Analysis of infections among patients with historical culture positive for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae: Is ESBL-targeted therapy always needed?

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions. Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP. Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3. Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Clinical impact of a multiplex rapid diagnostic pneumonia panel in critically ill patients.

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients. Design: Single-center, preintervention and postintervention retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Adult ICU patients. Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January-March 2021, preintervention period) or after (January-March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared. Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27). Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship.

Sustained impact of an antibiotic stewardship initiative targeting asymptomatic bacteriuria and pyuria in the emergency department.

Objective: To determine whether a multifaceted initiative resulted in maintained reduction in inappropriate treatment of asymptomatic pyuria (ASP) or bacteriuria (ASB) in the emergency department (ED). Design: Single-center, retrospective study. Methods: Beginning in December 2015, a series of interventions were implemented to decrease the inappropriate treatment of ASP or ASB in the ED. Patients discharged from the ED from August to October 2015 (preintervention period), from December 2016 to February 2017 (postintervention period 1), and from November 2019 to January 2020 (postintervention period 2) were included if they had pyuria and/or bacteriuria without urinary symptoms. The primary outcome was the proportion of patients prescribed antibiotics within 72 hours of discharge from the ED. The secondary outcome was the number of patients returning to the ED with symptomatic UTI within 30 days of discharge. Results: We detected a significant decrease in the proportion of patients with ASP or ASB who were inappropriately treated when comparing the preintervention group and post-intervention group 1 (100% vs 32.4%; P < .001). This reduced frequency of inappropriate treatment was noted 3 years after the intervention, with 28% of patients receiving treatment for ASP or ASB in postintervention group 2. (P was not significant fin the comparison with postintervention group 1.) Among the 3 groups analyzed, we detected no difference in the numbers of patients returning to the ED with a symptomatic UTI within 30 days of ED discharge regardless of whether patients received antibiotics. Conclusions: A multifaceted intervention resulted in a significant decrease in inappropriate use of antibiotics for ASP and/or ASB that was maintained 3 years after implementation.

A comparison of active versus passive methods of responding to rapid diagnostic blood culture results.

Objective: To compare 2 methods of communicating polymerase chain reaction (PCR) blood-culture results: active approach utilizing on-call personnel versus passive approach utilizing notifications in the electronic health record (EHR). Design: Retrospective observational study. Setting: A tertiary-care academic medical center. Patients: Adult patients hospitalized with ≥1 positive blood culture containing a gram-positive organism identified by PCR between October 2014 and January 2018. Methods: The standard protocol for reporting PCR results at baseline included a laboratory technician calling the patient's nurse, who would report the critical result to the medical provider. The active intervention group consisted of an on-call pager system utilizing trained pharmacy residents, whereas the passive intervention group combined standard protocol with real-time in-basket notifications to pharmacists in the EHR. Results: Of 209 patients, 105, 61, and 43 patients were in the control, active, and passive groups, respectively. Median time to optimal therapy was shorter in the active group compared to the passive group and control (23.4 hours vs 42.2 hours vs 45.9 hours, respectively; P = .028). De-escalation occurred 12 hours sooner in the active group. In the contaminant group, empiric antibiotics were discontinued faster in the active group (0 hours) than in the control group and the passive group (17.7 vs 7.2 hours; P = .007). Time to active therapy and days of therapy were similar. Conclusions: A passive, electronic method of reporting PCR results to pharmacists was not as effective in optimizing stewardship metrics as an active, real-time method utilizing pharmacy residents. Further studies are needed to determine the optimal method of communicating time-sensitive information.

Antiviral Pharmacology: A Standardized Patient Case for Preclinical Medical Students.

Introduction: Pharmacology is an important learning topic in preclinical medical education. Simulated patient encounters allow students to apply basic science knowledge in a clinical setting and have been useful in previous studies of pharmacology education. We developed a standardized patient (SP) encounter to reinforce antiviral pharmacology content for first-year medical students. Methods: Students were instructed to recommend a medication for shingles during an SP encounter and to answer questions from the SP on mechanism of action and adverse effects. Students then attended a large-group debrief session. Following the activity, students evaluated the exercise through a voluntary survey. For knowledge assessment, students were randomized into two groups to complete three multiple-choice questions either before or after the learning activity. Results: In 2020 and 2021, 144 and 145 students, respectively, participated. In 2020, there was no significant difference in the proportion of correct answers between the pre- and postsimulation groups (p > .05). In 2021, the postsimulation group significantly outperformed the presimulation group in knowledge of mechanism of action (p < .01) and adverse effects (p < .01), but no difference was seen between the groups regarding medication selection (p = .27). Most learners assessed the instructional design as effective for the tasks assigned. Discussion: This SP activity provided an opportunity for early medical students to practice integrating antiviral pharmacology knowledge into a patient encounter and was well received by learners. The instructional method offers a clinically relevant approach for reinforcing pharmacology knowledge for preclinical medical students.

Inpatient Antibiotic Costs Associated With Switching From Vancomycin to Daptomycin for Outpatient Parenteral Antibiotic Therapy.

Purpose: The common practice of changing patients to daptomycin for outpatient parenteral antibiotic therapy (OPAT) can increase inpatient daptomycin use and impact inpatient pharmacy expenses. The purpose of this study was to quantify the additional inpatient antibiotic expenditures associated with changing patients from vancomycin to daptomycin for OPAT. Methods: This study examined patients who were discharged from January 1, 2018 to June 30, 2019. Patients were included if they were ≥18 years old, transitioned from vancomycin to daptomycin prior to discharge, and were cared for by the Infectious Diseases OPAT program. Patients switched to daptomycin for therapeutic reasons were excluded. A cost analysis evaluating the vancomycin regimen prior to changing to daptomycin and the daptomycin doses given prior to discharge and during readmissions for the first 6 weeks after discharge was performed using Wholesale Acquisition Costs. The primary outcome was the inpatient antibiotic expense associated with changing to daptomycin for OPAT. Results: Sixty-eight patients met study criteria. The mean number of inpatient doses of daptomycin administered prior to discharge was 4.3. Twelve patients were readmitted and received a mean of 5.3 additional doses. The estimated cost difference between the inpatient daptomycin doses and equivalent vancomycin therapy was $2647 per patient. Limiting patients to only 1 pre-discharge dose of daptomycin would reduce this cost difference to $926 per patient. Conclusion: Switching from vancomycin to daptomycin for OPAT can be associated with substantial inpatient pharmacy costs. These excessive costs can be mitigated if only 1 dose of daptomycin is given before discharge.

Evaluating the Use of Dalbavancin for Off-Label Indications.

(1) Background: Dalbavancin is a long-acting lipoglycopeptide antibiotic approved for skin and soft-tissue infections. Post-marketing experience suggests dalbavancin is being used for off-label indications that normally require long-term intravenous (IV) antibiotics; however, data assessing this off-label usage are limited. The purpose of this study was to evaluate the real-world efficacy, safety, and financial impact of off-label dalbavancin use. (2) Methods: This is a retrospective, observational study conducted within a 4-hospital health system. Adult patients who received dalbavancin from January 2018 to January 2021 for an off-label indication were included. The primary outcome was clinical success at 90 days. Secondary outcomes included safety (nephrotoxicity and hepatotoxicity). A pharmacoeconomic analysis was performed by comparing the cost of dalbavancin to the anticipated cost of patient stay if standard IV therapy was given. (3) Results: Forty-eight patients met study criteria. Indications included osteomyelitis (54%), endocarditis (23%), bacteremia (15%), and prosthetic joint infection (8%). The predominant organism was S. aureus (60%), with 42% caused by methicillin-resistant S. aureus. Overall, 41 (85%) patients achieved clinical success at 90 days, including 85% with osteomyelitis, 82% with endocarditis, and 86% with bacteremia. There were no instances of nephrotoxicity or hepatotoxicity. Estimated cost avoidance per patient was USD 5313 and USD 1683 if traditional IV therapy would have been completed in the hospital and skilled nursing facility, respectively. (4) Conclusion: Dalbavancin was associated with a relatively high success rate for the treatment of off-label indications and may be a cost-effective alternative to traditional IV antibiotic therapy.

Evaluation of the Potential Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients With Hospital-Acquired Pneumonia.

Background Rapid diagnostic tools have emerged as valuable assets assisting clinicians in decision-making regarding patient management in the hospital setting. Our study sought to identify the potential impact of the BioFire® FilmArray® Pneumonia Panel (FP Panel) (BioFire Diagnostics, Salt Lake City, UT, USA) in patients with hospital-acquired pneumonia (HAP). Methods Respiratory samples obtained by bronchoalveolar lavage (BAL) or tracheal aspiration (TA) from ICU patients with a diagnosis of HAP were tested by the FP panel in addition to routine bacterial cultures. In addition, the electronic health records of these patients were reviewed to determine what potential changes in antimicrobial therapy could have been implemented if the panel results were known to the treatment team in real-time. A cost analysis was also performed incorporating the cost of the pneumonia panel and the savings associated with the potential decrease of antibiotic use and avoidance of the rapid viral diagnostic panel.  Results Fifty-six patients met the study criteria. The FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with an anticipated mean reduction in time to optimized therapy of approximately 51 hours. In addition, the panel identified three cases where antimicrobials should have been altered because patients were not receiving empiric therapy with activity against the causative pathogen and 34 opportunities for antibiotic de-escalation. The cost analysis calculated an additional cost of $10 per patient associated with using the FP panel.  Conclusions The FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include a more rapid time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.

Treatment of Candida nivariensis Blood Stream Infection With Oral Isavuconazole.

Candida nivariensis is a rarely isolated yeast that is now considered a species within the Candida glabrata complex. Anti-fungal susceptibilities and treatments of Candida nivariensis are often assessed on a case-by-case basis. In this case, a 70-year-old male with a complex medical history presented to a large academic medical center in the United States for vascular surgery. After surgery, the patient's white blood cell count increased prompting an infectious workup. The patient was found to have a Candida nivariensis bloodstream infection of unknown origin. Given the patient's clinical stability and QTc prolongation, he was treated with a 14-day course of oral isavuconazole. The patient experienced resolution of symptoms and clearance of subsequent blood cultures. At the time of writing this case report (11 months later), he has had no relapse of his fungal infection. Based on a search of the medical literature, this appears to be the first published case of Candida nivariensis fungemia successfully treated with oral isavuconazole.

Impact of an Interprofessional Collaborative Quality Improvement Initiative to Decrease Inappropriate Thyroid Function Testing.

Background: Published data show that thyroid function laboratory tests are often ordered inappropriately in the acute care setting, which leads to unnecessary costs and inappropriate therapy decisions. Pilot data at our institution indicated that approximately two-thirds of the thyroid-stimulating hormone (TSH) laboratories were unnecessary, correlating to a potential cost avoidance of more than $20,000 annually. The purpose of this study was to improve the appropriateness of thyroid function test ordering with a multipronged initiative. Methodology: This controlled, single-center, before and after study included inpatients or emergency department (ED) patients at Wake Forest Baptist Medical Center who were at least 18 years of age and had a TSH level ordered during the study period. Patients with a history of thyroid cancer were excluded. The initiative included an electronic ordering intervention, direct education of providers (medical residents, attendings, and clinical pharmacists), and distribution of pocket information cards with appropriate ordering criteria. The primary outcome was the number and percentage of inappropriate TSH tests ordered before and after implementing the 3 interventions. Secondary outcomes included cost savings, inappropriate changes in thyroid therapy based on improperly ordered tests, and the number of free T4 lab tests ordered on patients with a TSH within the therapeutic range. Results: All 3 interventions were implemented, except for education of ED residents and faculty, who chose to forgo the direct education component. Inappropriate ordering of TSH levels decreased from 63 to 50 (13% reduction, P = .062) after implementation. Inappropriate TSH ordering decreased across all services, except in the ED. Inappropriate Free T4 orders decreased from 191 to 133 (30% reduction, P = .01). There were no therapy changes based on inappropriate TSH orders. Extrapolated annual cost savings were approximately $6,000. Conclusion: This multipronged interprofessional collaborative quality improvement initiative was associated with a nonstatistically significant reduction in inappropriate TSH orders, statistically significant reduction in inappropriate free T4 orders, and cost savings. There was a reduction in inappropriate ordering across all services except the ED, which may have been due the ED not participating in the direct education component of the initiative.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19.

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

Impact of order entry alerts and modifications on doses of intravenous opioids dispensed during a national drug shortage.

PURPOSE: To address the intravenous (i.v.) opioid shortage, computer-based alerts and modifications were implemented over 2 phases beginning in August 2017 and February 2018, respectively. A study was conducted to assess the impact of these interventions on dispenses of intermittent doses of i.v. opioids during a national shortage. METHODS: A retrospective, single-center, pre- and postimplementation study was conducted to compare opioid dispenses from September 2017 through December 2017 (phase 1) and March 2018 through May 2018 (phase 2) with dispenses during the same time periods of the previous year (historical control periods). Dispense data for intermittent doses of i.v. fentanyl, hydromorphone, and morphine and select oral opioids were collected from automated dispensing cabinets (ADCs) located in nonprocedural areas. The primary endpoint was the percentage of total intermittent doses of i.v. and oral opioids that were dispensed for i.v. administration. A subanalysis accounting for unit type was conducted. Key secondary endpoints were the numbers of oral and i.v. opioid dispenses by month. RESULTS: The final analysis included data from 92 ADCs. The percentage of i.v. opioid dispenses significantly decreased, by 9.8% during phase 1 (P < 0.0001) and by 16.8% during phase 2 (P < 0.0001) compared to dispenses during the historical control periods. These decreases were significant across all unit types except pediatric units during phase 1. Average monthly dispenses of i.v. opioids were 49.9% and 74.2% fewer than dispenses during the historical control periods after the phase 1 and phase 2 implementations, respectively. CONCLUSION: Order entry alerts and modifications significantly decreased dispenses of intermittent doses of i.v. opioids during a national shortage, with demonstrated sustainability of decreases over 7 months.

Accuracy of and prescriber perceptions related to documenting antibiotic indications during order entry at an academic medical center.

PURPOSE: To assess the accuracy of antibiotic indication documentation provided during order entry and prescriber perceptions of the requirement to specify indications. METHODS: Patients who received 1 of 6 selected antibiotics from May 1 through June 30, 2017, were identified. Records of 30 randomly selected patients who received each study antibiotic were retrospectively reviewed. The primary endpoint was indication accuracy, defined as agreement of the indication entered during order entry with that documented in progress notes at the time of order entry. Secondary endpoints included correlation of entered indication and final diagnosis for empiric antibiotics. A brief survey was emailed to prescribers to assess the burden and perceptions of requiring an indication during order entry. RESULTS: Four thousand five hundred twenty-four patients received 1 or more doses of a study antibiotic. For the 180 patients selected for evaluation, 89.4% of indications were accurate. Indications for antibiotics ordered for prophylaxis were more likely to be inaccurate than those for empiric or definitive antibiotics (accuracy rates of 46%, 94%, and 92%, respectively, p < 0.05). For empiric antibiotics, 78.5% of indications documented at order entry matched the final diagnosis. Two hundred fifty-four of 863 prescribers (29%) responded to the survey request. Most respondents felt that documenting the indication took no more than 20 seconds, was a "minor nuisance" or "occasionally burdensome," and had no impact on their consideration of antibiotic appropriateness. CONCLUSION: With the exception of prophylaxis, the indications documented during order entry were sufficiently accurate to assist antimicrobial stewardship efforts. Although indication documentation was perceived as a minor burden, surveyed prescribers indicated it had only a minimal beneficial effect on antibiotic prescribing.

State of Privileging in Pharmacy: A Survey of Vizient-Affiliated Institutions.

Purpose: The process of privileging pharmacists is an important step in developing optimal pharmacy practice models. Currently, little published literature exists detailing the status of pharmacist privileging efforts. The objective of this study is to assess and characterize a snapshot of the current and future state of privileging practices in pharmacy at Vizient academic medical centers (AMCs) and their affiliate institutions. Methods: An electronic survey questionnaire was sent to Vizient pharmacy directors and their affiliates to assess institutional privileging practices and identify perceived or actual barriers. The survey was divided into 2 pathways based on the current status of privileging at the institution. Results: In total, 46 directors of pharmacy completed the survey. Only 33% (15/46) of pharmacy directors indicated they had a current privileging process in place. About 70% (21/30) of institutions without an established privileging process indicated they were considering establishing a process. For institutions without an established privileging process, most pharmacy directors identified a lack of organizational support and resources as barriers to implementation. Conclusion: Although credentialing and privileging is considered a national priority to aid in expanding and enhancing pharmacists' scope of practice, our survey demonstrated that few respondents currently have a privileging process in place. The results from this study may highlight important barriers and keys to success to be considered when implementing a privileging process.

Educational priorities of students in the entrustable professional activity era.

BACKGROUND: The Association of American Medical Colleges (AAMC) guidelines on the entrustable professional activities (EPAs) expected of graduating medical students were recently published. Although perceptions of educators, residents and programme directors have been described, the voice of senior medical students is lacking. METHODS: A single-institution cross-sectional study of senior medical students was performed. Student perceptions were collected and compared with: (1) national guidelines (i.e. the 13 newly developed undergraduate EPAs); (2) resident expectations (i.e. through comparison with a recently published survey from >28 000 residents); and (3) institutional objectives. Descriptive statistics were performed. RESULTS: A total of 113 students participated. The top three EPA-based educational priorities were 'recognising a patient requiring urgent/emergent care' (EPA10), 'performing procedures of a physician' (EPA12) and 'collaborating as an interprofessional' (EPA9). Over 80 per cent of students rated 'managing time efficiently' and 'communicating around care transitions' as very important pre-internship skills. Of the institutional objectives, 87 per cent rated 'recognising critically ill patients' and 'knowing when to ask for help' as the most important pre-internship skills. The voice of senior medical students is lacking CONCLUSIONS: Although the emphasis on knowing when to ask for help and communication around care transitions differed somewhat across stakeholders, educational priorities were shared by students, residents, educators and institutional objectives. These preliminary data support national assessments of perceptions and achievements of senior medical students to guide residency readiness in the EPA era.

Frequency of empiric antibiotic de-escalation in an acute care hospital with an established Antimicrobial Stewardship Program.

BACKGROUND: Expanding antimicrobial resistance patterns in the face of stagnant growth in novel antibiotic production underscores the importance of antibiotic stewardship in which de-escalation remains an integral component. We measured the frequency of antibiotic de-escalation in a tertiary care medical center with an established antimicrobial stewardship program to provide a plausible benchmark for de-escalation. METHODS: A retrospective, observational study was performed by review of randomly selected electronic medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at an 885-bed tertiary care medical center. Patient characteristics including antibiotic regimen, duration and indication, culture results, length of stay, and hospital mortality were evaluated. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or the discontinuation of antibiotics after initiation of piperacillin/tazobactam and vancomycin therapy. Subjects dying within 72 h of antibiotic initiation were considered not de-escalated for subsequent analysis and were subtracted from the study population in determining a modified mortality rate. RESULTS: The most commonly documented indications for piperacillin/tazobactam and vancomycin therapy were pneumonia and sepsis. Of the 240 patients studied, 151 (63%) had their antibiotic regimens de-escalated by 72 h. The proportion of patients de-escalated by 96 h with positive vs. negative cultures was similar, 71 and 72%, respectively. Median length of stay was 4 days shorter in de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82). CONCLUSIONS: The empiric antibiotic regimens of approximately two-thirds of patients were de-escalated by 72 h in an institution with a well-established antimicrobial stewardship program. While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation.

Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality.

PURPOSE: Pharmacy department contributions to a medical center's broad initiative to improve sepsis care outcomes are described. SUMMARY: Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital's multidisciplinary "Code Sepsis" initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital's intensive care units and to 51 minutes in non-critical care units, and the institution's performance on a widely used measure of sepsis-related mortality improved dramatically. CONCLUSION: Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality.

The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.

BACKGROUND: The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). METHODS: A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. CONCLUSIONS: Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.