Your activity: 169 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email:

Antimicrobial stewardship in hospital settings

Antimicrobial stewardship in hospital settings
Marisa Holubar, MD, MS
Stan Deresinski, MD
Section Editor:
David C Hooper, MD
Deputy Editor:
Keri K Hall, MD, MS
Literature review current through: Dec 2022. | This topic last updated: Jun 26, 2021.

INTRODUCTION — Antimicrobial stewardship consists of systematic measurement and coordinated interventions designed to promote the optimal use of antimicrobial agents, including their choice, dosing, route, and duration of administration [1,2]. This applies not only to antibacterial agents, but antifungals [3,4], antivirals, and antiretrovirals [5,6] as well. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use. Additional benefits include improving susceptibility rates to targeted antimicrobials and optimizing resource utilization [1].

The United States Centers for Disease Control and Prevention (CDC) and Centers for Medicare and Medicaid Services (CMS) promote implementation of antimicrobial stewardship programs in United States health care facilities that receive CMS funding and/or Joint Commission accreditation [7-10]. The program is described in a "playbook" that is designed to help facilities implement the CDC Core Elements of Hospital Antimicrobial Stewardship Programs [11]. The primary goal is to promote "smart use" of antimicrobials in the face of data demonstrating substantial overuse. Measurement of outcomes will be performed by comparing health care facilities of similar size and patient populations. Interventions to achieve this goal are discussed in the following sections.

Since 2017, the Joint Commission has required that all hospitals and nursing care centers have antimicrobial stewardship programs [12]. Implementation of antimicrobial stewardship programs in small hospitals (<200 beds) often requires confronting a number of barriers, such as a lack of dedicated staff trained in infectious diseases [13]. The CDC guidelines for the implementation of antimicrobial stewardship programs in small and critical access hospitals provide examples of how to overcome these barriers [14]. Potential solutions include pooling of resources among hospitals, utilizing the resources of a larger health care system if feasible, taking advantage of state health department resources, and use of telehealth activities.

Issues related to hospital-based stewardship are reviewed here. Issues related to outpatient antimicrobial stewardship are discussed separately. (See "Antimicrobial stewardship in outpatient settings".)

ADVERSE EFFECTS OF ANTIMICROBIAL USE — Adverse effects of antimicrobial use, which have been reported to occur in one-fifth of patients, include emergence of antimicrobial resistance, selection of pathogenic organisms such as Clostridioides difficile, and drug toxicity [15].

Antimicrobial misuse is widespread and has potentially profound adverse effects [16]. Administration of an antimicrobial course to a patient exposes the approximately 1012 bacteria (the microbiome) in that patient to selective pressure, which may alter the intestinal microbiota for as long as a year [17,18].

The United States Centers for Disease Control and Prevention estimates that more than 2.8 million infections caused by antimicrobial-resistant pathogens occur in the United States, resulting in more than 35,000 deaths [19].

PRINCIPLES OF OPTIMAL ANTIMICROBIAL USE — In general, management of patients with suspected or proven bacterial infection consists of initiation of empiric therapy (ie, prior to availability of definitive microbiology data), followed by adjustment once microbiology data become available [20,21].

Initiating empiric therapy — Initiation of empiric antibacterial therapy consists of the following:

Choosing the optimal antimicrobial regimen (after obtaining culture[s] from relevant sites), taking into consideration:

The severity and trajectory of illness

The likely pathogens and their anatomic source (with consideration of source control), based on information from Gram stain and other rapid tests as appropriate

The likelihood of drug resistance (eg, known colonization with resistant pathogens, recent antimicrobial use, exposure to health care facilities, local resistance patterns)

Host factors, including those that may preclude use of a particular antimicrobial class (eg, allergy), increase the risk of toxicity (eg, marginal or unstable renal function), or influence spectrum of coverage (eg, immunocompromise)

Determining the appropriate dosing and route of administration (eg, intravenous in the critically ill)

Initiating antimicrobial therapy as promptly as possible

Tailoring antimicrobial therapy ("antimicrobial time-out") — In patients receiving empiric antimicrobial therapy, the regimen should be re-evaluated on a continuing basis as the clinical status evolves and microbiology results become available (often after 48 to 72 hours). At this point, an "antimicrobial time-out" should be performed, in which microbiology results are reviewed and antimicrobial therapy is adjusted from empiric to definitive antimicrobial therapy. The spectrum of coverage may be narrowed or broadened as appropriate, the dose may be adjusted as needed, and unnecessary components of the regimen should be eliminated. If it is apparent that the patient's clinical status is not the result of bacterial infection, antimicrobials may be discontinued altogether. During the antimicrobial time-out, the indication and duration of antimicrobial therapy should be estimated and stated in the medical record.

Converting from intravenous to oral antimicrobial administration — Antimicrobial regimens should be converted from intravenous to oral administration as soon as is feasible and clinically indicated [22]. This intervention has been shown to decrease costs, facilitate discharges, and reduce complications associated with intravenous access without compromising clinical outcomes [23-27]. This transition is discussed further below. (See 'Transition from intravenous to oral therapy' below.)

Using the shortest effective duration of therapy — A critical element in the safe use of antimicrobials lies in restricting their administration to the minimum duration required for maximum efficacy. The appropriate durations of therapy are well studied for a number of infectious disease syndromes, such as pneumonia, Staphylococcus aureus infection, candidemia, and complicated intra-abdominal infections. Issues related to these syndromes are discussed separately. United States Centers for Disease Control and Prevention guidelines also recommend against the use of antibiotics for prophylaxis of surgical site infections after incision closure, even in the setting of retained drains [28]. (See "Antimicrobial approach to intra-abdominal infections in adults" and "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)

The use of serum procalcitonin measurements has been demonstrated to provide the clinician with confidence to discontinue therapy in critically ill patients with suspected bacterial pneumonia or undifferentiated sepsis [29-31]; in at least one study, this was associated with improved survival [29]. The use of procalcitonin in the management of respiratory tract infections is discussed separately. (See "Procalcitonin use in lower respiratory tract infections".)

Pharmacokinetic monitoring — Optimal antimicrobial dosing and administration necessitate adherence to relevant pharmacokinetic (PK)/pharmacodynamics principles. Individual PK monitoring and adjustment programs should be implemented for patients receiving aminoglycosides or vancomycin [1]. PK monitoring increases the likelihood of obtaining serum concentrations within the therapeutic range and reduces costs [32-34]. Some studies have also observed reductions in nephrotoxicity, length of stay, and mortality [32,35-37].

Dosing and monitoring of vancomycin and aminoglycoside are further discussed elsewhere. (See "Dosing and administration of parenteral aminoglycosides" and "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)


Core elements — Core elements of a hospital antimicrobial stewardship program as outlined by the United States Centers for Disease Control and Prevention (CDC) include [38]:

Leadership commitment – Leadership support is critical to the success of antimicrobial stewardship programs [39]. Resources must be allocated to personnel, financial, and information technology needs, and the program should report activities and outcomes regularly to senior executives and the hospital board.

Accountability – Program leader(s) who will be responsible for program outcomes must be identified. Some programs are coled by physicians and pharmacists.

Pharmacy expertise – A pharmacist leader should be identified.

Action – One or more actions should be implemented by the program. The 2019 CDC Core Elements highlight "priority interventions," including prospective audit and feedback, preauthorization, and facility-specific guidelines for common infections. (See 'Antimicrobial oversight' below.)

Tracking – Monitor antimicrobial use and resistance patterns. (See 'Stewardship program metrics' below.)

Reporting – Report information on antimicrobial use and resistance regularly to hospital personnel and leadership.

Education – Educate clinicians and patients about antimicrobial resistance and optimal use of antimicrobials.

In 2018, 85 percent of American acute care hospitals reported an antimicrobial stewardship program with all seven core elements (compared with 41 percent in 2014) [38]. Adherence to these core elements has been associated with a reduction in hospital-acquired C. difficile infections [40]. However, compliance with these elements may be affected by limited resources; therefore, consensus recommendations applicable to countries at all income levels have been developed [41]. The World Health Organization has released a practical antimicrobial stewardship program tool kit for low- and middle-income countries [42]. The CDC also released guidance for implementing antimicrobial stewardship in resource-limited settings [43]. These resources are particularly important since low- and middle-income countries play an important role in global antimicrobial consumption [44].

Similar principles may be applied to other settings, including long-term care facilities and nursing facilities [1]. The 2016 document "Antimicrobial Stewardship in Acute Care: A Practical Playbook" provides examples of how to implement these principles [11].

Staffing — The Antimicrobial Stewardship Task Force of the United States Department of Veterans Affairs tested and validated a staffing calculator to determine staffing needs for a comprehensive antimicrobial stewardship program [45]. It concluded that a robust antimicrobial stewardship program would require 1.0 pharmacist full-time equivalents (FTE) per 100 occupied beds and 0.25 physician FTE per 100 occupied beds. Thus, institutions with 301 to 500 beds would require 3 to 5 pharmacist FTEs and 0.75 to 1.25 physician FTEs.

A less rigorous cross-sectional survey (with only a 12 percent response rate) suggested that an institution with 301 to 500 beds would require 1.2 pharmacist FTE and 0.4 physician FTE [46].

STEWARDSHIP PROGRAM INTERVENTIONS — Many antimicrobial stewardship strategies have been shown to be effective [47,48]; programs should select interventions based on local antimicrobial utilization patterns, available resources, and expertise [49,50]. In initiating a program, it is important to focus efforts and, when possible, to avoid implementing multiple interventions at the same time [1]. The United States Centers for Disease Control and Prevention (CDC) guidelines prioritize three interventions: prospective audit and feedback (PAF), prior authorization, and facility-specific guidelines [38].

Antimicrobial oversight — Antimicrobial oversight is the foundation of any stewardship program and should include one or both of the following strategies [1,48,50]:

Prospective audit and feedback (PAF) – In programs that utilize PAF, trained staff (typically stewardship pharmacists or infectious disease physicians) review antimicrobial orders and provide verbal or written recommendations to prescribers regarding optimization of antimicrobial use. The intervention does not delay the first dose of antimicrobial therapy, and acceptance of recommendations is voluntary. With this approach, prescriber autonomy in clinical decision-making is preserved. Advantages and disadvantages of PAF are summarized in the table (table 1) and discussed further below. (See 'Prospective audit and feedback' below.)

Preauthorization – In programs that utilize preauthorization, approval is required (by an infectious disease physician or pharmacist) before certain antimicrobial agents may be administered [49,50]. In some programs, the availability of certain antimicrobial for specific indications is limited, and some antimicrobial may be rendered to a non-formulary status. This approach provides an opportunity to optimize the initial choice of antimicrobial therapy as well as an opportunity to educate individual prescribers about appropriate antimicrobial use, which may affect subsequent use. Advantages and disadvantages of preauthorization are summarized in the table (table 1) and discussed further below. (See 'Preauthorization' below.)

A few studies have compared these approaches. In one study, use of PAF was associated with greater reduction in antimicrobial utilization than use of preauthorization [51]. In another report, transition to PAF from preauthorization was associated with increased utilization of three broad-spectrum antimicrobials [52].

Few studies have assessed the combined efficacy of preauthorization and PAF. In one institution where preauthorization was required for targeted antimicrobials, retrospective review noted 30 percent of antimicrobial use was inappropriate despite preauthorization [53]. Another study noted that addition of preauthorization led to no significant reduction in vancomycin utilization beyond that attributed to the existing audit and feedback program [54].

Prospective audit and feedback — PAF is defined above (see 'Antimicrobial oversight' above). Advantages and disadvantages of PAF are summarized in the table (table 1).

PAF has been shown to reduce inappropriate antimicrobial use in multiple settings, including intensive care units, long-term care facilities, and pediatric and community hospitals as well as in outpatient clinics [55-58]. It has been associated with cost savings and, in some cases, reduction in hospital-acquired infections [47,56,57,59-61]. One study noted recommendation acceptance rates may improve when audit and feedback is part of an established stewardship program [59].

PAF is time and labor intensive, and the scope may be limited by available resources. Therefore, some programs target specific patient groups (eg, those in the intensive care unit or those receiving broad-spectrum, high-cost, toxic, or multiple antimicrobials) or use electronic systems to identify cases. One group optimized empiric antimicrobial theory with an automated algorithm that predicted the risk of a multidrug-resistant organism infection based upon a patient’s prior microbiologic data [62]. Thrice-weekly audit and feedback programs in community hospitals have been associated with reduced antimicrobial utilization and cost savings [60,61]. Once-weekly programs targeting asymptomatic bacteriuria in long-term care facility residents also reduced antimicrobial use [63]; however, a minority of recommendations were accepted, and the authors concluded that more frequent interventions would be more effective. Based on a meta-analysis of six observational studies including over 14,000 intensive care unit patients, no difference in mortality was observed despite reductions in antimicrobial use before and after the implementation of audit and feedback programs [64].

Face-to-face meetings with providers (known as "handshake stewardship") can increase the impact of PAF [65,66].

Preauthorization — Preauthorization is defined above (see 'Antimicrobial oversight' above). Advantages and disadvantages of preauthorization are summarized in the table (table 1).

Preauthorization has been shown to be effective in reducing antimicrobial use and cost [67-70]. Even in programs with high rates of antimicrobial approval, preauthorization has been associated with decreased utilization of targeted antimicrobials, suggesting preauthorization is also a passive barrier to prescribing [71]. The impact of preauthorization on antimicrobial resistance is mixed; some studies have demonstrated an association with improved antimicrobial susceptibilities [67,68,72,73], while others have shown no effect [74,75].

Preauthorization programs are often associated with a perceived imposition on prescriber autonomy in clinical decision-making [76]. Verbal misrepresentation of relevant clinical data may lead to inappropriate recommendations, so direct chart review is needed [77]. Preauthorization is time and labor intensive and requires around-the-clock coverage. Some programs with limited resources allow a first dose of antimicrobials in off-hours, with stewardship program review the following day [78]. Other programs focus preauthorization resources on certain antimicrobials that are misused commonly. Preauthorization can result in unintended increased use of other, nonrestricted antimicrobials ("squeezing the balloon"), mitigating the intervention's effect on overall antimicrobial use [79,80]. Thus, it is reasonable to monitor all antimicrobial use after implementation of formulary restriction.

Facility-specific clinical protocols — Antimicrobial stewardship programs should develop facility-specific clinical practice guidelines and pathways for common infections based on local epidemiology, susceptibility patterns, and drug availability or preference. These guidelines provide the foundation for both PAF and prior authorization by setting the standard for optimal antibiotic use for common indications at an institution. Infectious disease syndromes include community-acquired pneumonia, urinary tract infections, skin and soft tissue infections, fever, and neutropenia. Clinical pathways for surgical prophylaxis should include the choice of antimicrobials (narrowest spectrum to cover the most likely pathogens based upon surgical site), optimize dosing to allow for appropriate drug concentrations at the incision site (including weight-based dosing), and limit the duration of antibiotic exposure [1,49]. Implementation of inpatient pathways has been associated with more appropriate antimicrobial use and reduced length of hospital stay, readmission, and cost [81-86]. (See "Antimicrobial approach to intra-abdominal infections in adults".)

In many cases, clinical guidelines developed by national institutions are comprehensive, but their recommendations may be difficult to apply to individual patients. Institution-specific protocols can streamline information most relevant to daily practice into an easy-to-use format. Within these protocols, stewardship programs can highlight appropriate empiric therapy, reinforce de-escalation of antimicrobials based upon clinical and microbiologic data, encourage a switch from intravenous to oral therapy, and recommend an appropriate duration of therapy. One study found that the use of an algorithm-based management of patients with staphylococcal bacteremia was noninferior to routine clinical care and led to a two-day reduction in antibiotic duration overall [87]. Clinician involvement during the development process and promotion of the end product are critical. (See 'Tailoring antimicrobial therapy ("antimicrobial time-out")' above and 'Converting from intravenous to oral antimicrobial administration' above and 'Using the shortest effective duration of therapy' above and "Infection due to coagulase-negative staphylococci: Treatment" and "Clinical approach to Staphylococcus aureus bacteremia in adults" and "Antimicrobial approach to intra-abdominal infections in adults".)

Electronic decision support — Provision of decision support tools at the point of care have, in some cases, been demonstrated to be effective [88].

Point-of-care interventions by pharmacy — Inpatient point-of-care protocols can be used by pharmacists to optimize antimicrobial therapy, including dose optimization (eg, vancomycin dosing, extended infusion administration of beta-lactams), dose adjustments in the setting of organ dysfunction, and automatic conversion of intravenous to oral antimicrobial therapy. (See 'Pharmacokinetic monitoring' above.)

Transition from intravenous to oral therapy — Stewardship programs can develop a protocol defining the appropriate patients for this intervention, taking into account the indication for therapy, the suitability of the oral agent's coverage and bioavailability, the patient's clinical stability, and the patient's ability to tolerate oral or enteral medications. Pharmacy-driven protocols allow the pharmacist to make the transition in acceptable clinical situations for highly bioavailable antimicrobials (including fluoroquinolones, azithromycin, trimethoprim-sulfamethoxazole, metronidazole, fluconazole, and others) [1]. (See 'Converting from intravenous to oral antimicrobial administration' above.)

Prescriber-led review of antimicrobials — Stewardship programs can implement interventions that prompt clinicians to review antimicrobials in the absence of direct recommendations from antimicrobial stewardship programs (eg, antimicrobial stop dates, antimicrobial time-outs) [1]. (See 'Tailoring antimicrobial therapy ("antimicrobial time-out")' above.)

Antimicrobial allergy assessment — Antimicrobial allergy can complicate selection of appropriate antimicrobial therapy [89,90]. Patients with suspected antimicrobial allergy may receive suboptimal therapy and/or broader-spectrum antimicrobial therapy than necessary. In addition, patients with reported antimicrobial allergy have been observed to have longer hospital stay, increased risk for surgical site infection, greater likelihood of intensive care unit admissions, and higher rates of death than those without a reported antimicrobial allergy [91-93]. Patients labeled as penicillin allergic are significantly more likely to receive broad-spectrum antimicrobials and are at increased risk for infection due to C. difficile, vancomycin-resistant Enterococcus, and methicillin-resistant S. aureus than patients who are not labeled as penicillin allergic [94,95].

Collaborating with allergists is beneficial for implementation of routine antimicrobial allergy assessments to improve use of first-line antimicrobials [1,96,97]. Correcting an inaccurate antimicrobial allergy history in the medical record ("de-labeling") can be very useful for guiding subsequent decisions regarding a patient's antimicrobial therapy [98]. Increasing numbers of hospitals are developing decision-support tools to guide non-allergists in determining when patients labeled as penicillin allergic can safely receive penicillins and related antimicrobials. In addition, beta-lactam test dose protocols (for patients with a history of beta-lactam allergy) can also be used to reduce need for alternative antimicrobial agents [99]. (See "Choice of antibiotics in penicillin-allergic hospitalized patients", section on 'Our approach'.)

Many reported antimicrobial allergies are not confirmed by formal testing. In the case of penicillins, allergy evaluation will result in delabeling in >90 percent of patients. Penicillin skin testing in inpatient units and preoperative clinics has been associated with increased use of appropriate first-line antibiotics [96,99-106]. Evaluation of penicillin allergy also has economic benefit. In a study that analyzed 24 different economic models that accounted for differences in the diagnostic evaluation (skin testing versus no testing), setting (inpatient versus outpatient), and geographic region (United States versus Europe), evaluation was universally cost saving [107]. (See "Penicillin skin testing".)

Educating prescribers — Education is an important aspect of antimicrobial stewardship [1]. Effective education should target multiple groups with varied backgrounds, including pharmacy, advanced practice providers, nursing, and students. Educational outreach should be done regularly to both refresh and update the learners regarding principles of antimicrobial use and to reach new prescribers. Online education may be a way to ensure broad reach [108-110]. In addition, training programs should integrate antimicrobial stewardship program education in their core curriculum [1].

In one study evaluating education of clinicians about prudent use of antimicrobials, small-group education was more effective than interactive seminars, mailing campaigns, educational outreach visits, or dissemination of guidelines [111]. However, education alone may not lead to sustained change in behavior and is best performed in conjunction with antimicrobial oversight [112]. (See 'Antimicrobial oversight' above.)

Engaging staff — The presence of engaged infectious disease physicians is critical. One study evaluating 122 veteran affairs hospitals found that total antibiotic exposure and the use of broad-spectrum antibiotics were lower at site were infectious diseases specialists were present compared with sites without [113].

Nurses are important but underutilized members of the antimicrobial stewardship team [114]. Nurses can assist in intravenous to oral transitions, prompting "antibiotic timeouts" and optimizing the collection of specimens for microbiologic culture to avoid contamination [38], which may lead to suboptimal antibiotic use. (See 'Tailoring antimicrobial therapy ("antimicrobial time-out")' above and 'Converting from intravenous to oral antimicrobial administration' above.)

Reducing the incidence of C. difficile infection — Antimicrobial stewardship programs should implement interventions that reduce the incidence of C. difficile infection (CDI), in collaboration with infection control programs [1,115]. In general, CDI is a "two-hit" disease: it requires the acquisition of C. difficile and alteration of the intestinal microbiome, most often by exposure to antimicrobials.

It has been suggested that stewardship programs target the reduction of exposure to certain antimicrobials suggested to increase risk of CDI (such as fluoroquinolones, clindamycin, and cephalosporins). A population-based study in England found that a national decline in C. difficile infections was driven by the restriction of fluoroquinolones [116]. However, the risk associated with particular antimicrobials is best determined locally. In addition, almost all antimicrobials have been associated with the development of CDI; therefore, a general reduction of antimicrobial use is likely the optimal approach. On the other hand, retrospective data suggest that some antimicrobials, such as doxycycline, may actually protect against CDI [117-119].

Many stewardship program interventions have been shown to reduce the incidence of CDI when applied in conjunction with improved infection control measures. One study showed decreased CDI rates after implementation of multiple antimicrobial stewardship program interventions, including antimicrobial oversight (PAF), clinical guidelines, and encouraging shorter courses of therapy [120]. (See "Clostridioides difficile infection: Prevention and control", section on 'Antibiotic stewardship'.)

THE MICROBIOLOGY LABORATORY AND STEWARDSHIP — The clinical microbiology laboratory has an integral role in promoting appropriate antimicrobial use. The microbiology laboratory compiles antibiogram information at intervals (often annually) and makes decisions regarding implementation of rapid diagnostic tests in addition to ongoing communication with clinicians and infection control practitioners [121]. In some instances, selective reporting of susceptibility results by the microbiology laboratory may be a useful tool for guiding appropriate antimicrobial use [1,122]. Stewardship for diagnostic testing is also valuable (eg, ensuring appropriate use of microbiologic tests) [123].

Antibiogram — An antibiogram is a summary of antimicrobial susceptibility data for bacterial isolates recovered by a microbiology laboratory over a defined period of time (usually one year). Antibiograms may be used by clinicians to guide choice of empiric antimicrobial therapy and by stewardship programs to develop facility-specific clinical protocols and monitor resistance trends. The data are most useful when stratified by inpatient versus outpatient source, hospital site (eg, intensive care unit, general ward, emergency department) and population (eg, pediatric versus adult) [1].

The Clinical and Laboratory Standards Institute guideline on antibiogram preparation recommends the following [124]:

Analyze and present a cumulative antibiogram report at least annually.

Include only final, verified test results.

Include data for species with ≥30 isolates.

Include only diagnostic (not surveillance) cultures.

Eliminate duplicates by including only the first isolate of a species/patient/analysis period, irrespective of site or antimicrobial susceptibility profile.

Include only antimicrobial agents routinely tested and calculate the percent susceptible from results reported (as well as those that might be suppressed on patient reports using selective reporting rules); do not report supplemental agents selectively tested on resistant isolates only.

For Streptococcus pneumoniae and cefotaxime, ceftriaxone, and penicillin, list the percent susceptible using both meningitis and non-meningitis breakpoints; for penicillin, also indicate the percent susceptible using oral breakpoints.

For viridans group streptococci and penicillin, list both the percent intermediate and the percent susceptible.

For S. aureus, list the percent susceptible for all isolates and also the methicillin-resistant S. aureus (MRSA) subset.

Combination (contingent) antibiograms provide information about the likelihood that at least one drug in any combination of antimicrobials is active against a pathogen, thus providing better empiric coverage for the treatment of infection [125]. This provides the clinician with information allowing the optimal choice of combination antimicrobial therapy for likely or identified pathogens for which susceptibility data are not yet available. In addition, it provides an element of monitoring of multidrug resistance, something not provided by standard antibiograms.

A further iteration of the combination antibiogram is the weighted-incidence syndromic combination antibiogram (WISCA), which takes into account the body site from which an organism was recovered and provides a weighted susceptibility of all organisms causing a specific infection-related syndrome [126,127]. A study of critical care patients with ventilator-associated pneumonia or catheter-related bloodstream infections found that the use of WISCA provided significantly better empiric coverage advice than did a standard antibiogram, and this information was associated with earlier initiation of adequate antimicrobial coverage [127].

Combination antibiograms are especially helpful in dealing with infection due to multidrug-resistant organisms. Examples of their applications in the treatment of infections due to Pseudomonas aeruginosa [128] and carbapenemase-producing Enterobacteriaceae [129] have been published. The use of a unit-specific combination antibiogram of urine isolates (thus, a WISCA) has been described [130].

Nonculture-based diagnostic tools — Traditional microbiology techniques may delay prompt selection of appropriate antimicrobial therapy given the time required for culture incubation followed by organism identification and susceptibility testing.

In contrast, the use of rapid tests for diagnosis of bacterial, fungal, viral, and mycobacterial pathogens may facilitate earlier selection of tailored antimicrobial therapy and reduce the total duration of antimicrobial therapy [1,131]. Point-of-care tests available 24 hours, 7 days a week are optimal in this regard. One meta-analysis noted the available evidence is suggestive that rapid diagnostic techniques improve the timeliness of targeted antimicrobial therapy and, possibly, of outcomes in patients with bloodstream infections [132].

The laboratory and stewardship program must collaborate to assure rapid provision of test results to the clinician and that the clinician understands the implications of the results, particularly with regard to the optimization of antimicrobial therapy [133]. The procedures and their outcomes should be regularly reviewed and altered when appropriate.

Fungal markers are useful tests for immunocompromised patients at risk of invasive fungal disease to optimize antifungal use. (See "Diagnosis of invasive aspergillosis", section on 'Diagnostic modalities'.)

Procalcitonin may be useful in guiding decisions regarding need for continued antimicrobial therapy; this topic is discussed separately. (See 'Using the shortest effective duration of therapy' above and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'Serum biomarkers'.)

STEWARDSHIP PROGRAM METRICS — The optimal metrics for monitoring stewardship programs are uncertain. Traditionally, programs have focused on antimicrobial use and cost savings; focusing on process and outcome measures may better illustrate a program's value and sustainability (table 2) [49,134,135].

Stewardship programs must select a benchmarking source; examples include baseline institutional data prior to implementation of the stewardship programs or data from comparative institutions. The United States Centers for Disease Control and Prevention (CDC) Antibiotic Use (AU) option collects and reports antimicrobial utilization data through the National Healthcare Safety Network; participation is voluntary. The CDC developed the Standardized Antimicrobial Administration Ration, an observed to predicted ratio endorsed by the National Quality Forum, to provide a standardized risk-adjusted benchmark of antimicrobial use [136].

Measuring antimicrobial use and cost savings — Antimicrobial use may be estimated in days of therapy (DOT) or defined daily dose (DDD); use of DOT is preferred [1].

DOT is an aggregate sum of days for which any amount of a specific antimicrobial agent is administered to a particular patient (numerator) divided by a standardized denominator. DOT refers to the number of days a patient receives an antimicrobial, regardless of the dose administered. Therefore, the calculation can be distorted if a patient receives more than one antimicrobial agent (for example, if a patient receives 2 antimicrobials for 7 days, the DOT equals 14) or if a patient receives antimicrobials administered every other day. DOT can be used for both pediatric and adult populations. Cost cannot be calculated easily based on DOT because dose is not included. The CDC AU option collects and reports DOT.

DDD aggregates the total number of grams of each antimicrobial administered during a period of time divided by a standard DDD designated by the World Health Organization (WHO). Because the data needed are typically available from the pharmacy, it is relatively easy to calculate. However, DDD underestimates the antimicrobial exposure in patients with renal failure and does not account for weight-based dosing, making this metric inappropriate for pediatric populations.

Cost should be assessed according to drugs administered or prescribed (not just purchased) and should be normalized for census [1].

Process measures — Process measures include evaluating the way antimicrobials are used and the utility of the antimicrobial oversight measures (table 2). The CDC prioritizes the following process measures:

Types and acceptance of prospective audit and feedback recommendations

Utilization of restricted antibiotics that require prior authorization to ensure avoidance of clinically significant treatment delays

Frequency with which clinical practice is concordant with local guidelines for a specific condition (eg, choice of empiric therapy, appropriate duration of therapy for community-acquired pneumonia)

Other process measures include:

Frequency with which cultures were drawn from sterile sites (eg, blood cultures, urine cultures) prior to the initiation of empiric antimicrobial therapy

Frequency with which antimicrobial indication and expected duration are documented when an antimicrobial is prescribed

Frequency antimicrobials are adjusted in response to microbiologic data (eg, an "antimicrobial time-out")

Frequency of bug-drug mismatch

Proportion of eligible patients switched from intravenous to oral therapy

Outcome measures — Outcome measures in patients treated with antimicrobials for infectious disease syndromes include the following (table 2):

Hospital and intensive care unit length of stay

Readmission rates

Number of patients with infection due to multidrug-resistant organisms

Mortality due to infection

C. difficile infection rates (hospital acquired versus all)

Emergence of antimicrobial resistance over time

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Antimicrobial stewardship".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: What you should know about antibiotics (The Basics)")


Antimicrobial stewardship refers to systematic measurement and coordinated interventions designed to promote optimal use of antimicrobial agents, by advocating selection of appropriate antimicrobial drug regimens (including dosing, duration of therapy, and route of administration). (See 'Introduction' above.)

The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use (including toxicity, selection of pathogenic organisms such as Clostridioides difficile, and the emergence of antimicrobial resistance). (See 'Introduction' above.)

In general, management of patients with suspected or proven bacterial infection consists of initiation of empiric therapy (ie, prior to availability of definitive microbiology data), followed by adjustment once microbiology data become available. (See 'Initiating empiric therapy' above and 'Tailoring antimicrobial therapy ("antimicrobial time-out")' above.)

Antimicrobial oversight should include prospective audit and feedback (PAF), preauthorization, or both (table 1). In programs that use PAF, trained staff review antimicrobial orders and advise regarding optimization of antimicrobial use. In programs that use preauthorization, approval is required before certain agents may be administered. (See 'Antimicrobial oversight' above.)

Antimicrobial stewardship programs should develop facility-specific clinical practice guidelines for common infections based on local epidemiology, susceptibility patterns, and drug availability or preference. (See 'Facility-specific clinical protocols' above.)

Pharmacy-led interventions can be used by pharmacists to optimize antimicrobial therapy, including dose optimization (eg, vancomycin dosing) and systematic conversion of intravenous to oral antimicrobial therapy. (See 'Point-of-care interventions by pharmacy' above.)

Correcting an inaccurate antimicrobial allergy history in the medical record can be very useful for guiding subsequent decisions regarding a patient's antimicrobial therapy. (See 'Antimicrobial allergy assessment' above and "Penicillin skin testing".)

The clinical microbiology laboratory has an integral role in promoting appropriate antimicrobial use, by providing ongoing culture results and susceptibility data, preparing an annual antibiogram, and providing guidance regarding implementation and interpretation of rapid diagnostic tests. (See 'The microbiology laboratory and stewardship' above.)

The optimal metrics for monitoring stewardship programs are uncertain. Traditionally, programs have focused on antimicrobial use and cost savings; focusing on outcome and process measures may better illustrate a program's value and sustainability (table 2). (See 'Stewardship program metrics' above.)

  1. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016; 62:e51.
  2. Society for Healthcare Epidemiology of America, Infectious Diseases Society of America, Pediatric Infectious Diseases Society. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol 2012; 33:322.
  3. Johnson MD, Lewis RE, Dodds Ashley ES, et al. Core Recommendations for Antifungal Stewardship: A Statement of the Mycoses Study Group Education and Research Consortium. J Infect Dis 2020; 222:S175.
  4. Hamada Y, Ueda T, Miyazaki Y, et al. Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan. Mycoses 2020; 63:779.
  5. Jorgenson MR, Descourouez JL, Wong C, et al. Cytomegalovirus antiviral stewardship in the COVID-19 Era: Increasing complexity of prophylaxis and treatment and potential mitigation strategies. Transpl Infect Dis 2021; 23:e13586.
  6. Koren DE, Scarsi KK, Farmer EK, et al. A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine. Clin Infect Dis 2020; 70:2241.
  7. Centers for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs. (Accessed on March 16, 2021).
  8. Centers for Disease Control and Prevention. The Core Elements of Hospital Antibiotic Stewardship Programs. (Accessed on March 16, 2021).
  9. Centers for Disease Control and Prevention. The Core Elements of Hospital Antibiotic Stewardship Programs: Checklist. (Accessed on March 16, 2021).
  10. Centers for Diseaes Control and Prevention. Antibiotic Prescribing and Use. (Accessed on March 16, 2021).
  11. National Quality Forum. Antibiotic Stewardship in Acute Care: A Practical Playbook. NQF, Washington, DC 2016. (Accessed on March 16, 2021).
  12. Goff DA, Kullar R, Bauer KA, File TM Jr. Eight Habits of Highly Effective Antimicrobial Stewardship Programs to Meet the Joint Commission Standards for Hospitals. Clin Infect Dis 2017; 64:1134.
  13. Stenehjem E, Hyun DY, Septimus E, et al. Antibiotic Stewardship in Small Hospitals: Barriers and Potential Solutions. Clin Infect Dis 2017; 65:691.
  14. Centers for Disease Control and Prevention. Implementation of Antibiotic Stewardship Core Elements at Small and Critical Access Hospitals. (Accessed on March 17, 2021).
  15. Tamma PD, Avdic E, Li DX, et al. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med 2017; 177:1308.
  16. Meek RW, Vyas H, Piddock LJ. Nonmedical Uses of Antibiotics: Time to Restrict Their Use? PLoS Biol 2015; 13:e1002266.
  17. Rashid MU, Zaura E, Buijs MJ, et al. Determining the Long-term Effect of Antibiotic Administration on the Human Normal Intestinal Microbiota Using Culture and Pyrosequencing Methods. Clin Infect Dis 2015; 60 Suppl 2:S77.
  18. Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. J Clin Invest 2014; 124:4212.
  19. Antibiotic Resistance Threats in the United States, 2019. Centers for Disease Control and Prevention. Available at: (Accessed on March 17, 2021).
  20. Deresinski S. Principles of antibiotic therapy in severe infections: optimizing the therapeutic approach by use of laboratory and clinical data. Clin Infect Dis 2007; 45 Suppl 3:S177.
  21. Tamma PD, Miller MA, Cosgrove SE. Rethinking How Antibiotics Are Prescribed: Incorporating the 4 Moments of Antibiotic Decision Making Into Clinical Practice. JAMA 2019; 321:139.
  22. Goff DA, Bauer KA, Reed EE, et al. Is the "low-hanging fruit" worth picking for antimicrobial stewardship programs? Clin Infect Dis 2012; 55:587.
  23. Jones M, Huttner B, Madaras-Kelly K, et al. Parenteral to oral conversion of fluoroquinolones: low-hanging fruit for antimicrobial stewardship programs? Infect Control Hosp Epidemiol 2012; 33:362.
  24. Sevinç F, Prins JM, Koopmans RP, et al. Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital. J Antimicrob Chemother 1999; 43:601.
  25. Mertz D, Koller M, Haller P, et al. Outcomes of early switching from intravenous to oral antibiotics on medical wards. J Antimicrob Chemother 2009; 64:188.
  26. Omidvari K, de Boisblanc BP, Karam G, et al. Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis. Respir Med 1998; 92:1032.
  27. Laing RB, Mackenzie AR, Shaw H, et al. The effect of intravenous-to-oral switch guidelines on the use of parenteral antimicrobials in medical wards. J Antimicrob Chemother 1998; 42:107.
  28. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg 2017; 152:784.
  29. de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16:819.
  30. Bréchot N, Hékimian G, Chastre J, Luyt CE. Procalcitonin to guide antibiotic therapy in the ICU. Int J Antimicrob Agents 2015; 46 Suppl 1:S19.
  31. Rowland T, Hilliard H, Barlow G. Procalcitonin: potential role in diagnosis and management of sepsis. Adv Clin Chem 2015; 68:71.
  32. Kemme DJ, Daniel CI. Aminoglycoside dosing: a randomized prospective study. South Med J 1993; 86:46.
  33. Leehey DJ, Braun BI, Tholl DA, et al. Can pharmacokinetic dosing decrease nephrotoxicity associated with aminoglycoside therapy. J Am Soc Nephrol 1993; 4:81.
  34. Fernández de Gatta MD, Calvo MV, Hernández JM, et al. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin Pharmacol Ther 1996; 60:332.
  35. Bartal C, Danon A, Schlaeffer F, et al. Pharmacokinetic dosing of aminoglycosides: a controlled trial. Am J Med 2003; 114:194.
  36. Bond CA, Raehl CL. Clinical and economic outcomes of pharmacist-managed aminoglycoside or vancomycin therapy. Am J Health Syst Pharm 2005; 62:1596.
  37. Whipple JK, Ausman RK, Franson T, Quebbeman EJ. Effect of individualized pharmacokinetic dosing on patient outcome. Crit Care Med 1991; 19:1480.
  38. Core Elements of Hospital Antibiotic Stewardship Programs. Centers for Disease Control and Prevention. Available at: (Accessed on March 19, 2021).
  39. Spellberg B, Bartlett JG, Gilbert DN. How to Pitch an Antibiotic Stewardship Program to the Hospital C-Suite. Open Forum Infect Dis 2016; 3:ofw210.
  40. Garcia Reeves AB, Lewis JW, Trogdon JG, et al. Association between statewide adoption of the CDC's Core Elements of Hospital Antimicrobial Stewardship Programs and rates of methicillin-resistant Staphylococcus aureus bacteremia and Clostridioides difficile infection in the United States. Infect Control Hosp Epidemiol 2020; 41:430.
  41. Pulcini C, Binda F, Lamkang AS, et al. Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach. Clin Microbiol Infect 2019; 25:20.
  42. Antimicrobial stewardship programmes in health-care facilities in low-and middle-income countries: a WHO practical toolkit. Centers for Disease Control and Prevention. Available at: (Accessed on March 19, 2021).
  43. Centers for Disease Control and Prevention. Core Elements of Human Antibiotic Stewardship Programs in Resource-Limited Settings. (Accessed on March 16, 2021).
  44. Klein EY, Van Boeckel TP, Martinez EM, et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci U S A 2018; 115:E3463.
  45. Echevarria K, Groppi J, Kelly AA, et al. Development and application of an objective staffing calculator for antimicrobial stewardship programs in the Veterans Health Administration. Am J Health Syst Pharm 2017; 74:1785.
  46. Doernberg SB, Abbo LM, Burdette SD, et al. Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting. Clin Infect Dis 2018; 67:1168.
  47. Centers for Disease Control and Prevention. Implementation Resources. (Accessed on March 16, 2021).
  48. Davey P, Marwick CA, Scott CL, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2017; 2:CD003543.
  49. Centers for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs. (Accessed on March 16, 2021).
  50. 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.
  51. Tamma PD, Avdic E, Keenan JF, et al. What Is the More Effective Antibiotic Stewardship Intervention: Preprescription Authorization or Postprescription Review With Feedback? Clin Infect Dis 2017; 64:537.
  52. Mehta JM, Haynes K, Wileyto EP, et al. Comparison of prior authorization and prospective audit with feedback for antimicrobial stewardship. Infect Control Hosp Epidemiol 2014; 35:1092.
  53. Cosgrove SE, Patel A, Song X, et al. Impact of different methods of feedback to clinicians after postprescription antimicrobial review based on the Centers For Disease Control and Prevention's 12 Steps to Prevent Antimicrobial Resistance Among Hospitalized Adults. Infect Control Hosp Epidemiol 2007; 28:641.
  54. Chan S, Hossain J, Di Pentima MC. Implications and impact of prior authorization policy on vancomycin use at a tertiary pediatric teaching hospital. Pediatr Infect Dis J 2015; 34:506.
  55. Di Pentima MC, Chan S, Hossain J. Benefits of a pediatric antimicrobial stewardship program at a children's hospital. Pediatrics 2011; 128:1062.
  56. Di Pentima MC, Chan S. Impact of antimicrobial stewardship program on vancomycin use in a pediatric teaching hospital. Pediatr Infect Dis J 2010; 29:707.
  57. Newland JG, Stach LM, De Lurgio SA, et al. Impact of a Prospective-Audit-With-Feedback Antimicrobial Stewardship Program at a Children's Hospital. J Pediatric Infect Dis Soc 2012; 1:179.
  58. Meeker D, Linder JA, Fox CR, et al. Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing Among Primary Care Practices: A Randomized Clinical Trial. JAMA 2016; 315:562.
  59. Cosgrove SE, Seo SK, Bolon MK, et al. Evaluation of postprescription review and feedback as a method of promoting rational antimicrobial use: a multicenter intervention. Infect Control Hosp Epidemiol 2012; 33:374.
  60. LaRocco A Jr. Concurrent antibiotic review programs--a role for infectious diseases specialists at small community hospitals. Clin Infect Dis 2003; 37:742.
  61. Vettese N, Hendershot J, Irvine M, et al. Outcomes associated with a thrice-weekly antimicrobial stewardship programme in a 253-bed community hospital. J Clin Pharm Ther 2013; 38:401.
  62. Elligsen M, Pinto R, Leis JA, et al. Using Prior Culture Results to Improve Initial Empiric Antibiotic Prescribing: An Evaluation of a Simple Clinical Heuristic. Clin Infect Dis 2021; 72:e630.
  63. Doernberg SB, Dudas V, Trivedi KK. Implementation of an antimicrobial stewardship program targeting residents with urinary tract infections in three community long-term care facilities: a quasi-experimental study using time-series analysis. Antimicrob Resist Infect Control 2015; 4:54.
  64. Lindsay PJ, Rohailla S, Taggart LR, et al. Antimicrobial Stewardship and Intensive Care Unit Mortality: A Systematic Review. Clin Infect Dis 2019; 68:748.
  65. MacBrayne CE, Williams MC, Levek C, et al. Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later. Clin Infect Dis 2020; 70:2325.
  66. Moghnieh R, Awad L, Abdallah D, et al. Effect of a "handshake" stewardship program versus a formulary restriction policy on High-End antibiotic use, expenditure, antibiotic resistance, and patient outcome. J Chemother 2020; 32:368.
  67. 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.
  68. Pakyz AL, Oinonen M, Polk RE. Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 2009; 53:1983.
  69. Lewis GJ, Fang X, Gooch M, Cook PP. Decreased resistance of Pseudomonas aeruginosa with restriction of ciprofloxacin in a large teaching hospital's intensive care and intermediate care units. Infect Control Hosp Epidemiol 2012; 33:368.
  70. Buising KL, Thursky KA, Robertson MB, et al. Electronic antibiotic stewardship--reduced consumption of broad-spectrum antibiotics using a computerized antimicrobial approval system in a hospital setting. J Antimicrob Chemother 2008; 62:608.
  71. Reed EE, Stevenson KB, West JE, et al. Impact of formulary restriction with prior authorization by an antimicrobial stewardship program. Virulence 2013; 4:158.
  72. Quale J, Landman D, Saurina G, et al. Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis 1996; 23:1020.
  73. Lima AL, Oliveira PR, Paula AP, et al. Carbapenem stewardship: positive impact on hospital ecology. Braz J Infect Dis 2011; 15:1.
  74. Lautenbach E, LaRosa LA, Marr AM, et al. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Clin Infect Dis 2003; 36:440.
  75. Toltzis P, Yamashita T, Vilt L, et al. Antibiotic restriction does not alter endemic colonization with resistant gram-negative rods in a pediatric intensive care unit. Crit Care Med 1998; 26:1893.
  76. Seemungal IA, Bruno CJ. Attitudes of housestaff toward a prior-authorization-based antibiotic stewardship program. Infect Control Hosp Epidemiol 2012; 33:429.
  77. Linkin DR, Fishman NO, Landis JR, et al. Effect of communication errors during calls to an antimicrobial stewardship program. Infect Control Hosp Epidemiol 2007; 28:1374.
  78. LaRosa LA, Fishman NO, Lautenbach E, et al. Evaluation of antimicrobial therapy orders circumventing an antimicrobial stewardship program: investigating the strategy of "stealth dosing". Infect Control Hosp Epidemiol 2007; 28:551.
  79. Burke JP. Antibiotic resistance--squeezing the balloon? JAMA 1998; 280:1270.
  80. 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.
  81. Carratalà J, Garcia-Vidal C, Ortega L, et al. Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial. Arch Intern Med 2012; 172:922.
  82. Worrall CL, Anger BP, Simpson KN, Leon SM. Impact of a hospital-acquired/ventilator-associated/healthcare-associated pneumonia practice guideline on outcomes in surgical trauma patients. J Trauma 2010; 68:382.
  83. Hauck LD, Adler LM, Mulla ZD. Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia. Ann Epidemiol 2004; 14:669.
  84. Newman RE, Hedican EB, Herigon JC, et al. Impact of a guideline on management of children hospitalized with community-acquired pneumonia. Pediatrics 2012; 129:e597.
  85. Neuman MI, Hall M, Hersh AL, et al. Influence of hospital guidelines on management of children hospitalized with pneumonia. Pediatrics 2012; 130:e823.
  86. Jenkins TC, Irwin A, Coombs L, et al. Effects of clinical pathways for common outpatient infections on antibiotic prescribing. Am J Med 2013; 126:327.
  87. Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial. JAMA 2018; 320:1249.
  88. Ridgway JP, Robicsek A, Shah N, et al. A Randomized Controlled Trial of an Electronic Clinical Decision Support Tool for Inpatient Antimicrobial Stewardship. Clin Infect Dis 2021; 72:e265.
  89. MacFadden DR, LaDelfa A, Leen J, et al. Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study. Clin Infect Dis 2016; 63:904.
  90. Sakoulas G, Geriak M, Nizet V. Is a Reported Penicillin Allergy Sufficient Grounds to Forgo the Multidimensional Antimicrobial Benefits of β-Lactam Antibiotics? Clin Infect Dis 2019; 68:157.
  91. Charneski L, Deshpande G, Smith SW. Impact of an antimicrobial allergy label in the medical record on clinical outcomes in hospitalized patients. Pharmacotherapy 2011; 31:742.
  92. Blumenthal KG, Ryan EE, Li Y, et al. The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk. Clin Infect Dis 2018; 66:329.
  93. Huang KG, Cluzet V, Hamilton K, Fadugba O. The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With Hematologic Malignancies Requiring Antibiotics. Clin Infect Dis 2018; 67:27.
  94. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin "allergy" in hospitalized patients: A cohort study. J Allergy Clin Immunol 2014; 133:790.
  95. Blumenthal KG, Lu N, Zhang Y, et al. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ 2018; 361:k2400.
  96. Leis JA, Palmay L, Ho G, et al. Point-of-Care β-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation. Clin Infect Dis 2017; 65:1059.
  97. Blumenthal KG, Shenoy ES, Wolfson AR, et al. Addressing Inpatient Beta-Lactam Allergies: A Multihospital Implementation. J Allergy Clin Immunol Pract 2017; 5:616.
  98. Ressner RA, Gada SM, Banks TA. Antimicrobial Stewardship and the Allergist: Reclaiming our Antibiotic Armamentarium. Clin Infect Dis 2016; 62:400.
  99. Blumenthal KG, Shenoy ES, Varughese CA, et al. Impact of a clinical guideline for prescribing antibiotics to inpatients reporting penicillin or cephalosporin allergy. Ann Allergy Asthma Immunol 2015; 115:294.
  100. Unger NR, Gauthier TP, Cheung LW. Penicillin skin testing: potential implications for antimicrobial stewardship. Pharmacotherapy 2013; 33:856.
  101. Forrest DM, Schellenberg RR, Thien VV, et al. Introduction of a practice guideline for penicillin skin testing improves the appropriateness of antibiotic therapy. Clin Infect Dis 2001; 32:1685.
  102. Arroliga ME, Radojicic C, Gordon SM, et al. A prospective observational study of the effect of penicillin skin testing on antibiotic use in the intensive care unit. Infect Control Hosp Epidemiol 2003; 24:347.
  103. del Real GA, Rose ME, Ramirez-Atamoros MT, et al. Penicillin skin testing in patients with a history of beta-lactam allergy. Ann Allergy Asthma Immunol 2007; 98:355.
  104. Raja AS, Lindsell CJ, Bernstein JA, et al. The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency department setting. Ann Emerg Med 2009; 54:72.
  105. Trubiano JA, Thursky KA, Stewardson AJ, et al. Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation. Clin Infect Dis 2017; 65:166.
  106. Rimawi RH, Cook PP, Gooch M, et al. The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med 2013; 8:341.
  107. Sousa-Pinto B, Blumenthal KG, Macy E, et al. Penicillin Allergy Testing Is Cost-Saving: An Economic Evaluation Study. Clin Infect Dis 2021; 72:924.
  108. Rocha-Pereira N, Lafferty N, Nathwani D. Educating healthcare professionals in antimicrobial stewardship: can online-learning solutions help? J Antimicrob Chemother 2015; 70:3175.
  109. Standford Center for Continuing Medical Education. Optimizing Antimicrobial Therapy with Timeouts: Online CME/CPE Course. (Accessed on March 16, 2021).
  110. Future Learn. Antimicrobial Stewardship: Managing Antibiotic Resistance - Free Online Course. (Accessed on March 16, 2021).
  111. Lee CR, Lee JH, Kang LW, et al. Educational effectiveness, target, and content for prudent antibiotic use. Biomed Res Int 2015; 2015:214021.
  112. Landgren FT, Harvey KJ, Mashford ML, et al. Changing antibiotic prescribing by educational marketing. Med J Aust 1988; 149:595.
  113. Livorsi DJ, Nair R, Lund BC, et al. Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists. Clin Infect Dis 2021; 72:1810.
  114. Redefining the Antibiotic Stewardship Team: Recommendations from the American Nurses Association/Centers for Disease Control and Prevention Workgroup on the Role of Registered Nurses in Hospital Antibiotic Stewardship Practices. American Association of Colleges of Nursing and the Centers for Disease Control. Available at: (Accessed on March 19, 2021).
  115. Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis 2017; 17:990.
  116. Dingle KE, Didelot X, Quan TP, et al. Effects of control interventions on Clostridium difficile infection in England: an observational study. Lancet Infect Dis 2017; 17:411.
  117. Hung YP, Lee JC, Lin HJ, et al. Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection. Antibiotics (Basel) 2015; 4:216.
  118. Turner RB, Smith CB, Martello JL, Slain D. Role of doxycycline in Clostridium difficile infection acquisition. Ann Pharmacother 2014; 48:772.
  119. Doernberg SB, Winston LG, Deck DH, Chambers HF. Does doxycycline protect against development of Clostridium difficile infection? Clin Infect Dis 2012; 55:615.
  120. Valiquette L, Cossette B, Garant MP, et al. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007; 45 Suppl 2:S112.
  121. Avdic E, Carroll KC. The role of the microbiology laboratory in antimicrobial stewardship programs. Infect Dis Clin North Am 2014; 28:215.
  122. Langford BJ, Seah J, Chan A, et al. Antimicrobial Stewardship in the Microbiology Laboratory: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and Susceptibility of Gram-Negative Isolates to Ciprofloxacin in a Hospital Setting. J Clin Microbiol 2016; 54:2343.
  123. Fabre V, Klein E, Salinas AB, et al. A Diagnostic Stewardship Intervention To Improve Blood Culture Use among Adult Nonneutropenic Inpatients: the DISTRIBUTE Study. J Clin Microbiol 2020; 58.
  124. Clinical and Laboratory Standards Institute. M39QG - Antibiograms: Developing Cumulative Reports for Your Clinicians. (Accessed on March 16, 2021).
  125. Liang B, Wheeler JS, Blanchette LM. Impact of Combination Antibiogram and Related Education on Inpatient Fluoroquinolone Prescribing Patterns for Patients With Health Care-Associated Pneumonia. Ann Pharmacother 2016; 50:172.
  126. Hebert C, Ridgway J, Vekhter B, et al. Demonstration of the weighted-incidence syndromic combination antibiogram: an empiric prescribing decision aid. Infect Control Hosp Epidemiol 2012; 33:381.
  127. Randhawa V, Sarwar S, Walker S, et al. Weighted-incidence syndromic combination antibiograms to guide empiric treatment of critical care infections: a retrospective cohort study. Crit Care 2014; 18:R112.
  128. Smith ZR, Tajchman SK, Dee BM, et al. Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in an oncology population. J Oncol Pharm Pract 2016; 22:409.
  129. Hsu AJ, Carroll KC, Milstone AM, et al. The Use of a Combination Antibiogram to Assist with the Selection of Appropriate Antimicrobial Therapy for Carbapenemase-Producing Enterobacteriaceae Infections. Infect Control Hosp Epidemiol 2015; 36:1458.
  130. Rabs N, Wieczorkiewicz SM, Costello M, Zamfirova I. Development of a urinary-specific antibiogram for gram-negative isolates: impact of patient risk factors on susceptibility. Am J Infect Control 2014; 42:393.
  131. Bauer KA, Perez KK, Forrest GN, Goff DA. Review of rapid diagnostic tests used by antimicrobial stewardship programs. Clin Infect Dis 2014; 59 Suppl 3:S134.
  132. Buehler SS, Madison B, Snyder SR, et al. Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis. Clin Microbiol Rev 2016; 29:59.
  133. Luther VP. The Essential Role of Clinical Microbiology Laboratories in Antimicrobial Stewardship. Clin Lab News 2014. (Accessed on March 16, 2021).
  134. Morris AM, Brener S, Dresser L, et al. Use of a structured panel process to define quality metrics for antimicrobial stewardship programs. Infect Control Hosp Epidemiol 2012; 33:500.
  135. Morris AM. Antimicrobial Stewardship Programs: Appropriate Measures and Metrics to Study their Impact. Curr Treat Options Infect Dis 2014; 6:101.
  136. van Santen KL, Edwards JR, Webb AK, et al. The Standardized Antimicrobial Administration Ratio: A New Metric for Measuring and Comparing Antibiotic Use. Clin Infect Dis 2018; 67:179.
Topic 13943 Version 46.0