This trial was conducted at the University of Maryland Medical Center, a 648-bed, tertiary-care referral center in Baltimore, Maryland. Since 2001, the University of Maryland Medical Center has utilized an antimicrobial management team to actively monitor and intervene on restricted antimicrobial treatments on all inpatient wards, with the exception of shock trauma, pediatrics and cancer wards. The team consists of one infectious disease attending physician (50% FTE) and one clinical pharmacist (80% FTE).
The following describes the standard care provided by the antimicrobial management team prior to this trial and in the control arm during the trial. Each weekday the team received a list of all patients who had received any antimicrobial within the past 24 hours (on Mondays, the list also included patients who had received an antimicrobial the prior weekend). The list was generated by University of Maryland Medical Center's information technology group by querying the hospital's Cerner pharmacy database. The list was provided to the team as a Microsoft Excel worksheet. The clinical pharmacist would then reduce the list to patients who had received any of the hospital's 23 restricted antimicrobials. The team would then review the patients' charts and, if necessary, recommend changes to the patients' current antimicrobial therapy. The team would only intervene on patients who were receiving a restricted antimicrobial, however they were not limited to make changes to only restricted antimicrobials. It should be noted that the University of Maryland Medical Center did not possess a computerized physician order entry system or electronic medical records during the time-period of the randomized trial.
This study was a randomized controlled trial; patients admitted to wards managed by the antimicrobial management team (all wards except shock trauma, cancer, and pediatric wards) between May 10 and August 3, 2004 were randomized to one arm of the trial according to their medical record number (MRN). Patients with an even MRN were assigned to the control arm and received the standard care as provided by the team prior to start of this trial (described above). Patients with an odd MRN were assigned to the intervention arm and received the standard care provided by the team but supplemented with the web-based clinical decision support system (PharmWatch™, Cereplex Inc.) designed to assist in the management of antimicrobial utilization (hereafter referred to as ‘system'). Even and odd MRNs are, in effect, randomly distributed in the patient population since patients are assigned their MRNs consecutively at the time of their first visit to a University of Maryland Medical System institution.
Each weekday, for the intervention arm, the team would access the system via a secure internet connection and view a list of alerts for patients who may potentially require a change in their current antimicrobial therapy. The criteria for the alerts were created with the collaboration of the team and are based on the patient's antimicrobial use and microbiological laboratory results. The alerts were designed to detect all scenarios of potentially inappropriate or inadequate antimicrobial use that the team detected when providing the standard of care. Thirty-two alerts were created; examples of alert types include: 1) equivalent oral antimicrobial possibly indicated for a patient receiving an intravenous antimicrobial; 2) potentially unnecessary double coverage of antimicrobial therapy; 3) organism potentially resistant to current antimicrobial therapy. After accessing the alerts, the team could then view each patient's microbiologic laboratory results, medications, admission, discharge, and transfer information within the system. Patient data were automatically uploaded to the system from the hospital information systems nightly. If additional information were still needed to assess the appropriateness of the antimicrobial therapy, the team would then obtain this additional data from the patient charts. While the frequency that the antimicrobial management team referred to the patient charts was not recorded, the team estimates that the chart was reviewed for approximately 20% of those patients receiving alerts.
If, based on these data, the team decided to recommend a change in a patient's current antimicrobial therapy, they could complete and print an intervention form within the system that allowed them to describe the problem with the current therapy and make recommendations for more appropriate therapy. In the event that the antimicrobial management team was not able to verbally relay the message to a member of the admitting or primary team, the form, which included the antimicrobial management team's contact information, would then be temporarily placed within the patient's chart.
Note that all interventions were made every weekday in both arms of the study and that these interventions were made through the antimicrobial management team, just as was done both prior to the start of this study and in the control arm. Again, in both arms of the study, the primary treating team was responsible for making changes in patient antimicrobial therapy. Interventions consisted of therapy recommendations made by the antimicrobial management team. It should be noted that the system evaluated here differs from similar systems that have previously been evaluated in this field, in that the intended user is the antimicrobial management team and not all infectious disease physicians or all treating physicians.
The antimicrobial management team was blinded from receiving system alerts on patients assigned to the control arm of the trial. This blinding was accomplished by programming the system not to display alerts on control arm patients to the antimicrobial management team when they logged in to the system. However, these alerts were saved for subsequent data analyses. Patients and their healthcare providers did not have access to the system and were blinded as to the randomization status. The team could not be blinded as to the randomization status of patients, as their recommendations were the mode through which interventions were administered to patients thus making the team a component of both the intervention under study and the standard of care.
For each study patient, we collected the following demographic data: sex, age, and the chronic disease score (CDS). The CDS is a measure of patient comorbidity that utilizes patient medications as indicators for comorbid conditions. 16
The CDS includes seventeen different comorbid conditions such as diabetes, respiratory illness, cancer, and hypertension. Each condition contributes between one and five points to the total score, and the potential range of values for each patient's CDS is 0–35. The CDS was calculated using the medications ordered for each patient within the first 24 hours of admission.
The primary outcome of interest in this trial was hospital antimicrobial costs. The cost data were measured using the hospital's pharmacy purchase prices, which are assessed per unit dose. These data were obtained using the hospital's Cerner pharmacy database. Additional outcomes of interest were patient mortality, length of hospitalization, frequency of testing for Clostridium difficile (an indicator for the presence of diarrhea and adverse effect of antimicrobial therapy), and time spent by the team managing antimicrobial utilization. The time spent was measured during one week during the last full calendar week of the study period. The time spent by the antimicrobial management team was recorded on study timesheets and were separately recorded by both members of the team. The latter were compared using the Fisher's exact test, t-test, and Wilcoxon rank-sum test, where appropriate. Statistical significance was defined as p < 0.05. All data analyses were performed using SAS v. 8.02 (SAS Institute, Inc., Cary, North Carolina).
This study was approved by the University of Maryland, Baltimore Institutional Review Board. The primary purpose of this study was the evaluation of the system by the antimicrobial management team and by University of Maryland Medical Center infection control. Because antimicrobial management by the team is part of the patients' standard care, and because of the minimal risk to patients, the University of Maryland, Baltimore Institutional Review Board waived the requirement for individual consent. Initial power calculations for this study led to a targeted study duration of four months, however an interim data analysis was planned for two months post-study implementation. The results of the interim data analysis were evaluated by the study investigators and by the Medical Director for Infection Control and Antimicrobial Effectiveness at the University of Maryland Medical Center.