The Essential Role of Senior Care Pharmacists in Antimicrobial Stewardship: An Updated Position Statement on Behalf of the American Society of Consultant Pharmacists and the Society of Infectious Diseases Pharmacists.

Senior care pharmacists are well-positioned to lead and drive antimicrobial stewardship (AMS) initiatives, not only through audit and data collection, but also through communication, collaboration, and cooperation with prescribers and nurses to influence prescribing behaviors. Senior care pharmacists are in a unique position to take a leadership role within the interprofessional team to achieve AMS goals. They should engage with the interprofessional team to promote the judicious and appropriate use of antimicrobials at their practice sites. This position statement is an update of the 2017 version by the American Society of Consultant Pharmacists (ASCP) Antimicrobial Stewardship and Infection and Prevention Control Committee and the Society of Infectious Diseases Pharmacists (SIDP).

Reporting behaviors and perceptions toward the National Healthcare Safety Network antimicrobial use (AU) and antimicrobial resistance (AR) modules.

OBJECTIVES: To identify characteristics of US health systems and end users that report antimicrobial use and resistance (AUR) data, to determine how NHSN AUR data are used by hospitals and health systems and end users, and to identify barriers to AUR reporting. DESIGN: An anonymous survey was sent to Society of Infectious Diseases Pharmacists (SIDP) and Society for Healthcare Epidemiology of America (SHEA) Research Network members. METHODS: Data were collected via Survey Monkey from January 21 to February 21, 2020. Respondent and hospital data were analyzed using descriptive statistics. RESULTS: We received responses from 238 individuals across 43 US states. Respondents were primarily pharmacists (84%), from urban areas, (44%), from nonprofit medical centers (81%), and from hospitals with >250 beds (72%). Also, 62% reported data to the AU module and 19% reported data to the AR module. Use of software for local AU or AR tracking was associated with increased reporting to the AU module (19% vs 64%) and the AR module (2% vs 30%) (P < .001 each). Only 36% of those reporting data to the AU module used NHSN AUR data analysis tools regularly and only 9% reported data to the AR module regularly. Technical challenges and time and/or salary support were the most common barriers to AUR participation cited by all respondents. Among those not reporting AUR data, increased local expectations to report and better software solutions were the most commonly identified solutions to increase AUR reporting. CONCLUSIONS: Efforts to increase AUR reporting should focus on software solutions and salary support for data-entry activities. Increasing expectations to report may incentivize local resource allocation to improve AUR reporting rates.

Antimicrobials in Animal Agriculture in the United States: A Multidisciplinary Overview of Regulation and Utilization to Foster Collaboration: On Behalf Of the Society of Infectious Diseases Pharmacists.

Given the complexity of antimicrobial resistance and the dire implications of misusing antimicrobials, it is imperative to identify accurate and meaningful ways to understand and communicate the realities, challenges, and opportunities associated with antimicrobial utilization and measurement in all sectors, including in animal agriculture. The objectives of this article are to (i) describe how antimicrobials are regulated and used in US animal agriculture and (ii) highlight realities, challenges, and opportunities to foster multidisciplinary understanding of the common goal of responsible antimicrobial use. Recognition of the realities of medicine, practice, and policy in the agricultural setting is critical to identify realistic opportunities for improvement and collaboration.

Examining the Combination of Cefixime and Amoxicillin/Clavulanate against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates.

INTRODUCTION: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs. METHODS: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 µg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. RESULTS: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.

ß-Lactam Therapeutic Drug Monitoring in Critically Ill Patients: Weighing the Challenges and Opportunities to Assess Clinical Value.

OBJECTIVE: ß-lactams are the cornerstone of empiric and targeted antibiotic therapy for critically ill patients. Recently, there have been calls to use ß-lactam therapeutic drug monitoring (TDM) within 24-48 hours after the initiation of therapy in critically ill patients. In this article, we review the dynamic physiology of critically ill patients, ß-lactam dose response in critically ill patients, the impact of pathogen minimum inhibitory concentration (MIC) on ß-lactam TDM, and pharmacokinetics in critically ill patients. Additionally, we highlight available clinical data to better inform ß-lactam TDM for critically ill patients. DATA SOURCES: We retrospectively analyzed patients admitted for sepsis or septic shock at a single academic medical center who were treated with ß-lactam antibiotics. STUDY SELECTION: Indexed studies in PubMed in English language were selected for review on topics relative to critical care physiology, ß-lactams, pharmacokinetics/pharmacodynamics, TDM, and antibiotic susceptibility. DATA EXTRACTION: We reviewed potentially related studies on ß-lactams and TDM and summarized their design, patients, and results. This is a synthetic, nonsystematic, review. DATA SYNTHESIS: In the retrospective analysis of patients treated with ß-lactam antibiotics, approximately one-third of patients received less than 48 hours of ß-lactam therapy. Of those who continued beyond 48 hours, only 13.7% had patient-specific factors (augmented renal clearance, fluid overload, morbid obesity, and/or surgical drain), suggesting a potential benefit of ß-lactam TDM. CONCLUSIONS: These data indicate that a strategy of comprehensive ß-lactam TDM for critically ill patients is unwarranted as it has not been shown yet to improve patient-oriented outcomes. This review demonstrates that ß-lactam TDM in the ICU, while laudable, layers ambiguous ß-lactam exposure thresholds upon uncertain/unknown MIC data within a dynamic, unpredictable patient population for whom TDM results will not be available fast enough to significantly affect care. Judicious, targeted TDM for those with risk factors for ß-lactam over- or underexposure is a better approach but requires further study. Clinically, choosing the correct antibiotic and dosing ß-lactams aggressively, which have a wide therapeutic index, to overcome critical illness factors appears to give critically ill patients the best likelihood of survival.

Impact of Geodemographic Factors on Antibiotic Prescribing for Acute, Uncomplicated Bronchitis or Upper Respiratory Tract Infection.

OBJECTIVE: To assess the impact of geodemographic factors on antibiotic prescribing for adult acute, uncomplicated bronchitis or upper respiratory tract infection. METHODS: A retrospective, observational study of 63,051 single health-system, outpatient discharges with a primary diagnosis of bronchitis or upper respiratory tract infection in 2019. Univariate analyses of prescribing predictors and multivariable stepwise logistic modeling were performed. RESULTS: Patients who were older (aOR 1.02; 95% CI 1.02, 1.02), male (1.10; 1.06, 1.14), black (1.29; 1.22, 1.38), smoked (1.18; 1.14, 1.23), seen in urgent care (1.26; 1.22, 1.31) and living in an area with more owner-occupied housing (1.41; 1.30, 1.53) were more likely to receive antibiotics. Patients who were Asian (0.88; 0.77, 0.99), had Medicare (0.83; 0.78, 0.87), Medicaid (0.84; 0.79, 0.87) or Exchange insurance (0.90; 0.82, 0.98), or seen in the emergency department (0.43; 0.40, 0.46) were less likely to receive antibiotics. Distance from a patient's address and their encounter location did not predict antibiotic prescribing. CONCLUSIONS: Antibiotic prescribing interventions for adult acute bronchitis and upper respiratory tract infections could target patients living in an area with higher socioeconomic status.

Approaching 65 Years: Is It Time to Consider Retirement of Vancomycin for Treating Methicillin-Resistant Staphylococcus aureus Endovascular Infections?

Vancomycin was introduced nearly 65 years ago and remains the standard antibiotic for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Staphylococcus aureus remains highly susceptibility to vancomycin (>97%). Despite this, MRSA treatment failure with vancomycin is high in complicated bacteremia. Additionally, vancomycin can cause nephrotoxicity, leading to new therapeutic drug monitoring guidance. This demonstrates how difficult it is to dose vancomycin in a way that is both efficacious and safe, especially during long courses of therapy. Often underappreciated are the cost, resources, and complexity of vancomycin care at a time when alternative antibiotics are becoming cost comparable. This perspective highlights a bigger picture of how the treatment repertoires of many other diseases have changed and advanced since vancomycin's introduction in the 1950s, yet the vancomycin MRSA treatment standard remains. While vancomycin can still have a role, 65 years may be a practical retirement age for vancomycin in highly complex endovascular infections.

Impact of a Systematic Pharmacist-Initiated Antibiotic Time-Out Intervention for Hospitalized Adults.

INTRODUCTION: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. METHODS: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. RESULTS: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). DISCUSSION: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.

Long-Acting Lipoglycopeptides Can Interfere With Vancomycin Therapeutic Drug Monitoring.

Oritavancin and dalbavancin are long-acting lipoglycopeptides with activity against susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Though similar in structure to traditional glycopeptide antibiotics like vancomycin, these antibiotics have terminal half-lives >10 days, and, as a result, there is potential for administration of vancomycin to a patient while oritavancin or dalbavancin are still appreciably present in serum. Given the structural similarities, this creates an opportunity for lab assay interference when performing therapeutic drug monitoring for vancomycin. Following higher-than-expected serum vancomycin concentrations in a patient who received both oritavancin and vancomycin within a short time frame, we evaluated the potential for lipoglycopeptide interference with clinical vancomycin assays. Five platforms covering 3 immunoassay technologies were used to quantify vancomycin concentrations in serum spiked with oritavancin or dalbavancin. Oritavancin generated spurious vancomycin concentrations (20%-84% increase) in both enzyme-multiplied immunoassay technique and a particle-enhanced turbidimetric inhibition immunoassay. However, the improper detection of oritavancin was not consistent across all particle-enhanced turbidimetric inhibition immunoassay platforms. Dalbavancin interference was not detected on any of the platforms tested. The interference from oritavancin may result in falsely elevated vancomycin concentrations and, subsequently, inappropriately adjusted vancomycin doses.

Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?

Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.

Comparison of Clinical Outcomes among Intensive Care Unit Patients Receiving One or Two Grams of Ceftriaxone Daily.

Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 g of ceftriaxone daily for ≥72 h were included and categorized as receiving ceftriaxone 1 g or 2 g daily. The primary, composite outcome was treatment failure, defined as inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving 2 g of ceftriaxone daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort. A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 g and 2 g daily, respectively (P = 0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 g dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio [aOR] = 0.190; 95% confidence interval [CI] = 0.059 to 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR = 1.440; 95% CI = 1.254 to 1.653) and creatinine clearance at 72 h from ceftriaxone initiation (aOR = 0.980; 95% CI = 0.971 to 0.999). Therefore, ceftriaxone at 2 g daily, when used as appropriate antimicrobial coverage, may be appropriate for ICU patients with lower mortality risk.

Impact of an electronic best-practice advisory in combination with prescriber education on antibiotic prescribing for ambulatory adults with acute, uncomplicated bronchitis within a large integrated health system.

OBJECTIVE: To determine the impact of a passive, prescriber-directed, electronic best-practice advisory coupled with prescriber education on the rate of antibiotic prescribing for acute, uncomplicated bronchitis in ambulatory adults across a large health system. DESIGN: This study was a quasi-experiment examining antibiotic prescribing for ambulatory adults with acute bronchitis from January 1, 2016 through December 31, 2018. The intervention was implemented in December 2016 for emergency departments and urgent care clinics followed by ambulatory clinics in September 2017. SETTING: Outpatient settings across a health system, including 15 emergency departments, >30 urgent care clinics, and >150 ambulatory clinics. PARTICIPANTS: All adults with a primary diagnosis of acute bronchitis who were seen and discharged from a study site were included. INTERVENTIONS: A passive, prescriber-directed, best-practice advisory for treatment of acute bronchitis in the electronic health record and an optional, online education module regarding acute bronchitis. RESULTS: The study included 81,975 ambulatory adults with a primary diagnosis of acute bronchitis during the preintervention period (19.8% >65 years of age; 61.9% female) and 89,571 ambulatory adults during the postintervention period (16.5% >65 years of age; 61.1% female). Antibiotic prescribing rates decreased from 60.8% (49,877 of 81,975 patients) preintervention to 51.4% (46,018 of 89,571 patients) postintervention (absolute difference, 9.4%; P < .001). The largest reduction occurred in the emergency departments. CONCLUSIONS: An electronic best practice advisory combined with prescriber education was associated with a statistically significant reduction in antibiotic prescribing for adults with acute bronchitis. Future studies should incorporate patient education and address prescriber-reported barriers to appropriate antibiotic prescribing.

Examining the Relationship Between Vancomycin Area Under the Concentration Time Curve and Serum Trough Levels in Adults With Presumed or Documented Staphylococcal Infections.

BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing, but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using 2-level pharmacokinetic monitoring to inform changes to an institutional vancomycin dosing protocol. METHODS: This was a retrospective observational study performed in 2 acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20 mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to minimum inhibitory concentration ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected. RESULTS: Thirty-four patients were included in the study, with 2 patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%), and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± SD vancomycin Cmin was 16.6 ± 6.1 mg/L, and the mean AUC/MIC was 588 ± 156 mg/L × hour. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n = 31/34). Of the patients with a Cmin > 9 mg/L, 100% (n = 33) achieved AUC/MIC values >400 mg/L × hour and 93.9% were >500 mg/L × hour. There was a strong correlation between vancomycin Cmin and AUC24 hr (R = 0.731; P < 0.001). CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than that thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Exploring the Role of Piperacillin and Tazobactam in Combination with Vancomycin against Methicillin-Resistant Staphylococcus aureus.

Previous studies have demonstrated synergy between piperacillin (PIP)-tazobactam (TAZ) (TZP) and vancomycin (VAN) against methicillin-resistant Staphylococcus aureus (MRSA). However, it is unknown whether PIP and/or TAZ synergizes with VAN against MRSA. We sought to determine whether PIP and/or TAZ synergizes with VAN against MRSA in vitro. The activity of PIP and/or TAZ with and without VAN (1/2 the minimum inhibitory concentration) was tested against 5 clinical MRSA isolates using a 24-h time-kill methodology. Antibiotic susceptibilities, accessory gene regulator (agr) operon functionality, and US strain type were also determined for the isolates. The combination of VAN and TZP was bactericidal against 3/5 isolates and synergistic against 4/5 isolates tested. Neither PIP nor TAZ alone combined with VAN demonstrated a significant reduction in bacterial growth. The combination of TZP and VAN was less active against the lone isolate with agr dysfunction. In summation, the combination of VAN with both PIP and TAZ was required for synergy against MRSA. This antibiotic combination may not be effective against unique MRSA strain types.

Clinical and Economic Effects of a Pharmacist-Administered Antiretroviral Therapy Adherence Clinic for Patients Living with HIV.

BACKGROUND: Pharmacists have demonstrated the ability to improve patient adherence to antiretroviral therapy (ART). OBJECTIVE: To determine the clinical and economic effects of a pharmacist-administered ART adherence clinic for patients living with human immunodeficiency virus (HIV). METHODS: This pilot study with a pretest-posttest design examined the effect of a pharmacy adherence clinic on patient HIV viral load and CD4 count over a 6-month period. Patients with documented adherence problems were referred to the clinic. The pharmacist counseled patients at baseline and met with patients 1-2 weeks, 6 weeks, 3 months, and 6 months after starting ART. A societal perspective net cost analysis of the pharmacy adherence clinic was conducted to assess the economic efficiency of the intervention. RESULTS: Twenty-eight patients were enrolled in the study, and 16 patients reached completion. Median HIV RNA significantly decreased from 48,000 copies/mL (interquartile range [IQR] = 16,750-139,000) to undetectable (< 20 copies/mL) at 6 months for all study participants who completed the full intervention (P = 0.001). In the 3 months following the intervention, we estimated that it prevented approximately 0.13 secondary HIV infections among the sexual partners of the 16 participants who completed the intervention. The total cost of the intervention was $16,811 ($1,051 per patient), which was less than the future savings in averted HIV-related medical care expenditures ($49,702). CONCLUSIONS: A pharmacy adherence clinic that focused on early and sustained ART adherence interventions helped patients with documented medication adherence problems achieve an undetectable HIV RNA. The intervention was highly cost saving, with a return of nearly $3 in future medical care savings per dollar spent on the intervention. DISCLOSURES: This work was supported in part by a research grant to Dilworth, Mercier, and Borrego from the American Society of Health-System Pharmacists Foundation. Klein and Pinkerton were supported in part by grants T32-MH19985 and P30-MH52776, respectively, from the National Institute of Mental Health. No funding bodies had any role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Health Resources and Services Administration. The authors have no conflicts of interest to disclose. Study concept and design were contributed primarily by Dilworth, Mercier, and Borrego, along with the other authors. Dilworth took the lead in data collection, along with Pinkerton, Klein, Mercier, and Jakeman. Data interpretation was performed by Dilworth and Pinkerton, along with the other authors. The manuscript was written by Dilworth, Klein, and Jakeman, with assistance from the other authors, and revised by Dilworth, Jakeman, and Klein, with assistance from the other authors. The results from this study were presented in part at the 2015 United States Conference on AIDS in Washington, DC, on September 10-13, 2015.