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Clinical Investigations

Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation

Trivedi, Kavita K. MD1; Bartash, Rachel MD2; Letourneau, Alyssa R. MD, MPH3; Abbo, Lilian MD4; Fleisher, Jorge MD5; Gagliardo, Christina MD6; Kelley, Shannon MPA7; Nori, Priya MD2; Rieg, Gunter K. MD8; Silver, Phyllis MEd7; Srinivasan, Arjun MD9; Vargas, Jaclyn MD10; Ostrowsky, Belinda MD, MPH2; the Partnership for Quality Care (PQC) Inpatient Antimicrobial Stewardship Working Group

Author Information
doi: 10.1097/CCM.0000000000004344


Each year in the United States, approximately 2.8 million people develop multidrug-resistant bacterial infections and at least 35,000 people die of these infections (1). Use of antibiotics is the single most important modifiable risk factor for the development of multidrug-resistant bacterial infections (2). Studies suggest 30–50% of hospital antibiotic use is unnecessary or inappropriate in acute care and outpatient settings but standardized data regarding appropriateness in multicenter studies in the United States is lacking (3). The ability to identify and stop unnecessary use is essential to improve patient outcomes, promote patient safety, and reduce pressure for the emergence of resistance. Although there have been various definitions and studies to attempt to quantify inappropriate use as a definitive standard, a practical and widely used method of assessment does not exist (4).

Antibiotic use in the ICU is unique due to the severity of illness inherent to this patient population and often leads to broad-spectrum antibiotic use even when not indicated (5,6). An assessment utilizing national proprietary administrative data from the Truven Health Market Scan Hospital Drug Database for adult and pediatric inpatients from January 1, 2006, to December 31, 2012, identified ICU antibiotic utilization at 1,092 days of therapy/1,000 days-present compared with noncritical locations (720 d of therapy/1,000 d-present; p < 0.001) (7). Due in part to large volume antibiotic use, ICUs are epicenters for antibiotic resistance worldwide. In addition, patients are critically ill, require invasive devices, and multiple services coordinate input on treatment, which may contribute to antibiotic use. The use of vasopressors, hemodialysis, and transfusions also produce variable volumes of distribution, affecting pharmacokinetics and pharmacodynamics complicating appropriate antibiotic dosing (8,9). A 72-hour snapshot study conducted in 67 ICUs from 32 U.S. hospitals in 2011 reported 330 of 660 empiric antibiotic courses ordered in critically ill patients were inappropriately continued for at least 72 hours in absence of adjudicated therapy (10). Experts have highlighted the urgent need for antibiotic stewardship programs (ASPs) to target education and interventions focused on improving antibiotic use in the ICU; studies have demonstrated that ASPs can improve antibiotic use (11–13), be cost-effective (11,14), and safe (15) in the ICU setting, however, published literature on identifying inappropriate use in the ICU and how to address it is limited (16).

In 2016, the Partnership for Quality Care (PQC) developed the Antibiotic Stewardship Initiative with input and collaboration from the Centers for Disease Control and Prevention (CDC). PQC is a coalition of healthcare providers and healthcare workers dedicated to promoting affordable, high-quality healthcare. PQC includes public, private, religious, teaching and nonprofit hospitals, integrated health systems as well as more than 1 million U.S. healthcare workers.

PQC organizations involved in the Antibiotic Stewardship Initiative conducted a multicenter assessment of antibiotic appropriateness in ICUs using an actionable standardized CDC tool that they validated in order to identify local improvement opportunities. Results of this multicenter appropriateness assessment are described here.


The CDC Assessment of Appropriateness of Inpatient Antibiotics (17) was made actionable by an expert panel to evaluate and compare appropriate antibiotic use across hospitals. On October 5, 2016, 48 ICUs from 12 hospitals across five U.S. states piloted the ICU antibiotic point prevalence tool. The pilot served to gauge the feasibility of the tool and ease of use throughout a variety of ICUs. All PQC hospital staff that participated in the pilot, provided feedback on the point prevalence tool, including need for more ICU-specific data and clear definitions and criteria to categorize reasons for inappropriate antibiotic use. These recommendations were incorporated into the final tool. A subsequent multicenter antibiotic appropriateness assessment was performed using the enhanced tool on March 1, 2017.

Participating hospitals identified ASP personnel (infectious diseases [ID] physician or ID PharmD with knowledge of antibiotic resistance and antibiotic renal dose adjustment) to administer the tool in designated ICUs within their health systems and attend an online training session. ICUs were defined by CDC’s National Healthcare Safety Network (NHSN) type (18). The PQC individual tool (Appendix, Supplemental Digital Content 1, was completed for each patient receiving antibiotics in participating ICUs on March 1, 2017, by local ASP personnel to allow a standardized evaluation of antibiotic regimens for appropriateness using a point prevalence approach within and across facilities. Hospitals were instructed to only use culture results available by March 1, 2017, to help guide determination of appropriateness. Inappropriate antibiotic use was defined as follows across all participating hospitals:

  • 1) Antibiotics not indicated, (e.g., no infection, nonbacterial infection, treatment of colonization, or contamination);
  • 2) Lack of timely adjustment from empiric to targeted therapy based on available microbiology data;
  • 3) Selection of an inappropriate regimen due to unsuitable spectrum of activity for the targeted infection or inappropriate duration of therapy; and
  • 4) Incorrect dose, route, or interval for infection or renal function.

No hierarchy of reasons for inappropriate use was provided; it was the respondent’s discretion to determine which reason for inappropriateness was the most salient. For example, if antibiotics were not indicated at all then incorrect duration would not be the reason for inappropriate use. Antibiotics were also categorized as empiric (chosen as an educated guess to treat an infectious syndrome or presentation), directed (chosen based on identified culture or other microbiological result), or prophylactic (given to prevent infection); if any antibiotics in the regimen were considered empiric, the regimen was categorized as empiric. Other data collected from participating hospitals included hospital and ICU demographics; ASP characteristics and concordance with CDC’s Core Elements of Hospital Antibiotic Stewardship Programs (19); number of ICU beds, total number of patients from each participating ICU, and number of patients receiving antibiotics on March 1, 2017, in each ICU; and identified reasons for inappropriate antibiotic use by category and antibiotic agent.

Each hospital submitted de-identified aggregate data from each ICU in an online tool utilizing SurveyMonkey (SurveyMonkey Inc., San Mateo, CA). No patient-level data was transmitted. Data were imported into Microsoft Excel (Microsoft Office 2011, Microsoft Corporation, Seattle, WA) and aggregated by ICU. Data were analyzed both by comparing hospitals to one another and aggregating by ICU type. Epi Info (Version 7; Centers for Disease Control and Prevention, Atlanta, GA) was used for bivariate analyses and risk ratios were calculated with 95% CIs to evaluate for statistical significance. PQC provided anonymous benchmarking data by hospital and ICU type to participating hospitals similar to Figure 1. Institutional review board was waived since the study was deemed quality improvement and no patient-level data was shared with PQC.

Figure 1.
Figure 1.:
Inappropriate antibiotic prescribing in 47 ICUs from U.S. Hospitals (A–L) on March 1, 2017 (by facility) (see attached file).


Twelve PQC hospitals, with unique CDC NHSN identification numbers, voluntarily participated in this assessment from the following states: California (2), Florida (2), Massachusetts (3), Minnesota (1), and New York (4) (Table 1). Most (83%) hospitals self-identified as teaching hospitals. No rural hospitals or exclusive pediatric hospitals participated, but data from pediatric and neonatal ICUs was included. The median bed size of the 12 participating hospitals was 563 (range, 252–1,550) and the median number of licensed ICU beds within participating hospitals was 70 (range, 20–270).

Participating Hospital and ICU Demographics on March 1, 2017

All hospitals reported an active ASP defined as coordinated interventions to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of administration. These ASPs were reported in place for 2 years in one hospital (8%), 5–10 years in four hospitals (33%), and 10+ years in seven hospitals (58%). Ten hospitals (83%) reported an ID physician and ID PharmD leading their ASPs (83%) and two hospitals (17%) had an ID physician leader only. Nine hospitals (75%) reported all seven of CDC’s Core Elements of Hospital ASPs (19) in place at the time of the assessment; three hospitals (25%) reported not fully implementing either the tracking, reporting or education core elements. Rapid diagnostic strategies were available in all hospitals. Eleven hospitals (92%) reported robust antibiotic stewardship strategies including preauthorization coupled with a restricted formulary; clinical decision support systems such as TheraDoc (Premier Inc., Charlotte, NC) and VigiLanz (VigiLanz Corporation, Minneapolis, MN) to assist with identification of bug-drug mismatches, IV to oral conversions, positive blood cultures, and acute changes in renal function; prospective audit and feedback 1–5x/wk; antibiotic use review of individual providers and direct feedback; electronic medical record order sets to standardize care and documentation; and integration of microbiology services into daily and longitudinal ASP activities such as rapid diagnostics, antibiotic susceptibility testing, and Clostridioides difficile testing.

Forty-seven distinct ICUs from the 12 hospitals participated in this assessment: 38 adult ICUs (81%) and nine pediatric or neonatal ICUs (19%). Distribution by ICU type is shown in Table 1. As of midnight, on March 1, 2017, there were 667 patients in participating ICUs, of which 362 (54%) were on antibiotics (range among institutions: 8–81 patients). Of these, one patient was not assessed with the actionable CDC tool and was excluded from data analysis. Data for the remaining 361 patients are presented here.

Of the antibiotic regimens for these 361 patients, 220 (61%) were identified as empiric therapy, 88 (24%) as directed therapy, and 77 (21%) as prophylactic treatment (categorization of regimens was nonexclusive). Frequency of antibiotic prescribing within these ICUs on March 1, 2017, varied depending on ICU type (Table 2).

Inappropriate Antibiotic Prescribing by ICU Type in 47 U.S. ICUs on March 1, 2017

Antibiotic regimens for the 361 patients were reviewed and assessed for appropriateness. Of these, 112 (31%) were identified as inappropriate; all of the inappropriate regimens had been administered for greater than 72 hours. Frequency of inappropriate antibiotics ranged among participating hospitals from 9% to 82% (Fig. 1). For comparison, in the pilot, 314 patients on antibiotics were assessed and 95 (30%) of the antibiotic regimens were determined to be inappropriate or unnecessary.

Of the 112 patients on inappropriate regimens, 48% were identified as prophylactic treatment, 31% as empiric treatment, and 18% as directed therapy. Bivariate analyses comparing prophylactic to nonprophylactic regimens demonstrated a risk ratio of 1.76 (95% CI, 1.31–2.37) for inappropriate treatment; directed therapy versus nondirected therapy yielded a risk ratio of 0.51 (95% CI, 0.32–0.82) for inappropriate regimens. Empiric therapy versus nonempiric treatment yielded a risk ratio of 0.96 (95% CI, 0.72–1.30) for inappropriate treatment but was not statistically significant.

Table 2 displays inappropriate antibiotic use by ICU type. Patients in the PICU had the highest frequency of inappropriate antibiotics at 55%. Table 3 displays risk ratios for inappropriateness by ICU type and within an ICU type, stratified by prophylactic, directed, or empiric regimens. Comparing PICU patients to other ICU patients demonstrated a risk ratio 1.90 (95% CI, 1.33–2.72) for inappropriate treatment. Patients on prophylactic antibiotics in the surgical ICU compared with other patients on nonprophylactic antibiotics in the surgical ICU demonstrated a risk ratio of 2.20 (95% CI, 1.03–4.54) for inappropriate therapy. Similarly, patients on prophylactic antibiotics in all mixed surgical ICUs, mixed medical ICUs, and mixed cardiac ICUs demonstrated an elevated risk ratio for inappropriate treatment and were statistically significant (Table 3).

Bivariate Analyses of Inappropriate Antibiotic Prescribing by ICU Type in 47 U.S. ICUs on March 1, 2017

The most frequent overall reason for inappropriate antibiotic use was an antibiotic was indicated, but coverage or duration was not appropriate (63%) followed by no antibiotic was indicated (31%), and lastly that the dose, route, or interval was inappropriate (6%). The most common specific reasons for inappropriate antibiotic use included spectrum of activity too broad (29%), no infection or nonbacterial infection (22%), and duration longer than necessary (21%) (Supplementary Table 1, Supplemental Digital Content 2, This table also describes specific examples of reasons for inappropriate use identified at two of the participating hospitals.

Bivariate analyses comparing prophylactic to nonprophylactic inappropriate regimens demonstrated a risk ratio of 2.48 (95% CI, 1.20–5.10) for duration longer than necessary; empiric and directed therapy risk ratios were not statistically significant. Table 4 displays risk ratios by ICU type for reasons of inappropriate antibiotic use. Of inappropriate regimens in the neurologic ICU, the risk ratio was 6.89 (95% CI, 1.76–26.87) for dosing, route, or interval was the reason for inappropriate use.

Bivariate Analyses of Reasons for Inappropriate Therapy by ICU Type in 47 U.S. ICUs on March 1, 2017

The antibiotic most commonly used in inappropriate regimens was IV vancomycin in seven hospitals (58%), cefazolin in two hospitals (17%), followed by doxycycline, meropenem (adults), clindamycin (pediatrics), and piperacillin/tazobactam in one hospital each (8%).

Based on local findings, participants were asked to identify the most likely opportunities to improve prescribing in the ICU. The interventions identified included review of regimens for de-escalation or discontinuation of antibiotics (92%), improved empiric regimens (67%), avoidance of antibiotics for noninfectious syndromes or colonization (50%), promotion of shorter duration for infectious syndromes (33%), education on antibiogram and local microbiology (33%), and assistance with dose, route, or interval (8%).

On average, hospitals used four team members (range, 2–9) to complete this antibiotic appropriateness assessment. To assess ease of use, hospitals reported the length of time it took to complete the actionable CDC tool: eight hospitals (67%) reported 16–30 minutes per patient.


This 1-day point prevalence survey assessed 361 patients receiving antibiotics in 47 ICUs, inclusive of both adult and pediatric patients in 12 nonrural, mostly teaching U.S. hospitals on March 1, 2017. The hospitals that participated were heterogeneous when comparing bed size, ICU size, and ICU types but all had ASPs in place at the time of the study. An actionable CDC tool provided a simple and standard method of assessing antibiotic prescribing in ICUs. Of the 54% of patients in participating ICUs receiving antibiotics, the antibiotic regimen was identified as inappropriate in 31% of patients. The variability in number of patients on antibiotics (range, 8–81) and inappropriate antibiotic use (range of 9–82%) among participating hospitals is notable. Prophylactic antibiotics were 1.76x more likely to be inappropriate than nonprophylactic antibiotics overall; conversely, directed therapy was protective for inappropriateness. Although only four PICUs participated contributing 33 patients in total, bivariate analyses demonstrated that PICUs were 1.9x more likely to demonstrate inappropriate antibiotic use than non-PICUs. Although other countries have conducted similar multicenter point prevalence surveys to assess for appropriateness (20–22) and other U.S. studies have identified antibiotic prescribing improvement opportunities (10,23), this study successfully used standardized, validated, simple, inexpensive, and reproducible tools to assess antibiotic appropriateness within different U.S. hospitals and healthcare systems.

Other multicenter studies in the United States have shown that 30–50% of hospital-wide antibiotic use is inappropriate (3). Additional studies also suggest a high volume of inappropriate antibiotic use in acute care settings such as ICUs (6). Our data provide further evidence that ICU patients are often prescribed broad-spectrum antibiotics when they may not be warranted. Interestingly, 61% of all the patients on antibiotics at the time of this survey were receiving empiric treatment, and only one-third of these regimens were found to be inappropriate, highlighting the high degree of unavoidable empiricism that is integral to the practice of medicine in the ICU. Not all of the empiricism in the ICU is a function of poor provider behavior; ICU patients and circumstances are much different from routine, stable non-ICU patients.

Prophylactic antibiotics were designated as inappropriate 48% of the time in this survey and were more likely to be inappropriate in surgical ICUs, mixed surgical ICUs, mixed medical ICUs, and mixed cardiac ICUs. Perioperative prophylactic regimens in the ICU were included in this assessment, although some providers may feel that these should not be used in the ICU as life-saving measures. Despite the presence of robust ASPs in the participating hospitals, of the inappropriate prophylactic antibiotics, they were 2.48x more likely to be due to duration longer than necessary then inappropriate nonprophylactic regimens. These prophylactic antibiotic regimens may offer an easy target for ASP intervention in the ICU, particularly in surgical ICUs.

The most common reasons for unnecessary antibiotic use in the United States cited in previous studies include duration of therapy longer than necessary and treatment for noninfectious or nonbacterial syndromes, in addition to an overly broad spectrum of activity, as seen in the current study and the pilot (24). Overly broad spectrum and excess duration of therapy underscore the importance of the “antibiotic time-out” as a tool, which can address multiple reasons for inappropriate antibiotic use (25). Notably, every course of inappropriate antibiotic therapy identified in this survey would have been flagged in an “antibiotic time-out” at 72 hours.

Based on this survey experience, we developed Supplemental Table 1 (Supplemental Digital Content 2, to describe potential intervention strategies that can be employed throughout the hospital to address inappropriate antibiotic use. Specifically, information garnered from this assessment can help inform ICU-specific ASP policies focused on strategies that restrict the use of prophylactic antibiotic regimens. These potentially include as follows:

  • 1) Limiting use of anti-staphylococcal agents such as IV vancomycin when not indicated through ongoing educational initiatives, computerized alerts, and prospective audit and feedback protocols;
  • 2) Encouraging de-escalation of broad-spectrum antibiotic regimens, through antibiotic time-outs and antibiotic restrictions after 48–72 hours or rapid diagnostics;
  • 3) Improving durations of therapy based on available data, through updated treatment protocols that specifically address appropriate length of therapy and computerized order sets for surgical prophylaxis;
  • 4) Improving overall utilization of antibiotics in special populations such as pediatric and burn ICUs, through default renewals and documentation of indication for antibiotics; and
  • 5) Sharing data at critical care councils of individual hospitals, such as benchmarking appropriate antibiotic use between ICUs to engage critical care providers, patient safety, and quality officers in antibiotic stewardship efforts.

Strengths of this assessment include the participation of teaching hospitals with varied antibiotic resistance profiles as well as the ability to benchmark results among participating hospitals. In addition, although expert opinion was used and may not always be reproducible, the standardized tool used across facilities provided a clear definition for inappropriate antibiotic use. Many ASP teams agreed that this assessment is a helpful platform to collaborate further with hospitals’ ICUs. The assessment can also help to focus limited ASP resources, such as the PICU, prophylactic antibiotics, or duration of therapy greater than 72 hours. Other institutions are encouraged to use these tools to periodically assess antibiotic appropriateness. Last, the tool can be adapted to fit the needs of individual ICUs and likely extended to the non-ICU, acute care setting.

Limitations of this study include participation from mostly coastal urban centers, varying numbers of patients assessed at each hospital, lack of data on patient acuity other than requiring ICU level care, and inability to evaluate patient outcomes such as mortality and length of hospitalization. An in-depth analysis on risk factors for antibiotic use was not performed due to low numbers of antibiotic prescriptions by unit and lack of patient-specific data; further analysis on rapid diagnostics by hospital and ICU type was not done since it was not confirmed that they were universally available in the participating ICUs nor if there was guidance on interpretation of test results; the PQC individual tool used by facilities collected more patient-level data that could be reviewed by individual facilities, however, PQC only requested and aggregated limited details to increase facility participation and to protect patient health information. Given the use of expert opinion at each hospital, there may have been inter-operator variability in adjudication both within and among hospitals due to interpretation of the tool as well as differences in local prescribing habits, local guidelines, and institutional policies. Only 54% of the patients in these ICUs were on antibiotics on the day of the point prevalence, which was lower than expected as many studies report up to 70% of patients receiving antibiotics during an ICU stay (26). Point prevalence methodology limits the ability to draw larger conclusions about data outside the specified time frame. Additionally, a higher volume of antibiotic use may also be seen in peak winter months reflecting a high prevalence of bacterial pneumonia and viral respiratory syndromes. Finally, social desirability bias may have also been a factor, where hospitals might favorably report their own results; however, ASP personnel implemented the tool themselves and since specific patients were assessed, it would be difficult to identify an inappropriate regimen as appropriate.


Our study places the spotlight on the need for antibiotic stewardship in the ICU by highlighting that 31% of antibiotic use in urban, teaching hospital ICUs was inappropriate. Although the project scope was limited, it is important to highlight the tool used in this study as well as the data trends identified. CDC and national mandates require ASPs across the spectrum of healthcare; CDC core elements include a call for tracking process and outcome measures; and the National Strategy for Combating Antibiotic-Resistant Bacteria calls for major reductions in inappropriate antimicrobial prescribing by 2020 (27). This tool and point prevalence survey are key methods of evaluating ASPs and assessing progress toward these national goals. CDC’s NSHN Antimicrobial Use and Resistance Module guide facilities in tracking aggregate antibiotic use and benchmarking to like healthcare facilities throughout the United States. However, volume of antibiotics used provides only a piece of the picture. Unlike healthcare-associated infections where the goal is to prevent all events, the call to order with antibiotic use is to reduce inappropriateness. The challenge is to provide guidance to facilities on defining and identifying inappropriate prescribing and translating these findings to direct ASP interventions. In the ICU, our critical care colleagues are essential in these endeavors. In order for ICU ASP interventions to be successful, ASP personnel must partner with critical care leaders and use local data to change behavior. Our data indicate there is room for improvement. With support from critical care colleagues on timely de-escalation and antibiotic discontinuation, ASP interventions will be even more successful in the ICU improving patient care and therefore patient safety for our most critically ill patients.


We also acknowledge the work of Derek Renfeld (AKPD Media) in developing the figure and tables.


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The Partnership for Quality Care (PQC) Inpatient Antimicrobial Stewardship Working Group is as follows: Lina I. Alnajjar, PharmD (Brigham and Women’s Hospital, Boston, MA); Laura Aragon, PharmD (Jackson Memorial Hospital, Jackson Health System, Miami, FL); Fred Cassera, RPh (Maimonides Medical Center, Brooklyn, NY); K. C. Coffey, MD, MPH (Massachusetts General Hospital, Boston, MA); Eliza Dollard, PharmD (Jackson Memorial Hospital, Jackson Health System, Miami, FL); Ramy H. Elshaboury, PharmD (Massachusetts General Hospital, Boston, MA); Ronak G. Gandhi, PharmD (Massachusetts General Hospital, Boston, MA); Monica Ghitan, MD (Maimonides Medical Center, Brooklyn, NY); Amber Giles, PharmD (Jackson Memorial Hospital, Jackson Health System, Miami, FL); David W. Kubiak, PharmD (Brigham and Women’s Hospital, Boston, MA); Suri B. Mayer, PharmD (Maimonides Medical Center, Brooklyn, NY); Stephen M. Parodi, MD (The Permanente Medical Group, Oakland, CA); Jennifer Quevedo, PharmD (University of Miami Hospital, Miami, FL); Galina Shteyman, PharmD (Park Nicollet Methodist Hospital, St. Louis Park, MN); and Christine H. Suh, PharmD (Kaiser Permanente South Bay Medical Center, Harbor City, CA).


antibiotic appropriateness; antibiotic stewardship programs; inappropriate use; intensive care units; point prevalence

Supplemental Digital Content

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