William N. Kelly, PharmD

Although the idea for antimicrobial stewardship (AMS) has been around for a long time, it has not reached a tipping point where most hospitals have an effective antimicrobial stewardship program (ASP). The purpose of this manuscript is to report on the present status of AMS. Do ASPs have convincing data on patient survival, patient safety, and cost reduction? Is regulatory pressure converging to drive rapid development of ASPs? Are recent mandates in North America and the United Kingdom propelling ASPs toward a tipping point? If not, what needs to be done?

In his bestselling book, The Tipping Point, Malcolm Gladwell defines the “tipping point” as “the moment of critical mass, the threshold, or the boiling point” when an idea finally catches fire and becomes the norm or the generally accepted thing to do.

 Antimicrobial stewardship programs (ASPs) have been around for some time, but that tipping point has yet to be achieved at which most hospitals and long-term care facilities have effective programs.

Recent mandates and proposed standards for ASPs in North America and the United Kingdom (UK) are stimulating movement toward a tipping point. But what will it take to reach that point? The purpose of this article is to report on the present status of antimicrobial stewardship (AMS). Do ASPs have convincing data on patient survival, patient safety, and cost reduction? Is regulatory pressure rapidly converging to drive expedited development?

AMS is often defined as a systematic approach to the use of antimicrobial agents to achieve optimal outcomes, as close to 100% of the time as possible. This means using the correct agent, at the correct dose, with the correct route of administration and for the appropriate duration, to cure or prevent infection, while minimizing toxicity and emerging resistance. However, we think the current state of practice is more like:

Narrow-spectrum antibiotic used when cultures are available and patient is stable: ~10% to 20%

The likelihood that all sequential steps are optimal: ~4.5%

The increasing frequency of news reports about antimicrobial resistance contribute to a sense of impending doom, an “antimicrobial Armageddon.”

 Is this Chicken Little speaking or is the threat very real? Bacteria relentlessly reinvent themselves to resist the killing power of antibiotics. The World Bank lists antimicrobial resistance as one of the top 10 threats to global economic progress.

 The CDC says “superbugs” are emerging much more quickly than expected, and the problem is now “very serious.”

 Data from an AMS consultation (Figure 1) in a 350-bed community hospital (conducted by the healthcare consulting firm Visante, Inc) show how resistance to antibiotics emerges unless effective ASPs are in place.

In hospitals, infections caused by multidrug-resistant organisms (MDROs) are associated with higher mortality, excess stay, and additional cost.

 Driving antimicrobial resistance is the inappropriate use of antimicrobial agents, estimated by the CDC to be as high as 50% of overall use. Another concern is that the pipeline for developing new antimicrobial agents (Figure 2) is sparse.

In the early 1970s, clinical pharmacy services were established in North American hospitals, and some clinical pharmacists set about assessing the use of antibiotics due to the increases they were seeing in microorganism resistance. Evidence-based treatment guidelines and regulation of antibiotic use started to surface through hospital pharmacy and therapeutics committees.

In 1996, John McGowan, Jr, MD, and Dale N. Gerding, MD, then infectious disease specialists at Emory University School of Medicine in Atlanta, coined the term “AMS.”

 A decade later, bacterial, antiviral, and antifungal resistance had risen to such a degree that the CDC was alarmed, and in 2007, the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America published guidelines for developing an ASP.

Recent events are driving ASP development in North America and the UK:

: according to the California Department of Public Health, “California is the first (and remains the only state) to enact AMS legislation. Since 2008, California law has required that general acute care hospitals develop a process for monitoring the judicious use of antibiotics, and the results are monitored by quality improvement committee(s). In September of 2014, California Senate Bill 1311 was signed into law, further requiring hospitals to adopt and implement an AMS policy, under guidelines established by federal government and professional organizations, and to establish a physician-supervised multidisciplinary ASP with at least one physician or pharmacist who has undergone specific training related to stewardship.”

: the Presidential Executive Order “Combatting Antibiotic-Resistant Bacteria, issued in September 2014 requires federal agencies to review existing regulations and propose new regulations or other actions to require hospitals to implement robust ASPs that adhere to best practices—similar to California’s Senate bill. Agencies will also be required to define, promulgate, and implement ASPs in other settings, such as long-term care facilities and outpatient settings.

: in 2014, the CDC recommended that all US hospitals have an ASP.

: since 2013, Accreditation Canada mandates that all acute care facilities have an ASP.

: as part of the 5-year forward initiative to improve care by the National Health Service (NHS), AMS has become a central initiative of NHS England.

Unfortunately, most mandates are unfunded. However, with further actions outlined below, ASP development is moving forward toward its tipping point.

The Joint Commission (TJC) recently developed proposed medication standards, to be implemented beginning this summer, that cover general hospitals, critical access hospitals, ambulatory healthcare, nursing care centers, and office-based surgery.

having a ASP that is based on evidence-based national guidelines

the highest-level executives (C-suites) establishing ASPs as an organizational priority

educating staff members and independent practitioners—any and all involved in ordering, dispensing, administration, and monitoring&mdash;about antimicrobial resistance and AMS. The education would begin upon hiring and continue annually

educating patients and their families, as needed, on the proper use of antimicrobial medications, including antibiotics

having a multidisciplinary AMS team that includes pharmacists, infectious-disease physicians, and infection preventionists

core ASP elements: leadership commitment, drug expertise, action, tracking, reporting, and education

using organization-approved multidisciplinary protocols

collecting and analyzing data on its ASP, including prescribing and resistance patterns

taking action on improvement opportunities identified in its ASP.

CMS is now using the following criteria when doing surveys

The hospital has named a leader (eg, physician, pharmacist) responsible for program outcomes of antibiotic stewardship activities at the hospital

The hospital’s antibiotic stewardship policy and procedures require practitioners to document in the medical record, or during order entry, an indication for all antibiotics besides other required elements such as dose and duration

The hospital has a formal procedure for all practitioners to review the appropriateness of any antibiotics prescribed after 48 hours from the initial orders (eg, antibiotic time-out)

The hospital monitors antibiotic use (consumption) at the unit and/or hospital level.

Mark R. Chassin, MD, FACP, MPP, MPH, president and CEO of the Joint Commission, has said, “The Joint Commission knows that ASPs are a proven method of reducing the inappropriate use of antibiotics and improving patient safety.”

Although it seems intuitive that ASPs work, the quality of evidence for antimicrobial stewardship is poor. There are only 8 systematic reviews (none just looking at randomized controlled trials [RCTs]) and only 3 RCTs. A definitive, evidence-based study on ASPs has yet to be published. However, the anecdotal information and data are robust. For example, the CDC has authored a helpful document, “Impact of Antibiotic Stewardship Program Interventions and Cost,” that lists findings from 15 published manuscripts.

Other revealing data that support ASPs include what happens to total hospital antibiotic cost when an ASP is discontinued (Figure 3).

 Clearly, effective ASPs must be developed then consistently sustained over time.

A 2013 study revealed the impact of the temporary absence of a clinical pharmacist from an ASP.

 The rates of inappropriate use of imipenem-cilastatin, linezolid, and micafungin during the pharmacist’s absence increased by 27%, 39%, and 35%, respectively, with corresponding increases in the average duration of therapy of 0.7, 4.0, and 3.2 days. In addition, the number of cases of Clostridium difficile infection increased more than 3-fold (from 8 to 25) during the pharmacist’s absence.

Until a few years ago, AMS in the United States was reaching maturity only in larger, mostly academic hospitals; it had fledging status in midsize hospitals and was almost nonexistent in smaller hospitals. Although most practitioners agree that AMS is needed, it has not been at the top of C-suite concern. However, with the recent mandate from California, and renewed interest at the CDC, Joint Commission, and CMS, interest in ASPs is heating up in the United States.

ASPs are also garnering great interest in Canada, particularly in Ontario.

 An AMS project for that province includes multiple phases. In the first, a comprehensive survey examined the current state of hospital-based AMS practices in Ontario. In the second phase, the project team convened an international consensus forum to uncover and prioritize interventions considered to be appropriate and effective. The 6 interventions identified (in no particular order) were:

Use the antimicrobial stewardship self-assessment tool

Do a prospective audit with intervention and feedback at the individual patient and prescriber level

Provide education/training to build antimicrobial stewardship capacity

Collect data and feedback at an institutional or program level

Tailor antimicrobial therapy, with strategies including de-escalation, streamlining, and intravenous to oral switches.

The third phase, currently under discussion, proposes testing these interventions in a representative sample of pilot hospitals.

Several organizations offer advice on how to start an ASP and maintain the core elements necessary for success.

 One such organization, Visante, Inc, which helps hospitals start ASPs and do benchmarking, and makes recommendations on AMS, finds that success rests on a few rate-limiting steps:

Leadership. A leaderless ASP is ineffective. According to the CDC, a medical staff leader should be responsible for program outcomes, and a pharmacy leader should co-lead the program.

 The medical staff leader should be an infectious-disease physician, possibly a hospitalist with strong interest in infectious disease; the pharmacist leader, ideally, is a clinical pharmacist with infectious-disease training.

Medical staff buy-in and organizational approval. AMS consultants sometimes see ASPs with stalled progress because the program is solely pharmacy-based. For greatest effect, there must be buy-in by the hospital’s medical staff (executive committee) and C-suite. The ASP leadership and the director of pharmacy should negotiate with hospital administration to obtain enough authority, compensation, and administrative support for the necessary infrastructure to be successful.

Getting everyone on the same age. Collaboration must also exist among the antimicrobial stewardship team (physicians, pharmacists, nurses, microbiologists/infection control specialists, epidemiologists), the infection control committee, and the pharmacy and therapeutics committee.

Benchmarking. Developing a baseline of data for the ASP program is critical. What is the status of antimicrobial resistance? Are you playing in the bottom of the sixth inning or the top of the ninth, so to speak? How extensive is your usage of antimicrobial agents? Your antimicrobial cost? Benchmarking against yourself is the best benchmarking.

Implementing best practices. Some programs have been doing this for a long time, and representatives have shared in the literature what has gone right and wrong. Review the experiences of programs similar to yours, in same type and size of hospital.

Audit and feedback to prescribers. Data generated on comparing prescribing and prescribers is critical to continuing success. Data systems must be structured correctly to capture this important information.

The important steps in getting an ASP started include:

Gaining organizational approval. Two challenges must be overcome: convincing the medical staff and convincing the C-suite to support and take action. The program will go nowhere without medical staff support, so convincing the medical staff leadership comes first.

Making the clinical case for an ASP. The main components of the clinical case are:

Dealing with the rising tide of antimicrobial resistance

The reality that resistance is developing faster than new antibiotic therapies. Correcting this situation is a major component of the recent presidential initiative to fund new drug development

Potential therapeutic failure, with an increased mortality risk of 6.5% for each patient who becomes infected with resistant organisms

Potential malpractice threats associated with not treating patients using evidence-based antibiotic strategies

Articles

Antimicrobial stewardship programs have been around for some time. However, a tipping point has yet to be achieved where most hospitals and long-term care facilities have effective programs.

Antimicrobial Stewardship at the Tipping Point

Heart failure (HF) management involves drug  therapies familiar to all, such as angiotensinconverting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers (BBs), and hypertension and statin therapies. However, on critical chart review, one typically finds lapses in care continuity and monitoring. Recently, Medicare and JCAHO in the United States and the National Health Service and NICE (National Institute for Health and Care Excellence) in the United Kingdom have focused on whether these therapies are linked into an orderly care process to optimize physical function and quality of life (QOL) for patients, and to decrease avoidable readmissions.

Readmissions are common, with 20% of hospitalized patients readmitted within 30 days and 56% within a year.

 For HF, 90-day readmission rates can range from 30% to 50%.

 High rates of hospitalization reflect patients with HF that are not cured during hospitalization, but stabilized where their care can be managed in an outpatient setting.

In 2003, the Centers for Medicare & Medicaid Services (CMS) reported that 14% of its beneficiaries carried a diagnosis of HF, yet this population accounted for 43% of the total Medicare spending.

 As CMS has moved toward paying for results rather than process, the healthcare industry has had to adapt to earn full reimbursement. Thus, pressure on system managers is intensifying as payers incorporate financial and regulatory penalties for organizations which do not provide connected and consistent care processes. This article reviews current evidence-based drug therapies for HF, and best practices that integrate these recommendations into a patient care framework, improve patient adherence and QOL, and minimize risk of unmonitored deterioration and readmission to acute care— or death.

Treatment Optimization for Progressing HF

HF has historically been divided into 2 distinct classes: those with preserved ejection fraction (HF

EF), and those with reduced ejection fraction (HF

EF). The 2013 American College of Cardiology Foundation/American Heart Association HF Guidelines add 2 subgroups to the HF

EF category: those with borderline ejection fractions (EF 41- 49%), and those with improved EF (patients with previously reduced EF, but now with an EF 

 Several effective therapies have been proved to reduce morbidity and mortality in patients with HF

EF. However, so far, effective medication management has been limited to treating risk factors for patients with HF

Medication therapies shown to signifi cantly reduce mortality in HFrEF include ACEIs or ARBs, BBs, and aldosterone antagonists. In addition, in the IMPROVEHF analysis, the authors found significant reductions in mortality were additive with each successive therapy, plateauing at 4 to 5 treatments.

 Interestingly, they did not find that aldosterone antagonists provided additional mortality reduction when combined with BBs/ACEIs. This finding is contradictory to the EPHESUS trial which showed an additional relative risk reduction of 15% for all-cause mortality when eplerenone was added to ACEI/BB treatment.

For all patients with congestion related to HF, managing volume status is essential to controlling symptoms and improving QOL. Loop diuretics are the first-line agent for diuresis because of their powerful effects in the ascending loop of Henle. While proved to reduce symptoms, these medications have shown no benefit on mortality reduction.

), treatments should be aimed at treating comorbidities, reducing risk factors (like hypertension, coronary artery disease, obesity), and introducing lifestyle modifi cations. Where appropriate, it is reasonable to initiate an ACEI/ARB and/or a BB.

As patients progress to stage C, therapies proved to reduce morbidity and mortality should be optimized. One of the challenges in HF management is achieving doses which have been proved effective in clinical trials. Initiation of therapy with a low dose, followed by slow upward titration until maximum benefi t is achieved, is ideal for reducing adverse effects and improving tolerability. This requires a collaborative effort between inpatient and outpatient practitioners, as well as early follow-up upon hospital discharge.

The newest HF guidelines specifically recommend an outpatient practitioner visit within 7 to 14 days of release from the hospital.

 Follow-up is also important for discussions between patients and healthcare practitioners regarding progression to stage D and goals of therapy. HF education is thus crucial to the success of this population.

Once a patient transitions to stage D, medications which were optimized during stage C should be continued, but treatment options need to turn toward advanced heart care programs or palliation/hospice. At this point, medication therapy often becomes challenging due to the signifi cant weakening of the heart resulting in low blood pressures and worsening cardiac output.

Electrolyte management may also pose a problem due to renal insufficiency from poor kidney perfusion. Intravenous inotropes may provide benefit for symptom management, but this is a relatively short-term solution. Established relationships between hospitals, outpatient practitioners, advanced heart care centers, and hospice providers help transition patients once they have reached stage D.

—Most patients are newly diagnosed with significant HF while in the hospital. Thus, the starting point for improving an HF patient’s QOL is having an evidence-based formulary that only includes HF drugs that have been proved to be better (more effective and safer) than other HF drugs.

—The next step is to provide the evidence-based therapy according to the latest clinical guidelines.

The evidence showing that providing evidence-based therapy in HF patients is robust. The number needed to treat (NNT)—the number of people needed to be treated, on average, to prevent 1 more event&mdash;is often used to judge the effectiveness of therapy. For example, a systematic review of the impact of BBs on the secondary prevention of HF discovered the numbers needed to treat to prevent death or hospitalization and death after 1 year were 17 and 12, respectively.

 When using ACE inhibitors, the NNT was 20 for death and 3 for hospitalization after 3 years of therapy.

The use of HF-targeted order sets can provide a standardized framework to therapy optimization. For optimal effectiveness, these plans would be designed to be addressed upon admission and again at discharge and focus on medication selection, laboratory follow-up, and interdisciplinary counseling/discharge planning.

Approximately 20% of patients experience adverse events within 3 weeks of discharge

; nearly 1 in 3 HF patients is readmitted within a month after hospital discharge11; and 3 out of 4 post discharge follow-up visits occur without the benefi t of a discharge summary.

 A 2011 study revealed the types of issues that “fall through the cracks”: in a study of 564 patients discharged from a large academic medical center to a sub-acute care facility, 181 (32%) had pending laboratory tests.

 Of these, only 20 (11%) of the discharge summaries provided documentation of these pending tests. How can we organize ourselves to be more effective in connecting all components of care so fewer treatment failures occur, and patients can optimize their QOL?

An understanding of the condition of HF and its progression is important for reducing hospital admissions and improving compliance. Various studies have tested the hypothesis that HF education at hospital discharge will reduce readmission rates and improve self-care. One study showed that patients who received all 6 points of discharge education, as required by CMS (weight monitoring, diet, activity level, discharge medications, follow-up appointment, and course of action if symptoms worsen),were less likely to be readmitted.

 Another study found that patients who received 1 hour of HF education before hospital discharge were less likely to readmit, and had a lower mortality rate at 180 days.

Patient education should include a multidisciplinary team of healthcare professionals, and ideally be directed at the patient, as well as family members. Co-development of comprehensive education programs by medical staff, pharmacy, nursing, physical therapy, nutrition support, and care management can reinforce and elaborate on the information which has been given by the discharging physician. It is recommended that these groups work together to develop a standard written document which can be used in all subsequent teaching sessions.

A phone call within 3 days of hospital discharge is also recommended in the current HF guidelines. The purpose of these phone calls should be to ensure medication compliance and adherence to a follow-up appointment, and to answer any questions the patient may have related to their condition. It is also important that the patient be clear on the appropriate points of contact who should be alerted to any issues the patient may have.

An early follow-up office visit after hospital discharge should occur within 7 to 14 days. A recent study of 30,136 patients in 225 hospitals shows the importance of outpatient follow-up for HF patients.

 Patients with outpatient follow-up within 7 days of discharge for an HF hospitalization were less likely to be readmitted within 30 days in the “Get with the Guidelines (GWTG)-HF Registry of Patients.”

Home healthcare is a complementary strategy to delay or prevent hospital readmissions. A study examined the relationship between home care nursing services and hospital readmissions after 1176 patients were discharged from the hospital with a primary diagnosis of HF.

 Findings indicate that patients receiving home care nursing services were readmitted to the hospital signifi cantly less often within 90 days after hospital discharge.

Telemonitoring, a system where a communication device is placed in a patient’s home to transmit various data points such as blood pressure, weight, and oxygen saturation on a daily or frequent basis, has proved beneficial in some organizations. Home-based care and disease management programs have also had successes, although the defi nitions of these programs are not yet well established.

Perhaps the most diffi cult challenge is getting patients more interested in understanding and taking an active interest in their care. Patients vary in terms of having information, motivation, and behavioral skills necessary to self-manage their chronic disease, collaborate with healthcare providers, preserve functioning, and access appropriate care. Identifying the patient’s degree of activation toward self-management provides the key to interventions that lead to better medication adherence and lifestyle changes that improve a patient’s QOL.

Communicating Within a Patient-Centered Framework

A 10-question validated instrument, Patient Activation Management (PAM), can be used to assess the patient’s ability to self-manage their disease and medications. PAM assessment and patient coaching and counseling skills have been shown to be effective in managing HF patients, with a 28% drop in emergency department (ED) visits and a 12% drop in hospitalizations in the PAM group versus a control group.

This instrument underscores the importance of communicating with patients in a manner which is effective for them. Historically, communications have been instinctively based on each provider’s area of emphasis: doctors talk doctor issues, pharmacists focus on pharmacy issues, and so forth. The move toward patient-centered care involves organizing a simple but comprehensive educational package, which is framed in a way the patient can understand it.

For chronic HF, 1 study found the overall monthly cost of medication was $438, and this was back in 2002. Patients in class II and III had the highest costs, at $541 and $514 respectively.20 Also, in a study of a cohort (n = 192) nested within a randomized trial at a university-affiliated ambulatory practice, Murray et al demonstrated that refill adherence of <40% was associated with 3 times as many hospitalizations.

These findings underscore the need for refill adherence of ~80% (

 = .002). Programs which attempt to blend the distinct lines between hospital pharmacy and retail programs may provide a smooth transition from inpatient to home.

In addition to cost, a common concern of patients is not wishing to wait at a retail pharmacy on hospital discharge. This often leads to days of missed medications and the potential for readmissions. Through hospitalbased retail pharmacies and merged data systems, the ability to discharge a patient from the hospital with medications in hand is an opportunity which is improving as communities increasingly integrate inpatient and outpatient care and information.

Studying and understanding health-related QOL can be complex and diffi cult. It is easy to get caught up in trying to improve the patient’s medication therapy and seeing laboratory tests and biomarkers improve; however, the real challenge is improving the patient’s longevity and QOL.

Those who study this activity have developed a potpourri of definitions, tools, and measurements (like the SF-12 or SF-36) that are often conflicting. Because of the enormity of options, many clinicians ignore the issue. However, for HF, understanding QOL can be made simple—is the patient better, the same, or worse because of what you do? Here we are speaking of outcome measures, rather than process measures (interventions and clinical measures like laboratory results) or healthcare utilization measures (eg, hospital, physician, ED visits).

QOL measure what is most important to the patient— Will I live longer? Will I have less symptoms or exacerbation of my disease? Will I have more energy? When will I be able to climb more stairs or walk further without getting shortness of breath? Most patients measure their QOL by what they can do versus what they could do before they were ill.

Previously, we as professionals have been judged (and paid) according to whether we ordered or advised proper tests or therapies in our institution or office— patient understanding about their disease or therapies, motivation, accomplishment of recommended followup, monitoring, or self-care was beyond our required responsibilities.

Now, however, healthcare is rapidly transitioning from a “sick-care” model that emphasizes urgent interventions to maximizing patient benefit from coordinated and systematic “healthcare.” In our grandparents’ time, there were few supportive therapies, and treatment complexity exemplifi ed by HF did not exist.

For HF, and many other conditions, we now have effective therapies, and information technology allowing us to track multiple issues across many services and providers. Driving patient-centered care is a societal and economic mandate to bring more tangible benefi t to patients, such as emancipating an NYHA Class III patient who is short of breath moving across a room, constantly feeling the dread of knowing they are at the edge of decompensation, readmission, or possibly death, and transforming him or her into a person who can maintain reasonable activity, visit family, enjoy a beautiful day outside, or simply do routine daily tasks.

To accomplish this improvement consistently involves a transition from each of us having our own professional, siloed “guidelines” to participating in best practice processes to develop a smoothly running framework that coordinates all the professionals touching that patient.

Trying to coordinate without care process standards is as ineffective as fi elding a football team of all-stars who have no coordinated “plays,” where every movement by each team member has to be discussed anew after each down. Given a core play, or process, customization for individual variables needs would be analogous to calling for a “DRG 127 (HF) fl are, hold the BB for bradycardia and bifascicular block, cardiology consult regarding possible pacemaker, routine monitoring, education, and guideline therapies— GO!”, providing multiple physicians, pharmacists, respiratory therapists, physical therapists, discharge planners, and others with clear directions for coordinating “best practice” care both during and after acute hospitalization.

Times of dramatic change, such as now, are threatening to those who cannot imagine the benefits for patients of this transition to “patient-centered care,” or do not acquire new skill sets to leverage medical and information technologies and move out of our traditional silos toward a “collaborative care” model. Indeed, we are long overdue for the organizational transformation discussed in this paper, and are in fact the last major complex industry to adopt integrated logistics to improve the tangible value of our services to society.

This article reviews current drug therapies for heart failure and therapy integration into a patient care framework improving patient adherence, quality of life, and decreased risk of readmission to acute care facilities.

Redesigning Heart Failure Management to Optimize Patient and System Outcomes

Antibiotics are the most commonly used pharmacologic treatment in every hospital. Without effective antibiotics, failure rates for prophylaxis of surgical infections and medical treatment for all infectious syndromes increase dramatically, resulting in increased patient deaths, length of hospital stay, and readmissions. However, overuse of broad-spectrum antibiotics in hospitals is causing an accelerating prevalence of resistant organisms because of the collateral killing of normal bacterial populations. Without changes to our antibiotic use process, we are setting ourselves up for catastrophic consequences.

Antimicrobial Resistance in the News: “We Are Nearing Antimicrobial Armageddon!”

In March of this year, the Centers for Disease Control and Prevention (CDC) issued a major report on antimicrobial resistance.

 It stated that “The increase in the number of rare, but potentially deadly superbugs resistant to nearly all last-resort antibiotics has prompted health offi cials to renew warnings for US hospitals, nursing homes, and other healthcare settings.” A rare but potentially deadly superbug has now been identifi ed as carbapenem-resistant enterobacteriaceae (CRE). These organisms elude carbapenem antibiotics and other antibiotic classes, and typically strike people already vulnerable to infectious agents because of their use of devices such as ventilators or catheters. The report goes on to discuss how to limit these organisms, and recommends that health providers act “aggressively to prevent the emergence and spread of these unusual CRE organisms.”

Almost immediately the CDC report was followed by a paper from the United Kingdom’s chief medical director declaring antibiotic resistance a “nightmare.”

 Following up on this release, Reuters News Service related that CRE is only a small part of the superbug story.

 The truth is many other superbugs, such as MRSA (killing around 19,000 every year in the United States), are emerging and becoming increasingly resistant to current antibiotics. The other side of the story is that the pipeline for new antibiotics to address these resistant organisms is not forthcoming. The 

shows the decline of new antibiotics under development in recent years.

This situation has been on the radar for the World Bank, which has included antimicrobial resistance as one of the top 10 threats to global economic progress for the past several years.

 These conclusions are supported by overwhelming evidence gathered by the CDC, the World Health Organization, and the Cochrane Collaboration.

The continuing threat of antimicrobial resistance is not just hype—it is real. In fact, it is late in the game and the superbugs are winning!

As noted above, resistance is promoted by use of broad-spectrum antibiotics which kill off all but the most resistant bacteria. When patients are initially admitted in critical condition, broad-spectrum antibiotics are needed to cover all potential bacterial species. As patients improve and more data become available, physicians are often reluctant to narrow the spectrum of antibiotics to targeted treatment of the organism identifi ed. Physicians often hesitate to “de-escalate,” even when culture reports indicate it is safe to do so. Most of this reluctance is related to fear of therapeutic failure, potential liability, and detailed education about antimicrobial resistance and precise selection of alternative agents. Close teamwork with pharmacists to select the best narrower-spectrum agents, as well as providing dosing based on weight, optimized infusion timing, and duration are becoming more and more important for success given the prevalence of obesity, and the high blood levels required for successful treatment of relatively resistant bacteria.

Another common contribution to antimicrobial resistance is the use of an antibiotic when the infection is most likely viral. In Sweden, where there are stricter guidelines for casual antibiotic use, and less pressure for their use by patients, resistance is less common.

Antimicrobial resistance patterns in hospitals vary and are susceptible to various local conditions, including the:

• prescriber expertise for antibiotic selection

• use of locally derived guidelines regarding antibiotic use by infection type

• involvement of clinical pharmacists to optimize dosing, recommend alternatives, and support de-escalation when patients are more stable, and culture data are available

The only way for a hospital to know how its antimicrobial program compares with similar facilities (for use, cost, and resistance) is by assessing its current use process, then benchmarking its data and practices to discover the extent of antimicrobial resistance and the reasons driving it.

Scenarios for Responding to Increased Antimicrobial Resistance

Hospitals have 2 basic choices when dealing with antimicrobial resistance. The first is to carry on business “as usual.” The second is to be proactive, seeking better ways to handle these problem bugs. The problem of carrying on as usual, hoping it will go away, is it provides no solution at all. Without a fundamental change in antibiotic use, resistance always increases, and becomes assessment performed by a knowledgeable independent consultant.

—Information generated by a programmatic antimicrobial assessment:

—This is a community hospital that averages 250 beds

• Medicare acuity index during the assessment = 1.45

—An independent consultant performed an assessment of this hospital’s antimicrobial program and provided it with an analysis of its status. During this process, any issues noted by the assessment team were reported to the hospital group to work in concert to develop a sequential approach to ongoing AMSP improvements (

When compared with similar institutions, this hospital’s antimicrobial resistance was much higher. There was an overuse of antibiotics, especially of broad spectrum and expensive antibiotics. Also, there was a tendency not to use narrower-spectrum, less costly antibiotics when culture reports and clinical pharmacists indicated effective alternatives were available. The consultant’s finding wasthat this hospital had the potential for significant clinical improvement as well as antimicrobial cost savings in the range of $250 to $400 K per year with implementation of an effective AMSP. This is currently being considered by the hospital’s medical staff executive committee.

Recommendations for this hospital included:

• Development of a set of performance standards for improving antibiotic use that are routinely measured, and an ongoing process to review results and take actions to improve them where appropriate

• Creation and implementation of guidelines for treatment of common infections such as urinary tract infections and pneumonia to improve antibiotic use and optimize duration of therapy within the hospital and, if needed, at discharge

• Flow charting the antibiotic ordering and dispensing process from the time an antibiotic order is written until the first dose is administered

° Then identify where bottlenecks occur and take action to reduce them, with the goal of decreasing your average overall time of 3 hours and 20 minutes to the recommended 1 hour

• Increase the clinical involvement and supervision of its microbiology program

• Add 1 full-time equivalent infectious disease pharmacy specialist or provide funds and training for a pharmacist to gain additional knowledge of antimicrobial therapy

° Savings from the improved AMSP will more than pay for additional staff and/or training

• Routinely review written pharmacist chart notes to the medical staff as part of the pharmacy department’s quality improvement program

• Develop standard protocols for chart notes or other preferred ways to contact physicians

° Track feedback to ensure that communication methods are timely

• Reactivate the institution’s antimicrobial stewardship committee with new and committed physician leadership

° Committee to also include microbiology, pharmacy, and infection prevention/control membership. This committee should meet regularly to be effective

• Provide routine training on the use of Theradoc

• Consider greater controls of pharmaceutical industry representatives throughout the hospital

Achieving Improved Antimicrobial Use and Less Antimicrobial Resistance

The strongest evidence for improving antimicrobial use and reducing antimicrobial resistance is in implementing a hospitalwide, medical staff—approved antimicrobial stewardship program (AMSP).

 A well-implemented AMSP can produce the following benefi cial results in clinical quality and financial performance:

• reduced antimicrobial use of 11 to 38%6-10

• increase in the appropriate antibiotic use by 20 to 24%

• reduced duration of antibiotic therapy by 18%

• more cures and less therapeutic failures

• reduced stay by 0.5 to 1 day for patients with infection

• reduced 30-day readmissions for infection by 0.5 to 0.8%

• reduced cost—comprehensive AMSPs have routinely demonstrated annual savings of $200,000 to $900,000 in both larger academic hospitals and smaller community hospitals

The evidence is robust that antimicrobial resistance has become an increasingly critical issue in healthcare institutions everywhere. For hospitals, solutions cannot be found by traditional management of hospital departments. Instead, a hospitalwide program that coordinates physicians and their ordering profi les, pharmacists, infection control practitioners, discharge planners, and others is needed for success.

The most effective place for most facilities to begin is to have an assessment carried out by an independent team that is uninvolved with the issues and departmental biases. From this review, a new process can be formulated, negotiated, and implemented. Most clinicians are unaware of their specific hospital issues and comparisons, and have not thought of acting outside of traditional approaches of treating patients 1 at a time without a strategic vision of how their current prescribing habits impact future effectiveness of antibiotics for all patients in their hospital and community.

In this case study, the authors illustrate the diagnosis of institutional antibiotic resistance issues and drivers, and provide tailored recommendations for simultaneously reducing resistance, antibiotic costs, and treatment failure.