Antimicrobial stewardship in hospital settings

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 for all patients including patients who are critically ill or immunocompromised [1-5]. This applies not only to antibacterial agents, but antifungals [6,7], antivirals, and antiretrovirals [8,9] as well. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use. Additional goals 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) require implementation of antimicrobial stewardship programs in United States health care facilities that receive CMS funding and/or Joint Commission accreditation [10-13]. 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 [14,15]. 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 [16]. The CDC guidelines for the implementation of antimicrobial stewardship programs in small and critical access hospitals provide examples of how to overcome these barriers [17]. 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 [18].

Antimicrobial misuse is widespread and has potentially profound adverse effects [19]. 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 [20,21].

The United States Centers for Disease Control and Prevention (CDC) 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 [22]. Rates of multidrug-resistant organisms in United States hospitals is increasing and was especially noted during the COVID-19 pandemic [23].

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 [24,25].

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

●Determining that antibiotics are indicated

●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

●Initiating antimicrobial therapy as promptly as possible, especially in the presence of sepsis

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), an "antimicrobial time-out" should be performed that involves reviewing clinical and microbiology results and adjusting antimicrobial therapy 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 when clinically indicated and as soon as feasible [26]. This intervention has been shown to decrease costs, facilitate discharges, and reduce complications associated with intravenous access without compromising clinical outcomes [27-31]. This transition is further discussed 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 (CDC) guidelines also recommend against the use of antibiotics for prophylaxis of surgical site infections after incision closure for most procedures, even in the setting of retained drains [32]. (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 [33-35]; in at least one study, this was associated with improved survival [33]. 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 [36-38]. Some studies have also observed reductions in nephrotoxicity, length of stay, and mortality [36,39-41].

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".)

ESTABLISHING A STEWARDSHIP PROGRAM

Core elements — Core elements of a hospital antimicrobial stewardship program as outlined by the United States Centers for Disease Control and Prevention (CDC) include [42]:

●Leadership commitment – Leadership support is critical to the success of antimicrobial stewardship programs [43]. 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 co-led 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 2021, 95 percent of American acute care hospitals reported having an antimicrobial stewardship program with all seven core elements (compared with 41 percent in 2014) [42]. Adherence to these core elements has been associated with a reduction in hospital-acquired C. difficile infections [44]. However, compliance with these elements may be affected by resource limitation and, consequently, consensus recommendations applicable to countries at all income levels have been developed [45]. The World Health Organization has released a practical antimicrobial stewardship program tool kit for low- and middle-income countries [46,47]. The CDC also released guidance for implementing antimicrobial stewardship in resource-limited settings [48]. These resources are particularly important since low- and middle-income countries play an important role in global antimicrobial consumption [49].

Similar principles may be applied to other settings, including long-term care facilities and nursing facilities [1].

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 [50]. 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 [51].

STEWARDSHIP PROGRAM INTERVENTIONS — Many antimicrobial stewardship strategies have been shown to be effective [52,53]; programs should select interventions based on local antimicrobial utilization patterns, available resources, and expertise [54,55]. 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 [42].

Antimicrobial oversight — Antimicrobial oversight is the foundation of any stewardship program and should include one or both of the following strategies [1,53,55]:

●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 [54,55]. In some programs, the availability of certain antimicrobials for specific indications is limited, and some antimicrobials 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 [56]. In another report, transition to PAF from preauthorization was associated with increased utilization of three broad-spectrum antimicrobials [57].

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 [58]. 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 [59].

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 [60-63]. It has been associated with cost savings and, in some cases, reduction in hospital-acquired infections [52,61,62,64-66]. One study noted recommendation acceptance rates may improve when audit and feedback is part of an established stewardship program [64].

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 [67]. Thrice-weekly audit and feedback programs in community hospitals have been associated with reduced antimicrobial utilization and cost savings [65,66]. Once-weekly programs targeting asymptomatic bacteriuria in long-term care facility residents also reduced antimicrobial use [68]; 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 [69].

Face-to-face meetings with providers (known as "handshake stewardship") can increase the impact of PAF [70,71].

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 [72-75]. 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 [76]. The impact of preauthorization on antimicrobial resistance is mixed; some studies have demonstrated an association with improved antimicrobial susceptibilities [72,73,77,78], while others have shown no effect [79,80].

Preauthorization programs are often associated with a perceived imposition on prescriber autonomy in clinical decision-making [81]. Verbal misrepresentation of relevant clinical data may lead to inappropriate recommendations, so direct chart review is needed [82]. 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 [83]. 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 [84,85]. 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 [1,54]. Implementation of inpatient pathways has been associated with more appropriate antimicrobial use and reduced length of hospital stay, readmission, and cost [86-91]. (See "Antimicrobial approach to intra-abdominal infections in adults".)

In many cases, clinical guidelines developed by national organizations 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 [92]. 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 [93].

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 [94,95]. 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 [96-98]. 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 [99,100].

Collaborating with allergists is beneficial for implementation of routine antimicrobial allergy assessments to improve use of first-line antimicrobials [1,101,102]. 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 [103]. 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 [104]. (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 de-labeling 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 [101,104-111]. 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 [112]. (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 [113-115]. 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 [116]. However, education alone may not lead to sustained change in behavior and is best performed in conjunction with antimicrobial oversight [117]. (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 sites where infectious diseases specialists were present compared with sites without [118].

Nurses are important but underutilized members of the antimicrobial stewardship team [119]. Nurses can assist in intravenous to oral transitions, prompting "antibiotic timeouts" and optimizing the collection of specimens for microbiologic culture to avoid contamination [42], 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 [1,120]. In general, CDI is a "two-hit" disease: it requires the acquisition of toxin-positive 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 [121]. 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 [122-124].

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 [125]. (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 [126]. In some instances, selective reporting of susceptibility results by the microbiology laboratory may be a useful tool for guiding appropriate antimicrobial use [1,127]. Stewardship for diagnostic testing is also valuable (eg, ensuring appropriate use of microbiologic tests) [128].

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 [129]:

●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 [130]. 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 [131,132]. 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 [132].

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 [133] and carbapenemase-producing Enterobacterales [134] have been published. The use of a unit-specific combination antibiogram of urine isolates (thus, a WISCA) has been described [135].

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 [1,136]. 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 [137].

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 [138]. 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) [54,139,140].

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 and will be required by CMS starting in 2024 [141]. The CDC developed the Standardized Antimicrobial Administration Ratio, an observed to predicted ratio endorsed by the National Quality Forum, to provide a standardized risk-adjusted benchmark of antimicrobial use [142].

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".)

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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)")

SUMMARY

●Definition – 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.)

●Goal – 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.)

●Initiation and tailoring of antimicrobial therapy – 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 – 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.)

●Local protocols – 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.)

●Role of pharmacy – 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.)

●Antimicrobial allergies – 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".)

●Role of microbiology laboratory – 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.)

●Monitoring progress – 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.)