At the break point: What needs to change for antimicrobial stewardship program pharmacists?

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A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.

Improving Vancomycin Stewardship in Critically Ill Children.

BACKGROUND AND OBJECTIVES: Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU. METHODS: We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction. RESULTS: Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin. CONCLUSION: Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.

Increasing Cefazolin Use for Perioperative Antibiotic Prophylaxis in Penicillin-Allergic Children.

BACKGROUND AND OBJECTIVES: Cefazolin, a first-generation cephalosporin, is the most commonly recommended antibiotic for perioperative prophylaxis to reduce surgical site infections. Children with a reported penicillin allergy often receive an alternative antibiotic because of a common misunderstanding of the cross-reactivity between these antibiotics. This use of alternative antibiotics in surgical populations have been associated with increased infections, antibiotic resistance, and health care costs. We aimed to increase the percentage of patients with nonsevere penicillin-class allergies who receive cefazolin for antibiotic prophylaxis. METHODS: A multidisciplinary team conducted this quality improvement initiative, with a series of 3 plan-do-study-act cycles aimed at children with nonsevere penicillin-class allergies undergoing surgical procedures that require antibiotic prophylaxis. The primary outcome measure was the percentage of surgical encounters among patients with nonsevere penicillin-class allergies who received cefazolin as antibiotic prophylaxis. Statistical process control charts were used to measure improvement over time. RESULTS: Approximately 400 children were involved in this project. There was special cause variation and a shift in the center line from 60% to 80% of eligible patients receiving cefazolin for antibiotic prophylaxis, which was sustained for the duration of the project. In the last month, 90% of eligible patient received cefazolin, surpassing our goal of 85%. This improvement has been sustained in the 5 months after project completion. We had no cases of severe allergic reactions in the operating room. CONCLUSIONS: Our multidisciplinary education-focused interventions were associated with a significant increase in the use of cefazolin for perioperative antibiotic prophylaxis in patient with penicillin allergies.

Utilization of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list (listserv) by healthcare professionals.

Optimizing pediatric antimicrobial stewardship is challenging. In this retrospective study, we evaluated 515 original e-mails to 482 members of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list (idlistserv@kids.wustl.edu). The plurality of threads discussed clinical practice guidelines, and pharmacists were most likely to initiate and respond. Representation was geographically diverse within and outside the United States.

Threatened efficiency not autonomy: Prescriber perceptions of an established pediatric antimicrobial stewardship program.

BACKGROUND: Implementing antimicrobial stewardship programs (ASPs) can be challenging due to prescriber resistance. Although barriers to implementing new ASPs have been identified, little is known about how prescribers perceive established programs. This information is critical to promoting the sustainability of ASPs. OBJECTIVE: To identify how prescribers perceive an established pediatric inpatient ASP that primarily utilizes prior authorization. METHODS: We conducted a cross-sectional survey administered from February through June 2017 in a large children's hospital. The survey contained closed- and open-ended questions. Descriptive statistics and thematic content analysis approaches were used to analyze responses. RESULTS: Of 394 prescribers invited, 160 (41%) responded. Prescribers had an overall favorable impression of the ASP, believing that it improves the quality of care (92.4% agree) and takes their judgment seriously (73.8%). The most common criticism of the ASP was that it threatened efficiency (26.0% agreed). In addition, 68.7% of respondents reported occasionally engaging in workarounds. Analysis of 133 free-text responses revealed that prescribers perceived that interacting with the ASP involved too many phone calls, caused communication breakdowns with the dispensing pharmacy, and led to gaps between approval and dispensing of antibiotics. Reasons given for workarounds included not wanting to change therapy that appears to be working, consultant disagreement with ASP recommendations, and the desire to do everything possible for patients. CONCLUSIONS: Prescribers had a generally favorable opinion of an established ASP but found aspects to be inefficient. They reported engaging in workarounds occasionally for social and emotional reasons. Established ASPs should elicit feedback from frontline prescribers to optimize program impact.

Design and Implementation of a Visual Analytics Electronic Antibiogram within an Electronic Health Record System at a Tertiary Pediatric Hospital.

BACKGROUND: Hospitals use antibiograms to guide optimal empiric antibiotic therapy, reduce inappropriate antibiotic usage, and identify areas requiring intervention by antimicrobial stewardship programs. Creating a hospital antibiogram is a time-consuming manual process that is typically performed annually. OBJECTIVE: We aimed to apply visual analytics software to electronic health record (EHR) data to build an automated, electronic antibiogram ("e-antibiogram") that adheres to national guidelines and contains filters for patient characteristics, thereby providing access to detailed, clinically relevant, and up-to-date antibiotic susceptibility data. METHODS: We used visual analytics software to develop a secure, EHR-linked, condition- and patient-specific e-antibiogram that supplies susceptibility maps for organisms and antibiotics in a comprehensive report that is updated on a monthly basis. Antimicrobial susceptibility data were grouped into nine clinical scenarios according to the specimen source, hospital unit, and infection type. We implemented the e-antibiogram within the EHR system at Children's Hospital of Philadelphia, a tertiary pediatric hospital and analyzed e-antibiogram access sessions from March 2016 to March 2017. RESULTS: The e-antibiogram was implemented in the EHR with over 6,000 inpatient, 4,500 outpatient, and 3,900 emergency department isolates. The e-antibiogram provides access to rolling 12-month pathogen and susceptibility data that is updated on a monthly basis. E-antibiogram access sessions increased from an average of 261 sessions per month during the first 3 months of the study to 345 sessions per month during the final 3 months. CONCLUSION: An e-antibiogram that was built and is updated using EHR data and adheres to national guidelines is a feasible replacement for an annual, static, manually compiled antibiogram. Future research will examine the impact of the e-antibiogram on antibiotic prescribing patterns.

Development and Application of an Antibiotic Spectrum Index for Benchmarking Antibiotic Selection Patterns Across Hospitals.

Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics. Infect Control Hosp Epidemiol 2017;38:993-997.

Safety of Automatic End Dates for Antimicrobial Orders to Facilitate Stewardship.

Following implementation of automatic end dates for antimicrobial orders to facilitate antimicrobial stewardship at a large, academic children's hospital, no differences were observed in patient mortality, length of stay, or readmission rates, even among patients with documented bacteremia. Infect Control Hosp Epidemiol 2016;37:974-978.

Impact of Infectious Diseases Society of America/Pediatric Infectious Diseases Society guidelines on treatment of community-acquired pneumonia in hospitalized children.

We examined the impact of the Pediatric Infectious Diseases Society/Infectious Diseases Society of America guidelines that recommend ampicillin or amoxicillin for children hospitalized with community-acquired pneumonia. Prescribing of ampicillin/amoxicillin increased following guideline publication, but remains low. Cephalosporin and macrolide prescribing decreased but remains common. Further studies exploring outcomes of and reasons for compliance with guidelines are warranted.

Identifying targets for antimicrobial stewardship in children's hospitals.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts. DESIGN: Retrospective cross-sectional study. SETTING AND PATIENTS: Children admitted to 32 freestanding children's hospitals in the United States in 2010. METHODS: We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness. RESULTS: In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions-pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection-represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions. CONCLUSIONS: Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.

Pragmatic estimates of the proportion of pediatric inpatients exposed to specific medications in the USA.

PURPOSE: To provide pragmatic national estimates of the proportion of hospitalized pediatric patients exposed to specific drugs in the USA. METHODS: We used Premier Perspective Database and the Pediatric Health Information System data including specific drug exposures of 1.15 million inpatients <18 years old in 411 general and 52 children's hospitals throughout the USA in 2006, extrapolating this information into the probability-based Kids' Inpatient Database, which has demographic and clinical characteristics but no drug exposure data. We used a multivariable stratified resampling (MSR) technique to estimate the proportion of drug exposure for the 700 most commonly used drugs and performed additional stability and sensitivity analyses for 19 drugs. RESULTS: The estimated proportion of pediatric inpatients exposed to specific drugs in 2006 ranged from high levels such as that of acetaminophen (17.36; 95%CI: 17.32, 17.41) to rare exposures such as bosentan (0.0018; 95%CI: 0.0013, 0.0023). Additional analyses for 19 drugs revealed that the MSR estimates were close to estimates generated by multivariable multiple imputation, with a maximum absolute difference of 0.03 for acetaminophen (17.36 vs. 17.33) and famotidine (1.90 vs. 1.93), and that even with 50% of the hospitals removed at random, the proportion estimates did not vary by more than 2.5-fold at the upper 97.5 percentile. CONCLUSIONS: These pragmatic national estimates of the proportion of pediatric inpatient drug exposures, generated using an MSR technique, provide a context for interpretation of drug-related adverse event reports and prioritization of pediatric pharmacology research.

The use of intravenous colistin among children in the United States: results from a multicenter, case series.

BACKGROUND: A rapid increase in multidrug-resistant Gram-negative infections has led to a reemergence of colistin use globally. Although it is well described among adults, colistin use and its associated toxicities in children are poorly understood. We report findings from the largest case series of pediatric colistin use to date. METHODS: We queried pediatric infectious diseases specialists from the Emerging Infections Network to identify members who had prescribed intravenous colistin within the past 7 years. We collected relevant demographic and clinical data. Bivariate analyses and multivariable logistic regression were performed. RESULTS: Two hundred twenty-nine pediatric infectious diseases specialists completed the survey (84% response); 22% had prescribed colistin to children. Among respondents, 92 cases of colistin use from 25 institutions were submitted. The most commonly targeted organisms were multidrug-resistant Pseudomonas (67.4%), multidrug-resistant Acinetobacter -baumanii (11.9%), carbapenemase-producing Enterobacteriaceae (13.0%) and extended-spectrum ß-lactamase producing Enterobacteriaceae (5.4%). Development of resistance to colistin was observed in 20.5% of patients. Additional antimicrobial therapy was administered to 84% of patients, and 22% of children experienced nephrotoxicity (not associated with dosage or interval of colistin prescribed). Renal function returned to baseline in all patients. Children aged ≥13 years had approximately 7 times the odds of developing nephrotoxicity than younger children, even after controlling for receipt of additional nephrotoxic agents (odds ratio 7.16; 95% confidence interval: 1.51-14.06; P = 0.013). Four children exhibited reversible neurotoxicity. CONCLUSIONS: Most pediatric infectious diseases specialists have no experience prescribing colistin. Colistin use in children has been associated primarily with nephrotoxicity and, to a lesser extent, neurotoxicity, both of which are reversible. Emergence of resistance to colistin is concerning.

Prevalence of polypharmacy exposure among hospitalized children in the United States.

OBJECTIVE: To assess the prevalence and patterns of exposure to drugs and therapeutic agents among hospitalized pediatric patients. DESIGN: Retrospective cohort study. SETTING: A total of 411 general hospitals and 52 children's hospitals throughout the United States. PATIENTS: A total of 587 427 patients younger than 18 years, excluding healthy newborns, hospitalized in 2006, representing one-fifth of all pediatric admissions in the United States. MAIN OUTCOME MEASURES: Daily and cumulative exposure to drugs and therapeutic agents. RESULTS: The most common exposures varied by patient age and by hospital type, with acetaminophen, albuterol, various antibiotics, fentanyl, heparin, ibuprofen, morphine, ondansetron, propofol, and ranitidine being among the most prevalent exposures. A considerable fraction of patients were exposed to numerous medications: in children's hospitals, on the first day of hospitalization, patients younger than 1 year at the 90th percentile of daily exposure to distinct medications received 11 drugs, and patients 1 year or older received 13 drugs; in general hospitals, 8 and 12 drugs, respectively. By hospital day 7, in children's hospitals, patients younger than 1 year at the 90th percentile of cumulative exposure to distinct distinct medications had received 29 drugs, and patients 1 year or older had received 35; in general hospitals, 22 and 28 drugs, respectively. Patients with less common conditions were more likely to be exposed to more drugs (P = .001). CONCLUSION: A large fraction of hospitalized pediatric patients are exposed to substantial polypharmacy, especially patients with rare conditions.

Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza.

Many children with influenza are treated with antibiotics. In this report, we describe the rate and indications for antibacterial use in children hospitalized with influenza. A total of 333 of 729 (46%) patients received >2 days of treatment with antibacterial medications, of whom 36% did not have an apparent indication for therapy.

Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: review of five seasons and evaluation of an electronic reminder.

BACKGROUND: When initiated within 48 hours of the onset of symptoms, oseltamivir has been shown to reduce severity and length of influenza illness. Few studies have evaluated the use of oseltamivir in patients hospitalized with influenza. OBJECTIVE: To describe the prescribing practices for oseltamivir in children hospitalized with influenza and to evaluate a mechanism to improve the rate of appropriate prescription. DESIGN, SETTING, PATIENTS: Retrospective cohort study of 929 patients aged 21 years or younger hospitalized with community-acquired laboratory-confirmed influenza (CA-LCI) during 5 consecutive seasons (2000-2005). We examined oseltamivir eligibility, which included patients 1 year of age or older with an influenza test result available within 48 hours of symptom onset. During the 2005-2006 season, an observational trial of an electronic reminder was conducted to improve the frequency of oseltamivir prescription. MEASUREMENTS: Oseltamivir prescription. RESULTS: Of 305 patients (32.8%) eligible for treatment with oseltamivir, 49 (16.1% of those eligible) were prescribed oseltamivir during hospitalization. Prescription rates for indications consistent with the US Food and Drug Administration (FDA) approval ("on label") increased from 0% to 37.2% over 5 seasons (P < 0.0001). Prescriptions outside this recommendation ("off label") also increased over 5 seasons (P < 0.0001). Twenty-nine (5%) of 624 patients were treated with oseltamivir off label; 11 were less than 1 year of age. Initiation of a reminder had no impact on prescription (P > 0.05). CONCLUSIONS: Oseltamivir was used infrequently for children hospitalized with influenza. In addition, use inconsistent with the FDA label of oseltamivir occurs. Mechanisms are needed to improve appropriate prescription of oseltamivir.

Evaluation of an antimicrobial stewardship program at a pediatric teaching hospital.

BACKGROUND: Thirty to 50% of hospitalized patients receive antimicrobial therapy. Previous data suggest that inappropriate use results in higher mortality rates, longer lengths of stay, and increased medical costs. Antimicrobial Stewardship Programs (ASPs) reduce the improper use of antimicrobials and improve patient safety. Despite increased awareness about the benefits of these programs, few pediatric ASPs exist and fewer comprehensive studies evaluate their effects. METHODS: A prospective observational study was conducted to describe the use and impact of a pediatric ASP. Data were collected on the clinician's request for targeted antibiotics and the interventions made by the ASP. Retrospective chart review was performed to assess outcomes and compliance on empiric antimicrobial therapy decisions and recommendations to discontinue antimicrobial therapy. RESULTS: During the 4-month study period, calls were placed to the ASP for 652 patients. Forty-five percent of those calls required an intervention by the ASP. These interventions included: (1) Targeting the known or suspected pathogens (20%); (2) Consultation (43%); (3) Optimize antimicrobial treatment (33%); and (4) Stop antimicrobial treatment (4%). Three of the 84 (3.5%) patients recommended to receive alternative therapy developed an infection not covered by the ASP recommendations or the antimicrobial initially requested by the clinician. CONCLUSIONS: Our data demonstrate that an ASP improves the appropriate use of antimicrobial medications in hospitalized children. In addition, the ASP plays an integral role in providing guidance to clinicians and ensures that the appropriate antimicrobial agents are used.