli resistant to fluoroquinolones or third-generation cephalosporins or Klebsiella spp. resistant to third-generation cephalosporins (16% at $25 549 per patient), and Acinetobacter resistant to amikacin or imipenem (4% at $97 444 per patient) [20]. In addition, 6% of patients had multiple ARIs ($157 835 per patient). Figure 1 illustrates the projected cost savings if ARI rates were reduced from 13.5 to 10.0%. Total savings for the 1391 patients in the expanded cohort were calculated to be $1948 per patient, or $2.7 million total ($910 812 study hospital savings and $1.8 million in societal savings for reduced mortality and lost productivity).

This study illustrates the high costs associated with ARIs and the potential savings that could be realized by decreasing the rate through better antimicrobial stewardship and other means. Healthcare institutions can use these characteristics to assess their own practices, to determine how HAIs and multidrug-resistant infections are adding to their costs, and how much savings could be achieved by improved antimicrobial stewardship and other approaches to reduce resistance and HAIs. This type of information is useful when determining the cost-benefit ratio of a given program being considered for implementation. Although the results from the study are noteworthy, the authors identified a number of study limitations: it was a retrospective study involving data collected from a single institution in a single year; it excluded children and patients receiving obstetrical, trauma, and burn care; as the costs and mortality rates were measured in a subset of hospital patients at high risk and severity of illness, the results are not generalizable to all ARI patients in the community; the costs used to estimate lost productivity due to hospitalization and death were based on United States averages and, hence, might not apply to a sicker population; the retrospective design prevented access to quality-of-life information, as a measure of societal cost; and some infections categorized as community-acquired might actually have been acquired during a prior healthcare encounter that was not measured, and therefore, the study does not provide sufficient distinction between community-acquired and healthcare-acquired infections [20].

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Why have antimicrobial stewardship?

Antimicrobial stewardship refers to the responsible use of antimicrobials by healthcare professionals, and more specifically, to selection of the most appropriate antibiotic, duration, dose, and route of administration for a given patient with a demonstrated or suspected infection. Antibiotics (and other antimicrobials) are unlike other medicines in that use of the agent in one patient can compromise its efficacy in another. This is because antibiotic use, and particularly antibiotic overuse or misuse, can promote the development or selection of resistant bacteria, which can then spread to other patients who never received the antibiotic. The risk of antibiotic overuse/misuse is heightened because any physician can prescribe antibiotics, despite a lack of specialized training in infectious diseases.

ASPs are ideally carried out by multidisciplinary institutional teams, with the aim of improving clinical outcomes through promotion of appropriate antibiotic and other antimicrobial drug use [15,21]. Antimicrobial stewardship improves clinical outcomes by reducing the emergence of antibiotic resistance, limiting drug-related adverse events, and minimizing the risk of other unintentional consequences of antibiotic use (e.g., promoting C. difficile superinfection). Combining effective antimicrobial stewardship with a comprehensive infection control program has been shown to limit the emergence and transmission of antimicrobial-resistant bacteria [15]. A secondary goal of antimicrobial stewardship is to reduce societal and healthcare-related costs, which are linked with antimicrobial-resistant infections [15].

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The antimicrobial stewardship team and targeting key organisms

In 2007, the IDSA and the Society for Healthcare Epidemiology of America (SHEA) provided guidelines for the development of institutional programs to enhance antimicrobial stewardship [15]. The ideal ASP consists of a multidisciplinary core group, including an infectious diseases physician, clinical pharmacist with infectious diseases training, clinical microbiologist, information system specialist, infection control professional, and hospital epidemiologist. At the very least, an infectious diseases physician and clinical pharmacist with infectious diseases training should be members of the core team.

The focus should be on optimizing pharmacologic treatment of a small group of bacteria, increasingly prevalent in the current hospital environment, that are increasingly associated with antibiotic resistance. This group was originally designated by the acronym ESKAPE: Enterococcus faecium (E), S. aureus (S), Klebsiella pneumoniae (K), Acinetobacter baumannii (A), P. aeruginosa (P), and Enterobacter spp. (E) [22]. More recently, Peterson [23] recommended amending the group of pathogens and changing the acronym to ESCAPE. In ESCAPE, C. difficile (C) replaces K. pneumoniae (K), and E now stands for Enterobacteriaceae, which encompasses K. pneumoniae and Enterobacter spp., as well as other critically important pathogens that can express increasing levels of antibiotic resistance (e.g., E. coli).

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Impact of antimicrobial stewardship programs

ASPs have been demonstrated to improve patient outcomes and reduce healthcare costs [15,24]. In particular, worldwide studies of ASPs have demonstrated reduced antibiotic usage, improved susceptibility patterns/decreased resistance (relative to baseline or nonimplementation), and/or reduced healthcare costs associated with implementation of these programs [25–45]. Cost savings are typically observed after considering the costs to initiate the program.

A review by McQuillen et al. [24] examined the positive impact of ASPs and infectious diseases specialists on clinical outcomes and costs. Table 3 summarizes the key results from some of the reviewed studies. Note annual savings or cost reduction was over $150 000 for several of the studies. Benefits were observed for smaller hospitals (120 beds), larger hospitals (>1000 beds), and those in between. The studies also show a reduction in antimicrobial cost, which is only one of the multiple objectives of such programs. A 2005 Cochrane systematic review of interventions to improve antibiotic prescribing practices for hospital inpatients concluded that a wide variety of interventions are successful and can reduce HAIs and antimicrobial resistance [46]. However, the review also concluded that standardizing methods and data reporting for time series in single hospitals would enhance the ability to compare single-hospital results and generalizability (and only five of the 66 studies reviewed involved ≥10 hospitals). One potential drawback of an intervention involving restriction of one antibiotic and replacement with another is the so-called ‘squeezing the balloon’ effect, whereby reduction in resistance to the first class is simply replaced by resistance to the second class [47,48]. ASPs employing such an approach need to be cognizant of and monitor for such an outcome.

Despite the recognized benefits of institutional ASPs, a recent survey on implementation of the 2007 IDSA/SHEA guidelines for developing such programs demonstrated only 48% of hospital respondents had such an ASP at the time of the survey (20 March 2008, completion), although another 26% said their hospital was considering or in the process of developing an ASP [49]. Most hospitals with an ASP were using local antibiograms (95%) and tracking resistance patterns (76%), but only 26% were monitoring LOS and mortality as outcome measures. In addition, only 15% of respondents said their hospital had a commercial automated electronic surveillance system tool, and only 27% said the hospital utilized computerized physician order entry. Modernized healthcare informatics are a key component of ASPs, and the use of technology would presumably improve the effectiveness of such programs, in particular making it easier to monitor LOS and mortality outcomes. Incorporating computerized decision support systems and other informatics resources is expected to improve compliance and adherence to institutional ASPs, as well as outcomes in the ICU and other hospital settings [50,51].

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Developing antimicrobial stewardship programs: examples from the Ohio State University Medical Center program

Multiple factors need to be considered when developing an ASP. Reviewing the 2007 IDSA/SHEA guidelines for developing institutional programs, the Society of Infectious Diseases Pharmacists noted the guideline's emphasis on both improvement of clinical outcomes and minimization of antimicrobial-related adverse events, including the development of antimicrobial drug resistance [52].

Drug safety or adverse events, including development of antimicrobial resistance, are important considerations. Although antimicrobials are generally considered to be well tolerated, they – and particularly antibiotics – are among the most commonly administered drugs in the outpatient and inpatient setting. Hence, a large number of drug-related adverse events are due to antibiotic usage. A 1995 study showed that antibiotics were the second most common class of drugs to cause adverse drug reactions, behind analgesics [53]. In addition, a relationship has been shown between antibiotic use/overuse and increased risk of antibiotic resistance, and between antibiotic resistance and poorer treatment outcomes and elevated healthcare costs (reviewed in Drew et al. [52] and Sipahi [54]). Thus, drug-related adverse events are an important consideration when deciding whether to administer an antibiotic.

The focus of the ASP should be on optimizing clinical outcomes, while minimizing adverse events. This is particularly the case as poor efficacy, due to delayed treatment or other factors, can also dramatically increase healthcare costs. Hence, when implementing an institutional ASP, the focus should be on quality-of-care improvements, disease-based management rather than antibiotic management, and overall cost savings. There are costs associated with program implementation, drug acquisition, and drug-related adverse events, including the risk of antimicrobial resistance, but there are also costs associated with suboptimal treatment, and all of these factors have to be measured when evaluating the overall costs or savings associated with program implementation. Unfortunately, as antimicrobial use and cost is so easy to measure before and after beginning a program, this continues to be the most common and often only justification for program implementation [52].

Two other considerations when developing an ASP are the size of the hospital and making sure to identify the clear authority for the program. The size of the stewardship program needs to meet the size of the hospital. Although one infectious diseases physician and pharmacist might be able to provide minimal requirements at a 120-bed hospital, they would probably not be sufficient at a 1200-bed hospital. Also, before institutional interventions are made, it is important to discuss the scope of authority and obtain administrative approval. Infectious diseases pharmacists need oversight with physicians' involvement in the program, so when interventions are made, they are evidence-based and supported by the medical staff.

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Communicating guidelines

When developing an institutional program, it is important to know the audience who need to be advised on the benefits of the program, understand their concerns, and develop effective messages to communicate those benefits and overcome their concerns. The guidelines that are developed need to be focused and easy to understand and follow. For example, if there are 10 criteria for the use of a restricted antibiotic, the guideline may be too complicated to implement.

There are two basic approaches to institutional antimicrobial stewardship: a front-end review, in which there is formulary restriction and prior authorization to receive an antimicrobial (‘formulary restriction and preauthorization’), and a back-end review in which physicians prescribe the best they can to the guidelines, the orders are reviewed within 24 h, and if adjustments need to be made, they are made at that time (‘prospective audit with intervention and feedback’) [15]. Either method works (and they need not be mutually exclusive), but in order to work, the guidelines need to be easy to follow. Ideally, the ASP physician and pharmacist should meet daily to review, prioritize, and discuss cases. The other team members should participate in weekly discussions. The ‘steward’ must be seen on patient care rounds to develop the trust of the medical staff.

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Focus on the audience

The audience may be infectious diseases physicians, critical care members, emergency room physicians, infection control specialists, registered nurses, pharmacists, hospitalists, surgeons, or residents and fellows and the delivered message should differ somewhat based on the audience. The message points, for example, are going to be somewhat different for an emergency department physician who is just administering the first dose before passing the patient on to another healthcare professional, vs. a hospitalist who is following the patient until discharge and, hence, is more involved in drug de-escalation.

An example from my hospital at OSUMC illustrates the importance of identifying the audience and tailoring the message to their interests or concerns. By way of background, a 2007 study by Lodise et al. [55] showed that administering piperacillin-tazobactam by extended infusion vs. intermittent infusion lowered the mortality rate (12 vs. 32%, P = 0.04) and shortened hospital stay (21 vs. 38 days, P = 0.02) in critically ill patients with P. aeruginosa. We wanted to initiate a similar extended-infusion dosing strategy at our institution and tried to identify who at the hospital might have difficulty with it. The group identified was registered nurses, who might focus on the inconvenience the extended infusion would create by tying up the infusion line for 12 h out of the day. Rather than cultivating a message around how this new method would maximize the pharmacodynamics of the therapy, we focused on the improved mortality rate. In particular, we illustrated the study by Lodise et al. that demonstrated the dramatic improvement in mortality rate with the extended infusion strategy. We knew the nurses' primary focus was on patient care, so we emphasized the improved clinical outcome with the new strategy.

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Cumulative antibiograms: measuring local resistance trends

The clinical microbiology laboratory plays a crucial role in many ASPs, including the one at OSUMC. As mentioned earlier, the IDSA/SHEA guidelines indicate an optimal ASP includes a clinical microbiologist as part of the multidisciplinary team [15]. One of the microbiologist's roles is to create hospital-wide and ICU-specific antibiograms that inform about trends in local resistance rates. Antibiograms are typically summarized on an annual basis and reflect the results of laboratory testing for the sensitivity of various bacterial strains to various antibiotics. These findings are useful when making decisions about antibiotic treatment. The Clinical and Laboratory Standards Institute M39-A2 consensus guidelines provide recommendations for the preparation and use of antibiogram reports [56], and a recent review by Kuper et al. [57] provides a primer on antimicrobial susceptibility testing for clinicians.

Local trends in antibiotic susceptibility can differ from national trends, and resistance patterns can also differ within different areas of the hospital. Hence, antibiograms for the different areas of the local institution are a critical component of any effective ASP. We learned the importance of this at OSUMC in 1999, when we noted a marked difference in antibiograms for the entire hospital and those focused on susceptibility in the ICU. In particular, hospital-wide antibiograms indicated K. pneumoniae was susceptible to a wide range of antibiotic classes (≥88% for piperacillin-tazobactam, cefepime, imipenem, ciprofloxacin, tobramycin), whereas ICU antibiograms showed full susceptibility to only carbapenems (100% for imipenem; unpublished data). Susceptibility to piperacillin-tazobactam was 66%, cefepime 71%, ciprofloxacin 63%, and tobramycin 63% in the ICU. The reduced susceptibility was probably due to the entry of extended-spectrum β-lactamase (ESBL)-producing organisms at the institution.

The key point of this example is that failure to obtain separate antibiograms for different areas of the institution would have led to suboptimal treatment, treatment failures, and poor outcomes. Ineffective treatment is costly both to the patient and in terms of healthcare and societal costs. Infections caused by ESBL-producing bacteria have been shown to increase healthcare costs compared with infections caused by non-ESBL-producing bacteria. For example, a matched-cohort study by Lee et al. [58] reported increases in infection-related costs per patient ($41 353 vs. $24 902, P = 0.034) and infection-related LOS (21 vs. 11 days, P = 0.006) for patients with infections associated with ESBL-producing E. coli or Klebsiella spp. vs. non-ESBL-producing species.

Therefore, it is important to utilize antibiograms and look beyond the cost of antimicrobials alone when developing an ASP. The cost of infection also needs to be calculated, because a more expensive antimicrobial might be needed to effectively eradicate an infection caused by a pathogen resistant to less expensive agents. As illustrated by the study by Lee et al., failure to select the most effective antibiotic initially can be costly.

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Complicated intraabdominal infections: using antibiograms and targeted messages

Complicated intraabdominal infections present an additional challenge; the IDSA and Surgical Infection Society recently provided guidelines for the diagnosis and management of these infections [59]. The guidelines recommend performance of susceptibility studies if there is significant resistance (10–20%) of common community isolates (e.g., E. coli), and against use of ampicillin/sulbactam because of high rates of resistance to this agent among community-acquired E. coli. For adults with mild-to-moderate complicated intraabdominal infections, the guidelines recommend single-agent therapy with ertapenem, cefoxitin, moxifloxacin, tigecycline, or ticarcillin-clavulanate or combination therapy with cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin or levofloxacin with metronidazole.

Several years ago, OSUMC devised an ASP for the management of complicated intraabdominal infections. The program was developed prior to the 2010 IDSA/Surgical infection Society guidelines, based on antibiograms of the surgical ICU (SICU) and housewide hospital antibiogram, and is consistent with the current guidelines. Results of the antibiograms showed reduced susceptibility of E. coli (42 and 45% in the SICU and hospital) and K. pneumoniae (75 and 78% in the SICU and hospital) and no coverage of ESBL-producing E. coli or ESBL-producing K. pneumoniae to ampicillin/sulbactam (unpublished data). Conversely, all of these pathogens were fully susceptible to ertapenem in the hospital and SICU. The results were presented to the surgical division, and in collaboration with the surgeons we developed computerized order entry (CPOE) forms for physicians to use when ordering antibiotics.

Of importance, through conversations with surgeons, we came to understand that they were more likely to think in terms of infection site than antibiotic; hence, we adapted our screens to represent this thought process: the ordering screens provided the recommended antibiotic via a search of infection site (e.g., abdominal non-ICU, with subcategories for C. difficile, upper gastrointestinal, lower gastrointestinal, and biliary/cholangitis). It is important to design a system that reflects the thought processes of the end user, rather than that of the program designer.

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Evaluating the impact of formulary changes on susceptibility patterns

Ertapenem is a group 1 carbapenem with activity against ESBL-producing Enterobacteriaceae, but not P. aeruginosa [60,61]. Hence, various institutions have developed programs adding ertapenem to their formulary and restricting use of group 2 carbapenems with broader coverage (imipenem, doripenem, and meropenem) for patients wherein activity against P. aeruginosa is desired.

One concern is that increased ertapenem use will lead to cross-resistance of aerobic Gram-negative bacteria (including P. aeruginosa) to imipenem, doripenem, and meropenem. A 5-year analysis of OSUMC data showed the formulary addition of ertapenem had no effect on imipenem susceptibility to Gram-negative pathogens [62]. A multidisciplinary team approach was used to implement this treatment plan at OSUMC, beginning with microbiologist-provided antibiograms and emphasizing the lack of cross-resistance, the fact that many patients do not need coverage of P. aeruginosa, and concern about development of resistance to group 2 carbapenems. A more recent report by Eagye and Nicolau [63] similarly did not detect any significant change in P. aeruginosa susceptibility to imipenem or meropenem following replacement of these antipseudomonal carbapenems with ertapenem. An expanded discussion of the impact (or lack thereof) of replacing carbapenem with ertapenem appears in the corresponding supplement article by Goldstein.

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Incorporation of new diagnostic tests into antimicrobial stewardship programs

In 2008, OSUMC took steps to incorporate real-time PCR into the ASP, enabling rapid detection of MRSA or methicillin-susceptible S. aureus (MSSA) from blood cultures. This process was initiated by the clinical microbiologist who was aware of the new technology and who presented data to the antibiotic subcommittee with recommendations to implement the test as part of the institutional ASP. An in-house validation was performed, and it was decided that the rapid PCR test would be an important addition to the program, providing more rapid diagnosis of S. aureus (within 1 h of growth in the blood cultures bottle) than was previously possible. Test results are rapidly communicated to the infectious diseases pharmacist, who then calls the physician with targeted antibiotic recommendations. If MRSA is detected, the patient is continued on vancomycin or switched to daptomycin. However, if the test detects MSSA, the patient is switched from vancomycin to nafcillin or cefazolin.

Although the benefits of early detection were clear, there were concerns about the high costs associated with carrying out real-time PCR (rPCR) for MRSA/MSSA. Data were collected to better evaluate the clinical and financial costs of incorporating rPCR technology into the OSUMC program. Mean time to switch from empiric vancomycin to cefazolin or nafcillin in patients with MSSA bacteremia was 1.7 days shorter post-rPCR (P = 0.002). In the post-rPCR MSSA and MRSA groups, the mean length of stay was 6.2 days shorter (P = 0.07) and the mean hospital costs were $21 387 less per episode of bacteremia (P = 0.02) [64].

This is an example of how the OSUMC stewardship team worked together to justify a new expensive instrument, GeneXpert (Cepheid, Sunnyvale, California, USA), that otherwise might have appeared cost prohibitive. In addition, it highlights the importance of focusing on overall costs, rather than simply antimicrobial costs. We used more expensive antimicrobials in MRSA management, but by diagnosing and treating patients sooner, we were able to optimally treat and reduce LOS, resulting in reduced hospitalization costs.

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Conclusion

A well designed ASP has the potential to improve patient care while reducing healthcare and societal costs associated with inappropriately or poorly treated infections. Guidelines have been published for the development of institutional ASPs and point to the benefits of a well coordinated multidisciplinary team for the initiation and delivery of such programs. Our own experiences at OSUMC reinforce the importance of a multidisciplinary ASP team and highlight the importance of effective and timely communication among team members. They have also taught us that it is important to identify early those who might not be willing to embrace a new institutional guideline or plan of action, understand their concerns, and then tailor messages around those concerns. Communication of new guidelines should be in a straightforward manner that is easy to understand and implement, and that addresses the concerns of the targeted audience and dovetails with their professional skills and motivations. The clinical microbiology laboratory plays a key role through development of antibiograms that highlight interdepartmental trends in antibiotic resistance, prior to and after initiating changes in antibiotic practices. Measures of ASP outcomes should include measures of clinical efficacy, safety, drug resistance patterns, and overall costs that go beyond simply reductions in drug acquisition costs.

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Acknowledgement

This supplement was supported through an educational grant from Merck & Co., Inc.

The author declares no conflicts of interest.

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References

1 Klevens RM, Edwards JR, Richards CL Jr, et al. Estimating healthcare-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007; 122:160–166.
2 Stone PW, Hedblom EC, Murphy DM, Miller SB. The economic impact of infection control: making the business case for increased infection control resources. Am J Infect Control 2005; 33:542–547.
3 Heffler S, Smith S, Keehan S, et al. Health spending projections through 2013. Health Aff (Millwood) 2004; Jan-Jun; Suppl Web Exclusives: W4-79-93.
4 Centers for Medicare & Medicaid Services. Media release database (4 August 2008): CMS improves patient safety for Medicare and Medicaid by addressing never events. http://www.cms.hhs.gov/apps/media/press/factsheet.asp?Counter=3224. [Accessed 17 February 2010].
5 Graves N, McGowan JE Jr. Nosocomial infection, the Deficit Reduction Act, and incentives for hospitals. JAMA 2008; 300:1577–1579.
6 Centers for Disease Control and Prevention. Department of Health and Human Services. Infection control in healthcare settings. http://www.cdc.gov/nidod/dhqp/. [Accessed 17 February 2010].
7 Centers for Disease Control and Prevention. Healthcare Infection Control Practices Advisory Committee (HICPAC). http://www.cdc.gov/hicpac/. [Accessed 18 February 2010].
8 Centers for Disease Control and Prevention. Campaign to prevent antimicrobial resistance in healthcare settings. http://www.cdc.gov/drugresistance/healthcare/default.htm. [Accessed 18 February 2010].
9 Department of Health and Human Services. Action plan to prevent healthcare-associated infections. http://www.hhs.gov/ophs/initiations/hai/actionplan/index.html. [Accessed 14 April 2010].
10 Bad bugs, no drugs: as antibiotic R&D stagnates, a public health crisis brews. Alexandria, VA: Infectious Diseases Society of America; 2004.
11 Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:1–12.
12 Spellberg B, Guidos R, Gilbert D, et al. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 2008; 46:155–164.
13 Talbot GH, Bradley J, Edwards JE Jr, et al. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 2006; 42:657–668.
14 Gould IM. Antibiotic resistance: the perfect storm. Int J Antimicrob Agents 2009; 34(Suppl 3):S2–S5.
15 Dellit TH, Owens RC, McGowan JE Jr, 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; 44:159–177.
16 Tacconelli E. Antimicrobial use: risk driver of multidrug resistant microorganisms in healthcare settings. Curr Opin Infect Dis 2009; 22:352–358.
17 Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006; 119:S3–10, discussion S62–S70.
18 Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and healthcare costs. Clin Infect Dis 2006; 42(Suppl 2):S82–S89.
19 Maragakis LL, Perencevich EN, Cosgrove SE. Clinical and economic burden of antimicrobial resistance. Expert Rev Anti Infect Ther 2008; 6:751–763.
20 Roberts RR, Hota B, Ahmad I, et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis 2009; 49:1175–1184.
21 Drew RH. Antimicrobial stewardship programs: how to start and steer a successful program. J Manag Care Pharm 2009; 15:S18–S23.
22 Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008; 197:1079–1081.
23 Peterson LR. Bad bugs, no drugs: no ESCAPE revisited. Clin Infect Dis 2009; 49:992–993.
24 McQuillen DP, Petrak RM, Wasserman RB, et al. The value of infectious diseases specialists: nonpatient care activities. Clin Infect Dis 2008; 47:1051–1063.
25 Allegranzi B, Luzzati R, Luzzani A, et al. Impact of antibiotic changes in empirical therapy on antimicrobial resistance in intensive care unit-acquired infections. J Hosp Infect 2002; 52:136–140.
26 Ansari F, Gray K, Nathwani D, et al. Outcomes of an intervention to improve hospital antibiotic prescribing: interrupted time series with segmented regression analysis. J Antimicrob Chemother 2003; 52:842–848.
27 Bantar C, Sartori B, Vesco E, et al. A hospitalwide intervention program to optimize the quality of antibiotic use: impact on prescribing practice, antibiotic consumption, cost savings, and bacterial resistance. Clin Infect Dis 2003; 37:180–186.
28 Bennett KM, Scarborough JE, Sharpe M, et al. Implementation of antibiotic rotation protocol improves antibiotic susceptibility profile in a surgical intensive care unit. J Trauma 2007; 63:307–311.
29 Blanc P, Von Elm BE, Geissler A, et al. Economic impact of a rational use of antibiotics in intensive care. Intensive Care Med 1999; 25:1407–1412.
30 Carling P, Fung T, Killion A, et al. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003; 24:699–706.
31 Fraser GL, Stogsdill P, Dickens JD Jr, et al. Antibiotic optimization: an evaluation of patient safety and economic outcomes. Arch Intern Med 1997; 157:1689–1694.
32 Geissler A, Gerbeaux P, Granier I, et al. Rational use of antibiotics in the intensive care unit: impact on microbial resistance and costs. Intensive Care Med 2003; 29:49–54.
33 Gentry CA, Greenfield RA, Slater LN, et al. Outcomes of an antimicrobial control program in a teaching hospital. Am J Health Syst Pharm 2000; 57:268–274.
34 Gross R, Morgan AS, Kinky DE, et al. Impact of a hospital-based antimicrobial management program on clinical and economic outcomes. Clin Infect Dis 2001; 33:289–295.
35 Hughes MG, Evans HL, Chong TW, et al. Effect of an intensive care unit rotating empiric antibiotic schedule on the development of hospital-acquired infections on the nonintensive care unit ward. Crit Care Med 2004; 32:53–60.
36 LaRocco A Jr. Concurrent antibiotic review programs: a role for infectious diseases specialists at small community hospitals. Clin Infect Dis 2003; 37:742–743.
37 Ludlam H, Brown N, Sule O, et al. An antibiotic policy associated with reduced risk of Clostridium difficile-associated diarrhoea. Age Ageing 1999; 28:578–580.
38 Lutters M, Harbarth S, Janssens JP, et al. Effect of a comprehensive, multidisciplinary, educational program on the use of antibiotics in a geriatric university hospital. J Am Geriatr Soc 2004; 52:112–116.
39 Montecalvo MA, Jarvis WR, Uman J, et al. Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting. Infect Control Hosp Epidemiol 2001; 22:437–442.
40 Ozkurt Z, Erol S, Kadanali A, et al. Changes in antibiotic use, cost and consumption after an antibiotic restriction policy applied by infectious disease specialists. Jpn J Infect Dis 2005; 58:338–343.
41 Philmon C, Smith T, Williamson S, Goodman E. Controlling use of antimicrobials in a community teaching hospital. Infect Control Hosp Epidemiol 2006; 27:239–244.
42 Ruttimann S, Keck B, Hartmeier C, et al. Long-term antibiotic cost savings from a comprehensive intervention program in a medical department of a university-affiliated teaching hospital. Clin Infect Dis 2004; 38:348–356.
43 Schentag JJ, Ballow CH, Fritz AL, et al. Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory. Diagn Microbiol Infect Dis 1993; 16:255–264.
44 White AC Jr, Atmar RL, Wilson J, et al. Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes. Clin Infect Dis 1997; 25:230–239.
45 Woodward RS, Medoff G, Smith MD, Gray JL 3rd. Antibiotic cost savings from formulary restrictions and physician monitoring in a medical-school-affiliated hospital. Am J Med 1987; 83:817–823.
46 Davey P, Brown E, Fenelon L, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2005; 4:CD003543.
47 Burke JP. Antibiotic resistance: squeezing the balloon? JAMA 1998; 280:1270–1271.
48 Rahal JJ, Urban C, Horn D, et al. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA 1998; 280:1233–1237.
49 Pope SD, Dellit TH, Owens RC, Hooton TM. Results of survey on implementation of Infectious Diseases Society of America and Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Infect Control Hosp Epidemiol 2009; 30:97–98.
50 Helmons PJ, Grouls RJ, Roos AN, et al. Using a clinical decision support system to determine the quality of antimicrobial dosing in intensive care patients with renal insufficiency. Qual Saf Healthcare 2010; 19:22–26.
51 Yong MK, Buising KL, Cheng AC, Thursky KA. Improved susceptibility of Gram-negative bacteria in an intensive care unit following implementation of a computerized antibiotic decision support system. J Antimicrob Chemother 2010; 65:1062–1069.
52 Drew RH, White R, MacDougall C, et al. Insights from the Society of Infectious Diseases Pharmacists on antimicrobial stewardship guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Pharmacotherapy 2009; 29:593–607.
53 Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events: implications for prevention. ADE Prevention Study Group. JAMA 1995; 274:29–34.
54 Sipahi OR. Economics of antibiotic resistance. Expert Rev Anti Infect Ther 2008; 6:523–539.
55 Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis 2007; 44:357–363.
56 Hindler JF, Stelling J. Analysis and presentation of cumulative antibiograms: a new consensus guideline from the Clinical and Laboratory Standards Institute. Clin Infect Dis 2007; 44:867–873.
57 Kuper KM, Boles DM, Mohr JF, Wanger A. Antimicrobial susceptibility testing: a primer for clinicians. Pharmacotherapy 2009; 29:1326–1343.
58 Lee SY, Kotapati S, Kuti JL, et al. Impact of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol 2006; 27:1226–1232.
59 Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133–164.
60 Burkhardt O, Derendorf H, Welte T. Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice. Expert Opin Pharmacother 2007; 8:237–256.
61 Keating GM, Perry CM. Ertapenem: a review of its use in the treatment of bacterial infections. Drugs 2005; 65:2151–2178.
62 Goff DA, Mangino JE. Ertapenem: no effect on aerobic Gram-negative susceptibilities to imipenem. J Infect 2008; 57:123–127.
63 Eagye KJ, Nicolau DP. Absence of association between use of ertapenem and change in antipseudomonal carbapenem susceptibility rates in 25 hospitals. Infect Control Hosp Epidemiol 2010; 31:485–490.
64 Bauer KA, West JE, Balada-Llasat JM, et al. An antimicrobial stewardship program's impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia. Clin Infect Dis 2010; 51:1074–1080.
Keywords:

antibiogram; antibiotic resistance; antimicrobial stewardship; hospital-acquired infections

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